WorldWideScience

Sample records for brugia malayi l3

  1. Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.

    Science.gov (United States)

    Rajan, T V; Bailis, J M; Yates, J A; Shultz, L D; Greiner, D L; Nelson, F K

    1994-12-01

    We have used the severe combined immunodeficient C.B-17-scid/scid mouse to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infection with the human filarial parasite, Brugia malayi. C.B-17-scid/scid mice are permissive for infection while immunocompetent C.B-17(-)+/+ mice are uniformly resistant. Reciprocal matings of C.B-17-scid/scid and C.B-17(-)+/+ mice were performed. The C.B-17-scid/scid females were either naive or infected with Brugia malayi. The resulting immunocompetent C.B-17-scid/+ and C.B-17(-)+/scid progeny were challenged at weaning with an intraperitoneal injection of Brugia malayi third stage larvae known to produce patent infection in > 95% of C.B-17-scid/scid mice. We observed that 40.0%l (34/85) of the immunocompetent offspring of C.B-17-scid/scid females x C.B-17(-)+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was observed in susceptibility to infection between the progeny of infected or uninfected C.B-17-scid/scid mothers mated with C.B-17(-)+/+ fathers, arguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous progeny of wild type C.B-17(-)+/+ females mated with C.B-17-scid/scid males were permissive. These observations document conversion of a 'resistant' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offspring susceptibility to infection with Brugia malayi.

  2. Deteksi Brugia malayi pada Armigeres subalbatus dan Culex quinquefasciatusyang diinfeksikan darah penderita filariasis dengan metode PCR

    Directory of Open Access Journals (Sweden)

    Yahya Yahya

    2015-01-01

    Full Text Available Abstract. Pemayungdistricts, Batanghari regency of Jambi province classified as filariasis endemic areas in Jambi province since the Mf rate reached 1.5% in 2011. A study was conducted to identify Brugia malayi on experimentally infected Ar. subalbatus and Cx. quinquefasciatus. An experimental study was performed with completely randomized design and six repetitions. Standard of treatment in this study was time (hours that selected for mosquitoes to bite the patients with filariasis (experimental infection. Selected time is at 9.00 a.m, 5.00 p.m, 9.00 p.m, and at 1.00 a.m. The results showed that filarial L3 larvae did not found on Ar. subalbatus and Cx. quinquefasciatus mosquitoes during surgery at day 11th to 13th after infection. Density of microfilariae in the blood of humans as a source of infection was 17 microfilariae per 20 micro liter blood. Otherwise, after detection by PCR, our study found positive B.malayi on Cx. quinquefasciatus thorax and proboscis. It indicates that Cx. quinquefasciatusas potential vector of B.malayi filariasis compared to Ar. subalbatus. Keywords: PCR, filariasis, Armigeres subalbatus, Culex quinquefasciatus, Brugia malayi   Abstrak. Kecamatan Pemayung Kabupaten Batanghari Provinsi Jambi merupakan wilayah endemis filariasis di Provinsi Jambi Karena angka Mf rate mencapai 1,5% pada tahun 2011. Penelitian ini untuk mengetahui tingkat kerentanan nyamuk Ar. subalbatus dan Cx. quinquefasciatus terhadap infeksi B. malayi subperiodik nokturna yang dilakukan pada tahun 2013, sehingga dapat dianalisis potensi nyamuk tersebut sebagai vektor filariasis di lokasi penelitian. Desain penelitian adalah eksperimental dengan rancangan acak lengkap dan enam kali pengulangan. Variabel perlakuan dalam penelitian ini adalah waktu (jam yang dipilih untuk menggigitkan nyamuk pada penderita filariasis (infeksi percobaan. Waktu yang dipilih adalah pukul 09.00 WIB, pukul 17.00 WIB, pukul 21.00 WIB dan pukul 01.00 WIB. Hasil penelitian

  3. Detection of a new focus of Brugia malayi infection in Orissa.

    Science.gov (United States)

    Rath, R N; Mohapatra, B N; Das, B

    1989-03-01

    526 people were surveyed in a village called Chudamani, in Balasore district of Orissa, for detection of asymptomatic microfilaria (mf) carriers. Of these 36 (6.8 per cent) were cases found to harbour mf; 19 cases had Brugia malayi, 4 Wuchereria bancrofti and 5 cases had mixed infection. In 8 cases, species could not be ascertained. For the first time after 1955, a focus of B. malayi has been detected in Orissa.

  4. Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin.

    Directory of Open Access Journals (Sweden)

    Hiruni Harischandra

    2018-04-01

    Full Text Available The filarial nematode Brugia malayi is an etiological agent of Lymphatic Filariasis. The capability of B. malayi and other parasitic nematodes to modulate host biology is recognized but the mechanisms by which such manipulation occurs are obscure. An emerging paradigm is the release of parasite-derived extracellular vesicles (EV containing bioactive proteins and small RNA species that allow secretion of parasite effector molecules and their potential trafficking to host tissues. We have previously described EV release from the infectious L3 stage B. malayi and here we profile vesicle release across all intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female worms. Nanoparticle Tracking Analysis was used to quantify and size EVs revealing discrete vesicle populations and indicating a secretory process that is conserved across the life cycle. Brugia EVs are internalized by murine macrophages with no preference for life stage suggesting a uniform mechanism for effector molecule trafficking. Further, the use of chemical uptake inhibitors suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling of adult male and female EVs using nano-scale LC-MS/MS described quantitative and qualitative differences in the adult EV proteome, helping define the biogenesis of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia life stages. Further this drug effect was also observed in the related filarial nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin-unresponsive field isolate of that parasite, highlighting a potential mechanism of action for this drug and suggesting new screening platforms for anti-filarial drug development.

  5. The solution structure of the forkhead box-O DNA binding domain of Brugia malayi DAF-16a.

    Science.gov (United States)

    Casper, Sarah K; Schoeller, Scott J; Zgoba, Danielle M; Phillips, Andrew J; Morien, Thomas J; Chaffee, Gary R; Sackett, Peter C; Peterson, Francis C; Crossgrove, Kirsten; Veldkamp, Christopher T

    2014-12-01

    Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. Here the solution structure of the forkhead DNA binding domain of Brugia malayi DAF-16a, a putative ortholog of Caenorhabditis elegans DAF-16, is reported. It is believed to be the first structure of a forkhead or winged helix domain from an invertebrate. C. elegans DAF-16 is involved in the insulin/IGF-I signaling pathway and helps control metabolism, longevity, and development. Conservation of sequence and structure with human FOXO proteins suggests that B. malayi DAF-16a is a member of the FOXO family of forkhead proteins. © 2014 Wiley Periodicals, Inc.

  6. Suppression of Brugia malayi (sub-periodic larval development in Aedes aegypti (Liverpool strain fed on blood of animals immunized with microfilariae

    Directory of Open Access Journals (Sweden)

    K Athisaya Mary

    2005-07-01

    Full Text Available Preliminary studies were carried out to investigate the role of filarial specific antibodies, raised in an animal model against the filarial parasite, Brugia malayi (sub-periodic, in blocking their early development in an experimental mosquito host, Aedes aegypti (Liverpool strain. In order to generate filarial specific antibodies, Mongolian gerbils, Meriones unguiculatus, were immunized either with live microfilariae (mf of B. malayi or their homogenate. Mf were harvested from the peritoneal cavity of Mongolian gerbils with patent infection of B. malayi and fed to A. aegypti along with the blood from immunized animals. Development of the parasite in infected mosquitoes was monitored until they reached infective stage larvae (L3. Fewer number of parasites developed to first stage (L1 and subsequently to L2 and L3 in mosquitoes fed with blood of immunized animals, when compared to those fed with blood of control animals. The results thus indicated that filarial parasite specific antibodies present in the blood of the immunized animals resulted in the reduction of number of larvae of B. malayi developing in the mosquito host.

  7. Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3

    Directory of Open Access Journals (Sweden)

    Spiro David

    2009-06-01

    Full Text Available Abstract Background Filarial nematode parasites cause serious diseases such as elephantiasis and river blindness in humans, and heartworm infections in dogs. Third stage filarial larvae (L3 are a critical stage in the life cycle of filarial parasites, because this is the stage that is transmitted by arthropod vectors to initiate infections in mammals. Improved understanding of molecular mechanisms associated with this transition may provide important leads for development of new therapies and vaccines to prevent filarial infections. This study explores changes in gene expression associated with the transition of Brugia malayi third stage larvae (BmL3 from mosquitoes into mammalian hosts and how these changes are affected by radiation. Radiation effects are especially interesting because irradiated L3 induce partial immunity to filarial infections. The underlying molecular mechanisms responsible for the efficacy of such vaccines are unkown. Results Expression profiles were obtained using a new filarial microarray with 18, 104 64-mer elements. 771 genes were identified as differentially expressed in two-way comparative analyses of the three L3 types. 353 genes were up-regulated in mosquito L3 (L3i relative to cultured L3 (L3c. These genes are important for establishment of filarial infections in mammalian hosts. Other genes were up-regulated in L3c relative to L3i (234 or irradiated L3 (L3ir (22. These culture-induced transcripts include key molecules required for growth and development. 165 genes were up-regulated in L3ir relative to L3c; these genes encode highly immunogenic proteins and proteins involved in radiation repair. L3ir and L3i have similar transcription profiles for genes that encode highly immunogenic proteins, antioxidants and cuticle components. Conclusion Changes in gene expression that normally occur during culture under conditions that support L3 development and molting are prevented or delayed by radiation. This may explain

  8. Mining predicted essential genes of Brugia malayi for nematode drug targets.

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar

    Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.

  9. Inventory and analysis of ATP-binding cassette (ABC) systems in Brugia malayi.

    Science.gov (United States)

    Ardelli, B F; Stitt, L E; Tompkins, J B

    2010-07-01

    ABC systems are one of the largest described protein superfamilies. These systems have a domain organization that may contain 1 or more transmembrane domains (ABC_TM1F) and 1 or 2 ATP-binding domains (ABC_2). The functions (e.g., import, export and DNA repair) of these proteins distinguish the 3 classes of ABC systems. Mining and PCR-based cloning were used to identify 33 putative ABC systems from the Brugia malayi genome. There were 31 class 2 genes, commonly called ABC transporters, and 2 class 3 genes. The ABC transporters were divided into subfamilies. Three belonged to subfamily A, 16 to subfamily B, 5 to subfamily C, 1 to subfamily E and 3 to subfamilies F and G, respectively. None were placed in subfamilies D and H. Similar to other ABC systems, the ABC_2 domain of B. malayi genes was conserved and contained the Walker A and B motifs, the signature sequence/linker region and the switch region with the conserved histidine. The ABC_TM1F domain was less conserved. The relative abundance of ABC systems was quantified using real-time reverse transcription PCR and was significantly higher in female adults of B. malayi than in males and microfilaria, particularly those in subfamilies B and C, which are associated with drug resistance.

  10. Effects of Doxycycline on gene expression in Wolbachia and Brugia malayi adult female worms in vivo

    Directory of Open Access Journals (Sweden)

    Rao Ramakrishna U

    2012-02-01

    Full Text Available Abstract Background Most filarial nematodes contain Wolbachia symbionts. The purpose of this study was to examine the effects of doxycycline on gene expression in Wolbachia and adult female Brugia malayi. Methods Brugia malayi infected gerbils were treated with doxycycline for 6-weeks. This treatment largely cleared Wolbachia and arrested worm reproduction. RNA recovered from treated and control female worms was labeled by random priming and hybridized to the Version 2- filarial microarray to obtain expression profiles. Results and discussion Results showed significant changes in expression for 200 Wolbachia (29% of Wolbachia genes with expression signals in untreated worms and 546 B. malayi array elements after treatment. These elements correspond to known genes and also to novel genes with unknown biological functions. Most differentially expressed Wolbachia genes were down-regulated after treatment (98.5%. In contrast, doxycycline had a mixed effect on B. malayi gene expression with many more genes being significantly up-regulated after treatment (85% of differentially expressed genes. Genes and processes involved in reproduction (gender-regulated genes, collagen, amino acid metabolism, ribosomal processes, and cytoskeleton were down-regulated after doxycycline while up-regulated genes and pathways suggest adaptations for survival in response to stress (energy metabolism, electron transport, anti-oxidants, nutrient transport, bacterial signaling pathways, and immune evasion. Conclusions Doxycycline reduced Wolbachia and significantly decreased bacterial gene expression. Wolbachia ribosomes are believed to be the primary biological target for doxycycline in filarial worms. B. malayi genes essential for reproduction, growth and development were also down-regulated; these changes are consistent with doxycycline effects on embryo development and reproduction. On the other hand, many B. malayi genes involved in energy production, electron

  11. Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner.

    Directory of Open Access Journals (Sweden)

    Jan-Hendrik Schroeder

    2017-05-01

    Full Text Available Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators.

  12. Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.

    Directory of Open Access Journals (Sweden)

    Alexandra Grote

    2017-03-01

    Full Text Available Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis.To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode's development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response.This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.

  13. Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling.

    Directory of Open Access Journals (Sweden)

    Sasisekhar Bennuru

    Full Text Available Relatively little is known about the filarial proteins that interact with the human host. Although the filarial genome has recently been completed, protein profiles have been limited to only a few recombinants or purified proteins of interest. Here, we describe a large-scale proteomic analysis using microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry to identify the excretory-secretory (ES products of the L3, L3 to L4 molting ES, adult male, adult female, and microfilarial stages of the filarial parasite Brugia malayi. The analysis of the ES products from adult male, adult female, microfilariae (Mf, L3, and molting L3 larvae identified 852 proteins. Annotation suggests that the functional and component distribution was very similar across each of the stages studied; however, the Mf contributed a higher proportion to the total number of identified proteins than the other stages. Of the 852 proteins identified in the ES, only 229 had previous confirmatory expressed sequence tags (ESTs in the available databases. Moreover, this analysis was able to confirm the presence of 274 "hypothetical" proteins inferred from gene prediction algorithms applied to the B. malayi (Bm genome. Not surprisingly, the majority (160/274 of these "hypothetical" proteins were predicted to be secreted by Signal IP and/or SecretomeP 2.0 analysis. Of major interest is the abundance of previously characterized immunomodulatory proteins such as ES-62 (leucyl aminopeptidase, MIF-1, SERPIN, glutathione peroxidase, and galectin in the ES of microfilariae (and Mf-containing adult females compared to the adult males. In addition, searching the ES protein spectra against the Wolbachia database resulted in the identification of 90 Wolbachia-specific proteins, most of which were metabolic enzymes that have not been shown to be immunogenic. This proteomic analysis extends our knowledge of the ES and provides insight into the host-parasite interaction.

  14. Live Brugia malayi microfilariae inhibit transendothelial migration of neutrophils and monocytes.

    Directory of Open Access Journals (Sweden)

    Jan-Hendrik Schroeder

    Full Text Available Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi. Microfilariae (Mf circulate in the peripheral blood for 2-3 hours in synchronisation with maximal feeding of the mosquito vector. When absent from the peripheral blood, Mf sequester in the capillaries of the lungs. Mf are therefore in close contact with vascular endothelial cells (EC and may induce EC immune function and/or wound repair mechanisms such as angiogenesis. In this study, Mf were co-cultured with human umbilical vein EC (HUVEC or human lung microvascular EC (HLMVEC and the transendothelial migration of leukocyte subsets was analysed. In addition, the protein and/or mRNA expression of chemokine, cytokine and angiogenic mediators in endothelial cells in the presence of live microfilariae were measured by a combination of cDNA arrays, protein arrays, ELISA and fluorescence antibody tests.Surprisingly, our findings indicate that Mf presence partially blocked transendothelial migration of monocytes and neutrophils, but not lymphocytes. However, Mf exposure did not result in altered vascular EC expression of key mediators of the tethering stage of extravasation, such as ICAM-1, VCAM-1 and various chemokines. To further analyse the immunological function of vascular EC in the presence of Mf, we measured the mRNA and/or protein expression of a number of pro-inflammatory mediators. We found that expression levels of the mediators tested were predominantly unaltered upon B. malayi Mf exposure. In addition, a comparison of angiogenic mediators induced by intact Mf and Wolbachia-depleted Mf revealed that even intact Mf induce the expression of remarkably few angiogenic mediators in vascular EC. Our study suggests that live microfilariae are remarkably inert in their induction and/or activation of vascular cells in their immediate local environment. Overall, this work presents important insights into the immunological function of the vascular endothelium during

  15. Identification of anti-filarial leads against aspartate semialdehyde dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular docking and molecular dynamics approaches.

    Science.gov (United States)

    Amala, Mathimaran; Rajamanikandan, Sundaraj; Prabhu, Dhamodharan; Surekha, Kanagarajan; Jeyakanthan, Jeyaraman

    2018-02-06

    Lymphatic filariasis is a debilitating vector borne parasitic disease that infects human lymphatic system by nematode Brugia malayi. Currently available anti-filarial drugs are effective only on the larval stages of parasite. So far, no effective drugs are available for humans to treat filarial infections. In this regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic pathway from Wolbachia endosymbiont Brugia malayi represents an attractive therapeutic target for the development of novel anti-filarial agents. In this present study, molecular modeling combined with molecular dynamics simulations and structure-based virtual screening were performed to identify potent lead molecules against ASDase. Based on Glide score, toxicity profile, binding affinity and mode of interactions with the ASDase, five potent lead molecules were selected. The molecular docking and dynamics results revealed that the amino acid residues Arg103, Asn133, Cys134, Gln161, Ser164, Lys218, Arg239, His246, and Asn321 plays a crucial role in effective binding of Top leads into the active site of ASDase. The stability of the ASDase-lead complexes was confirmed by running the 30 ns molecular dynamics simulations. The pharmacokinetic properties of the identified lead molecules are in the acceptable range. Furthermore, density functional theory and binding free energy calculations were performed to rank the lead molecules. Thus, the identified lead molecules can be used for the development of anti-filarial agents to combat the pathogenecity of Brugia malayi.

  16. Detection of human filarial parasite Brugia malayi in dogs by histochemical staining and molecular techniques.

    Science.gov (United States)

    Ambily, V R; Pillai, Usha Narayana; Arun, R; Pramod, S; Jayakumar, K M

    2011-09-27

    Human filariasis caused by Brugia malayi is still a public health problem in many countries of Asia including India, Indonesia, Malaysia and Thailand. The World Health Organization (WHO) has targeted to eliminate filariasis by the year 2020 by Mass annual single dose Diethylcarbamazine Administration (MDA). Results of the MDA programme after the first phase was less satisfactory than expected. Malayan filariasis caused by B. malayi is endemic in the south of Thailand where domestic cat serves as the major reservoir host. There is no report about the occurrence of B. malayi in dogs. The present work was carried out to find out the incidence of microfilariasis in dogs and also to detect the presence of human filarial infection in dogs, if any. One hundred dogs above 6 months of age presented to the veterinary college Hospital, Mannuthy, Kerala, with clinical signs suggestive of microfilariasis - fever, anorexia, conjunctivitis, limb and scrotal oedema - were screened for microfilariae by wet film examination. Positive cases were subjected to Giemsa staining, histochemical staining and molecular techniques. Results of the study showed that 80% of dogs had microfilariasis; out of which 20% had sheathed microfilaria. Giemsa and histochemical staining character, PCR and sequencing confirmed it as B. malayi. High prevalence of B. malayi in dogs in this study emphasized the possible role of dogs in transmission of human filariasis. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Comparison of an enzyme linked immunosorbent assay (ELISA) and a radioallergosorbent test (RAST) for detection of IgE antibodies to Brugia malayi

    NARCIS (Netherlands)

    Wahyuni, Sitti; van Ree, Ronald; Mangali, Andarias; Supali, Taniawati; Yazdanbakhsh, Maria; Sartono, Erliyani

    2003-01-01

    The enzyme linked immunosorbent assay (ELISA) for specific IgE antibodies to Brugia malayi was compared with the radioallergosorbent test (RAST) for use in immunoepidemiological studies of lymphatic filariasis. Sera used were from individuals (aged 5-82 years) living in an area endemic for lymphatic

  18. Galactolipids from Bauhinia racemosa as a new class of antifilarial agents against human lymphatic filarial parasite, Brugia malayi.

    Science.gov (United States)

    Sashidhara, Koneni V; Singh, Suriya P; Misra, Sweta; Gupta, Jyoti; Misra-Bhattacharya, Shailja

    2012-04-01

    Bioassay guided fractionation of ethanolic extract of the leaves of Bauhinia racemosa led to the isolation of galactolipid and catechin class of the compounds (1-7) from the most active n-butanol fraction (F4). Among the active galactolipids, 1 emerged as the lead molecule which was active on both forms of lymphatic filarial parasite, Brugia malayi. It was found to be better than the standard drug ivermectin and diethylcarbamazine (DEC) in terms of dose and efficacy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Identification and characterization of nematode specific protective epitopes of Brugia malayi TRX towards development of synthetic vaccine construct for lymphatic filariasis.

    Science.gov (United States)

    Madhumathi, Jayaprakasam; Prince, Prabhu Rajaiah; Anugraha, Gandhirajan; Kiran, Pote; Rao, Donthamsetty Nageswara; Reddy, Maryada Venkata Rami; Kaliraj, Perumal

    2010-07-12

    Although multi-epitope vaccines have been evaluated for various diseases, they have not yet been investigated for lymphatic filariasis. Here, we report for the first time identification of two immunodominant B epitopes (TRXP1 and TRXP2) from the antioxidant Brugia malayi thioredoxin by studying their immune responses in mice model and human subjects. TRXP1 was also found to harbor a T epitope recognized by human PBMCs and mice splenocytes. Further, the epitopic peptides were synthesized as a single peptide conjugate (PC1) and their prophylactic efficacy was tested in a murine model of filariasis with L3 larvae. PC1 conferred a significantly high protection (75.14%) (P TRX (63.03%) (P < 0.018) in experimental filariasis. Our results suggest that multi-epitope vaccines could be a promising strategy in the control of lymphatic filariasis.

  20. Production of Brugia malayi BmSXP Recombinant Protein Expressed in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Khoo, T. K.

    2010-01-01

    Full Text Available A rapid antibody detection test is very useful for detection of lymphatic filariasis, especially for certification and surveillance of post-mass drug administration. One such kit, panLF RapidTM (commercialized by Malaysian BioDiagnostic Research Sdn. Bhd. had been developed in our laboratory for the detection of all species of filarial infections. It is based on the detection of anti-filarial IgG4 antibodies that react with recombinant Brugia malayi antigens, BmR1 and BmSXP. In this study, the growth of recombinant bacteria that produce BmSXP was optimized under shake flask fermentation for high yield of the recombinant antigen. The optimizations involved selection of suitable growth medium, IPTG concentration and induction time. The medium that yielded the highest biomass as well as total protein was Terrific Broth (TB medium, which is an undefined medium. Initiation of induction of protein expression was found to be best at mid-log phase (OD600 = 1.5, with IPTG concentration of 1.0 mM, and harvest time at 9 h post-induction. This study showed that under the optimized conditions, the shake flask culture produced 4 g/L biomass (dry cell weight of recombinant Escherichia coli BmSXP/pPROEXHTa/TOP10F’, which yielded 2.42 mg/L of purified BmSXP recombinant antigen. The purified antigen was analyzed by SDS-PAGE and the antigenicity of protein was confirmed by Western blot.

  1. Expression of five acetylcholine receptor subunit genes in Brugia malayi adult worms

    Directory of Open Access Journals (Sweden)

    Ben-Wen Li

    2015-12-01

    Full Text Available Acetylcholine receptors (AChRs are required for body movement in parasitic nematodes and are targets of “classical” anthelmintic drugs such as levamisole and pyrantel and of newer drugs such as tribendimidine and derquantel. While neurotransmission explains the effects of these drugs on nematode movement, their effects on parasite reproduction are unexplained. The levamisole AChR type (L-AChRs in Caenorhabditis elegans is comprised of five subunits: Cel-UNC-29, Cel-UNC-38, Cel-UNC-63, Cel-LEV-1 and Cel-LEV-8. The genome of the filarial parasite Brugia malayi contains nine AChRs subunits including orthologues of Cel-unc-29, Cel-unc-38, and Cel-unc-63. We performed in situ hybridization with RNA probes to localize the expression of five AChR genes (Bm1_35890-Bma-unc-29, Bm1_20330-Bma-unc-38, Bm1_38195-Bma-unc-63, Bm1_48815-Bma-acr-26 and Bm1_40515-Bma-acr-12 in B. malayi adult worms. Four of these genes had similar expression patterns with signals in body muscle, developing embryos, spermatogonia, uterine wall adjacent to stretched microfilariae, wall of Vas deferens, and lateral cord. Three L-AChR subunit genes (Bma-unc-29, Bma-unc-38 and Bma-unc-63 were expressed in body muscle, which is a known target of levamisole. Bma-acr-12 was co-expressed with these levamisole subunit genes in muscle, and this suggests that its protein product may form receptors with other alpha subunits. Bma-acr-26 was expressed in male muscle but not in female muscle. Strong expression signals of these genes in early embryos and gametes in uterus and testis suggest that AChRs may have a role in nervous system development of embryogenesis and spermatogenesis. This would be consistent with embryotoxic effects of drugs that target these receptors in filarial worms. Our data show that the expression of these receptor genes is tightly regulated with regard to localization in adult worms and developmental stage in embryos and gametes. These results may help to explain the

  2. Infective Larvae of Brugia malayi Induce Polarization of Host Macrophages that Helps in Immune Evasion

    Directory of Open Access Journals (Sweden)

    Aditi Sharma

    2018-02-01

    Full Text Available Filarial parasites suppress, divert, or polarize the host immune response to aid their survival. However, mechanisms that govern the polarization of host MΦs during early filarial infection are not completely understood. In this study, we infected BALB/c mice with infective larvae stage-3 of Brugia malayi (Bm-L3 and studied their effect on the polarization of splenic MΦs. Results showed that MΦs displayed M2-phenotype by day 3 p.i. characterized by upregulated IL-4, but reduced IL-12 and Prostaglandin-D2 secretion. Increased arginase activity, higher arginase-1 but reduced NOS2 expression and poor phagocytic and antigen processing capacity was also observed. M2 MΦs supported T-cell proliferation and characteristically upregulated p-ERK but downregulated NF-κB-p65 and NF-κB-p50/105. Notably, Bm-L3 synergized with host regulatory T-cells (Tregs and polarized M2 MΦs to regulatory MΦs (Mregs by day 7 p.i., which secreted copious amounts of IL-10 and prostaglandin-E2. Mregs also showed upregulated expression levels of MHC-II, CD80, and CD86 and exhibited increased antigen-processing capacity but displayed impaired activation of NF-κB-p65 and NF-κB-p50/105. Neutralization of Tregs by anti-GITR + anti-CD25 antibodies checked the polarization of M2 MΦs to Mregs, decreased accumulation of regulatory B cells and inflammatory monocytes, and reduced secretion of IL-10, but enhanced IL-4 production and percentages of eosinophils, which led to Bm-L3 killing. In summary, we report hitherto undocumented effects of early Bm-L3 infection on the polarization of splenic MΦs and show how infective larvae deftly utilize the functional plasticity of host MΦs to establish themselves inside the host.

  3. Immunization with Brugia malayi Myosin as Heterologous DNA Prime Protein Boost Induces Protective Immunity against B. malayi Infection in Mastomys coucha.

    Directory of Open Access Journals (Sweden)

    Jyoti Gupta

    Full Text Available The current control strategies employing chemotherapy with diethylcarbamazine, ivermectin and albendazole have reduced transmission in some filaria-endemic areas, there is growing interest for complementary approaches, such as vaccines especially in light of threat of parasite developing resistance to mainstay drugs. We earlier demonstrated recombinant heavy chain myosin of B. malayi (Bm-Myo as a potent vaccine candidate whose efficacy was enhanced by heterologous DNA prime/protein boost (Myo-pcD+Bm-Myo vaccination in BALB/c mice. BALB/c mouse though does not support the full developmental cycle of B. malayi, however, the degree of protection may be studied in terms of transformation of challenged infective larvae (L3 to next stage (L4 with an ease of delineating the generated immunological response of host. In the current investigation, DNA vaccination with Bm-Myo was therefore undertaken in susceptible rodent host, Mastomys coucha (M. coucha which sustains the challenged L3 and facilitates their further development to sexually mature adult parasites with patent microfilaraemia. Immunization schedule consisted of Myo-pcD and Myo-pcD+Bm-Myo followed by B. malayi L3 challenge and the degree of protection was evaluated by observing microfilaraemia as well as adult worm establishment. Myo-pcD+Bm-Myo immunized animals not only developed 78.5% reduced blood microfilarial density but also decreased adult worm establishment by 75.3%. In addition, 75.4% of the recovered live females revealed sterilization over those of respective control animals. Myo-pcD+Bm-Myo triggered higher production of specific IgG and its isotypes which induced marked cellular adhesion and cytotoxicity (ADCC to microfilariae (mf and L3 in vitro. Both Th1 and Th2 cytokines were significantly up-regulated displaying a mixed immune response conferring considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges

  4. Functional analysis of the cathepsin-like cysteine protease genes in adult Brugia malayi using RNA interference.

    Directory of Open Access Journals (Sweden)

    Louise Ford

    Full Text Available Cathepsin-like enzymes have been identified as potential targets for drug or vaccine development in many parasites, as their functions appear to be essential in a variety of important biological processes within the host, such as molting, cuticle remodeling, embryogenesis, feeding and immune evasion. Functional analysis of Caenorhabditis elegans cathepsin L (Ce-cpl-1 and cathepsin Z (Ce-cpz-1 has established that both genes are required for early embryogenesis, with Ce-cpl-1 having a role in regulating in part the processing of yolk proteins. Ce-cpz-1 also has an important role during molting.RNA interference assays have allowed us to verify whether the functions of the orthologous filarial genes in Brugia malayi adult female worms are similar. Treatment of B. malayi adult female worms with Bm-cpl-1, Bm-cpl-5, which belong to group Ia of the filarial cpl gene family, or Bm-cpz-1 dsRNA resulted in decreased numbers of secreted microfilariae in vitro. In addition, analysis of the intrauterine progeny of the Bm-cpl-5 or Bm-cpl Pro dsRNA- and siRNA-treated worms revealed a clear disruption in the process of embryogenesis resulting in structural abnormalities in embryos and a varied differential development of embryonic stages.Our studies suggest that these filarial cathepsin-like cysteine proteases are likely to be functional orthologs of the C. elegans genes. This functional conservation may thus allow for a more thorough investigation of their distinct functions and their development as potential drug targets.

  5. Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

    Directory of Open Access Journals (Sweden)

    Susheela Kushwaha

    Full Text Available Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF.

  6. The role of polymorphisms in the spliced leader addition domain in determining promoter activity in Brugia malayi.

    Science.gov (United States)

    Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R

    2011-03-01

    Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Immunogenicity and Protective Efficacy of Brugia malayi Heavy Chain Myosin as Homologous DNA, Protein and Heterologous DNA/Protein Prime Boost Vaccine in Rodent Model.

    Directory of Open Access Journals (Sweden)

    Jyoti Gupta

    Full Text Available We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo of Brugia malayi (B. malayi in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+ and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%±2.32 against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%±2.23 and pcD-Myo (41.6%±2.45. In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD-Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC to B. malayi infective larvae (L3. pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-γ and anti-inflammatory (IL-4, IL-10 cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of

  8. The n-hexane and chloroform fractions of Piper betle L. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filarid Brugia malayi.

    Science.gov (United States)

    Singh, Meghna; Shakya, Shilpy; Soni, Vishal Kumar; Dangi, Anil; Kumar, Nikhil; Bhattacharya, Shailja-Misra

    2009-06-01

    Modulation of immune functions by using herbal plants and their products has become fundamental regime of therapeutic approach. Piper betle Linn. (Piperaceae) is a widely distributed plant in the tropical and subtropical regions of the world and has been attributed as traditional herbal remedy for many diseases. We have recently reported the antifilarial and antileishmanial efficacy in the leaf extract of Bangla Mahoba landrace of P. betle which is a female plant. The present report describes the in vivo immunomodulatory efficacy of the crude methanolic extract and its n-hexane, chloroform, n-butanol fractions of the female plant at various dose levels ranging between 0.3 and 500 mg/kg in BALB/c. Attempts were also made to observe antifilarial activity of the active extracts and correlate it with the antigen specific immune responses in another rodent Mastomys coucha infected with human lymphatic filarial parasite Brugia malayi. The crude methanol extract and n-hexane fraction were found to potentiate significant (p<0.001) enhancement of both humoral (plaque forming cells, hemagglutination titre) as well as cell-mediated (lymphoproliferation, macrophage activation, delayed type hypersensitivity) immune responses in mice. The flow cytometric analysis of splenocytes of treated mice indicated enhanced population of T-cells (CD4(+), CD8(+)) and B-cells (CD19(+)). The n-hexane fraction (3 mg/kg) was found to induce biased type 2 cytokine response as revealed by increased IL-4(+) and decreased IFN-gamma(+) T-cell population while the chloroform fraction (10 mg/kg) produced a predominant type 1 cytokines. Crude methanolic extract (100 mg/kg) demonstrated a mixed type 1 and type 2 cytokine responses thus suggesting a remarkable immunomodulatory property in this plant. The induction of differential T-helper cell immune response appears ideal to overcome immunosuppression as observed in case of lymphatic, filarial Brugia malayi infection which may also be extended to other

  9. Brugia malayi gene expression in response to the targeting of the Wolbachia endosymbiont by tetracycline treatment.

    Directory of Open Access Journals (Sweden)

    Elodie Ghedin

    2009-10-01

    Full Text Available Brugia malayi, like most human filarial parasite species, harbors an endosymbiotic bacterium of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female. Previous biochemical and genetic studies have established that communication with its endobacterium is essential for survival of the worm.We used electron microscopy to examine the effects of antibiotic treatment on Wolbachia cell structure. We have also used microarray and quantitative RT-PCR analyses to examine the regulation of the B. malayi transcripts altered in response to the anti-Wolbachia treatment. Microscopy of worms taken from animals treated with tetracycline for 14 and 21 days (14 d and 21 d demonstrated substantial morphologic effects on the Wolbachia endobacterium by 14 d and complete degeneration of the endobacterial structures by 21 d. We observed upregulation of transcripts primarily encoding proteins involved in amino acid synthesis and protein translation, and downregulation of transcripts involved in cuticle biosynthesis after both 7 d and 14 d of treatment. In worms exposed to tetracycline in culture, substantial effects on endobacteria morphology were evident by day 3, and extensive death of the endobacteria was observed by day 5. In a detailed examination of the expression kinetics of selected signaling genes carried out on such cultured worms, a bimodal pattern of regulation was observed. The selected genes were upregulated during the early phase of antibiotic treatment and quickly downregulated in the following days. These same genes were upregulated once more at 6 days post-treatment.Upregulation of protein translation and amino acid synthesis may indicate a generalized stress response induced in B. malayi due to a shortage of essential nutrients/factors that are otherwise supplied by Wolbachia. Downregulation of transcripts involved in cuticle biosynthesis perhaps reflects a disruption in the normal embryogenic program. This is

  10. Poly(d,l)-lactide-co-glycolide (PLGA) microspheres as immunoadjuvant for Brugia malayi antigens.

    Science.gov (United States)

    Saini, Vinay; Verma, Shiv Kumar; Murthy, P Kalpana; Kohli, Dharmveer

    2013-08-28

    Recently we identified in Brugia malayi adult worm extract (BmA) a pro-inflammatory 54-68kDa SDS-PAGE resolved fraction F6 that protects the host from the parasite via Th1/Th2 type responses. We are currently investigating F6 as a potential source of vaccine candidate(s) and the present study is aimed at investigating the suitability of poly(d,l)-lactide-co-glycolide microspheres (PLGA-Ms) as immunoadjuvant for the antigen administration in a single dose. PLGA-Ms were prepared aseptically by a modified double emulsion (w/o/w) solvent evaporation technique and their size, shape, antigen adsorption efficiency, in-process stability, and antigen release were characterized. Swiss mice were immunized by a single subcutaneous administration of BmA and F6 adsorbed on PLGA-Ms (lactide:glycolide ratios 50:50 and 75:25) and the immune responses were compared with administration of 1 or 2 doses of plain BmA and F6. Specific IgG, IgG1, IgG2a, IgG2b, IgE levels in serum, cellular-proliferative response and release of IFN-γ, TNF-α and nitric oxide from the cells of immunized host in response to the antigens/LPS/Con A challenge and antibody-dependant cellular cytotoxicity (ADCC) to parasite life stages were determined. The average size of PLGA-Ms 50:50 was smaller than the size of PLGA-Ms 75:25 and the % antigen adsorption efficiency of PLGA-Ms 50:50 was greater than PLGA-Ms 75:25. Single shot injection of PLGA-Ms 50:50/75:25-BmA/F6 produced better and stronger IgG, IgG1/IgG2a and cell-mediated immune responses than even two injections of plain BmA or F6. Further, PLGA-Ms 50:50-F6 produced stronger responses than PLGA-Ms 50:50-BmA. Anti-PLGA-Ms 50:50-F6 antibodies elicited higher ADCC response to infective larval and microfilarial stages of the parasite than anti-PLGA-Ms 75:25-F6 antibodies. The findings demonstrate that PLGA-Ms 50:50 is an excellent adjuvant for use with F6 in a single administration. This is the first ever report on PLGA as immunoadjuvant for filarial antigens

  11. Distribution of Brugia malayi larvae and DNA in vector and non-vector mosquitoes: implications for molecular diagnostics

    Directory of Open Access Journals (Sweden)

    Christensen Bruce M

    2009-11-01

    Full Text Available Abstract Background The purpose of this study was to extend prior studies of molecular detection of Brugia malayi DNA in vector (Aedes aegypti- Liverpool and non-vector (Culex pipiens mosquitoes at different times after ingestion of infected blood. Results Parasite DNA was detected over a two week time course in 96% of pooled thoraces of vector mosquitoes. In contrast, parasite DNA was detected in only 24% of thorax pools from non-vectors; parasite DNA was detected in 56% of midgut pools and 47% of abdomen pools from non-vectors. Parasite DNA was detected in vectors in the head immediately after the blood meal and after 14 days. Parasite DNA was also detected in feces and excreta of the vector and non-vector mosquitoes which could potentially confound results obtained with field samples. However, co-housing experiments failed to demonstrate transfer of parasite DNA from infected to non-infected mosquitoes. Parasites were also visualized in mosquito tissues by immunohistololgy using an antibody to the recombinant filarial antigen Bm14. Parasite larvae were detected consistently after mf ingestion in Ae. aegypti- Liverpool. Infectious L3s were seen in the head, thorax and abdomen of vector mosquitoes 14 days after Mf ingestion. In contrast, parasites were only detected by histology shortly after the blood meal in Cx. pipiens, and these were not labeled by the antibody. Conclusion This study provides new information on the distribution of filarial parasites and parasite DNA in vector and non-vector mosquitoes. This information should be useful for those involved in designing and interpreting molecular xenomonitoring studies.

  12. Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products.

    Directory of Open Access Journals (Sweden)

    Yovany Moreno

    Full Text Available INTRODUCTION: While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection. METHODOLOGY/PRINCIPAL FINDINGS: To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP. CONCLUSIONS/SIGNIFICANCE: A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host-parasite interaction.

  13. Physicochemical properties of the modeled structure of astacin metalloprotease moulting enzyme NAS-36 and mapping the druggable allosteric space of Heamonchus contortus, Brugia malayi and Ceanorhabditis elegans via molecular dynamics simulation.

    Science.gov (United States)

    Sharma, Om Prakash; Agrawal, Sonali; Kumar, M Suresh

    2013-12-01

    Nematodes represent the second largest phylum in the animal kingdom. It is the most abundant species (500,000) in the planet. It causes chronic, debilitating infections worldwide such as ascariasis, trichuriasis, hookworm, enterobiasis, strongyloidiasis, filariasis and trichinosis, among others. Molecular modeling tools can play an important role in the identification and structural investigation of molecular targets that can act as a vital candidate against filariasis. In this study, sequence analysis of NAS-36 from H. contortus (Heamonchus contortus), B. malayi (Brugia malayi) and C. elegans (Ceanorhabditis elegans) has been performed, in order to identify the conserved residues. Tertiary structure was developed for an insight into the molecular structure of the enzyme. Molecular Dynamics Simulation (MDS) studies have been carried out to analyze the stability and the physical properties of the proposed enzyme models in the H. contortus, B. malayi and C. elegans. Moreover, the drug binding sites have been mapped for inhibiting the function of NAS-36 enzyme. The molecular identity of this protease could eventually demonstrate how ex-sheathment is regulated, as well as provide a potential target of anthelmintics for the prevention of nematode infections.

  14. Tissue and stage-specific distribution of Wolbachia in Brugia malayi.

    Directory of Open Access Journals (Sweden)

    Kerstin Fischer

    2011-05-01

    Full Text Available BACKGROUND: Most filarial parasite species contain Wolbachia, obligatory bacterial endosymbionts that are crucial for filarial development and reproduction. They are targets for alternative chemotherapy, but their role in the biology of filarial nematodes is not well understood. Light microscopy provides important information on morphology, localization and potential function of these bacteria. Surprisingly, immunohistology and in situ hybridization techniques have not been widely used to monitor Wolbachia distribution during the filarial life cycle. METHODS/PRINCIPAL FINDINGS: A monoclonal antibody directed against Wolbachia surface protein and in situ hybridization targeting Wolbachia 16S rRNA were used to monitor Wolbachia during the life cycle of B. malayi. In microfilariae and vector stage larvae only a few cells contain Wolbachia. In contrast, large numbers of Wolbachia were detected in the lateral chords of L4 larvae, but no endobacteria were detected in the genital primordium. In young adult worms (5 weeks p.i., a massive expansion of Wolbachia was observed in the lateral chords adjacent to ovaries or testis, but no endobacteria were detected in the growth zone of the ovaries, uterus, the growth zone of the testis or the vas deferens. Confocal laser scanning and transmission electron microscopy showed that numerous Wolbachia are aligned towards the developing ovaries and single endobacteria were detected in the germline. In inseminated females (8 weeks p.i. Wolbachia were observed in the ovaries, embryos and in decreasing numbers in the lateral chords. In young males Wolbachia were found in distinct zones of the testis and in large numbers in the lateral chords in the vicinity of testicular tissue but never in mature spermatids or spermatozoa. CONCLUSIONS: Immunohistology and in situ hybridization show distinct tissue and stage specific distribution patterns for Wolbachia in B. malayi. Extensive multiplication of Wolbachia occurs in the

  15. Cofactor Independent Phosphoglycerate Mutase of Brugia malayi Induces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host

    Directory of Open Access Journals (Sweden)

    Prashant K. Singh

    2014-01-01

    Full Text Available Lymphatic filariasis is a major debilitating disease, endemic in 72 countries putting more than 1.39 billion people at risk and 120 million are already infected. Despite the significant progress in chemotherapeutic advancements, there is still need for other measures like development of an effective vaccine or discovery of novel drug targets. In this study, structural and immunological characterization of independent phosphoglycerate mutase of filarial parasite Brugia malayi was carried out. Protein was found to be expressed in all major parasite life stages and as an excretory secretory product of adult parasites. Bm-iPGM also reacted to all the categories of human bancroftian patient’s sera including endemic normals. In vivo immunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice and Mastomys coucha. Immunization with Bm-iPGM led to generation of a mixed Th1/Th2 type immune response offering 58.2% protection against larval challenge in BALB/c and 65–68% protection in M. coucha. In vitro studies confirmed participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.

  16. Wolbachia lipoproteins: abundance, localisation and serology of Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6 from Brugia malayi and Aedes albopictus.

    Science.gov (United States)

    Voronin, Denis; Guimarães, Ana F; Molyneux, Gemma R; Johnston, Kelly L; Ford, Louise; Taylor, Mark J

    2014-10-06

    Lipoproteins are the major agonists of Wolbachia-dependent inflammatory pathogenesis in filariasis and a validated target for drug discovery. Here we characterise the abundance, localisation and serology of the Wolbachia lipoproteins: Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6. We used proteomics to confirm lipoprotein presence and relative abundance; fractionation, immunoblotting and confocal and electron immuno-microscopy for localisation and ELISA for serological analysis. Proteomic analysis of Brugia malayi adult female protein extracts confirmed the presence of two lipoproteins, previously predicted through bioinformatics: Wolbachia peptidoglycan associated lipoprotein (wBmPAL) and the Type IV Secretion System component, VirB6 (wBmVirB6). wBmPAL was among the most abundant Wolbachia proteins present in an extract of adult female worms with wBmVirB6 only detected at a much lower abundance. This differential abundance was reflected in the immunogold-labelling, which showed wBmPAL localised at numerous sites within the bacterial membranes, whereas wBmVirB6 was present as a single cluster on each bacterial cell and also located within the bacterial membranes. Immunoblotting of fractionated extracts confirmed the localisation of wBmPAL to membranes and its absence from cytosolic fractions of C6/36 mosquito cells infected with wAlbB. In whole worm mounts, antibody labelling of both lipoproteins were associated with Wolbachia. Serological analysis showed that both proteins were immunogenic and raised antibody responses in the majority of individuals infected with Wuchereria bancrofti. Two Wolbachia lipoproteins, wBmPAL and wBmVirB6, are present in extracts of Brugia malayi with wBmPAL among the most abundant of Wolbachia proteins. Both lipoproteins localised to bacterial membranes with wBmVirB6 present as a single cluster suggesting a single Type IV Secretory System on each Wolbachia cell.

  17. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

    KAUST Repository

    Juneja, Punita

    2015-03-27

    Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.

  18. Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq

    Directory of Open Access Journals (Sweden)

    Maeghan O'Neill

    2016-12-01

    Full Text Available The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ, a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. Identification of drug-derived effects is important in ascertaining a dosage regimen which is predicted to be lethal to the parasite in situ. In previous histological studies, exposure to FLBZ induced damage to tissues required for reproduction and survival at pharmacologically relevant concentrations. However, more precise and quantitative indices of drug effects are needed. This study assessed drug effects using a transcriptomic approach to confirm effects observed histologically and to identify genes which were differentially expressed in treated adult female Brugia malayi. Comparative analysis across different concentrations (1 μM and 5 μM and durations (48 and 120 h provided an overview of the processes which are affected by FLBZ exposure. Genes with dysregulated expression were consistent with the reproductive effects observed via histology in our previous studies. This study revealed transcriptional changes in genes involved in embryo development. Additionally, significant downregulation was observed in genes encoding cuticle components, which may reflect changes in developing embryos, the adult worm cuticle or both. These data support the hypothesis that FLBZ acts predominantly on rapidly dividing

  19. The heme biosynthetic pathway of the obligate Wolbachia endosymbiont of Brugia malayi as a potential anti-filarial drug target.

    Directory of Open Access Journals (Sweden)

    Bo Wu

    2009-07-01

    Full Text Available Filarial parasites (e.g., Brugia malayi, Onchocerca volvulus, and Wuchereria bancrofti are causative agents of lymphatic filariasis and onchocerciasis, which are among the most disabling of neglected tropical diseases. There is an urgent need to develop macro-filaricidal drugs, as current anti-filarial chemotherapy (e.g., diethylcarbamazine [DEC], ivermectin and albendazole can interrupt transmission predominantly by killing microfilariae (mf larvae, but is less effective on adult worms, which can live for decades in the human host. All medically relevant human filarial parasites appear to contain an obligate endosymbiotic bacterium, Wolbachia. This alpha-proteobacterial mutualist has been recognized as a potential target for filarial nematode life cycle intervention, as antibiotic treatments of filarial worms harboring Wolbachia result in the loss of worm fertility and viability upon antibiotic treatments both in vitro and in vivo. Human trials have confirmed this approach, although the length of treatments, high doses required and medical counter-indications for young children and pregnant women warrant the identification of additional anti-Wolbachia drugs.Genome sequence analysis indicated that enzymes involved in heme biosynthesis might constitute a potential anti-Wolbachia target set. We tested different heme biosynthetic pathway inhibitors in ex vivo B. malayi viability assays and report a specific effect of N-methyl mesoporphyrin (NMMP, which targets ferrochelatase (FC, the last step. Our phylogenetic analysis indicates evolutionarily significant divergence between Wolbachia heme genes and their human homologues. We therefore undertook the cloning, overexpression and analysis of several enzymes of this pathway alongside their human homologues, and prepared proteins for drug targeting. In vitro enzyme assays revealed a approximately 600-fold difference in drug sensitivities to succinyl acetone (SA between Wolbachia and human 5

  20. Recombinant Brugia malayi pepsin inhibitor (rBm33) exploits host signaling events to regulate inflammatory responses associated with lymphatic filarial infections.

    Science.gov (United States)

    Sreenivas, Kirthika; Kalyanaraman, Haripriya; Babu, Subash; Narayanan, Rangarajan Badri

    2017-11-01

    Prolonged existence of filarial parasites and their molecules within the host modulate the host immune system to instigate their survival and induce inflammatory responses that contribute to disease progression. Recombinant Brugia malayi pepsin inhibitor (rBm33) modulates the host immune responses by skewing towards Th1 responses characterized by secretion of inflammatory molecules such as TNF-α, IL-6, nitric oxide (NO). Here we also specified the molecular signaling events triggered by rBm33 in peripheral blood mononuclear cells (PBMCs) of filarial endemic normals (EN). rBm33 predominantly enhanced the levels of nitric oxide in cultured PBMCs but did not result in oxidative stress to the host cells. Further, rBm33 treatment of human PBMCs resulted in higher GSH/GSSG levels. MYD88 dependent activation was found to be associated with rBm33 specific inflammatory cytokine production. rBm33 triggered intracellular signaling events also involved JNK activation in host PBMCs. In addition, c-Fos and not NF-κB was identified as the transcription factor regulating the expression of inflammatory cytokines in rBm33 stimulated PBMCs. rBm33 marked its role in filarial pathology by altered levels of growth factors but did not have a significant impact on matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) activity of host PBMCs. Thus, the study outlines the signaling network of rBm33 induced inflammatory responses within the host immune cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. In vitro silencing of Brugia malayi trehalose-6-phosphate phosphatase impairs embryogenesis and in vivo development of infective larvae in jirds.

    Directory of Open Access Journals (Sweden)

    Susheela Kushwaha

    Full Text Available The trehalose metabolic enzymes have been considered as potential targets for drug or vaccine in several organisms such as Mycobacterium, plant nematodes, insects and fungi due to crucial role of sugar trehalose in embryogenesis, glucose uptake and protection from stress. Trehalose-6-phosphate phosphatase (TPP is one of the enzymes of trehalose biosynthesis that has not been reported in mammals. Silencing of tpp gene in Caenorhabditis elegans revealed an indispensable functional role of TPP in nematodes.In the present study, functional role of B. malayi tpp gene was investigated by siRNA mediated silencing which further validated this enzyme to be a putative antifilarial drug target. The silencing of tpp gene in adult female B. malayi brought about severe phenotypic deformities in the intrauterine stages such as distortion and embryonic development arrest. The motility of the parasites was significantly reduced and the microfilarial production as well as their in vitro release from the female worms was also drastically abridged. A majority of the microfilariae released in to the culture medium were found dead. B. malayi infective larvae which underwent tpp gene silencing showed 84.9% reduced adult worm establishment after inoculation into the peritoneal cavity of naïve jirds.The present findings suggest that B. malayi TPP plays an important role in the female worm embryogenesis, infectivity of the larvae and parasite viability. TPP enzyme of B. malayi therefore has the potential to be exploited as an antifilarial drug target.

  2. Brugia malayi Antigen (BmA Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells.

    Directory of Open Access Journals (Sweden)

    Emily E I M Mouser

    Full Text Available One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA and excretory-secretory product 62 (ES-62 from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs.

  3. A PRELIMINARY STUDY OF MALAYAN FILARIASIS IN PUDING VILLAGE, JAMBI PROVINCE (SUMATERA, INDONESIA

    Directory of Open Access Journals (Sweden)

    Sudomo M.

    2012-09-01

    Full Text Available Beberapa daerah di Propinsi Jambi akan dikembangkan menjadi daerah transmigrasi, satu di antara­nya adalah daerah Kumpeh yang terletak berdekatan dengan daerah endemik filariasis malayi. Desa yang paling dekat dengan lokasi transmigrasi tersebut adalah desa Puding. Penelitian pendahuluan tentang penyakit filariasis telah dikerjakan di desa Puding untuk mengetahui tingkat endemisitas, periodisitas B. malayi, fauna nyamuk, jenis nyamuk yang potensial menjadi vektor filariasis, hospes reservoir dan keadaan sosial-ekonomi-budaya penduduk setempat. Mf rate pada penduduk desa Puding adalah 18,7% dan dari B. malayi jenis subperiodiknokturna. Nyamuk yang tertangkap terdiri dari enam genera yaitu genus Anopheles, Aedes, Culex, Coquilletidia, Mansonia dan Tripteroides. Dari enam genera tersebut yang potensial untuk menjadi vektor filariasis adalah genus Mansonia dan ini didukung dengan diketemukannyd larva stadium L3 (infektif Brugia sp di tubuh nyamuk tersebut. Keadaan sosial-ekonomi-budaya, khususnya menyangkut adat istiadat dan kebiasaan penduduk setempat, telah dipelajari.

  4. ORF Alignment: NC_006833 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available TRS of Brugia malayi] ... Length = 188 ... Query: 439 HPLGFARCQVYNTYIIAEARGK...LIIVDQHAAHERLVYECLKQKSSIKRQKLLLSEVVEIK 498 ... HPLGFARCQVYNTYIIAEARGKLIIVDQHAAHERLVYECLKQKSSIKRQKLLLSEVVEIK Sbjct: 1 ... HPLGFAR

  5. Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis.

    Directory of Open Access Journals (Sweden)

    Christina A Bulman

    2015-02-01

    Full Text Available Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC, and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

  6. Diagnosis of brugian filariasis by loop-mediated isothermal amplification.

    Directory of Open Access Journals (Sweden)

    Catherine B Poole

    Full Text Available In this study we developed and evaluated a Brugia Hha I repeat loop-mediated isothermal amplification (LAMP assay for the rapid detection of Brugia genomic DNA. Amplification was detected using turbidity or fluorescence as readouts. Reactions generated a turbidity threshold value or a clear visual positive within 30 minutes using purified genomic DNA equivalent to one microfilaria. Similar results were obtained using DNA isolated from blood samples containing B. malayi microfilariae. Amplification was specific to B. malayi and B. timori, as no turbidity was observed using DNA from the related filarial parasites Wuchereria bancrofti, Onchocerca volvulus or Dirofilaria immitis, or from human or mosquito. Furthermore, the assay was most robust using a new strand-displacing DNA polymerase termed Bst 2.0 compared to wild-type Bst DNA polymerase, large fragment. The results indicate that the Brugia Hha I repeat LAMP assay is rapid, sensitive and Brugia-specific with the potential to be developed further as a field tool for diagnosis and mapping of brugian filariasis.

  7. Attempts at immunization against Malayan filariasis using X-irradiated infective larvae

    International Nuclear Information System (INIS)

    Ramachandran, C.P.

    1975-01-01

    Recent studies on immunity to helminthic infections have shown that some degree of protective immunity may be stimulated by inoculations of attenuated living worms or their metabolites. Although much on these lines has been done with several helminths, little if any has been done with filarial infections in general. Experiments were designed to observe the effects of attempted immunization in the rhesus monkey as well as the domestic cat by the use of attenuated infective larvae of Brugia malayi. The sub-periodic strain of Brugia malayi, the major filarial parasite of man in Malaysia, maintained in the laboratory on experimentally infected cats and rhesus monkeys were used for the preparation of X-irradiated vaccines as well as for challenge inoculations. Third-stage infective larvae of Brugia malayi were obtained from experimentally fed Aedes togoi mosquitoes. Infective larvae were irradiated by X-rays, using a Dermopan X-ray unit at exposures between 10 - 40 kR. Rhesus monkeys and cats were inoculated twice with 100 - 400 attenuated larvae per inoculation at 2 week intervals and challenged about a month later by inoculation of 100 normal larvae. Control animals for each vaccination dose as well as for challenge doses were maintained. In rhesus monkeys persistent immunity to challenge infections (expressed as failure to cause microfilaraemia) were obtained in animals vaccinated with 200 infective larvae attenuated by X-irradiation at 20000 R. Encouraged with the results obtained on rhesus monkeys, similar experiments on an enlarged scale using varying strengths of the vaccines were carried out on the domestic cat, which is a more receptive animal host for Brugia malayi. However, all cats vaccinated when challenged came down with patent infection indicating lack of any definite immunity. In all these experiments, results of vaccine control animals showed that inoculation of irradiated larvae was not followed by the infection of microfilaria in the blood, indicating

  8. ASPEK ZOONOTIK PARASIT NEMATODA PADA KERA DAN BINATANG MENGERAT DI BENGKULU, SUMATERA. INDONESIA

    Directory of Open Access Journals (Sweden)

    Untung S.

    2012-09-01

    Full Text Available Twentyfive monkeys and 481 rats were examined for parasitic nematodes in Bengkulu, nine species of nematode were found infecting these animals. Five of filarían nematodes, i.e. Brugia malayi, Brugia pahangi, Dirofilaria magnilarvatum and Edesonfilaria malayensis were infecting monkeys and one speciesTBreinlia booliati, was found infecting rats. Three species of gastrointestinal helminths, i.e. Trichuris trichiura, Enterobius vermicularis and Oestophagomomum spp were found in monkeys; a lung worm, Angiostrongylus cantonensis, was found in rats. The most important nematode species is B. malayi, which was found in Presbytis cristatus (36.8 % and in Macaca fascicularis (20.0 %. T. trichiura was found in R. cristatus (47.9 % and A. cantonensis in Rattus argentiventer (4.0 % and Rattus tiomanicus (2.9%.

  9. SURVEI DARAH JARI FILARIASIS DI DESA BATUMARTA X KEC. MADANG SUKU III KABUPATEN OGAN KOMERING ULU (OKU TIMUR, SUMATERA SELATAN TAHUN 2012

    Directory of Open Access Journals (Sweden)

    R. Irpan Pahlepi

    2015-01-01

    Full Text Available AbstrakFilariasis atau penyakit kaki gajah adalah golongan penyakit menular yang disebabkan oleh cacing filaria  yang  ditularkan  melalui  berbagai  jenis  nyamuk.  Penyebaran  filariasis  hampir  meliputi  seluruh wilayah di Indonesia termasuk Kabupaten Ogan Komering Ulu (OKU Timur. Angka kesakitan filarisis di Kabupaten OKU Timur tahun 2007 sebesar 1,05%. Kegiatan pengobatan massal di Kabupaten OKU Timur belum pernah dilakukan sampai saat ini, sehingga perlu dilakukan penelitian yang bertujuan untuk mengetahui tingkat penyebaran penyakit filariasis. Penelitian ini merupakan penelitian survei dengan desain potong lintang. Pengambilan dan pemeriksaan sediaan darah jari dilakukan pada malam hari dimulai pukul 19.00 WIB. Jumlah penduduk yang diperiksa sebanyak 502. Hasil pemeriksaan diperoleh 4 orang positif mikrofilaria (Mf_ rate 0,8% dengan spesies Brugia  malayi  dan  kepadatan  rata-rata  200mf/ml.  Seluruh  kasus  yang  ditemukan  merupakan  kasus baru. Hasil penelitian ini menunjukkan bahwa penularan filariasis masih terjadi di Kabupaten OKU Timur sehingga perlu adanya pengobatan massal untuk mencegah penularan lebih lanjut.Kata kunci : Filariasis, Brugia malayi, Survei darah jari, OKU TimurAbstractFilariasis or elephantiasis is an infectious diseases caused by filarial worms that transmitted by various species of mosquitoes. Filariasis distributions almost covers all districts in Indonesia including East Ogan Komering Ulu (OKU. Filarisais morbidity in East OKU regency in 2007 was 1.05 %. Mass treatment in the district of East OKU have not been done yet, so it is necessary to do a research that aim to determine the prevalen of filariasis. This study is a cross-sectional survey design. Collection and examination of finger’s blood was done at night starting at 19:00. Number of people examined were 502. Examination results obtained 4 positive microfilariae (Mf_ rate 0.8 % of Brugia malayi and the average density of 200

  10. Primary structure of and immunoglobulin E response to the repeat subunit of gp15/400 from human lymphatic filarial parasites

    NARCIS (Netherlands)

    Paxton, W. A.; Yazdanbakhsh, M.; Kurniawan, A.; Partono, F.; Maizels, R. M.; Selkirk, M. E.

    1993-01-01

    We have isolated and sequenced clones encoding the repeated subunit of the surface-associated glycoprotein gp15/400 from the two nematode species predominantly responsible for lymphatic filariasis in humans: Brugia malayi and Wuchereria bancrofti. The amino acid sequence of the 15-kDa subunit,

  11. A reverse transcriptase-PCR assay for detecting filarial infective larvae in mosquitoes.

    Directory of Open Access Journals (Sweden)

    Sandra J Laney

    2008-06-01

    Full Text Available Existing molecular assays for filarial parasite DNA in mosquitoes cannot distinguish between infected mosquitoes that contain any stage of the parasite and infective mosquitoes that harbor third stage larvae (L3 capable of establishing new infections in humans. We now report development of a molecular L3-detection assay for Brugia malayi in vectors based on RT-PCR detection of an L3-activated gene transcript.Candidate genes identified by bioinformatics analysis of EST datasets across the B. malayi life cycle were initially screened by PCR using cDNA libraries as templates. Stage-specificity was confirmed using RNA isolated from infected mosquitoes. Mosquitoes were collected daily for 14 days after feeding on microfilaremic cat blood. RT-PCR was performed with primer sets that were specific for individual candidate genes. Many promising candidates with strong expression in the L3 stage were excluded because of low-level transcription in less mature larvae. One transcript (TC8100, which encodes a particular form of collagen was only detected in mosquitoes that contained L3 larvae. This assay detects a single L3 in a pool of 25 mosquitoes.This L3-activated gene transcript, combined with a control transcript (tph-1, accession # U80971 that is constitutively expressed by all vector-stage filarial larvae, can be used to detect filarial infectivity in pools of mosquito vectors. This general approach (detection of stage-specific gene transcripts from eukaryotic pathogens may also be useful for detecting infective stages of other vector-borne parasites.

  12. Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic human filariasis

    NARCIS (Netherlands)

    Kurniawan, A.; Yazdanbakhsh, M.; van Ree, R.; Aalberse, R.; Selkirk, M. E.; Partono, F.; Maizels, R. M.

    1993-01-01

    A population of 164 adult individuals resident in an area endemic for Brugia malayi lymphatic filariasis has been studied for humoral immune responses to filarial parasites. Antibody levels to Ag extracted from adult worms were determined for each of the IgG subclasses, for IgM and for IgE. The

  13. Identification of antigenic proteins of setaria cervi by immunoblotting technique

    International Nuclear Information System (INIS)

    Kaushal, N.A.; Kaushal, D.C.; Ghatak, S.

    1987-01-01

    Identification and characterization of antigenic proteins of Setaria cervi (bovine filarial parasite) adults and microfilariae was done by immunoblotting technique using hyperimmune rabbit sera against S. cervi and Brugia malayi. The antigens recognized by these sera were detected by using 125 I protein-A followed by autoradiography. Fifteen different antigens were observed to be common between adult and microfilarial stages of the parasite. Some stage specific antigens were also identified. Many antigens of S. cervi adults and microfilariae were also recognized by rabbit anti-B.malayi serum showing the existence of common antigenic determinants between the bovine and human filarial parasites

  14. STUDI ENDEMISITAS FILARIASIS DI WILAYAH KECAMATAN PEMAYUNG, KABUPATEN BATANGHARI PASCA PENGOBATAN MASSAL TAHAP III

    Directory of Open Access Journals (Sweden)

    Yahya Yahya

    2013-05-01

    Full Text Available Abstract Filariasis endemicity research in District Pemayung, Batanghari Regency Post-Mass Drug Administration Phase III has been implemented. The study aims to determine the prevalence of filariasis, microfilaria worm species, the periodicity, reservoir determination and evaluate the results of mass treatment activities that have been 3 times. The number of people who checked their blood preparation for the examination as many as 538. Blood sampling for the periodicity of the parasite examinations performed on 4 persons, each carried out blood sampling every 2 hours for 24 hours. People microfilariae with microfilariae positive number as many as 8 people to rate microfilariae (Mf rate 1.5%.. The highest parasite density of 17.493 per 20 cu mm of blood occurred at 1:00 am and decresing to 0,415 per 20 cu mm of blood at 07.00 am. The parasite was found in sub periodic nokturna 3 subjects and 1 subject was found only be found in the morning and afternoon. The results of examination of 12 cats and two monkeys were found two positive cats with Brugia malayi microfilariae. Cats that were examined and the positive was one house cat and one stray cat. The conclusion from this study showed that filariasis was still endemic with periodicity of microfilariae was sub periodic nokturna and was zoonotic. Recommendations of this study was that mass treatment  was done by giving the drug directly and took medicine in front of the officers, examination and treatment of microfilariae positive cats. Key words: microfilariae rate, periodicity, Brugia malayi, reservoir. Abstrak  Submit : 28-03-2012  Review : 04-04-2012 Review : 11-06-2012 revisi : 29–08-2012Penelitian untuk menentukan tingkat endemisitas filariasis di wilayah Kecamatan Pemayung, Kabupaten Batanghari Pasca Pengobatan Massal Tahap III telah dilaksanakan. Penelitian bertujuan untuk mengetahui prevalensi filariasis, mengetahui spesies cacing mikrofilaria, periodisitas mikrofilaria dan pemeriksaan

  15. Screening of the ‘Open Scaffolds’ collection from Compounds Australia identifies a new chemical entity with anthelmintic activities against different developmental stages of the barber's pole worm and other parasitic nematodes

    Directory of Open Access Journals (Sweden)

    Sarah Preston

    2017-12-01

    Full Text Available The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the ‘Open Scaffolds’ collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the ‘Open Scaffolds’ collection against the exsheathed third-stage larvae (xL3s of Haemonchus contortus using recently developed whole-organism screening assays. We identified a hit compound, called SN00797439, which was shown to reproducibly reduce xL3 motility by ≥ 70%; this compound induced a characteristic, “coiled” xL3 phenotype (IC50 = 3.46–5.93 μM, inhibited motility of fourth-stage larvae (L4s; IC50 = 0.31–12.5 μM and caused considerable cuticular damage to L4s in vitro. When tested on other parasitic nematodes in vitro, SN00797439 was shown to inhibit (IC50 = 3–50 μM adults of Ancylostoma ceylanicum (hookworm and first-stage larvae of Trichuris muris (whipworm and eventually kill (>90% these stages. Furthermore, this compound completely inhibited the motility of female and male adults of Brugia malayi (50–100 μM as well as microfilariae of both B. malayi and Dirofilaria immitis (heartworm. Overall, these results show that SN00797439 acts against genetically (evolutionarily distant parasitic nematodes i.e. H. contortus and A. ceylanicum [strongyloids] vs. B. malayi and D. immitis [filarioids] vs. T. muris [enoplid], and, thus, might offer a novel, lead-like scaffold for the development of a relatively broad-spectrum anthelmintic. Our future work will focus on assessing the activity of SN00797439 against other pathogens that cause neglected tropical diseases, optimising analogs with improved biological activities and

  16. Lymphatic filarial species differentiation using evolutionarily modified tandem repeats: generation of new genetic markers.

    Science.gov (United States)

    Sakthidevi, Moorthy; Murugan, Vadivel; Hoti, Sugeerappa Laxmanappa; Kaliraj, Perumal

    2010-05-01

    Polymerase chain reaction based methods are promising tools for the monitoring and evaluation of the Global Program for the Elimination of Lymphatic Filariasis. The currently available PCR methods do not differentiate the DNA of Wuchereria bancrofti or Brugia malayi by a single PCR and hence are cumbersome. Therefore, we designed a single step PCR strategy for differentiating Bancroftian infection from Brugian infection based on a newly identified gene from the W. bancrofti genome, abundant larval transcript-2 (alt-2), which is abundantly expressed. The difference in PCR product sizes generated from the presence or absence of evolutionarily altered tandem repeats in alt-2 intron-3 differentiated W. bancrofti from B. malayi. The analysis was performed on the genomic DNA of microfilariae from a number of patient blood samples or microfilariae positive slides from different Indian geographical regions. The assay gave consistent results, differentiating the two filarial parasite species accurately. This alt-2 intron-3 based PCR assay can be a potential tool for the diagnosis and differentiation of co-infections by lymphatic filarial parasites. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  17. Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi

    International Nuclear Information System (INIS)

    Bancroft, A.J.; Devaney, E.; Grencis, R.K.; Else, K.J.

    1993-01-01

    BALB/c mice immunized with radiation-attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-γ by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite-specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation-attenuated larvae of filarial nematodes stimulate immunity. 5l refs., 3 figs., 3 tabs

  18. Brugia timori INFECTION IN LEKEBAI, FLORES: clinical aspects

    Directory of Open Access Journals (Sweden)

    Arbain Joesoef

    2012-09-01

    Full Text Available Pengamatan filariasis pada penduduk Nualolo-Lekebai, Pulau Flores telah dilakukan pada bulan Februari 1975. Kampung Nualolo-Lekebai berpenduduk 680 jiwa, pekerjaan bertani dan menganut agama Nasrani. Kebiasaan hidup di antara penduduk di daerah ini adalah menyerahkan pelaksanaan pekerjaan berat pada kaum wanita, baik di rumah ataupun di kebun. Dalam perjalanan jauh baik ke kebun atau ke pasar, kaum wanitanya selalu berjalan kaki sedangkan kaum prianya menunggang kuda. Sejumlah 80% dari penduduk kampung ini telah diperiksa terhadap infeksi parasit filaria dan terhadap gejala filariasis. Dari hasil yang ditemukan ternyata penduduk kampung ini menderita infeksi Brugia timori dengan angka derajat infeksi sebesar 7.0% dan angka derajat elephantiasis sebesar 10.3%. Hal yang menarik yang ditemukan dalam pengamatan ini adalah tingginya angka derajat elephantiasis pada kaum wanita dibandingkan dengan pada kaum pria. Fenomena ini mungkin disebabkan oleh kebiasaan hidup kaum wanita di daerah ini sehari-hari yang bekerja lebih berat dan berjalan kaki lebih sering dan lebih jauh dibandingkan kaum prianya.

  19. Filarial worms reduce Plasmodium infectivity in mosquitoes.

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    2011-02-01

    Full Text Available Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG. Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness.Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria parasite infections.These results could have an

  20. Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy.

    Directory of Open Access Journals (Sweden)

    Zhiru Li

    2011-11-01

    Full Text Available The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans. Availability of genomic sequences for the Wolbachia (wBm present in the human filarial parasite Brugia malayi has enabled genome-wide searching for new potential drug targets. In the present study, we investigated the cell division machinery of wBm and determined that it possesses the essential cell division gene ftsZ which was expressed in all developmental stages of B. malayi examined. FtsZ is a GTPase thereby making the protein an attractive Wolbachia drug target. We described the molecular characterization and catalytic properties of Wolbachia FtsZ. We also demonstrated that the GTPase activity was inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. Furthermore, berberine was also effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel anti-symbiotic approach for controlling filarial infection. NOTE: The nucleotide sequences reported in this paper are available in GenBank™ Data Bank under the accession number wAlB-FtsZ (JN616286.

  1. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis.

    Science.gov (United States)

    Joseph, S K; Ramaswamy, K

    2013-07-18

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and protein or protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-protein) and 48% (BmHAT protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

    Science.gov (United States)

    Joseph, SK; Ramaswamy, K

    2013-01-01

    The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and Protein or Protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-Protein) and 48% (BmHAT Protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. PMID:23735679

  3. Morphological and molecular characteristics of Malayfilaria sofiani Uni, Mat Udin & Takaoka n. g., n. sp. (Nematoda: Filarioidea) from the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia) in Peninsular Malaysia.

    Science.gov (United States)

    Uni, Shigehiko; Mat Udin, Ahmad Syihan; Agatsuma, Takeshi; Saijuntha, Weerachai; Junker, Kerstin; Ramli, Rosli; Omar, Hasmahzaiti; Lim, Yvonne Ai-Lian; Sivanandam, Sinnadurai; Lefoulon, Emilie; Martin, Coralie; Belabut, Daicus Martin; Kasim, Saharul; Abdullah Halim, Muhammad Rasul; Zainuri, Nur Afiqah; Bhassu, Subha; Fukuda, Masako; Matsubayashi, Makoto; Harada, Masashi; Low, Van Lun; Chen, Chee Dhang; Suganuma, Narifumi; Hashim, Rosli; Takaoka, Hiroyuki; Azirun, Mohd Sofian

    2017-04-20

    The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono, Oemijati & Cross, 1977 cause lymphatic diseases in humans in the tropics, while B. pahangi (Buckley & Edeson, 1956) infects carnivores and causes zoonotic diseases in humans in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri, Pulnomo, Dennis & Marwoto, 1980 and six out of ten Brugia spp. have been described from Australia, Southeast Asia, Sri Lanka and India. However, the origin and evolution of the species in the Wuchereria-Brugia clade remain unclear. While investigating the diversity of filarial parasites in Malaysia, we discovered an undescribed species in the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia). We examined 81 common treeshrews from 14 areas in nine states and the Federal Territory of Peninsular Malaysia for filarial parasites. Once any filariae that were found had been isolated, we examined their morphological characteristics and determined the partial sequences of their mitochondrial cytochrome c oxidase subunit 1 (cox1) and 12S rRNA genes. Polymerase chain reaction (PCR) products of the internal transcribed spacer 1 (ITS1) region were then cloned into the pGEM-T vector, and the recombinant plasmids were used as templates for sequencing. Malayfilaria sofiani Uni, Mat Udin & Takaoka, n. g., n. sp. is described based on the morphological characteristics of adults and microfilariae found in common treeshrews from Jeram Pasu, Kelantan, Malaysia. The Kimura 2-parameter distance between the cox1 gene sequences of the new species and W. bancrofti was 11.8%. Based on the three gene sequences, the new species forms a monophyletic clade with W. bancrofti and Brugia spp. The adult parasites were found in tissues surrounding the lymph nodes of the neck of common treeshrews. The newly described species appears most closely related to Wuchereria spp. and Brugia spp., but differs from these in

  4. Serine protease inhibitors of parasitic helminths.

    Science.gov (United States)

    Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

    2012-05-01

    Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.

  5. Dicty_cDB: Contig-U12802-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available cobacter cetorum strain MIT-0... 38 0.23 AF237484_1( AF237484 |pid:none) Dirofilaria immitis intermed...87 ( O97594 ) RecName: Full=Structural maintenance of chromosomes pro... 36 0.87 U00680_1( U00680 |pid:none) Brugia malayi intermed...1305( CP000879 |pid:none) Petrotoga mobilis SJ95, complet... 38 0.30 (Q9BZF9) RecName: Full=Uveal autoantigen with coiled...ns BAC clone RP11-764E7 from 2, complet... 34 0.79 6 ( FK620261 ) 454GmaGlobSeed354893 Soybean Seed...ditis elegans clone Y71H2X, *** SEQUENCI... 38 4.5 7 ( AC146972 ) Medicago truncatula clone mth2-128d9, compl

  6. 周期型马来丝虫复合基因重组质粒和相应表达蛋白的免疫学研究%Immunology comparision of composite gene recombinant plasmid and expressed protein of periodical Brugia malayi

    Institute of Scientific and Technical Information of China (English)

    王慧; 方政; 徐倩; 陆施娟; 钱一言; 徐怿琳; 方浩; 徐邦生

    2014-01-01

    的复合重组质粒/复合重组蛋白/CpG组小鼠淋巴细胞刺激增殖指数(1.629±0.235)高于复合重组蛋白组(1.248±0.110,P<0.05);免疫4、6周后,复合重组质粒/复合重组蛋白/CpG组和复合重组质粒/CpG组小鼠血清IFN-γ水平[(101.660±5.101)、(178.265±7.139)mg/L,(102.067±3.722)、(115.148±6.031)mg/L]均高于复合重组蛋白组[(75.438±2.102)、(82.004±3.777) mg/L,P均<0.05];免疫后6周,复合重组质粒/复合重组蛋白/CpG组和复合重组蛋白/CpG组的小鼠血清IL-4水平[(75.385±3.318)、(46.363±3.672)mg/L]均明显高于复合重组质粒/CpG组[(36.691±3.443)mg/L,P均<0.05).结论 pcDNA3.1-BmCPI/BmGAPDH核酸疫苗和相应蛋白疫苗均可诱导BALB/c小鼠产生特异性体液和细胞免疫应答反应.核酸疫苗-蛋白疫苗联合免疫效果有明显的优势.%Objective To construct a plasmid DNA vector expressing cysteine protease inhibitor and glyceraldehydes-3-phosphate dehydrogenase of periodic Brugia malayi(BmCPI/BmGAPDH),and purify the recombinant protein after transfecting the vector into human cervical carcinoma cells(Hela) for expression.To make a comparison of immunity efficacy between the recombinant plasmid and the homologous protein and to a lay theoretic and experimental basis for developing novel anti-filarial genetic engineering vaccines.Methods The amplified genes BmCPI and BmGAPDH and a plasmid vector were double enzymes digested and ligated to construct a recombinant plasmid pcDNA3.1 (+)-BmCPI/BmGAPDH,and this plasmid was transfected to Hela cells after being identified.G418 was used for screening transfectants,and the monoclonal resistant cell strain was determined by RT-PCR and SDS-PAGE.The recombinant protein was purified by affnity chromatography and identified by Western blotting.Sixty BALB/c mice were divided into 5 groups,12 per group,and they were immunized at 2,4,and 6 weeks.Mice in control groups were injected with PBS 100 μ1 or pcDNA3.1 100 μg/CpG 30 μg,and mice in experimental groups were injected with pcDNA3.1-BmCPI/BmGAPDH 100 μg/CpG 30

  7. Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: "The Worminator".

    Science.gov (United States)

    Storey, Bob; Marcellino, Chris; Miller, Melissa; Maclean, Mary; Mostafa, Eman; Howell, Sue; Sakanari, Judy; Wolstenholme, Adrian; Kaplan, Ray

    2014-12-01

    A major hindrance to evaluating nematode populations for anthelmintic resistance, as well as for screening existing drugs, new compounds, or bioactive plant extracts for anthelmintic properties, is the lack of an efficient, objective, and reproducible in vitro assay that is adaptable to multiple life stages and parasite genera. To address this need we have developed the "Worminator" system, which objectively and quantitatively measures the motility of microscopic stages of parasitic nematodes. The system is built around the computer application "WormAssay", developed at the Center for Discovery and Innovation in Parasitic Diseases at the University of California, San Francisco. WormAssay was designed to assess motility of macroscopic parasites for the purpose of high throughput screening of potential anthelmintic compounds, utilizing high definition video as an input to assess motion of adult stage (macroscopic) parasites (e.g. Brugia malayi). We adapted this assay for use with microscopic parasites by modifying the software to support a full frame analysis mode that applies the motion algorithm to the entire video frame. Thus, the motility of all parasites in a given well are recorded and measured simultaneously. Assays performed on third-stage larvae (L3) of the bovine intestinal nematode Cooperia spp., as well as microfilariae (mf) of the filarioid nematodes B. malayi and Dirofilaria immitis, yielded reproducible dose responses using the macrocyclic lactones ivermectin, doramectin, and moxidectin, as well as the nicotinic agonists, pyrantel, oxantel, morantel, and tribendimidine. This new computer based-assay is simple to use, requires minimal new investment in equipment, is robust across nematode genera and developmental stage, and does not require subjective scoring of motility by an observer. Thus, the "Worminator" provides a relatively low-cost platform for developing genera- and stage-specific assays with high efficiency and reproducibility, low labor input

  8. Cakupan Pemberian Obat Pencegahan Massal Filariasis di Kabupaten Sumba Barat Daya Tahun 2012-2013

    Directory of Open Access Journals (Sweden)

    Zahrotul Habibah

    2016-03-01

    Full Text Available Filariasis merupakan masalah kesehatan masyarakat terutama di Indonesia Timur antara lain di Kabupaten Sumba Barat Daya (SBD. Untuk mengeliminasi filariasis, WHO membuat program PemberianObat Pencegahan Masal (POPM dengan dietilkarbamazin sitrat dan albendazol setiap tahun selama 5tahun berturut-turut. Untuk mengetahui keberhasilan POPM, perlu dilakukan evaluasi cakupan POPM setiaptahun. Tujuan penelitian ini adalah mengetahui cakupan POPM di SBD pada tahun 2012-2013. Penelitanini menggunakan data POPM Dinas Kesehatan SBD pada tahun 2012 dan 2013. Cakupan POPM filariasisdihitung berdasarkan jumlah penduduk minum obat dibagi penduduk total dan jumlah penduduk sasaran.Target cakupan pengobatan penduduk sasaran adalah >85% dan dari penduduk total adalah  > 65%. Hasilpenelitian menunjukkan cakupan POPM filariasis berdasarkan penduduk total pada tahun 2012 adalah 1,96%dan tahun 2013 sebesar 1,13%. Cakupan POPM filariasis berdasarkan penduduk sasaran pada tahun 2012adalah 2,51% dan tahun 2013 adalah 1,35%. Disimpulkan bahwa cakupan POPM filariasis berdasarkanpenduduk sasaran dan penduduk total di SBD sangat rendah dan cakupan tahun 2013 lebih rendahdibandingkan tahun 2012. Kata kunci: W. bancrofti, B.malayi, B.timori, pemberian obat masal pencegahan, Sumba Barat Daya   Coverage of Mass Drugs Administration (MDA for Filariasis inSouth West Sumba on 2012-2013 AbstractFilariasis is a disease caused by Wuchereria bancrofti, Brugia malayi and Brugia timori. It is transmitted by mosquitos. It cause defect in patient’s physical condition, decrease social life, and increase health spending.WHO concepts a program to eliminate filariasis by Massal Drugs Administration (MDA of filariasis. It hasto be evaluated each year in five years by counting the coverage of MDA of filariasis in total population andtargeted population. This research used secondary data from Dinas Kesehatan in SBD to know the coverageof MDA of filariasis in SBD on 2012-2013. The coverage

  9. Plasmodium knowlesi and Wucheriria bancrofti: Their vectors and challenges for the future

    Directory of Open Access Journals (Sweden)

    Indra eVythilingam

    2012-05-01

    Full Text Available Malaria and filariasis still continue to pose public health problems in developing countries of the tropics. Although plans are ongoing for the elimination of both these parasitic vector borne diseases, we are now faced with a daunting challenge as we have a fifth species, Plasmodium knowlesi a simian malaria parasite affecting humans. Similarly in peninsular Malaysia, filariasis was mainly due to Brugia malayi, however, we now see cases of W. bancrofti in immigrant workers coming into the country. Work is on going to eliminate malaria and filariasis from the country. In order to be successful we need to revamp our control measures. Thus this paper attempts to review the vectors of malaria and filariasis in Southeast Asia with special emphasis on P. knowlesi and W. bancrofti and their control strategies.

  10. Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: “The Worminator”

    Directory of Open Access Journals (Sweden)

    Bob Storey

    2014-12-01

    Full Text Available A major hindrance to evaluating nematode populations for anthelmintic resistance, as well as for screening existing drugs, new compounds, or bioactive plant extracts for anthelmintic properties, is the lack of an efficient, objective, and reproducible in vitro assay that is adaptable to multiple life stages and parasite genera. To address this need we have developed the “Worminator” system, which objectively and quantitatively measures the motility of microscopic stages of parasitic nematodes. The system is built around the computer application “WormAssay”, developed at the Center for Discovery and Innovation in Parasitic Diseases at the University of California, San Francisco. WormAssay was designed to assess motility of macroscopic parasites for the purpose of high throughput screening of potential anthelmintic compounds, utilizing high definition video as an input to assess motion of adult stage (macroscopic parasites (e.g. Brugia malayi. We adapted this assay for use with microscopic parasites by modifying the software to support a full frame analysis mode that applies the motion algorithm to the entire video frame. Thus, the motility of all parasites in a given well are recorded and measured simultaneously. Assays performed on third-stage larvae (L3 of the bovine intestinal nematode Cooperia spp., as well as microfilariae (mf of the filarioid nematodes B. malayi and Dirofilaria immitis, yielded reproducible dose responses using the macrocyclic lactones ivermectin, doramectin, and moxidectin, as well as the nicotinic agonists, pyrantel, oxantel, morantel, and tribendimidine. This new computer based-assay is simple to use, requires minimal new investment in equipment, is robust across nematode genera and developmental stage, and does not require subjective scoring of motility by an observer. Thus, the “Worminator” provides a relatively low-cost platform for developing genera- and stage-specific assays with high efficiency and

  11. Limitations of the radioimmunoprecipitation polyethylene glycol assay (RIPEGA) for detection of filarial antigens in serum

    International Nuclear Information System (INIS)

    Hamilton, R.G.; Alexander, E.; Adkinson, N.F.

    1984-01-01

    The performance of the radioimmunoprecipitation polyethylene glycol assay (RIPEGA) was examined for quantitation of filarial antigens (Brugia malayi and Dirofilaria immitis) in serum from infected human and animal hosts and non-infected controls. Multiple PEG concentrations were employed to determine the level of non-specific binding (NSB) in non-exposed human sera (NEHS) containing no filarial antigen. The NSB observed when 3 different 125 I-labelled IgG antibodies were added to 26 NEHS varied 3-fold and was correlated significantly with total serum IgM (r = 0.80, P 2 fragment of the 125 I-labelled antibody was used, but the correlation of NSB with total serum IgM remained significant (r = 0.57, P < 0.01). The presence of rheumatoid factor in NEHS sera also significantly increased NSB by an average of 3-fold. These effects eliminated the assay's ability to detect in sera from infected hosts filarial antigen the presence of which could be readily demonstrated by an immunoradiometric assay. The RIPEGA's precision (intra-assay coefficient of variation (CV) = 21% at 35% Bsub(max)) and reproducibility (inter-assay CV = 29% at 35% Bsub(max)) are less satisfactory than many alternative immunoassays. (Auth.)

  12. Genome mining offers a new starting point for parasitology research.

    Science.gov (United States)

    Lv, Zhiyue; Wu, Zhongdao; Zhang, Limei; Ji, Pengyu; Cai, Yifeng; Luo, Shiqi; Wang, Hongxi; Li, Hao

    2015-02-01

    Parasites including helminthes, protozoa, and medical arthropod vectors are a major cause of global infectious diseases, affecting one-sixth of the world's population, which are responsible for enormous levels of morbidity and mortality important and remain impediments to economic development especially in tropical countries. Prevalent drug resistance, lack of highly effective and practical vaccines, as well as specific and sensitive diagnostic markers are proving to be challenging problems in parasitic disease control in most parts of the world. The impressive progress recently made in genome-wide analysis of parasites of medical importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini, Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis; cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium; protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L. donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis, Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti, Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been systematically covered in this review for a comprehensive understanding of the genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or endosymbiotic bacterial genomes of parasites, further valuable insight into parasite-host interactions and development of promising novel drug and vaccine candidates and preferable diagnostic tools, thereby underpinning the prevention and control of parasitic diseases.

  13. Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms.

    Directory of Open Access Journals (Sweden)

    Andrea M Binnebose

    Full Text Available Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment.

  14. A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia

    Science.gov (United States)

    Bray, Walter M.; White, Pamela M.; Ruybal, Jordan; Lokey, R. Scott; Debec, Alain; Sullivan, William

    2012-01-01

    Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts. PMID:23028321

  15. Characterizing Ancylostoma caninum transcriptome and exploring nematode parasitic adaptation

    Directory of Open Access Journals (Sweden)

    Hawdon John

    2010-05-01

    Full Text Available Abstract Background Hookworm infection is one of the most important neglected diseases in developing countries, with approximately 1 billion people infected worldwide. To better understand hookworm biology and nematode parasitism, the present study generated a near complete transcriptome of the canine hookworm Ancylostoma caninum to a very high coverage using high throughput technology, and compared it to those of the free-living nematode Caenorhabditis elegans and the parasite Brugia malayi. Results The generated transcripts from four developmental stages, infective L3, serum stimulated L3, adult male and adult female, covered 93% of the A. caninum transcriptome. The broad diversity among nematode transcriptomes was confirmed, and an impact of parasitic adaptation on transcriptome diversity was inferred. Intra-population analysis showed that A. caninum has higher coding sequence diversity than humans. Examining the developmental expression profiles of A. caninum revealed major transitions in gene expression from larval stages to adult. Adult males expressed the highest number of selectively expressed genes, but adult female expressed the highest number of selective parasitism-related genes. Genes related to parasitism adaptation and A. caninum specific genes exhibited more expression selectivity while those conserved in nematodes tend to be consistently expressed. Parasitism related genes were expressed more selectively in adult male and female worms. The comprehensive analysis of digital expression profiles along with transcriptome comparisons enabled identification of a set of parasitism genes encoding secretory proteins in animal parasitic nematode. Conclusions This study validated the usage of deep sequencing for gene expression profiling. Parasitic adaptation of the canine hookworm is related to its diversity and developmental dynamics. This comprehensive comparative genomic and expression study substantially improves our understanding of

  16. Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes

    Directory of Open Access Journals (Sweden)

    Slatko Barton E

    2010-10-01

    Full Text Available Abstract Background Lymphatic filariasis and onchocerciasis are debilitating diseases caused by filarial nematodes. Disease pathogenesis is induced by inflammatory responses following the death of the parasite. Wolbachia endosymbionts of filariae are potent inducers of innate and adaptive inflammation and bacterial lipoproteins have been identified as the ligands that bind toll-like receptors (TLR 2 and TLR6. Lipoproteins are important structural and functional components of bacteria and therefore enzymes involved in Wolbachia lipoprotein biosynthesis are potential chemotherapeutic targets. Results Globomycin, a signal peptidase II (LspA inhibitor, has activity against Gram-negative bacteria and a putative lspA gene has been identified from the Wolbachia genome of Brugia malayi (wBm. The amino acids required for function are strictly conserved and functionality was verified by complementation tests in a temperature-sensitive Escherichia coli lspA mutant. Also, transformation of wild type E. coli with Wolbachia lspA conferred significant globomycin resistance. A cell-based screen has been developed utilizing a Wolbachia-containing Aedes albopictus cell line to assay novel compounds active against Wolbachia. Globomycin was screened using this assay, which resulted in a dose-dependent reduction in Wolbachia load. Furthermore, globomycin was also effective in reducing the motility and viability of adult B. malayi in vitro. Conclusions These studies validate lipoprotein biosynthesis as a target in an organism for which no genetic tools are available. Further studies to evaluate drugs targeting this pathway are underway as part of the A-WOL drug discovery and development program.

  17. Helminth Genomics: The Implications for Human Health

    Science.gov (United States)

    Brindley, Paul J.; Mitreva, Makedonka; Ghedin, Elodie; Lustigman, Sara

    2009-01-01

    More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings. PMID:19855829

  18. Macrofilaricidal and microfilaricidal effects of Neurolaena lobata, a Guatemalan medicinal plant, on Brugia pahangi.

    Science.gov (United States)

    Fujimaki, Y; Kamachi, T; Yanagi, T; Cáceres, A; Maki, J; Aoki, Y

    2005-03-01

    Twelve extracts of 11 Guatemalan medicinal plants were initially screened in vitro for potential macrofilaricidal activity against Brugia pahangi, a lymphatic dwelling filarial worm, using concentrations from 125 to 1000 microg ml(-1) of each extract that could be dissolved in the culture medium. Of 12 extracts used, the ethanol extract of leaves of Neurolaena lobata showed the strongest activity against the motility of adult worms. Subsequently, the extract of N. lobata was extensively examined in vitro for macro- and micro-filaricidal effects using a series of concentrations of 500, 250, 100, 50 and 10 microg ml(-1). The effects were assessed by worm motility, microfilarial release by female worms and a MTT assay. The effect on the motility of adult worms was observed in a concentration- and time-dependent manner. The time required to stop motility of both sexes of adult worms was 6 h at 500 microg ml(-1), 24 h at 250 microg ml(-1), and 3 days for females and 4 days for males at 100 microg ml(-1). The movement of females ceased at 4 days at a concentration of 50 microg ml(-1) whereas the motility of males was only reduced. The loss of worm's viability was confirmed by the MTT assay and was similar to the motility results. These concentrations, including 10 microg ml(-1), prevented microfilarial release by females in a concentration- and time-dependent manner. Concentrations higher than 100 microg ml(-1) even induced mortality of the microfilariae. The present study suggested that the ethanol extract of Neurolaena lobata has potential macro- and micro-filaricidal activities.

  19. Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence

    Science.gov (United States)

    Gordon, Kacy L.; Arthur, Robert K.; Ruvinsky, Ilya

    2015-01-01

    Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2) from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements. PMID:26020930

  20. Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence.

    Directory of Open Access Journals (Sweden)

    Kacy L Gordon

    2015-05-01

    Full Text Available Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2 from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements.

  1. Electrode Potentials of l-Tryptophan, l-Tyrosine, 3-Nitro-l-tyrosine, 2,3-Difluoro-l-tyrosine, and 2,3,5-Trifluoro-l-tyrosine.

    Science.gov (United States)

    Mahmoudi, Leila; Kissner, Reinhard; Nauser, Thomas; Koppenol, Willem H

    2016-05-24

    Electrode potentials for aromatic amino acid radical/amino acid couples were deduced from cyclic voltammograms and pulse radiolysis experiments. The amino acids investigated were l-tryptophan, l-tyrosine, N-acetyl-l-tyrosine methyl ester, N-acetyl-3-nitro-l-tyrosine ethyl ester, N-acetyl-2,3-difluoro-l-tyrosine methyl ester, and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester. Conditional potentials were determined at pH 7.4 for all compounds listed; furthermore, Pourbaix diagrams for l-tryptophan, l-tyrosine, and N-acetyl-3-nitro-l-tyrosine ethyl ester were obtained. Electron transfer accompanied by proton transfer is reversible, as confirmed by detailed analysis of the current waves, and because the slopes of the Pourbaix diagrams obey Nernst's law. E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) at pH 7 are 0.99 ± 0.01 and 0.97 ± 0.01 V, respectively. Pulse radiolysis studies of two dipeptides that contain both amino acids indicate a difference in E°' of approximately 0.06 V. Thus, in small peptides, we recommend values of 1.00 and 0.96 V for E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH), respectively. The electrode potential of N-acetyl-3-nitro-l-tyrosine ethyl ester is higher, while because of mesomeric stabilization of the radical, those of N-acetyl-2,3-difluoro-l-tyrosine methyl ester and N-acetyl-2,3,5-trifluoro-l-tyrosine methyl ester are lower than that of tyrosine. Given that the electrode potentials at pH 7 of E°'(Trp(•),H(+)/TrpH) and E°'(TyrO(•),H(+)/TyrOH) are nearly equal, they would be, in principle, interchangeable. Proton-coupled electron transfer pathways in proteins that use TrpH and TyrOH are thus nearly thermoneutral.

  2. An integrated in vitro imaging platform for characterizing filarial parasite behavior within a multicellular microenvironment.

    Directory of Open Access Journals (Sweden)

    Timothy Kassis

    2014-11-01

    Full Text Available Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele. The mechanisms driving worm migration and retention within the lymphatics are currently unknown. We have developed an integrated in vitro imaging platform capable of quantifying B. malayi migration and behavior in a multicellular microenvironment relevant to the initial site of worm injection by incorporating the worm in a Polydimethylsiloxane (PDMS microchannel in the presence of human dermal lymphatic endothelial cells (LECs and human dermal fibroblasts (HDFs. The platform utilizes a motorized controllable microscope with CO2 and temperature regulation to allow for worm tracking experiments with high resolution over large length and time scales. Using post-acquisition algorithms, we quantified four parameters: 1 speed, 2 thrashing intensity, 3 percentage of time spent in a given cell region and 4 persistence ratio. We demonstrated the utility of our system by quantifying these parameters for L3 B. malayi in the presence of LECs and HDFs. Speed and thrashing increased in the presence of both cell types and were altered within minutes upon exposure to the anthelmintic drug, tetramisole. The worms displayed no targeted migration towards either cell type for the time course of this study (3 hours. When cells were not present in the chamber, worm thrashing correlated directly with worm speed. However, this correlation was lost in the presence of cells. The described platform provides the ability to further study B. malayi migration and behavior.

  3. The complete mitochondrial genome of Setaria digitata (Nematoda: Filarioidea): Mitochondrial gene content, arrangement and composition compared with other nematodes.

    Science.gov (United States)

    Yatawara, Lalani; Wickramasinghe, Susiji; Rajapakse, R P V J; Agatsuma, Takeshi

    2010-09-01

    In the present study, we determined the complete mitochondrial (mt) genome sequence (13,839bp) of parasitic nematode Setaria digitata and its structure and organization compared with Onchocerca volvulus, Dirofilaria immitis and Brugia malayi. The mt genome of S. digitata is slightly larger than the mt genomes of other filarial nematodes. S. digitata mt genome contains 36 genes (12 protein-coding genes, 22 transfer RNAs and 2 ribosomal RNAs) that are typically found in metazoans. This genome contains a high A+T (75.1%) content and low G+C content (24.9%). The mt gene order for S. digitata is the same as those for O. volvulus, D. immitis and B. malayi but it is distinctly different from other nematodes compared. The start codons inferred in the mt genome of S. digitata are TTT, ATT, TTG, ATG, GTT and ATA. Interestingly, the initiation codon TTT is unique to S. digitata mt genome and four protein-coding genes use this codon as a translation initiation codon. Five protein-coding genes use TAG as a stop codon whereas three genes use TAA and four genes use T as a termination codon. Out of 64 possible codons, only 57 are used for mitochondrial protein-coding genes of S. digitata. T-rich codons such as TTT (18.9%), GTT (7.9%), TTG (7.8%), TAT (7%), ATT (5.7%), TCT (4.8%) and TTA (4.1%) are used more frequently. This pattern of codon usage reflects the strong bias for T in the mt genome of S. digitata. In conclusion, the present investigation provides new molecular data for future studies of the comparative mitochondrial genomics and systematic of parasitic nematodes of socio-economic importance. 2010 Elsevier B.V. All rights reserved.

  4. In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

    Directory of Open Access Journals (Sweden)

    Komal Kalani

    Full Text Available As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM and female adult worms (LC100: 100; IC50: 35.36 µM as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock scores for UA (-8.6 with respect to the standard antifilarial drugs, ivermectin (IVM -8.4 and diethylcarbamazine (DEC-C -4.6 on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection, which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

  5. FAKTOR-FAKTOR YANG MEMPENGARUHI KEJADIAN FILARIASIS DI INDONESIA (DATA RISKESDAS 2007

    Directory of Open Access Journals (Sweden)

    Mardiana Mardiana

    2012-11-01

    Full Text Available Filariasis or elephantiasis diseases which caused by filaria worm and contagious through mosquito bite, still the major community health problem in Indonesia. There are several type of filaria worm in Indonesia, i.e. Wuchereria bancrofti, Brugia malayi and Brugia timori. The vectors of filariasis are Culex quinquefasciatus in the urban area, Anopheles spp, Aedes spp and Mansonia spp in the rural area. The infection risk in some area of filariasis related to the situation of local area. Various factor of environmental area which area physical, biological and also cultural social to be influence to development of transmitted filariasis by mosquito. The analysis of data Riskesdas 2007 has been done to perform of factor influence filariasis case in Indonesia. Same parameters was analyzed to case of filariasis in last 12 months; gender, ages, educations, work, mosquito net usage, sources of water, effluent dismissal, residences, water dismissal channel, existence of livestock in house. From analysis inferential, show there is no relation between genders, age, education, work, and mosquito net usage, sources of water, water dismissal channel, and existence of livestock in house to case filariasis. Statistically indicates that there is significantly difference between residences in rural and in urban to case of filariasis in last 12 months. Responder who live in rural areas (0,05% have 2,4 times risk higher than responder who live in urban (0,03%. The same as condition of water dismissal channel shows to existence of significantly differences. Responder who have water dismissal channel without cover have high risk infections of filariasis in the last 12 months were 0,05%, while the responder have water dismissal channel with cover have high risk in last 12 months were 0,03%. Keywords: Filariasis, endemic area, factors

  6. Molecular characterization and functional analysis of serine/threonine protein phosphatase of Toxocara canis.

    Science.gov (United States)

    Ma, Guang Xu; Zhou, Rong Qiong; Hu, Shi Jun; Huang, Han Cheng; Zhu, Tao; Xia, Qing You

    2014-06-01

    Toxocara canis (T. canis) is a widely prevalent zoonotic parasite that infects a wide range of mammalian hosts, including humans. We generated the full-length complementary DNA (cDNA) of the serine/threonine phosphatase gene of T. canis (Tc stp) using 5' rapid amplification of the cDNA ends. The 1192-bp sequence contained a continuous 942-nucleotide open reading frame, encoding a 313-amino-acid polypeptide. The Tc STP polypeptide shares a high level of amino-acid sequence identity with the predicted STPs of Loa loa (89%), Brugia malayi (86%), Oesophagostomum columbianum (76%), and Oesophagostomumdentatum (76%). The Tc STP contains GDXHG, GDXVDRG, GNHE motifs, which are characteristic of members of the phosphoprotein phosphatase family. Our quantitative real-time polymerase chain reaction analysis showed that the Tc STP was expressed in six different tissues in the adult male, with high-level expression in the spermary, vas deferens, and musculature, but was not expressed in the adult female, suggesting that Tc STP might be involved in spermatogenesis and mating behavior. Thus, STP might represent a potential molecular target for controlling T. canis reproduction. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Recent Advances on the Use of Biochemical Extracts as Filaricidal Agents

    Directory of Open Access Journals (Sweden)

    Nazeh M. Al-Abd

    2013-01-01

    Full Text Available Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented.

  8. VECTORS OF MALARIA AND FILARIASIS IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Hoedojo Hoedojo

    2012-09-01

    Full Text Available Malaria at present is still one of the important mosquito-borne diseases in Indonesia. The disease is widespread all over the country and involves nearly all islands. Sixteen Anopheles species have been reconfirmed as malaria vectors. They were distributed geographi­cally as follows: Coastal areas and lagoons ------------------------------------- An sundaicus and An.subpictus Cultivated ricefields and swampy areas -------------------- An.aconitus, An.barbirostris, An.nigerrimus and An.sinensis Forest inland areas in shaded temporary pools, muddy animal wallows and hoof-prints -------------------------------------------------------- An.balabacensis, An.bancrofti, An.farauti, An.koliensis and An.punctulatus Swamp forest edge in ditches with vegeta- ---------------- An.letifer and An.ludlowae don Hilly areas in seepages, streams and clear moving water ---------------------------------------------- Anflavirostris, An.maculatus and Anminimus.   The species (of most general importance is An.sundaicus, which is restricted by its preference for brackish water and is prevalent in coastal areas of Java. Their types in behaviour of An.sundaicus appear as follows : 1. An.sundaicus in South Coast of Java in general. This species is essentially anthropophilic, exophagic and rests outdoor. It shows susceptible to DDT. 2. An.sundaicus in Cilacap, Central Java. This mosquito is a pure anthropophilic form. It bites man in houses and outdoors, rests indoors and is known resistant to DDT. 3. An.sundaicus in Yogyakarta and Purworejo, Central Java. This mosquito is a strong zoophilic species. It rests and prefers to bite outdoors and shows tolerance to DDT. Human filariasis in Indonesia is the result of infection by three endemic species, namely, Wuchereria bancrofti, Brugia malayi, and Brugia timori.W.bancrofti infection is found in both urban and rural areas. Twenty species of mosquitoes are confirmed as filariasis vectors. The urban type bancroftian filariasis

  9. L1 and L2 Distance Effects in Learning L3 Dutch

    Science.gov (United States)

    Schepens, Job J.; der Slik, Frans; Hout, Roeland

    2016-01-01

    Many people speak more than two languages. How do languages acquired earlier affect the learnability of additional languages? We show that linguistic distances between speakers' first (L1) and second (L2) languages and their third (L3) language play a role. Larger distances from the L1 to the L3 and from the L2 to the L3 correlate with lower…

  10. Reactive oxygen species production and Brugia pahangi survivorship in Aedes polynesiensis with artificial Wolbachia infection types.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Andrews

    Full Text Available Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB" experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive oxygen species (ROS in the MTB strain differ significantly relative to that of the wild-type, indicating an impaired ability to regulate oxidative stress. Following a challenge with Brugia pahangi, the number of filarial worms achieving the infective stage is significantly reduced in MTB as compared to the naturally infected and aposymbiotic strains. Survivorship of MTB differed significantly from that of the wild-type, with an interactive effect between survivorship and blood feeding. The results demonstrate a direct correlation between decreased ROS levels and decreased survival of adult female Aedes polynesiensis. The results are discussed in relation to the interaction of Wolbachia with ROS production and antioxidant expression, iron homeostasis and the insect immune system. We discuss the potential applied use of the MTB strain for impacting Ae. polynesiensis populations and strategies for reducing LF incidence in the South Pacific.

  11. Generation and selection of naïve Fab library for parasitic antigen: Anti-BmSXP antibodies for lymphatic filariasis.

    Science.gov (United States)

    Omar, Noorsharmimi; Hamidon, Nurul Hamizah; Yunus, Muhammad Hafiznur; Noordin, Rahmah; Choong, Yee Siew; Lim, Theam Soon

    2018-05-01

    Phage display has been applied successfully as a tool for the generation of monoclonal antibodies (mAbs). Naive antibody libraries are unique as they are able to overcome several limitations associated with conventional mAb generation methods like the hybridoma technology. Here, we performed an in vitro selection and generation of Fab antibodies against Brugia malayi SXP protein (BmSXP), a recombinant antigen for the detection of lymphatic filariasis. We developed a naïve multi ethnic Fab antibody library with an estimated diversity of 2.99 × 10 9 . The antibody library was used to screen for mAbs against BmSXP recombinant antigen. Soluble monoclonal Fab antibodies against BmSXP were successfully isolated from the naïve library. The Fab antibodies obtained were expressed and analyzed to show its binding capability. The diversity obtained from a pool of donors from various ethnic groups allowed for a diverse antibody library to be generated. The mAbs obtained were also functional in soluble form, which makes it useful for further downstream applications. We believe that the Fab mAbs are valuable for further studies and could also contribute to improvements in the diagnosis of filariasis. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  12. Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation.

    Science.gov (United States)

    Ariani, Cristina V; Juneja, Punita; Smith, Sophia; Tinsley, Matthew C; Jiggins, Francis M

    2015-01-01

    Mosquitoes are one of the most important vectors of human disease. The ability of mosquitoes to transmit disease is dependent on the age structure of the population, as mosquitoes must survive long enough for the parasites to complete their development and infect another human. Age could have additional effects due to mortality rates and vector competence changing as mosquitoes senesce, but these are comparatively poorly understood. We have investigated these factors using the mosquito Aedes aegypti and the filarial nematode Brugia malayi. Rather than observing any effects of immune senescence, we found that older mosquitoes were more resistant, but this only occurred if they had previously been maintained on a nutrient-poor diet of fructose. Constant blood feeding reversed this decline in vector competence, meaning that the number of parasites remained relatively unchanged as mosquitoes aged. Old females that had been maintained on fructose also experienced a sharp spike in mortality after an infected blood meal ("refeeding syndrome") and few survived long enough for the parasite to develop. Again, this effect was prevented by frequent blood meals. Our results indicate that old mosquitoes may be inefficient vectors due to low vector competence and high mortality, but that frequent blood meals can prevent these effects of age. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Assembly of the Genome of the Disease Vector Aedes aegypti onto a Genetic Linkage Map Allows Mapping of Genes Affecting Disease Transmission

    KAUST Repository

    Juneja, Punita

    2014-01-30

    The mosquito Aedes aegypti transmits some of the most important human arboviruses, including dengue, yellow fever and chikungunya viruses. It has a large genome containing many repetitive sequences, which has resulted in the genome being poorly assembled - there are 4,758 scaffolds, few of which have been assigned to a chromosome. To allow the mapping of genes affecting disease transmission, we have improved the genome assembly by scoring a large number of SNPs in recombinant progeny from a cross between two strains of Ae. aegypti, and used these to generate a genetic map. This revealed a high rate of misassemblies in the current genome, where, for example, sequences from different chromosomes were found on the same scaffold. Once these were corrected, we were able to assign 60% of the genome sequence to chromosomes and approximately order the scaffolds along the chromosome. We found that there are very large regions of suppressed recombination around the centromeres, which can extend to as much as 47% of the chromosome. To illustrate the utility of this new genome assembly, we mapped a gene that makes Ae. aegypti resistant to the human parasite Brugia malayi, and generated a list of candidate genes that could be affecting the trait. © 2014 Juneja et al.

  14. Comparative studies on the biology and filarial susceptibility of selected blood-feeding and autogenous Aedes togoi sub-colonies

    Directory of Open Access Journals (Sweden)

    Anuluck Junkum

    2003-06-01

    Full Text Available Blood-feeding and autogenous sub-colonies were selected from a laboratory, stock colony of Aedes togoi, which was originally collected from Koh Nom Sao, Chanthaburi province, Southeast Thailand. Comparative biology and filarial susceptibility between the two sub-colonies (blood-feeding: F11, F13; autogeny: F38, F40 were investigated to evaluate their viability and vectorial capacity. The results of comparison on biology revealed intraspecific differences, i.e., the average egg deposition/gravid female (F11/F38; F13/F40, embryonation rate (F13/F40, hatchability rate (F11/F38; F13/F40, egg width (F11/F38, wing length of females (F13/F40, and wing length and width of males (F11/F38 in the blood-feeding sub-colony were significantly greater than that in the autogenous sub-colony; and egg length (F11/F38 and width (F13/F40, and mean longevity of adult females (F11/F38 and males (F13/F40 in the blood-feeding sub-colony were significantly less than that in the autogenous sub-colony. The results of comparison on filarial susceptibility demonstrated that both sub-colonies yielded similar susceptibilities to Brugia malayi [blood-feeding/autogeny = 56.7% (F11/53.3%(F38, 60%(F13/83.3%(F40] and Dirofilaria immitis [blood-feeding/autogeny = 85.7%(F11/75%(F38, 45%(F13/29.4%(F40], suggesting autogenous Ae. togoi sub-colony was an efficient laboratory vector in study of filariasis.

  15. Sequencing and analysis of the complete mitochondrial genome in Anopheles sinensis (Diptera: Culicidae).

    Science.gov (United States)

    Chen, Kai; Wang, Yan; Li, Xiang-Yu; Peng, Heng; Ma, Ya-Jun

    2017-10-02

    Anopheles sinensis (Diptera: Culicidae) is a primary vector of Plasmodium vivax and Brugia malayi in most regions of China. In addition, its phylogenetic relationship with the cryptic species of the Hyrcanus Group is complex and remains unresolved. Mitochondrial genome sequences are widely used as molecular markers for phylogenetic studies of mosquito species complexes, of which mitochondrial genome data of An. sinensis is not available. An. sinensis samples was collected from Shandong, China, and identified by molecular marker. Genomic DNA was extracted, followed by the Illumina sequencing. Two complete mitochondrial genomes were assembled and annotated using the mitochondrial genome of An. gambiae as reference. The mitochondrial genomes sequences of the 28 known Anopheles species were aligned and reconstructed phylogenetic tree by Maximum Likelihood (ML) method. The length of complete mitochondrial genomes of An. sinensis was 15,076 bp and 15,138 bp, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and an AT-rich control region. As in other insects, most mitochondrial genes are encoded on the J strand, except for ND5, ND4, ND4L, ND1, two rRNA and eight tRNA genes, which are encoded on the N strand. The bootstrap value was set as 1000 in ML analyses. The topologies restored phylogenetic affinity within subfamily Anophelinae. The ML tree showed four major clades, corresponding to the subgenera Cellia, Anopheles, Nyssorhynchus and Kerteszia of the genus Anopheles. The complete mitochondrial genomes of An. sinensis were obtained. The number, order and transcription direction of An. sinensis mitochondrial genes were the same as in other species of family Culicidae.

  16. Immune responses of B. malayi thioredoxin (TRX) and venom allergen homologue (VAH) chimeric multiple antigen for lymphatic filariasis.

    Science.gov (United States)

    Anugraha, Gandhirajan; Jeyaprita, Parasurama Jawaharlal; Madhumathi, Jayaprakasam; Sheeba, Tamilvanan; Kaliraj, Perumal

    2013-12-01

    Although multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.

  17. L3 + Cosmics Experiment

    CERN Multimedia

    2002-01-01

    %RE4 %title\\\\ \\\\The L3+C experiment takes advantage of the unique properties of the L3 muon spectrometer to get an accurate measurement of cosmic ray muons 30 m underground. A new muon trigger, readout and DAQ system have been installed, as well as a scintillator array covering the upper surfaces of the L3 magnet for timing purposes. The acceptance amounts to 200 $m^2 sr$. The data are collected independently in parallel with L3 running. In spring 2000 a scintillator array will be installed on the roof of the SX hall in order to estimate the primary energy of air showers associated with events observed in L3+C.\\\\ \\\\The cosmic ray muon momentum spectrum, the zenith angular dependence and the charge ratio are measured with high accuracy between 20 and 2000 GeV/c. The results will provide new information about the primary composition, the shower development in the atmosphere, and the inclusive pion and kaon (production-) cross sections (specifically the "$\\pi$/K ratio") at high energies. These data will also hel...

  18. The Effects of L2 Experience on L3 Perception

    Science.gov (United States)

    Onishi, Hiromi

    2016-01-01

    This study examines the influence of experience with a second language (L2) on the perception of phonological contrasts in a third language (L3). This study contributes to L3 phonology by examining the influence of L2 phonological perception abilities on the perception of an L3 at the beginner level. Participants were native speakers of Korean…

  19. Analysis of LOFT loss-of-coolant experiments L2-2, L2-3, and L3-0

    International Nuclear Information System (INIS)

    Leach, L.P.; Linebarger, J.H.

    1979-01-01

    A summary of results from Loss-of-Coolant Experiments (LOCE) L2-2, L2-3, and L3-0, conducted in the Loss-of-Fluid Test (LOFT) facility, and conclusions from posttest analyses of the experimental data are presented. LOCEs L2-2 and L2-3 were nuclear large break experiments and were dominated by a core-wide fuel rod cladding rewet, which limited the maximum fuel temperature. Analytical models only conservatively predicted the measured fuel rod temperatures and will require improvements to provide best estimate predictions in this area. Analysis of a large commercial pressurized water reactor (PWR) indicates that the cladding rewet observed in LOFT is also likely to occur in a large PWR, and that, therefore, safety analysis calculations of large loss-of-coolant accidents (LOCA) are more conservative than previously thought. LOCE L3-0 was an isothermal small break (top of pressurizer) experiment and illustrated that the pressurizer fills after the primary system fluid saturates someplace other than the pressurizer itself, that the indicated pressurizer level is higher than the actual level, and that additional model development and assessment work is necessary in order to predict small LOCAs as accurately as large LOCAs

  20. Development of lymphatic filarial parasite Wuchereria bancrofti (Spirurida: Onchocercidae) in mosquito species (Diptera: Culicidae) fed artificially on microfilaremic blood.

    Science.gov (United States)

    Paily, K P; Hoti, S L; Balaraman, K

    2006-11-01

    The efficiency of laboratory colonies of mosquitoes such as Anopheles stephensi Liston, Aedes aegypti (L.) Liverpool strain, Ae. aegypti wild type, Aedes albopictus (Skuse), Culex tritaeniorhynchus Giles, Culex sitiens Wiedemann, and Armigeres subalbatus Coquillett in supporting the development of Wuchereria bancrofti (Cobbold) (Spirurida: Onchocercidae) microfilariae to infective larvae was investigated. The mosquitoes were fed on heparinized microfilaremic human blood by using a membrane-feeding unit with Parafilm as membrane. The rate of infection, parasite development, and parasite burden were compared with that in the known vector mosquito Culex quinquefasciatus Say. Cx. quinquefasciatus showed the highest percentage of infection, followed by Ae. aegypti Liverpool strain and An. stephensi. The rate of development of the parasite was more or less similar in all the three species, and infective larvae were found on day 13. When the larvae were harvested on day 17, Cx. quinquefasciatus yielded the highest numbers, followed by Ae. aegypti Liverpool strain and An. stephensi. The percentage of infection was low, and the development was slow in Cx. tritaeniorhynchus compared with the other susceptible species. The parasite developed to second-stage larvae only by day 22 and to infective larvae by day 28. When 2-wk-old Cx. tritaeniorhynchus were fed on microfilaremic blood, they could develop the parasite to infective larvae by day 13 postfeeding. All other species of mosquitoes tested were found to be refractory to parasite development. It is shown that Cx. quinquefasciatus is the most suitable mosquito host for the production of infective larvae. However, Ae. aegypti Liverpool strain, which is commonly used for Brugia malayi filarial parasite, also can be used for generation of W. bancrofti infective larvae to circumvent the problem of maintaining two mosquito species.

  1. A new member of the GM130 golgin subfamily is expressed in the optic lobe anlagen of the metamorphosing brain of Manduca sexta

    Directory of Open Access Journals (Sweden)

    Chiou-Miin Wang

    2003-12-01

    Full Text Available During metamorphosis of the insect brain, the optic lobe anlagen generate the proliferation centers for the visual cortices. We show here that, in the moth Manduca sexta, an 80 kDa Golgi complex protein (Ms-golgin80 is abundantly expressed in the cytoplasm of neuroblasts and ganglion mother cells in the optic lobe anlagen and proliferation centers. The predicted amino acid sequence for Ms-golgin80 is similar to that of several members of the GM130 subfamily of Golgi-associated proteins, including rat GM130 and human golgin-95. Homologs of Ms-golgin80 from Drosophila melanogaster, Caenorhabditis elegans, and Brugia malayi were identified through homology sequence search. Sequence similarities are present in three regions: the N-terminus, an internal domain of 89 amino acids, and another domain of 89 amino acids near the C-terminus. Structural similarities further suggest that these molecules play the same cellular role as GM130. GM130 is involved in the docking and fusion of coatomer (COP I coated vesicles to the Golgi membranes; it also regulates the fragmentation and subsequent reassembly of the Golgi complex during mitosis. Abundant expression of Ms-golgin80 in neuroblasts and ganglion mother cells and its reduced expression in the neuronal progeny of these cells suggest that this protein may be involved in the maintenance of the proliferative state.

  2. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

    KAUST Repository

    Juneja, Punita; Ariani, Cristina V.; Ho, Yung Shwen; Akorli, Jewelna; Palmer, William J.; Pain, Arnab; Jiggins, Francis M.

    2015-01-01

    to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously

  3. Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Li Hailan

    2011-12-01

    Full Text Available Abstract Background Phosphatidylcholine (PPC formulation is used for lipolytic injection, even though its mechanism of action is not well understood. Methods The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD, and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways. Results PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations Conclusions PPC results in apoptosis of 3T3-L1 cells.

  4. Duration of detection of anti-BmR1 IgG4 antibodies after mass-drug administration (MDA) in Sarawak, Malaysia.

    Science.gov (United States)

    Noordin, R; Muhi, J; Md Idris, Z; Arifin, N; Kiyu, A

    2012-03-01

    The detection rates of brugian filariasis in three regions of Sarawak namely Central, North and South after three courses of mass drug administration (MDA) from year 2004 to 2006 was investigated. A recombinant BmR1 antigen-based IgG4 detection test, named Brugia Rapid and night blood smear for microfilaria (mf) detection were used. All three regions recorded a sharp fall in mf positive rates after a year post-MDA. Meanwhile Brugia Rapid positive rates declined more gradually to 3.8% and 5.6% of the pre-MDA levels in the Central and North regions, respectively. This study showed that in filariasis endemic areas in Sarawak, anti-filarial IgG4 antibodies to BmR1, as detected by the Brugia Rapid test, were positive for one to two years after mf disappearance.

  5. Analysis list: l(3)mbt [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available l(3)mbt Cell line,Larvae + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/l(3)mbt.1.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/l(3)mbt.5.tsv http://dbarchive.bioscie...ncedbc.jp/kyushu-u/dm3/target/l(3)mbt.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/l(3)mbt.Cell_line.tsv,http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/l(3)mbt.Larvae.tsv http:...//dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Cell_line.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Larvae.gml ...

  6. How elimination of lymphatic filariasis as a public health problem in the Kingdom of Cambodia was achieved.

    Science.gov (United States)

    Khieu, Virak; Or, Vandine; Tep, Chhakda; Odermatt, Peter; Tsuyuoka, Reiko; Char, Meng Chuor; Brady, Molly A; Sidwell, Joshua; Yajima, Aya; Huy, Rekol; Ramaiah, Kapa D; Muth, Sinuon

    2018-02-20

    Endemicity of lymphatic filariasis (LF) in Cambodia was proven in 1956 when microfilariae were detected in mosquitos in the Kratié province. In 2001, an extensive study confirmed the presence of both Brugia malayi and Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a national task force to develop policies and strategies for controlling and eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF by 2015. This article summarizes the work accomplished to eliminate LF as a public health problem in Cambodia. The National Program to Eliminate Lymphatic Filariasis made excellent progress in the goal towards elimination due to strong collaboration between ministries, intensive supervision by national staff, and advocacy for mobilization of internal and external resources. Mass drug administration (MDA) with diethylcarbamazine citrate and albendazole was conducted in six implementation units, achieving > 70% epidemiological coverage for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces, healthcare workers developed a line list of lymphedema and hydrocele patients, many of whom were > 40 years old and had been affected by LF for many years. The national program also trained healthcare workers and provincial and district staff in morbidity management and disability prevention, and designated health centers to provide care for lymphedema and acute attack. Two reference hospitals were designated to administer hydrocele surgery. Effectiveness of MDA was proven with transmission assessment surveys. These found that less than 1% of school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015. A separate survey in one province in 2015 using Brugia Rapid tests to test for LF antibody found one child positive among 1677 children. The list of chronic LF patients was most recently updated and confirmed in 2011-2012, with 32 lymphoedema patients and 17 hydrocele patients listed. All

  7. L-rhamnose induces browning in 3T3-L1 white adipocytes and activates HIB1B brown adipocytes.

    Science.gov (United States)

    Choi, Minji; Mukherjee, Sulagna; Kang, Nam Hyeon; Barkat, Jameel Lone; Parray, Hilal Ahmad; Yun, Jong Won

    2018-04-11

    Induction of the brown adipocyte-like phenotype in white adipocytes (browning) is considered as a novel strategy to fight obesity due to the ability of brown adipocytes to increase energy expenditure. Here, we report that L-rhamnose induced browning by elevating expression levels of beige-specific marker genes, including Cd137, Cited1, Tbx1, Prdm16, Tmem26, and Ucp1, in 3T3-L1 adipocytes. Moreover, L-rhamnose markedly elevated expression levels of proteins involved in thermogenesis both in 3T3-L1 white and HIB1B brown adipocytes. L-rhamnose treatment in 3T3-L1 adipocytes also significantly elevated protein levels of p-HSL, p-AMPK, ACOX, and CPT1 as well as reduced levels of ACC, FAS, C/EBPα, and PPARγ, suggesting its possible role in enhancement of lipolysis and lipid catabolism as well as reduced adipogenesis and lipogenesis, respectively. The quick technique of efficient molecular docking provided insight into the strong binding of L-rhamnose to the fat-digesting glycine residue of β 3 -adrenergic receptor (AR), indicating strong involvement of L-rhamnose in fat metabolism. Further examination of the molecular mechanism of L-rhamnose revealed that it induced browning of 3T3-L1 adipocytes via coordination of multiple signaling pathways through β 3 -AR, SIRT1, PKA, and p-38. To the best of our knowledge, this is the first study to demonstrate that L-rhamnose plays multiple modulatory roles in the induction of white fat browning, activation of brown adipocytes, as well as promotion of lipid metabolism, thereby demonstrating its therapeutic potential for treatment of obesity. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  8. 3l1rhiral ~nlIrnaL

    African Journals Online (AJOL)

    tissue injury and carcinogenesis, are highlighted. Neutrophil production ... a family of 3 distinct glycoprotein adhesion molecules (L, E and P selectins), each of which .... transition metal-independent pathway of ·OH has been demonstrated in ...

  9. Delayed vertebral diagnosed L4 pincer vertebral fracture, L2-L3 ruptured vertebral lumbar disc hernia, L5 vertebral wedge fracture - Case report

    Directory of Open Access Journals (Sweden)

    Balasa D

    2016-08-01

    Full Text Available An association between delayed ruptured lumbar disc hernia, L5 vertebral wedge fracture and posttraumaticL4 pincer vertebral fracture (A2.3-AO clasification at different levels is a very rare entity. We present the case of a 55 years old male who falled down from a bicycle. 2 months later because of intense and permanent vertebral lumbar and radicular L2 and L3 pain (Visual Scal Autologus of Pain7-8/10 the patient came to the hospital. He was diagnosed with pincer vertebral L4 fracture (A2.3-AO clasification and L2-L3 right ruptured lumbar disc hernia in lateral reces. The patient was operated (L2-L3 right fenestration, and resection of lumbar disc hernia, bilateral stabilisation, L3-L4-L5 with titan screws and postero-lateral bone graft L4 bilateral harvested from iliac crest.

  10. Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment.

    Science.gov (United States)

    Kar, Shantanu K; Dwibedi, Bhagirathi; Das, Birendra K; Agrawala, Bikash K; Ramachandran, Cherubala P; Horton, John

    2017-10-01

    Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. ClinicalTrials.gov No CTRI/2013/10/004121.

  11. Isolation of eukaryotic ribosomal proteins. Purification and characterization of 60 S ribosomal subunit proteins L3, L6, L7', L8, L10, L15, L17, L18, L19, L23', L25, L27', L28, L29, L31, L32, L34, L35, L36, L36', and L37'.

    Science.gov (United States)

    Tsurugi, K; Collatz, E; Todokoro, K; Wool, I G

    1977-06-10

    The proteins of the large subunit of rat liver ribosomes were separated into seven groups by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5. Twenty-one proteins (L3, L6, L7', L8, L10, L15, L17, L18, L19, L23', L25, L27', L28, L29, L31, L32, L34, L35, L36, L36', and L37') were isolated from three groups (C60, E60, and F60) by ion exchange chromatography on carboxymethycellulose and by filtration through Sephadex. The amount of protein obtained varied from 0.3 to 25 mg. Nine of the proteins (L6, L8, L18, L27', L28, L29, L34, L36, and L36') had no detectable contamination: the impurities in the others were no greater than 9%. The molecular weight of the proteins was estimated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate; the amino acid composition was determined.

  12. Cutting the L3 torque tube

    CERN Multimedia

    Laurent Guiraud

    2001-01-01

    Workers cut the torque tube, with a plasma-cutting device on the L3 experiment, which closed with the LEP accelerator in 2000. L3 was housed in a huge red solenoid, which will be taken over by the ALICE detector when the new LHC is completed.

  13. Cognitive approaches to L3 acquisition

    Directory of Open Access Journals (Sweden)

    Maria del Pilar Garcia Mayo

    2012-06-01

    Full Text Available Multilingualism has established itself as an area of systematic research in linguistic studies over the last two decades. The multilingual phenomenon can be approached from different perspectives: educational, formal linguistic, neurolinguistic, psycholinguistic and sociolinguistic, among others. This article presents an overview of cognitive (psychological and formal linguistic approaches to third language (L3 acquisition where the assumption is that language acquisition is a complex multi-faceted process. After identifying what is meant by L3, the article briefly reviews the major issues addressed from both the psycholinguistic strand and the emerging L3 linguistic strand and concentrates on those aspects that are in need of further research in both.El plurilingüismo se ha ganado su propia área de investigación dentro de los estudios de lingüística en las últimas dos décadas. El fenómeno se puede abordar desde perspectivas diferentes: educativa, lingüística de carácter formal, neurolingüística, psicolingüística y sociolingüística, entre otras. Este artículo presenta una visión general de dos perspectivas cognitivas, la psicológica y la procedente de la lingüística formal, al tema de la adquisición de la tercera lengua (L3. Ambas perspectivas comparten la asunción de que la adquisición del lenguaje es un proceso complejo y con varias vertientes. Después de identificar lo que entendemos por L3, el artículo revisa de forma sucinta los principales temas que se han tratado tanto desde la perspectiva psicolingüística como desde la más emergente perspectiva lingüística en materia de L3 y se concentra en aquellos aspectos que consideramos que necesitan mayor investigación en ambas.

  14. Combination L-T3 and L-T4 therapy for hypothyroidism.

    Science.gov (United States)

    Wartofsky, Leonard

    2013-10-01

    Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population. Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment. Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.

  15. Kosmische Myonen im L3-Detektor

    CERN Document Server

    Saidi, Rachid

    2000-01-01

    Durch die Untersuchung des Mondschattens in der primaren kosmischen Strahlung konnen Informationen uber die Winkelau osung des L3-Detektors gewonnen werden, sowie mit ausreichender Statistik das Verhaltnis von Antiprotonen zu Protonen fur Protonenergien um 1 TeV abgeschatzt werden. Die Bahn der Protonen vom Mond zur Erde wird durch folgende Eekte beein ut: Das Magnetfeld zwischen Mond und Erde lenkt die geladenen Teilchen ab. Fur 1 TeV Protonenenergie wurde ein Wert von 1:70 abgeschatzt. Die Mehrfachstreuung in der 30 m dicken Erdschicht uber L3 verursacht eine Winkelverschmierung von 3.5 mrad fur 100 GeV Myonen. Der Winkel zwischen Proton und den sekundaren Myonen, die durch Wechselwirkung von primaren Kernen mit den oberen Schichten der Atmosphare entstehen, betragt 3 mrad fur 100 GeV Myonen. Die berechnete Winkelau osung dieser Untersuchung fur den L3-Detektor mit verschiedenen Energien betragt einen Wert von 0:170 0:030 fur das starkste Myonschattensignal bei 150 GeV Myonenenergie. Dabei wurde fur den Mon...

  16. Summary and evaluation: fuel dynamics loss-of-flow experiments (tests L2, L3, and L4)

    International Nuclear Information System (INIS)

    Barts, E.W.; Deitrich, L.W.; Eberhart, J.G.; Fischer, A.K.; Meek, C.C.

    1975-09-01

    Three similar experiments conducted to support the analyses of hypothetical LMFBR unprotected-loss-of-flow accidents are summarized and evaluated. The tests, designated L2, L3, and L4, provided experimental data against which accident-analysis codes could be compared, so as to guide further analysis and modeling of the initiating phases of the hypothetical accident. The tests were conducted using seven-pin bundles of mixed-oxide fuel pins in Mark-II flowing-sodium loops in the TREAT reactor. Test L2 used fresh fuel. Tests L3 and L4 used irradiated fuel pins having, respectively, ''intermediate-power'' (no central void) and ''high-power'' (fully developed central void) microstructure. 12 references

  17. Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.

    Science.gov (United States)

    Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Valenti, Vincenza; Ingrassia, Valeria; Giammanco, Antonina; Panno, Maria D; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

    2015-12-01

    Cyclic AMP responsive element-binding protein 3-like 3 (CREB3L3) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this family, we analyzed the candidate genes of recessive and dominant forms of primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3 gene, predicted to result in the formation of a truncated protein devoid of function (c.359delG-p.K120fsX20). Heterozygosity for the c.359delG mutation resulted in a severe phenotype occurring later in life in the proband and her brother and a good response to diet and a hypotriglyceridemic treatment. The same mutation was detected in a 13-year-old daughter who to date is normotriglyceridemic. We have identified a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance. © 2015 American Heart Association, Inc.

  18. L3 English acquisition in Denmark and Greenland

    DEFF Research Database (Denmark)

    Spellerberg, Stine Marie

    2011-01-01

    This paper presents findings of gender-related tendencies found in a study of factors influential in third language acquisition of English in Denmark and Greenland. A survey consisting of a questionnaire and an English test was carried out amongst pupils in their last year of compulsory schooling...... in Copenhagen, Denmark, and Nuuk, Greenland. In total, responses from 187 pupils were included, some of which were responses from pupils learning English as a second language; these respondents were included for comparisons (Copenhagen: L2 learners N =59, L3 learners N=32; Nuuk: L3 learners N=96; age: 14......' degree of English classroom anxiety. The results differentiate the view that L3 learners as a group do less well in English than L2 learner peers, warranting further research into gender-related tendencies and extra focus on the English acquisition of L3 learner boys in particular in the Danish context....

  19. Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chenglin; Chen, Dongrui; Xie, Qihai [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China); Yang, Ying, E-mail: yangying_sh@yahoo.com [Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China); Shen, Weili, E-mail: weili_shen@hotmail.com [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China)

    2013-08-16

    Highlights: •Nebivolol may act as a partial agonist of β3-adrenergic receptor (AR). •Nebivolol stimulates mitochondrial DNA replication and protein expression. •Nebivolol promotes mitochondrial synthesis via activation of eNOS by β3-AR. -- Abstract: Nebivolol is a third-generation β-adrenergic receptor (β-AR) blocker with additional beneficial effects, including the improvement of lipid and glucose metabolism in obese individuals. However, the underlying mechanism of nebivolol’s role in regulating the lipid profile remains largely unknown. In this study, we investigated the role of nebivolol in mitochondrial biogenesis in 3T3-L1 adipocytes. Exposure of 3T3-L1 cells to nebivolol for 24 h increased mitochondrial DNA copy number, mitochondrial protein levels and the expression of transcription factors involved in mitochondrial biogenesis, including PPAR-γ coactivator-1α (PGC-1α), Sirtuin 3 (Sirt3), mitochondrial transcription factor A (Tfam) and nuclear related factor 1 (Nrf1). These changes were accompanied by an increase in oxygen consumption and in the expression of genes involved in fatty acid oxidation and antioxidant enzymes in 3T3-L1 adipocytes, including nebivolol-induced endothelial nitric oxide synthase (eNOS), as well as an increase in the formation of cyclic guanosine monophosphate (cGMP). Pretreatment with NG-nitro-L-arginine methyl ester (l-NAME) attenuated nebivolol-induced mitochondrial biogenesis, as did the soluble guanylate cyclase inhibitor, ODQ. Treatment with nebivolol and β3-AR blocker SR59230A markedly attenuated PGC-1α, Sirt3 and manganese superoxide dismutase (MnSOD) protein levels in comparison to treatment with nebivolol alone. These data indicate that the mitochondrial synthesis and metabolism in adipocytes that is promoted by nebivolol is primarily mediated through the eNOS/cGMP-dependent pathway and is initiated by the activation of β3-AR receptors.

  20. The structure of carbon nanotubes formed of graphene layers L4-8, L5-7, L3-12, L4-6-12

    Science.gov (United States)

    Shapovalova, K. E.; Belenkov, E. A.

    2017-11-01

    We geometrically calculate the optimized structure of nanotubes based on the graphene layers, using the method of molecular mechanics MM+. It was found that only the nanotubes, based on the graphene layers L4-8, L5-7, L3-12, L4-6-12, have a cylindrical form. Calculations of the sublimation energy, carried out using the semi-empirical quantum-mechanic method PM3, show that energy increases with the increase of nanotube diameters.

  1. L3 detector

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1992-01-15

    This is the final article in the CERN Courier series marking a decade of the four big experiments - Aleph, Delphi, L3 and Opal - at CERN's LEP electron-positron collider. Data-taking started soon after LEP became operational in July 1989, followed by substantial runs in 1990 and 1991. Because of the long lead times involved in today's major physics undertakings, preparations for these four experiments got underway in the early 1980s.

  2. RNAi effector diversity in nematodes.

    Directory of Open Access Journals (Sweden)

    Johnathan J Dalzell

    2011-06-01

    Full Text Available While RNA interference (RNAi has been deployed to facilitate gene function studies in diverse helminths, parasitic nematodes appear variably susceptible. To test if this is due to inter-species differences in RNAi effector complements, we performed a primary sequence similarity survey for orthologs of 77 Caenorhabditis elegans RNAi pathway proteins in 13 nematode species for which genomic or transcriptomic datasets were available, with all outputs subjected to domain-structure verification. Our dataset spanned transcriptomes of Ancylostoma caninum and Oesophagostomum dentatum, and genomes of Trichinella spiralis, Ascaris suum, Brugia malayi, Haemonchus contortus, Meloidogyne hapla, Meloidogyne incognita and Pristionchus pacificus, as well as the Caenorhabditis species C. brenneri, C. briggsae, C. japonica and C. remanei, and revealed that: (i Most of the C. elegans proteins responsible for uptake and spread of exogenously applied double stranded (dsRNA are absent from parasitic species, including RNAi-competent plant-nematodes; (ii The Argonautes (AGOs responsible for gene expression regulation in C. elegans are broadly conserved, unlike those recruited during the induction of RNAi by exogenous dsRNA; (iii Secondary Argonautes (SAGOs are poorly conserved, and the nuclear AGO NRDE-3 was not identified in any parasite; (iv All five Caenorhabditis spp. possess an expanded RNAi effector repertoire relative to the parasitic nematodes, consistent with the propensity for gene loss in nematode parasites; (v In spite of the quantitative differences in RNAi effector complements across nematode species, all displayed qualitatively similar coverage of functional protein groups. In summary, we could not identify RNAi effector deficiencies that associate with reduced susceptibility in parasitic nematodes. Indeed, similarities in the RNAi effector complements of RNAi refractory and competent nematode parasites support the broad applicability of this research

  3. Direct identification of the Meloidogyne incognita secretome reveals proteins with host cell reprogramming potential.

    Directory of Open Access Journals (Sweden)

    Stéphane Bellafiore

    2008-10-01

    Full Text Available The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling infection to occur; they can also release pathogen-associated molecular patterns (PAMPs, e.g., flagellin that trigger basal immunity through the nematode stylet into the plant cell. This leads to suppression of innate immunity and reprogramming of plant cells to form a feeding structure containing multinucleate giant cells. Effectors have generally been discovered using genetics or bioinformatics, but M. incognita is non-sexual and its genome sequence has not yet been reported. To partially overcome these limitations, we have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. These proteins contain at least segmental sequence identity to those found in our 3 reference databases (published nematode proteins; unpublished M. incognita ESTs; published plant proteins. Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions (e.g., regulating the plant cell cycle or growth. Others have regulatory domains that could reprogram cells. Using in situ hybridization we observed that most secreted proteins were produced by the subventral glands, but we found that phasmids also secreted proteins. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi, suggesting a common parasitic behavior and a possible

  4. L3 detector

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This is the final article in the CERN Courier series marking a decade of the four big experiments - Aleph, Delphi, L3 and Opal - at CERN's LEP electron-positron collider. Data-taking started soon after LEP became operational in July 1989, followed by substantial runs in 1990 and 1991. Because of the long lead times involved in today's major physics undertakings, preparations for these four experiments got underway in the early 1980s

  5. Hepatic CREB3L3 controls whole-body energy homeostasis and improves obesity and diabetes.

    Science.gov (United States)

    Nakagawa, Yoshimi; Satoh, Aoi; Yabe, Sachiko; Furusawa, Mika; Tokushige, Naoko; Tezuka, Hitomi; Mikami, Motoki; Iwata, Wakiko; Shingyouchi, Akiko; Matsuzaka, Takashi; Kiwata, Shiori; Fujimoto, Yuri; Shimizu, Hidehisa; Danno, Hirosuke; Yamamoto, Takashi; Ishii, Kiyoaki; Karasawa, Tadayoshi; Takeuchi, Yoshinori; Iwasaki, Hitoshi; Shimada, Masako; Kawakami, Yasushi; Urayama, Osamu; Sone, Hirohito; Takekoshi, Kazuhiro; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Yamada, Nobuhiro; Shimano, Hitoshi

    2014-12-01

    Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

  6. L3-forward-backward muon spectrometer

    International Nuclear Information System (INIS)

    Deiters, K.

    1995-01-01

    The performance of the distance sensors could be successfully tested in the L3 detector. One sensor of each type got installed together with a precision sensor. This sensor is based on a glass rod with optical marks which are scanned by a system of light diodes. It has a measurement accuracy of 1 μm. We proved, that the desired accuracy of 10 μm was reached and that the sensors work in the environment of the L3 detector. (author) 11 figs., 5 refs

  7. 38 CFR 3.953 - Pub. L. 85-56 and Pub. L. 85-857.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Pub. L. 85-56 and Pub. L... ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Protection § 3.953 Pub. L. 85-56 and Pub. L. 85-857. (a) In receipt of or entitled to receive benefits on December 31, 1958. Any person...

  8. IPD3 and IPD3L Function Redundantly in Rhizobial and Mycorrhizal Symbioses

    Directory of Open Access Journals (Sweden)

    Yue Jin

    2018-03-01

    Full Text Available Legume plants form symbiotic associations with either nitrogen-fixing bacteria or arbuscular mycorrhizal (AM fungi, which are regulated by a set of common symbiotic signaling pathway genes. Central to the signaling pathway is the activation of the DMI3/IPD3 protein complex by Ca2+ oscillations, and the initiation of nodule organogenesis and mycorrhizal symbiosis. DMI3 is essential for rhizobial infection and nodule organogenesis; however, ipd3 mutants have been shown to be impaired only in infection thread formation but not in root nodule organogenesis in Medicago truncatula. We identified an IPD3-like (IPD3L gene in the M. truncatula genome. A single ipd3l mutant exhibits a normal root nodule phenotype. The ipd3l/ipd3-2 double mutant is completely unable to initiate infection threads and nodule primordia. IPD3L can functionally replace IPD3 when expressed under the control of the IPD3 promoter, indicating functional redundancy between these two transcriptional regulators. We constructed a version of IPD3 that was phosphomimetic with respect to two conserved serine residues (IPD3-2D. This was sufficient to trigger root nodule organogenesis, but the increased multisite phosphorylation of IPD3 (IPD3-8D led to low transcriptional activity, suggesting that the phosphorylation levels of IPD3 fine-tune its transcriptional activity in the root nodule symbiosis. Intriguingly, the phosphomimetic version of IPD3 triggers spontaneous root-like nodules on the roots of dmi3-1 and dmi2-1 (DMI2 is an LRR-containing receptor-like kinase gene which is required for Ca2+ spiking, but not on the roots of wild-type or ipd3l ipd3-2 plants. In addition, fully developed arbuscules were formed in the ipd3l ipd3-2 mutants but not the ccamk/dmi3-1 mutants. Collectively, our data indicate that, in addition to IPD3 and IPD3L, another new genetic component or other new phosphorylation sites of IPD3 function downstream of DMI3 in rhizobial and mycorrhizal symbioses.

  9. Exact one-loop results for l_i → l_jγ in 3-3-1 models

    Science.gov (United States)

    Hue, L. T.; Ninh, L. D.; Thuc, T. T.; Dat, N. T. T.

    2018-02-01

    We investigate the decays l_i→ l_j γ , with l_i=e,μ ,τ in a general class of 3-3-1 models with heavy exotic leptons with arbitrary electric charges. We present full and exact analytical results keeping external lepton masses. As a by product, we perform numerical comparisons between exact results and approximate ones where the external lepton masses are neglected. As expected, we found that branching fractions can reach the current experimental limits if mixings and mass differences of the exotic leptons are large enough. We also found unexpectedly that, depending on the parameter values, there can be huge destructive interference between the gauge and Higgs contributions when the gauge bosons connecting the Standard Model leptons to the exotic leptons are light enough. This mechanism should be taken into account when using experimental constraints on the branching fractions to exclude the parameter space of the model.

  10. WEHI-3 cells inhibit adipocyte differentiation in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Jing [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China); Liu, Gexiu [Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong (China); Yan, Guoyao [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China); He, Dongmei [Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong (China); Zhou, Ying [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China); Chen, Shengting, E-mail: shengtingchen@sina.cn [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China)

    2015-06-26

    By investigating the anti-adipogenic effects of WEHI-3 cells – a murine acute myelomonocytic leukemia cell line – we sought to improve the efficiency of hematopoietic stem cell transplantation (HSCT). Analysis of Oil Red O staining and the expression of adipogenic genes, including PPARγ, C/EBPα, FAS and LPL, indicated that WEHI-3 cells significantly inhibited 3T3-L1 mouse preadipocyte cells from differentiating into adipocytes. In vivo, fat vacuoles in mice injected with WEHI-3 cells were also remarkably reduced in the murine bone marrow pimelosis model. Moreover, the key gene in the Rho signaling pathway, ROCKII, and the key gene in the Wnt signaling pathway, β-catenin, were both upregulated compared with the control group. siRNA-mediated knockdown of ROCKII and β-catenin reversed these WEHI-3-mediated anti-adipogenic effects. Taken together, these data suggest that WEHI-3 cells exert anti-adipogenic effects and that both ROCKII and β-catenin are involved in this process. - Highlights: • WEHI-3, an acute myelomonocytic leukemia cell line, inhibited 3T3-L1 preadipocyte from differentiating into adipocyte. • WEHI-3 cells can arrest 3T3-L1 cells in G0/G1 phase by secreting soluble factors and thus inhibit their proliferation. • WEHI-3 cells reduced bone marrow pimelosis in the murine model. • Both ROCKII and β-catenin were involved in the WEHI-3-mediated anti-adipogenic effects.

  11. First analysis of the secretome of the canine heartworm, Dirofilaria immitis

    Directory of Open Access Journals (Sweden)

    Geary James

    2012-07-01

    Full Text Available Abstract Background The characterization of proteins released from filariae is an important step in addressing many of the needs in the diagnosis and treatment of these clinically important parasites, as well as contributing to a clearer understanding of their biology. This report describes findings on the proteins released during in vitro cultivation of adult Dirofilaria immitis , the causative agent of canine and feline heartworm disease. Differences in protein secretion among nematodes in vivo may relate to the ecological niche of each parasite and the pathological changes that they induce. Methods The proteins in the secretions of cultured adult worms were run on Tris-Glycine gels, bands separated and peptides from each band analysed by ultra mass spectrometry and compared with a FastA dataset of predicted tryptic peptides derived from a genome sequence of D. immitis. Results This study identified 110 proteins. Of these proteins, 52 were unique to D. immitis . A total of 23 (44% were recognized as proteins likely to be secreted. Although these proteins were unique, the motifs were conserved compared with proteins secreted by other nematodes. Conclusion The present data indicate that D. immitis secretes proteins that are unique to this species, when compared with Brugia malayi. The two major functional groups of molecules represented were those representing cellular and of metabolic processes. Unique proteins might be important for maintaining an infection in the host environment, intimately involved in the pathogenesis of disease and may also provide new tools for the diagnosis of heartworm infection.

  12. SO(2 ell + 1) contains ? contains SO/sub L/(3) in group chains for L-S coupling

    International Nuclear Information System (INIS)

    Wu, Z.Y.; Sun, C.P.; Zhang, L.; Li, B.F.

    1986-01-01

    Racah pointed out in his 1949 article that there exists a proper subgroup of SO(7) which properly contains SO/sub L/(3) in group chains for L-S coupling. This paper investigates whether such a proper subgroup exists for SO(2l + 1) which contains SO/sub L/(3) for an arbitrary l and concludes that this subgroup exists only for the case in which l is equal to 3. 4 references

  13. Recent results from the L3 Collaboration

    International Nuclear Information System (INIS)

    Ting, S.C.C.

    1993-01-01

    In this report we summarize the recent results from the L3 Collaboration. The L3 Collaboration is one of the largest international collaborations in high energy physics and consists of many universities from the United States including University of Michigan, M.I.T., Caltlech, Princeton and Harvard, and leading research centers from France, Germany, Switzerland, Holland, India, China, Korea, Russia and other nations

  14. Delayed vertebral diagnosed L4 pincer vertebral fracture, L2-L3 ruptured vertebral lumbar disc hernia, L5 vertebral wedge fracture - Case report

    OpenAIRE

    Balasa D; Schiopu M; Tunas A; Baz R; Hancu Anca

    2016-01-01

    An association between delayed ruptured lumbar disc hernia, L5 vertebral wedge fracture and posttraumaticL4 pincer vertebral fracture (A2.3-AO clasification) at different levels is a very rare entity. We present the case of a 55 years old male who falled down from a bicycle. 2 months later because of intense and permanent vertebral lumbar and radicular L2 and L3 pain (Visual Scal Autologus of Pain7-8/10) the patient came to the hospital. He was diagnosed with pincer vertebral L4 fracture (A2....

  15. Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Raciti, Gregory Alexander; Fiory, Francesca; Campitelli, Michele; Desiderio, Antonella; Spinelli, Rosa; Longo, Michele; Nigro, Cecilia; Pepe, Giacomo; Sommella, Eduardo; Campiglia, Pietro; Formisano, Pietro; Beguinot, Francesco; Miele, Claudia

    2018-01-01

    Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1 cells adipocyte differentiation and function in vitro. We found that CAde enhances terminal adipocyte differentiation of 3T3-L1 cells raising the expression of CCAAT/enhancer binding protein beta (C/Ebpβ), peroxisome proliferator activated receptor gamma (Pparγ), glucose transporter type 4 (Glut4) and fatty acid binding protein 4 (Fabp4). CAde improves insulin-induced glucose uptake of 3T3-L1 adipocytes, as well. A focused analysis of the phases occurring in the pre-adipocytes differentiation to mature adipocytes furthermore revealed that CAde promotes the early differentiation stage by up-regulating C/ebpβ expression at 2, 4 and 8 h post the adipogenic induction and anticipating the 3T3-L1 cell cycle entry and progression during mitotic clonal expansion (MCE). These findings provide evidence that the exposure to CAde enhances in vitro fat cell differentiation of pre-adipocytes and functional capacity of mature adipocytes, and pave the way to the development of products derived from Citrus aurantium L. fruit juice, which may improve WAT functional capacity and may be effective for the prevention and/or treatment of T2D.

  16. Technetium(I) complexes Tc(CO)3BrL2 (L = phosphine, pyridine, isocyanide)

    International Nuclear Information System (INIS)

    Lorenz, B.; Findeisen, M.; Olk, B.; Schmidt, K.

    1988-01-01

    Technetium pentacarbonyl bromide reacts with π-acceptor ligands L (L = phosphine, pyridine, isocyanide) to form disubstituted compounds of the type Tc(CO) 3 BrL 2 . The stereochemistry of the complexes was established by infrared and 1 H-NMR measurement. Chemical shifts and the half-widths of the 99 Tc-NMR signals are discussed. (author)

  17. Technicians dismantle the inner section of L3

    CERN Multimedia

    Laurent Guiraud

    2001-01-01

    The technicians are dismantling the forward tracking chamber located at the heart of the L3 detector. This formed part of the hadronic calorimeter, which is used for measuring particle energies. L3 was an experiment at the LEP collider that ran from 1989 to 2000.

  18. GLONASS CDMA L3 ambiguity resolution and positioning

    NARCIS (Netherlands)

    Zaminpardaz, Safoora; Teunissen, P.J.G.; Nadarajah, Nandakumaran

    2016-01-01

    A first assessment of GLONASS CDMA L3 ambiguity resolution and positioning performance is provided. Our analyses are based on GLONASS L3 data from the satellite pair SVNs 755-801, received by two JAVAD receivers at Curtin University, Perth, Australia. In our analyses, four different versions of

  19. Synthesis and evaluation of the 99mtc-complexes of L-cysteine acetyldiglycine (a hybrid of MAG3 and L,L-EC) and of L-β-homocysteine acetyldiglycine

    International Nuclear Information System (INIS)

    Mang'era, K.; Vanbilloen, H.; Cleynhens, B.; Groot, T. de; Bormans, G.; Verbruggen, A.; Verbeke, K.

    2000-01-01

    L-Cysteine acetyldiglycine (L-CAG2), a hybrid compound of L,L-EC and MAG3, and its L-β-homocysteine analogue L-HAG2 were synthesized. After labeling with 99m Tc, 99m Tc-L-CAG2 and 99m Tc-L-HAG2 gave two peaks on high performance liquid chromatography. Urinary excretion of both isomers of 99m Tc-L-CAG2 and 99m Tc-L-HAG2 was slower than for the 'parent' complexes 99m Tc-MAG3 or 99m Tc-L,L-EC. Isomer B of 99m Tc-L-CAG2 showed pronounced kidney retention in mice (57% of ID in kidneys at 30 min postinjection), but further evaluation in baboon did not reproduce this phenomenon

  20. The Orf virus E3L homologue is able to complement deletion of the vaccinia virus E3L gene in vitro but not in vivo

    International Nuclear Information System (INIS)

    Vijaysri, Sangeetha; Talasela, Latha; Mercer, Andrew A.; Mcinnes, Colin J.; Jacobs, Bertram L.; Langland, Jeffrey O.

    2003-01-01

    Orf virus (OV), the prototypic parapoxvirus, is resistant to the effects of interferon (IFN) and this function of OV has been mapped to the OV20.0L gene. The protein product of this gene shares 31% amino acid identity to the E3L-encoded protein of vaccinia virus (VV) that is required for the broad host range and IFN-resistant phenotype of VV in cells in culture and for virulence of the virus in vivo. In this study we investigated whether the distantly related OV E3L homologue could complement the deletion of E3L in VV. The recombinant VV (VV/ORF-E3L) expressing the OV E3L homologue in place of VV E3L was indistinguishable from wt VV in its cell-culture phenotype. But VV/ORF-E3L was over a 1000-fold less pathogenic than wt VV (LD 50 > 5 x 10 6 PFU, compared to LD 50 of wtVV = 4 x 10 3 PFU) following intranasal infection of mice. While wt VV spread to the lungs and brain and replicated to high titers in the brain of infected mice, VV/ORF-E3L could not be detected in the lungs or brain following intranasal infection. VV/ORF-E3L was at least 100,000-fold less pathogenic than wt VV on intracranial injection. Domain swap experiments demonstrate that the difference in pathogenesis maps to the C-terminal domain of these proteins. This domain has been shown to be required for the dsRNA binding function of the VV E3L

  1. Synthesis and aqueous phase behavior of thermoresponsive biodegradable poly(D,L-3-methylglycolide)-block-poly(ethyelene glycol)-block-poly(D,L-3-methylglycolide) triblock copolymers

    NARCIS (Netherlands)

    Zhong, Zhiyuan; Dijkstra, Pieter J.; Feijen, Jan; Kwon, Young-Min; Bae, You Han; Kim, Sung Wan

    2002-01-01

    Novel biodegradable thermosensitive triblock copolymers of poly(D,L-3-methylglycolide)-block-poly(ethylene glycol)-block-poly(D,L-3-methylglycolide) (PMG-PEG-PMG) have been synthesized. Ring-opening polymerization of D,L-3-methyl-glycolide (MG) initiated with poly(ethylene glycol) (PEG) and

  2. Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Akio, E-mail: watanabea@jfrl.or.jp [Japan Food Research Laboratories, Osaka 567-0085 (Japan); Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555 (Japan); Kato, Tsuyoshi; Ito, Yusuke; Yoshida, Izumi; Harada, Teppei; Mishima, Takashi; Fujita, Kazuhiro; Watai, Masatoshi [Japan Food Research Laboratories, Osaka 567-0085 (Japan); Nakagawa, Kiyotaka; Miyazawa, Teruo [Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555 (Japan)

    2014-10-31

    Highlights: • Aculeatin promoted adipocyte differentiation. • Aculeatin improved glucose uptake. • Aculeatin enhanced adipocyte lipolysis. - Abstract: Toddalia asiatica (L.) Lam. (T. asiatica) has been utilized traditionally for medicinal purposes such as the treatment of diabetes. Currently, the extract is considered to be a good source of anti-diabetic agents, but the active compounds have yet to be identified. In this study, we investigated the effects of fractionated T. asiatica extracts on the differentiation of 3T3-L1 preadipocytes and identified aculeatin as a potential active agent. When 3T3-L1 preadipocytes were treated with aculeatin isolated from T. asiatica in the presence of insulin, aculeatin increased cellular triglyceride levels and glycerol-3-phosphate dehydrogenase activity. This indicated that aculeatin could enhance the differentiation of preadipocytes into adipocytes. Further analyses using a DNA microarray and real-time quantitative reverse-transcription PCR showed an increase in the expression of peroxisome proliferator-activated receptor-γ target genes (Pparg, Ap2, Cd36, Glut4 and Adipoq) by aculeatin, suggesting that aculeatin enhances the differentiation of 3T3-L1 cells by modulating the expression of genes critical for adipogenesis. Interestingly, after treatment of differentiated adipocytes with aculeatin, glucose uptake and lipolysis were enhanced. Overall, our results suggested that aculeatin is an active compound in T. asiatica for enhancing both differentiation and lipolysis of adipocytes, which are useful for the treatment of lipid abnormalities as well as diabetes.

  3. Cross-Linguistic Influence in Third Language Perception: L2 and L3 Perception of Japanese Contrasts

    Science.gov (United States)

    Onishi, Hiromi

    2013-01-01

    This dissertation examines the possible influence of language learners' second language (L2) on their perception of phonological contrasts in their third language (L3). Previous studies on Third Language Acquisition (TLA) suggest various factors as possible sources of cross-linguistic influence in the acquisition of an L3. This dissertation…

  4. Averrhoa carambola L. peel extract suppresses adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Rashid, Asyifah Mohamed; Lu, Kaihui; Yip, Yew Mun; Zhang, Dawei

    2016-02-01

    Obesity is associated with an increased risk of many chronic diseases. Recently, a growing body of evidence has shown that phytochemicals may inhibit adipogenesis and obesity. In this study, we report for the first time, the ability of Averrhoa carambola L. peel extract commonly known as star fruit (SFP) to effectively suppress adipocyte differentiation in 3T3-L1 preadipocytes and therefore, address it as a potential candidate to treat obesity and its related diseases. (-)-Epicatechin was identified as a bioactive compound likely responsible for this suppression. As the genetic expression studies revealed that the adipogenic activity of SFP extract was due to the simultaneous downregulation of the C/EBPα and PPARγ as well as the upregulation of PPARα receptor genes, a detailed computational docking study was also elucidated to reveal the likely binding mode of (-)-epicatechin to the receptor of interest, accounting for the likely mechanism that results in the overall suppression of adipocyte differentiation.

  5. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

    Science.gov (United States)

    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Asymmetric light transmission based on coupling between photonic crystal waveguides and L1/L3 cavity

    Science.gov (United States)

    Zhang, Jinqiannan; Chai, Hongyu; Yu, Zhongyuan; Cheng, Xiang; Ye, Han; Liu, Yumin

    2017-09-01

    A compact design of all-optical diode with mode conversion function based on a two-dimensional photonic crystal waveguide and an L1 or L3 cavity is theoretically investigated. The proposed photonic crystal structures comprise a triangular arrangement of air holes embedded in a silicon substrate. Asymmetric light propagation is achieved via the spatial mode match/mismatch in the coupling region. The simulations show that at each cavity's resonance frequency, the transmission efficiency of the structure with the L1 and L3 cavities reach 79% and 73%, while the corresponding unidirectionalities are 46 and 37 dB, respectively. The functional frequency can be controlled by simply adjusting the radii of specific air holes in the L1 and L3 cavities. The proposed structure can be used as a frequency filter, a beam splitter and has potential applications in all-optical integrated circuits.

  7. Anti-Obesity Effects of Starter Fermented Kimchi on 3T3-L1 Adipocytes

    Science.gov (United States)

    Lee, Kyung-Hee; Song, Jia-Le; Park, Eui-Seong; Ju, Jaehyun; Kim, Hee-Young; Park, Kun-Young

    2015-01-01

    The anti-obesity effects of starter (Leuconostoc mesenteroides+Lactobacillus plantarum) fermented kimchi on 3T3-L1 adipocyte were studied using naturally fermented kimchi (NK), a functional kimchi (FK, NK supplemented with green tea), and FK supplemented with added starters (FKS). Oil red O staining and cellular levels of triglyceride (TG) and glycerol were used to evaluate the in vitro anti-obesity effects of these kimchis in 3T3-L1 cells. The expressions of adipogenesis/lipogenesis-related genes of peroxisome proliferator-active receptor (PPAR)-γ, CCAAT/enhance-binding protein (C/EBP)-α, and fatty acid synthase (FAS) were determined by RT-PCR. Kimchis, especially FKS, markedly decreased TG levels and increased levels of intracellular glycerol and lipid lipolysis. In addition, FKS also reduced the mRNA levels of PPAR-γ, C/EBP-α, and FAS, which are related to adipogenesis/lipogenesis in 3T3-L1 cells. These results suggest the anti-obesity effects of FKS were to due to enhanced lipolysis and reduced adipogenesis/lipogenesis in 3T3-L1 adipocytes. PMID:26770918

  8. IceBridge DMS L3 Photogrammetric DEM

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge DMS L3 Photogrammetric DEM (IODMS3) data set contains gridded digital elevation models and orthorectified images of Greenland derived from the Digital...

  9. The Forward Muon Detector of L3

    CERN Document Server

    Adam, A; Alarcon, J; Alberdi, J; Alexandrov, V S; Aloisio, A; Alviggi, M G; Anderhub, H; Ariza, M; Azemoon, T; Aziz, T; Bakker, F; Banerjee, S; Banicz, K; Barcala, J M; Becker, U; Berdugo, J; Berges, P; Betev, B L; Biland, A; Bobbink, Gerjan J; Böck, R K; Böhm, A; Borisov, V S; Bosseler, K; Bouvier, P; Brambilla, Elena; Burger, J D; Burgos, C; Buskens, J; Carlier, J C; Carlino, G; Causaus, J; Cavallo, N; Cerjak, I; Cerrada-Canales, M; Chang, Y H; Chen, H S; Chendvankar, S R; Chvatchkine, V B; Daniel, M; De Asmundis, R; Decreuse, G; Deiters, K; Djambazov, L; Duraffourg, P; Erné, F C; Esser, H; Ezekiev, S; Faber, G; Fabre, M; Fernández, G; Freudenreich, Klaus; Fritschi, M; García-Abia, P; González, A; Gurtu, A; Gutay, L J; Haller, C; Herold, W D; Herrmann, J M; Hervé, A; Hofer, H; Höfer, M; Hofer, T; Homma, J; Horisberger, Urs; Horváth, I L; Ingenito, P; Innocente, Vincenzo; Ioudine, I; Jaspers, M; de Jong, P; Kästli, W; Kaspar, H; Kitov, V; König, A C; Koutsenko, V F; Lanzano, S; Lapoint, C; Lebedev, A; Lecomte, P; Lista, L; Lübelsmeyer, K; Lustermann, W; Ma, J M; Milesi, M; Molinero, A; Montero, A; Moore, R; Nahn, S; Navarrete, J J; Okle, M; Orlinov, I; Ostojic, R; Pandoulas, D; Paolucci, P; Parascandolo, P; Passeggio, G; Patricelli, S; Peach, D; Piccolo, D; Pigni, L; Postema, H; Puras, C; Ren, D; Rewiersma, P A M; Rietmeyer, A; Riles, K; Risco, J; Robohm, A; Rodin, J; Röser, U; Romero, L; Van Rossum, W; Rykaczewski, H; Sarakinos, M E; Sassowsky, M; Shchegelskii, V; Scholz, N; Schultze, K; Schuylenburg, H; Sciacca, C; Seiler, P G; Siedenburg, T; Siedling, R; Smith, B; Soulimov, V; Sadhakar, K; Syben, O; Tonutti, M; Udovcic, A; Ulbricht, J; Veillet, L; Vergain, M; Viertel, Gert M; Von Gunten, H P; Vorobyov, A A; Vrankovic, V; De Waard, A; Waldmeier-Wicki, S; Wallraff, W; Walter, H C; Wang, J C; Wei, Z L; Wetter, R; Willmott, C; Wittgenstein, F; Wu, R J; Yang, K S; Zhou, L; Zhou, Y; Zuang, H L

    1996-01-01

    The Forward-Backward muon detector of the L3 experiment is presented. Intended to be used for LEP 200 physics, it consists of 96 self-calibrating drift chambers of a new design enclosing the magnet pole pieces of the L3 solenoid. The pole pieces are toroidally magnetized to form two independent analyzing spectrometers. A novel trigger is provided by resistive plate counters attached to the drift chambers. Details about the design, construction and performance of the whole system are given together with results obtained during the 1995 running at LEP.

  10. The effect of myostatin on proliferation and lipid accumulation in 3T3-L1 preadipocytes.

    Science.gov (United States)

    Zhu, Hui Juan; Pan, Hui; Zhang, Xu Zhe; Li, Nai Shi; Wang, Lin Jie; Yang, Hong Bo; Gong, Feng Ying

    2015-06-01

    Myostatin is a critical negative regulator of skeletal muscle development, and has been reported to be involved in the progression of obesity and diabetes. In the present study, we explored the effects of myostatin on the proliferation and differentiation of 3T3-L1 preadipocytes by using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide spectrophotometry, intracellular triglyceride (TG) assays, and real-time quantitative RT-PCR methods. The results indicated that recombinant myostatin significantly promoted the proliferation of 3T3-L1 preadipocytes and the expression of proliferation-related genes, including Cyclin B2, Cyclin D1, Cyclin E1, Pcna, and c-Myc, and IGF1 levels in the medium of 3T3-L1 were notably upregulated by 35.2, 30.5, 20.5, 33.4, 51.2, and 179% respectively (all Pmyostatin-treated 3T3-L1 cells. Meanwhile, the intracellular lipid content of myostatin-treated cells was notably reduced as compared with the non-treated cells. Additionally, the mRNA levels of Pparγ, Cebpα, Gpdh, Dgat, Acs1, Atgl, and Hsl were significantly downregulated by 22-76% in fully differentiated myostatin-treated adipocytes. Finally, myostatin regulated the mRNA levels and secretion of adipokines, including Adiponectin, Resistin, Visfatin, and plasminogen activator inhibitor-1 (PAI-1) in 3T3-L1 adipocytes (all Pmyostatin promoted 3T3-L1 proliferation by increasing the expression of cell-proliferation-related genes and by stimulating IGF1 secretion. Myostatin inhibited 3T3-L1 adipocyte differentiation by suppressing Pparγ and Cebpα expression, which consequently deceased lipid accumulation in 3T3-L1 cells by inhibiting the expression of critical lipogenic enzymes and by promoting the expression of lipolytic enzymes. Finally, myostatin modulated the expression and secretion of adipokines in fully differentiated 3T3-L1 adipocytes. © 2015 Society for Endocrinology.

  11. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  12. Fluorescence lifetime imaging of lipids during 3T3-L1 cell differentiation

    Science.gov (United States)

    Song, Young Sik; Won, Young Jae; Lee, Sang-Hak; Kim, Dug Young

    2014-03-01

    Obesity is becoming a big health problem in these days. Since increased body weight is due to increased number and size of the triglyceride-storing adipocytes, many researchers are working on differentiation conditions and processes of adipocytes. Adipocytes also work as regulators of whole-body energy homeostasis by secreting several proteins that regulate processes as diverse as haemostasis, blood pressure, immune function, angiogenesis and energy balance. 3T3-L1 cells are widely used cell line for studying adipogenesis because it can differentiate into an adipocyte-like phenotype under appropriate conditions. In this paper, we propose an effective fluorescence lifetime imaging technique which can easily distinguish lipids in membrane and those in lipid droplets. Nile red dyes are attached to lipids in 3T3-L1 cells. Fluorescence lifetime images were taken for 2 week during differentiation procedure of 3T3-L1 cells into adipocytes. We used 488 nm pulsed laser with 5MHz repetition rate and emission wavelength is 520 nm of Nile Red fluorescent dye. Results clearly show that the lifetime of Nile red in lipid droplets are smaller than those in cell membrane. Our results suggest that fluorescence lifetime imaging can be a very powerful tool to monitor lipid droplet formation in adipocytes from 3T3-L1 cells.

  13. Aspartame downregulates 3T3-L1 differentiation.

    Science.gov (United States)

    Pandurangan, Muthuraman; Park, Jeongeun; Kim, Eunjung

    2014-10-01

    Aspartame is an artificial sweetener used as an alternate for sugar in several foods and beverages. Since aspartame is 200 times sweeter than traditional sugar, it can give the same level of sweetness with less substance, which leads to lower-calorie food intake. There are reports that consumption of aspartame-containing products can help obese people lose weight. However, the potential role of aspartame in obesity is not clear. The present study investigated whether aspartame suppresses 3T3-L1 differentiation, by downregulating phosphorylated peroxisome proliferator-activated receptor γ (p-PPARγ), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1), which are critical for adipogenesis. The 3T3-L1 adipocytes were cultured and differentiated for 6 d in the absence and presence of 10 μg/ml of aspartame. Aspartame reduced lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. qRT-PCR analysis showed that the PPARγ, FABP4, and C/EBPα mRNA expression was significantly reduced in the aspartame-treated adipocytes. Western blot analysis showed that the induction of p-PPARγ, PPARγ, SREBP1, and adipsin was markedly reduced in the aspartame-treated adipocytes. Taken together, these data suggest that aspartame may be a potent substance to alter adipocyte differentiation and control obesity.

  14. Exact one-loop results for l{sub i} → l{sub j}γ in 3-3-1 models

    Energy Technology Data Exchange (ETDEWEB)

    Hue, L.T. [Duy Tan University, Institute for Research and Development, Da Nang (Viet Nam); Vietnam Academy of Science and Technology, Institute of Physics, Hanoi (Viet Nam); Ninh, L.D. [Institute for Interdisciplinary Research in Science and Education, ICISE, Ghenh Rang, Quy Nhon (Viet Nam); Humboldt-Universitaet zu Berlin, Institut fuer Physik, Berlin (Germany); Thuc, T.T. [Department of Education and Training of Ca Mau, Ca Mau (Viet Nam); Dat, N.T.T. [Universita di Trieste, Dipartimento di Fisica, Theoretical Section, Trieste (Italy); International Center for Theoretical Physics, Trieste (Italy)

    2018-02-15

    We investigate the decays l{sub i} → l{sub j}γ, with l{sub i} = e, μ, τ in a general class of 3-3-1 models with heavy exotic leptons with arbitrary electric charges. We present full and exact analytical results keeping external lepton masses. As a by product, we perform numerical comparisons between exact results and approximate ones where the external lepton masses are neglected. As expected, we found that branching fractions can reach the current experimental limits if mixings and mass differences of the exotic leptons are large enough. We also found unexpectedly that, depending on the parameter values, there can be huge destructive interference between the gauge and Higgs contributions when the gauge bosons connecting the Standard Model leptons to the exotic leptons are light enough. This mechanism should be taken into account when using experimental constraints on the branching fractions to exclude the parameter space of the model. (orig.)

  15. Recent results from L3+COSMICS at CERN L3 collaboration

    CERN Document Server

    Bertaina, M

    2002-01-01

    11x10 sup 9 cosmic ray muon events above 20 GeV have been collected with the L3+C detector at LEP, CERN, in 1999 and 2000. During the last year the energy, core position and direction of the air showers causing the observed muons could be derived for part of the data. Preliminary results for the vertical muon flux and charge ratio depending on the muon momentum are shown. The influence of the air shower energy on the muon properties is studied. A search for muon rate increase during the solar flare of the 14 sup t sup h July 2000 is performed. Meteorological effects on cosmic ray intensity measurements are discussed.

  16. ATF3 inhibits adipocyte differentiation of 3T3-L1 cells

    International Nuclear Information System (INIS)

    Jang, Min Kyung; Kim, Cho Hee; Seong, Je Kyung; Jung, Myeong Ho

    2012-01-01

    Highlights: ► Overexpression of ATF3 inhibits adipocyte differentiation in 3T3-L1 cells. ► Overexpression of ATF3 represses C/EBPα expression. ► ATF3 directly binds to mouse C/EBPα promoter spanning from −1928 to −1907. ► ATF3 may play a role in hypoxia-mediated inhibition of adipocyte differentiation. -- Abstract: ATF3 is a stress-adaptive gene that regulates proliferation or apoptosis under stress conditions. However, the role of ATF3 is unknown in adipocyte cells. Therefore, in this study, we investigated the functional role of ATF3 in adipocytes. Both lentivirus-mediated overexpression of ATF3 and stably-overexpressed ATF3 inhibited adipocyte differentiation in 3T3-L1 cells, as revealed by decreased lipid staining with oil red staining and reduction in adipogenic genes. Thapsigargin treatment and overexpression of ATF3 decreased C/EBPα transcript and repressed the activity of the 3.6-kb mouse C/EBPα promoter, demonstrating that ATF3 downregulates C/EBPα expression. Transfection studies using mutant constructs containing 5′-deletions in the C/EBPα promoter revealed that a putative ATF/CRE element, GGATGTCA, is located between −1921 and −1914. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that ATF3 directly binds to mouse C/EBPα promoter spanning from −1928 to −1907. Both chemical hypoxia-mimetics or physical hypoxia led to reduce the C/EBPα mRNA and repress the promoter activity of the C/EBPα gene, whereas increase ATF3 mRNA, suggesting that ATF3 may contribute to the inhibition of adipocyte differentiation in hypoxia through downregulation of C/EBPα expression. Collectively, these results demonstrate that ATF3 represses the C/EBPα gene, resulting in inhibition of adipocyte differentiation, and thus plays a role in hypoxia-mediated inhibition of adipocyte differentiation.

  17. Laboratory Study of the OH + Permethylsiloxane (L2, L3, D3, and D4) Reaction Rate Coefficients Between 240 and 370 K

    Science.gov (United States)

    Burkholder, J. B.; Bernard, F.; Papadimitriou, V. C.

    2016-12-01

    The atmospheric chemistry of organosiloxanes has recently been implicated in the formation of new particles as well as regional and indoor air quality. Methylsiloxanes with Sitextiles, health care and household products and in industrial applications as solvents and lubricants. They are released into the atmosphere during manufacturing, use, and disposal and have been observed in the atmosphere in ppb levels in certain locations. However, the fundamental chemical properties of this class of compounds, particularly their reactivity with the OH radical, are presently not fully characterized. In this work, the temperature dependence of the rate coefficients for the OH radical reaction with the simplest linear (L2 and L3) and cyclic (D3 and D4) siloxanes were measured: OH + (CH3)3SiOSi(CH3)3 = Products L2OH + [(CH3)3SiO]2Si(CH3)2 = Products L3OH + [-Si(CH3)2O-]3 = Products D3OH + [-Si(CH3)2O-]4 = Products D4OH rate coefficients were measured under pseudo-first conditions in OH over the temperature range 240-370 K using a pulsed laser photolysis-laser induced fluorescence (PLP-LIF) technique and at 296 K using a relative rate method. The present results are compared with available literature data where possible and discrepancies are discussed. The results from this work will be discussed in terms of the atmospheric lifetimes of these methylsiloxanes and the reactivity trends for this class of compound.

  18. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Directory of Open Access Journals (Sweden)

    Prakash Babu Narasimhan

    2018-04-01

    Full Text Available A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma or to live microfilariae (mf of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β, M2-associated (CCL13, CD206, Mreg-associated (IL-10, TGF-β, and angiogenesis associated (MMP9, VEGF genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  19. Similarities and differences between helminth parasites and cancer cell lines in shaping human monocytes: Insights into parallel mechanisms of immune evasion.

    Science.gov (United States)

    Narasimhan, Prakash Babu; Akabas, Leor; Tariq, Sameha; Huda, Naureen; Bennuru, Sasisekhar; Sabzevari, Helen; Hofmeister, Robert; Nutman, Thomas B; Tolouei Semnani, Roshanak

    2018-04-01

    A number of features at the host-parasite interface are reminiscent of those that are also observed at the host-tumor interface. Both cancer cells and parasites establish a tissue microenvironment that allows for immune evasion and may reflect functional alterations of various innate cells. Here, we investigated how the phenotype and function of human monocytes is altered by exposure to cancer cell lines and if these functional and phenotypic alterations parallel those induced by exposure to helminth parasites. Thus, human monocytes were exposed to three different cancer cell lines (breast, ovarian, or glioblastoma) or to live microfilariae (mf) of Brugia malayi-a causative agent of lymphatic filariasis. After 2 days of co-culture, monocytes exposed to cancer cell lines showed markedly upregulated expression of M1-associated (TNF-α, IL-1β), M2-associated (CCL13, CD206), Mreg-associated (IL-10, TGF-β), and angiogenesis associated (MMP9, VEGF) genes. Similar to cancer cell lines, but less dramatically, mf altered the mRNA expression of IL-1β, CCL13, TGM2 and MMP9. When surface expression of the inhibitory ligands PDL1 and PDL2 was assessed, monocytes exposed to both cancer cell lines and to live mf significantly upregulated PDL1 and PDL2 expression. In contrast to exposure to mf, exposure to cancer cell lines increased the phagocytic ability of monocytes and reduced their ability to induce T cell proliferation and to expand Granzyme A+ CD8+ T cells. Our data suggest that despite the fact that helminth parasites and cancer cell lines are extraordinarily disparate, they share the ability to alter the phenotype of human monocytes.

  20. Colorimetric tests for diagnosis of filarial infection and vector surveillance using non-instrumented nucleic acid loop-mediated isothermal amplification (NINA-LAMP.

    Directory of Open Access Journals (Sweden)

    Catherine B Poole

    Full Text Available Accurate detection of filarial parasites in humans is essential for the implementation and evaluation of mass drug administration programs to control onchocerciasis and lymphatic filariasis. Determining the infection levels in vector populations is also important for assessing transmission, deciding when drug treatments may be terminated and for monitoring recrudescence. Immunological methods to detect infection in humans are available, however, cross-reactivity issues have been reported. Nucleic acid-based molecular assays offer high levels of specificity and sensitivity, and can be used to detect infection in both humans and vectors. In this study we developed loop-mediated isothermal amplification (LAMP tests to detect three different filarial DNAs in human and insect samples using pH sensitive dyes for enhanced visual detection of amplification. Furthermore, reactions were performed in a portable, non-instrumented nucleic acid amplification (NINA device that provides a stable heat source for LAMP. The efficacy of several strand displacing DNA polymerases were evaluated in combination with neutral red or phenol red dyes. Colorimetric NINA-LAMP assays targeting Brugia Hha I repeat, Onchocerca volvulus GST1a and Wuchereria bancrofti LDR each exhibit species-specificity and are also highly sensitive, detecting DNA equivalent to 1/10-1/5000th of one microfilaria. Reaction times varied depending on whether a single copy gene (70 minutes, O. volvulus or repetitive DNA (40 min, B. malayi and W. bancrofti was employed as a biomarker. The NINA heater can be used to detect multiple infections simultaneously. The accuracy, simplicity and versatility of the technology suggests that colorimetric NINA-LAMP assays are ideally suited for monitoring the success of filariasis control programs.

  1. Draft genome of neurotropic nematode parasite Angiostrongylus cantonensis, causative agent of human eosinophilic meningitis.

    Science.gov (United States)

    Yong, Hoi-Sen; Eamsobhana, Praphathip; Lim, Phaik-Eem; Razali, Rozaimi; Aziz, Farhanah Abdul; Rosli, Nurul Shielawati Mohamed; Poole-Johnson, Johan; Anwar, Arif

    2015-08-01

    Angiostrongylus cantonensis is a bursate nematode parasite that causes eosinophilic meningitis (or meningoencephalitis) in humans in many parts of the world. The genomic data from A. cantonensis will form a useful resource for comparative genomic and chemogenomic studies to aid the development of diagnostics and therapeutics. We have sequenced, assembled and annotated the genome of A. cantonensis. The genome size is estimated to be ∼260 Mb, with 17,280 genomic scaffolds, 91X coverage, 81.45% for complete and 93.95% for partial score based on CEGMA analysis of genome completeness. The number of predicted genes of ≥300 bp was 17,482. A total of 7737 predicted protein-coding genes of ≥50 amino acids were identified in the assembled genome. Among the proteins of known function, kinases are the most abundant followed by transferases. The draft genome contains 34 excretory-secretory proteins (ES), a minimum of 44 Nematode Astacin (NAS) metalloproteases, 12 Homeobox (HOX) genes, and 30 neurotransmitters. The assembled genome size (260 Mb) is larger than those of Pristionchus pacificus, Caenorhabditis elegans, Necator americanus, Caenorhabditis briggsae, Trichinella spiralis, Brugia malayi and Loa loa, but smaller than Haemonchus contortus and Ascaris suum. The repeat content (25%) is similar to H. contortus. The GC content (41.17%) is lower compared to P. pacificus (42.7%) and H. contortus (43.1%) but higher compared to C. briggsae (37.69%), A. suum (37.9%) and N. americanus (40.2%) while the scaffold N50 is 42,191. This draft genome will facilitate the understanding of many unresolved issues on the parasite and the disorder it causes. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. L3 experiment dismantling at LEP

    CERN Multimedia

    Laurent Guiraud

    2001-01-01

    The last muon chamber is removed from the L3 experiment at the LEP collider, which was in operation from 1989 to 2000. The large red magnet yoke will be reused by the ALICE experiment when the LHC is constructed.

  3. Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups

    DEFF Research Database (Denmark)

    Janssen, M F; Pickard, A Simon; Golicki, Dominik

    2012-01-01

    PURPOSE: The aim of this study was to assess the measurement properties of the 5-level classification system of the EQ-5D (5L), in comparison with the 3-level EQ-5D (3L). METHODS: Participants (n = 3,919) from six countries, including eight patient groups with chronic conditions (cardiovascular...... of the 3-level system which improves upon the measurement properties, reducing the ceiling while improving discriminatory power and establishing convergent and known-groups validity.......), redistribution properties, ceiling, discriminatory power, convergent validity, and known-groups validity. RESULTS: Missing values were on average 0.8 % for 5L and 1.3 % for 3L. In total, 2.9 % of responses were inconsistent between 5L and 3L. Redistribution from 3L to 5L using EQ dimension-specific rating scales...

  4. Xenon spectator and diagram L3-M4,5M4,5 Auger intensities near the L3 threshold

    International Nuclear Information System (INIS)

    Armen, G.B.; Levin, J.C.; Southworth, S.H.; LeBrun, T.; Arp, U.; MacDonald, M.A.

    1997-01-01

    Calculations based on the theory of radiationless resonant Raman scattering are employed in the interpretation of new XeL 3 -M 4,5 M 4,5 Auger spectra recorded using synchrotron radiation tuned to energies across the L 3 edge. Fits of theoretical line shapes to the spectra are employed in separating intensities due to nd spectator (resonant) and diagram Auger processes. Near-threshold Auger intensity, previously attributed to diagram decay, is found to be due to the large-n spectator lines that result from postcollision-interaction endash induced open-quotes recaptureclose quotes of threshold photoelectrons to nd orbitals. copyright 1997 The American Physical Society

  5. High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes

    OpenAIRE

    Lee, Haemi; Kim, Jae-woo

    2013-01-01

    Background Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes. Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to obs...

  6. Coculture with BJ fibroblast cells inhibits the adipogenesis and lipogenesis in 3T3-L1 cells

    International Nuclear Information System (INIS)

    Jeong, Hyun Jeong; Park, Sahng Wook; Kim, Hojeong; Park, Sang-Kyu; Yoon, Dojun

    2010-01-01

    Mouse or human fibroblasts are commonly used as feeder cells to prevent differentiation in stem or primary cell culture. In the present study, we addressed whether fibroblasts can affect the differentiation of adipocytes. We found that the differentiation of 3T3-L1 preadipocytes was strongly suppressed when the cells were cocultured with human fibroblast (BJ) cells. BrdU incorporation analysis indicated that mitotic clonal expansion, an early event required for 3T3-L1 cell adipogenesis, was not affected by BJ cells. The 3T3-L1 cell expression levels of peroxisome proliferator-activated receptor γ2, CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c, and Krueppel-like factor 15, but not those of C/EBPβ or C/EBPδ, were decreased by coculture with BJ cells. When mature 3T3-L1 adipocytes were cocultured with BJ cells, their lipid contents were significantly reduced, with decreased fatty acid synthase expression and increased phosphorylated form of acetyl-CoA carboxylase 1. Our data indicate that coculture with BJ fibroblast cells inhibits the adipogenesis of 3T3-L1 preadipocytes and decreases the lipogenesis of mature 3T3-L1 adipocytes.

  7. RKIP phosphorylation–dependent ERK1 activation stimulates adipogenic lipid accumulation in 3T3-L1 preadipocytes overexpressing LC3

    Energy Technology Data Exchange (ETDEWEB)

    Hahm, Jong Ryeal [Department of Internal Medicine, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Ahmed, Mahmoud [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Kim, Deok Ryong, E-mail: drkim@gnu.ac.kr [Department of Biochemistry and Convergence Medical Science, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of); Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, 527-27 (Korea, Republic of)

    2016-09-09

    3T3-L1 preadipocytes undergo adipogenesis in response to treatment with dexamethaxone, 1-methyl-3-isobutylxanthine, and insulin (DMI) through activation of several adipogenic transcription factors. Many autophagy-related proteins are also highly activated in the earlier stages of adipogenesis, and the LC3 conjugation system is required for formation of lipid droplets. Here, we investigated the effect of overexpression of green fluorescent protein (GFP)-LC3 fusion protein on adipogenesis. Overexpression of GFP-LC3 in 3T3-L1 preadipocytes using poly-L-lysine-assisted adenoviral GFP-LC3 transduction was sufficient to produce intracellular lipid droplets. Indeed, GFP-LC3 overexpression stimulated expression of some adipogenic transcription factors (e.g., C/EBPα or β, PPARγ, SREBP2). In particular, SREBP2 was highly activated in preadipocytes transfected with adenoviral GFP-LC3. Also, phosphorylation of Raf kinase inhibitory protein (RKIP) at serine 153, consequently stimulating extracellular-signal regulated kinase (ERK)1 activity, was significantly increased during adipogenesis induced by either poly-L-lysine-assisted adenoviral GFP-LC3 transduction or culture in the presence of dexamethasone, 1-methyl-3-isobutylxanthine, and insulin. Furthermore, RKIP knockdown promoted ERK1 and PPARγ activation, and significantly increased the intracellular accumulation of triacylglycerides in DMI-induced adipogenesis. In conclusion, GFP-LC3 overexpression in 3T3-L1 preadipocytes stimulates adipocyte differentiation via direct modulation of RKIP-dependent ERK1 activity. - Highlights: • Overexpression of GFP-LC3 in 3T3-L1 cells produces intracellular lipid droplets. • SREBP2 is highly activated in preadipocytes transfected with adenoviral GFP-LC3. • RKIP phosphorylation at serine 153 is significantly increased during adipogenesis. • RKIP knockdown promotes ERK1 and PPARγ activation during adipogenesis. • RKIP-dependent ERK1 activation increases triacylglycerides in

  8. Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L in psoriasis patients.

    Science.gov (United States)

    Poór, Adrienn Katalin; Rencz, Fanni; Brodszky, Valentin; Gulácsi, László; Beretzky, Zsuzsanna; Hidvégi, Bernadett; Holló, Péter; Kárpáti, Sarolta; Péntek, Márta

    2017-12-01

    The purpose of this study is to assess the measurement properties of EQ-5D-5L compared to EQ-5D-3L in psoriasis patients. A cross-sectional survey was carried out at an academic dermatology clinic in Hungary. Psoriasis patients completed the EQ-5D-3L, EQ-5D-5L and Dermatology Life Quality Index (DLQI) questionnaires, and Psoriasis Area and Severity Index (PASI) was assessed. The UK value sets were used to calculate the 3L and 5L index scores. We tested the feasibility, ceiling effect, redistribution properties, the level of inconsistency and informativity (Shannon and Shannon Evenness indices). Spearman's rank-order correlations were performed between EQ-5D, EQ VAS, DLQI and PASI scores. Known-groups validity was evaluated by comparing age groups, clinical subtypes and treatment groups. Mean age of the 238 patients was 47 years, and 36.6% of them received biological therapy. Mean EQ-5D index score was 0.77 (SD: 0.26) with the 3L and 0.84 (SD: 0.19) with the 5L. The overall ceiling effect decreased from 37.1 (3L) to 32.9% (5L). Shannon index improved significantly for most dimensions, but Shannon Evenness index improved only in three dimensions. Compared to the 3L, the 5L version confirmed a better convergent validity with PASI, but not with the DLQI. Known-groups validity was equally demonstrated both for the 5L and 3L. The EQ-5D-5L seems to improve measurement properties by reducing ceiling effects, strengthening correlations with PASI and improving informativity. Follow-up studies are needed to test responsiveness and reliability in psoriasis.

  9. Mapping MOS-HIV to HUI3 and EQ-5D-3L in Patients With HIV

    Directory of Open Access Journals (Sweden)

    Vilija R. Joyce MS

    2017-07-01

    Full Text Available Objectives: The Medical Outcomes Study HIV Health Survey (MOS-HIV is frequently used in HIV clinical trials; however, scores generated from the MOS-HIV are not suited for cost-effectiveness analyses as they do not assign utility values to health states. Our objective was to estimate and externally validate several mapping algorithms to predict Health Utilities Index Mark 3 (HUI3 and EQ-5D-3L utility values from the MOS-HIV. Methods: We developed and validated mapping algorithms using data from two HIV clinical trials. Data from the first trial (n = 367 formed the estimation data set for the HUI3 (4,610 observations and EQ-5D-3L (4,662 observations mapping algorithms; data from the second trial (n = 168 formed the HUI3 (1,135 observations and EQ-5D-3L (1,152 observations external validation data set. We compared ordinary least squares (OLS models of increasing complexity with the more flexible two-part, beta regression, and finite mixture models. We assessed model performance using mean absolute error (MAE and mean squared error (MSE. Results: The OLS model that used MOS-HIV dimension scores along with squared terms gave the best HUI3 predictions (mean observed 0.84; mean predicted 0.80; MAE 0.0961; the finite mixture model gave the best EQ-5D-3L predictions (mean observed 0.90; mean predicted 0.88; MAE 0.0567. All models produced higher prediction errors at the lower end of the HUI3 and EQ-5D-3L score ranges (<0.40. Conclusions: The proposed mapping algorithms can be used to predict HUI3 and EQ-5D-3L utility values from the MOS-HIV, although greater error may pose a problem in samples where a substantial proportion of patients are in poor health. These algorithms may be useful for estimating utility values from the MOS-HIV for cost-effectiveness studies when HUI3 or EQ-5D-3L data are not available.

  10. Analysis of Multi Muon Events in the L3 Detector

    CERN Document Server

    Schmitt, Volker

    2000-01-01

    The muon density distribution in air showers initiated by osmi parti les is sensitive to the hemi al omposition of osmi rays. The density an be measured via the multipli ity distribution in a nite size dete tor, as it is L3. With a shallow depth of 30 meters under ground, the dete tor provides an ex ellent fa ility to measure a high muon rate, but being shielded from the hadroni and ele troni shower omponent. Subje t of this thesis is the des ription of the L3 Cosmi s experiment (L3+C), whi h is taking data sin e May 1999 and the analysis of muon bundles in the large magneti spe trometer of L3. The new osmi trigger and readout system is brie y des ribed. The in uen e of dierent primaries on the multipli ity distribution has been investigated using Monte Carlo event samples, generated with the CORSIKA program. The simulation results showed that L3+C measures in the region of the \\knee" of the primary spe trum of osmi rays. A new pattern re ognition has been developed and added to the re onstru tion ode, whi h ...

  11. Roles of linguistic knowledge, metacognitive knowledge and processing speed in L3, L2 and L1 reading comprehension: a structural equation modeling approach

    NARCIS (Netherlands)

    van Gelderen, A.; Schoonen, R.; de Glopper, K.; Hulstijn, J.; Snellings, P.; Simis, A.; Stevenson, M.

    2003-01-01

    In this article we present an analysis of the relationship between L3 reading comprehension and its constituent skills for bilingual Dutch students for whom English is a third language(L3) compared to monolingual Dutch students for whom English is a second language(L2). An analogous analysis is made

  12. 31 CFR 203.3 - TT&L depositaries.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false TT&L depositaries. 203.3 Section 203.3 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE PAYMENT OF FEDERAL TAXES AND THE TREASURY TAX AND...

  13. Alignment following Au L$_{3}$ photoionization by synchrotron radiation

    CERN Document Server

    Yamaoka, H; Takahiro, K; Morikawa, T; Ito, S; Mizumaki, M; Semenov, S; Cherepkov, N; Kabachnik, N M; Mukoyama, T; 10.1088/0953-4075/36/19/001

    2003-01-01

    The alignment of Au/sup +/ ions following L/sub 3/ photoionization has been studied using a high-resolution X-ray spectrometer. We observed a small anisotropy for the angular dependence of Au L/sub l/ and L alpha emissions. The alignment parameter A/sub 20/ derived from the experimental results is compared with theoretical calculations by Hartree-Fock approximation and random phase approximation with exchange. The contribution to the alignment of quadruple interaction is discussed. (40 refs).

  14. Baker's yeast: production of D- and L-3-hydroxy esters

    DEFF Research Database (Denmark)

    Dahl, Allan Carsten; Madsen, Jørgen Øgaard

    1998-01-01

    harvested while growing. In contrast, the stereoselectivity was shifted towards L-hydroxy esters when the oxo esters were added slowly to ordinary baker's yeast supplied with gluconolactone as co-substrate. The reduction rate with gluconolactone was increased by active aeration. Ethyl L-(S)-3......Baker's yeast grown under oxygen limited conditions and used in the reduction of 3-oxo esters results in a shift of the stereoselectivity of the yeast towards D-hydroxy esters as compared with ordinary baker's yeast. The highest degree of stereoselectivity was obtained with growing yeast or yeast......-hydroxybutanoate was afforded in >99% ee. Both enantiomers of ethyl 3-hydroxypentanoate, D-(R) in 96% ee and L-(S) in 93% ee, and of ethyl 4-chloro-3-hydroxybutanoate, D-(S) in 98% ee and L-(R) in 94% ee, were obtained. The results demonstrate that the stereoselectivity of baker's yeast can be controlled...

  15. Is L-Carnitine Supplementation Beneficial in 3-Methylcrotonyl-CoA Carboxylase Deficiency?

    DEFF Research Database (Denmark)

    Thomsen, Jákup Andreas; Lund, Allan Meldgaard; Olesen, Jess Have

    2015-01-01

    suffered from self-reported fatigue with some alleviation after L-carnitine supplementation. Conclusion: 3-MCCd is common in the Faroe Islands. Some symptomatic 3-MCCd patients may benefit biochemically and clinically from L-carnitine supplementation, a more general recommendation cannot be given....... and muscle tissue with and without L-carnitine supplementation to evaluate the current treatment strategy of not recommending L-carnitine supplementation to Faroese 3-MCCd patients. Methods: Blood and urine samples and muscle biopsies were collected from patients at inclusion and at 3 months. Eight patients...... received L-carnitine supplementation when recruited; five did not. Included patients who received supplementation were asked to stop L-carnitine, the others were asked to initiate L-carnitine supplementation during the study. Symptoms were determined by review of hospital medical records and questionnaires...

  16. Cell Volume Regulation and Signaling in 3T3-L1 Pre-adipocytes and Adipocytes

    DEFF Research Database (Denmark)

    Eduardsen, Kathrine; Larsen, Susanne; Novak, Ivana

    2011-01-01

    Caveolae have been implicated in sensing of cell volume perturbations, yet evidence is still limited and findings contradictory. Here, we investigated the possible role of caveolae in cell volume regulation and volume sensitive signaling in an adipocyte system with high (3T3-L1 adipocytes......); intermediate (3T3-L1 pre-adipocytes); and low (cholesterol-depleted 3T3-L1 pre-adipocytes) caveolae levels. Using large-angle light scattering, we show that compared to pre-adipocytes, differentiated adipocytes exhibit several-fold increased rates of volume restoration following osmotic cell swelling (RVD......) and osmotic cell shrinkage (RVI), accompanied by increased swelling-activated taurine efflux. However, caveolin-1 distribution was not detectably altered after osmotic swelling or shrinkage, and caveolae integrity, as studied by cholesterol depletion or expression of dominant negative Cav-1, was not required...

  17. Uptake and metabolism of L-[3H]glutamate and L-[3H]glutamine in adult rat cerebellar slices

    International Nuclear Information System (INIS)

    de Barry, J.; Vincendon, G.; Gombos, G.

    1983-01-01

    Using very low concentrations (1 mumol range) of L-2-3-[ 3 H]glutamate, ( 3 H-Glu) or L-2-3-[ 3 H]glutamine ( 3 H-Gln), the authors have previously shown by autoradiography that these amino acids were preferentially taken up in the molecular layer of the cerebellar cortex. Furthermore, the accumulation of 3 H-Glu was essentially glial in these conditions. Uptake and metabolism of either ( 3 H-Glu) or ( 3 H-Gln) were studied in adult rat cerebellar slices. Both amino acids were rapidly converted into other metabolic compounds: after seven minutes of incubation in the presence of exogenous 3 H-Glu, 70% of the tissue accumulated radioactivity was found to be in compounds other than glutamate. The main metabolites were Gln (42%), alpha-ketoglutarate (25%) and GABA (1,4%). In the presence of exogenous 3 H-Gln the rate of metabolism was slightly slower (50% after seven minutes of incubation) and the metabolites were also Glu (29%), alpha-ketoglutarate (15%) and GABA (5%). Using depolarizing conditions (56 mM KCl) with either exogenous 3 H-Glu or 3 H-Gln, the radioactivity was preferentially accumulated in glutamate compared to control. From these results we conclude: i) there are two cellular compartments for the neurotransmission-glutamate-glutamine cycle; one is glial, the other neuronal; ii) these two cellular compartments contain both Gln and Glu; iii) transmitter glutamate is always in equilibrium with the so-called ''metabolic'' pool of glutamate; iv) the regulation of the glutamate-glutamine cycle occurs at least at two different levels: the uptake of glutamate and the enzymatic activity of the neuronal glutaminase

  18. Characterization of new cell line stably expressing CHI3L1 oncogene

    Directory of Open Access Journals (Sweden)

    Chekhonin V. P.

    2011-06-01

    Full Text Available Aim. To characterize the immortalized 293 cell line after stable transfection with human oncogene (CHI3L1. Methods. 293 cells, stably transfected with pcDNA3.1_CHI3L1, and 293 cells, stably transfected with pcDNA3.1 as a negative control, were used throughout all experiments. The clones of CHI3L1-expressing 293 cells and 293 cells, transfected with pcDNA3.1, were analyzed by immunofluorescence and confocal microscopy. Cell proliferation was measured using MTT assay; analyses of ERK1/2 and AKT activation and their cellular localization were performed with anti-phospho-ERK and anti-phospho-AKT antibodies. Specific activation of MAP and PI3 kinases was measured by densitometric analysis of Western-blot signals. Results. The obtained results show quite modest ability of CHI3L1 to stimulate cell growth and reflect rather an improved cellular plating efficiency of the 293 cells stably transfected with pcDNA3.1_CHI3L1 as compared to the 293 cells transfected with an «empty» vector. ERK1/2 and AKT are activated in the 293_CHI3L1 cells. In these cells phosphorylated ERK1/2 were localized in both cell cytoplasm and nuclei while AKT only in cytoplasm. The 293_CHI3L1 cells differed from the 293 cells, transfected with an «empty» vector, in their size and ability to adhere to the culture plates. Conclusions. The overexpression of CHI3L1 is likely to have an important role in tumorigenesis via a mechanism which involves activation of PI3K and ERK1/2 pathways. The tumors which can be induced by orthotopic implantation of the transformed human cells with overexpressed human oncogene CHI3L1 into the rat brain can be used as a target for anticancer drug development.

  19. Analysis of the TREAT loss-of-flow tests L6 and L7 using SAS3D

    International Nuclear Information System (INIS)

    Morris, E.E.; Simms, R.; Gruber, E.E.

    1985-01-01

    The TREAT loss-of-flow tests L6 and L7 have been analyzed using the SAS3D accident analysis code. The impetus for the analysis was the need for experimentally supported fuel motion modeling in whole core accident studies performed in support of licensing of the Clinch River Breeder Reactor Project. The input prescription chosen for the SAS3D/SLUMPY fuel motion model gave reasonable agreement with the test results. Tests L6 and L7, each conducted with a cluster of three fuel pins, were planned to simulate key events in the loss-of-flow accident scenario for the Clinch River homogeneous reactor

  20. L-series of elliptic curves with CM by √-3

    International Nuclear Information System (INIS)

    Qiu Derong; Zhang Xianke

    2001-09-01

    Let E:y 2 =x 3 -2 4 3 3 D 2 be elliptic curves defined over the quadratic field Q(√-3). Hecke L-series attached to E are studied, formulae for the values of the L-series at s=1 are given, and the bound of 3-adic valuations of these values are obtained. These results are consistent with the predictions of the conjecture of Birch and Swinnerton-Dyer, and generalize results in recent literature about elliptic curves defined over rationals. (author)

  1. Molecular structure and vibrational spectrum of the complex [ErL(H2O)(NO3)3] (L 1,4,10,13-tetraoxi-7,16-diaza(diphenylphosphinylmethyl) cyclooctadecane

    International Nuclear Information System (INIS)

    Minacheva, L.Kh.; Ivanova, I.S.; Kireeva, I.K.; Sakharova, V.G.; Tsivadze, A.Yu.; Sergienko, V.S.; Baulin, V.E.

    2000-01-01

    Synthesis of podandocoronand on the basis of diazo-18-crown-6 (DA18K6) 1,4,10,13-tetraoxi-7,16-diazo (diphenylphosphynylmethyl)cyclooctadecane (L) and erbium nitrate complex with L of the [ErL(H 2 O)(NO 3 ) 3 ] (I) composition is described. The IR-spectra of the free ligand L and complex I are studied and interpreted.The crystals are monoclinic: a = 10.432(2), b = 19.909(4), c = 21.361(4), β = 100.39(3) Deg, V = 4364(2) A 3 , sp. gr. P2 1 /n, Z = 4, ρ = 1.617 g/cm 3 . The structure I is formed of discrete molecular complexes. The Er atom coordination number is equal to 9. Three nitrate groups are bidentate-cyclic coordinated; two of them are in trans-position to each other; the H 2 O molecule is trans-position to the third NO 3 -group. The ligand L is coordinated by metal through two oxygen phosphoryl atoms. Thus, the Er atom coordination polyhedron may be described as octahedron, if each NO 3 -group occupies one coordination position. The Er-O(L) and Er-O(NO 3 ) overage distances are equal to 2.25 and 2.43 A correspondingly. Er-O(H 2 O) - 2.29 A. The H 2 O coordinated molecule forms intermolecular hydrogen atom and two oxygen atoms of the DA18K6 macrocycle [ru

  2. Mutations in the bacterial ribosomal protein l3 and their association with antibiotic resistance

    DEFF Research Database (Denmark)

    Klitgaard, Rasmus N; Ntokou, Eleni; Nørgaard, Katrine

    2015-01-01

    -type genes with mutated L3 genes in a chromosomal L3 deletion strain. In this way, the essential L3 gene is available for the bacteria while allowing replacement of the wild type with mutated L3 genes. This enables investigation of the effect of single mutations in Escherichia coli without a wild-type L3...

  3. L3 Experiment

    CERN Multimedia

    Falagan bobillo, M A; Chen, E F A; Prokofiev, D; Prokofiev, D; Shvorab, A; Galaktionov, Y; Kopal, M; Cotorobai, F; Le goff, J; Tully, C; Van hoek, W; Nozik, V Z; Nessi-tedaldi, F; De la cruz, B; Wadhwa, M; Chtcheguelski, V; Anderhub, H B; Guo, Y; Garcia-abia, P; Piroue, P; Della marina, R; Cerrada, M; Gailloud, M; Xia, L; Chaturvedi, U K; Pistolesi, E; Zhang, S

    2002-01-01

    % L3 \\\\ \\\\ The detector consists of a large volume low field solenoid magnet, a small central tracking system with very high spatial resolution, a high resolution electromagnetic calorimeter encapsulating the central detector, a hadron calorimeter acting also as a muon filter, and high precision muon tracking chambers. \\\\ \\\\The detector is designed to measure energy and position of leptons with the highest obtainable precision allowing a mass resolution $\\Delta$m/m smaller than 2\\% in dilepton final states. Hadronic energy flux is detected by a fine-grained calorimeter, which also serves as muon filter and tracking device. \\\\ \\\\The outer boundary of the detector is given by the iron return-yoke of a conventional magnet, using aluminium plates for the coil. The field is 0.5~T over a length of 12~m. This large volume allows a high precision muon momentum measurement, performed by three sets of drift chambers in the central detector region. From the multiple measurement of the coordinate in the bending plane a m...

  4. FROM ENGLISH AS L1 TO PORTUGUESE AS L3 THROUGH SPANISH AS L2: TRANSFERS IN VERB REGENCY/TRANSITIVITY, WITH SPECIAL EMPHASIS ON PREPOSITIONS

    OpenAIRE

    RENATA DE OLIVEIRA RAZUK

    2008-01-01

    Do Inglês L1 ao Português L3 passando pelo Espanhol L2: transferências em regência/transitividade verbal, com foco nas preposições transita por temas pouco explorados - não só pela combinação de línguas adotada, como também pela especificidade do fenômeno analisado e pelo tópico gramatical escolhido -, contribuindo para o desenvolvimento de uma área de pesquisa extremamente recente e promissora: a aquisição de terceira língua. Os estudos em AL3 ainda estão mui...

  5. Multilingual students' acquisition of English as their L3

    DEFF Research Database (Denmark)

    Samal Jalal, Rawand

    with regard to English proficiency. The current study conducted in Denmark investigated multilingual students’ English proficiency compared to their monolingual peers’, and examined which learning strategies proficient L3 learners utilize. The sample was comprised of 9-graders who are monolinguals (N = 82......) and multilinguals with Turkish L1 (N = 134). The participants provided basic demographic information, and were tested in their general English proficiency. Out of the 70 multilinguals with Turkish L1, 12 participants were selected for further testing; i.e., the four participants who scored the lowest, four...... participants with intermediate scores, and the four who scored the highest, on a test of English proficiency. These participants were tested in their L1 (Turkish) and their L2 (Danish) in order to examine whether their proficiency in their L1 and L2 was associated with English proficiency. Furthermore, the 12...

  6. Ionization cross sections of the Au L subshells by electron impact from the L3 threshold to 100 keV

    Science.gov (United States)

    Barros, Suelen F.; Vanin, Vito R.; Maidana, Nora L.; Martins, Marcos N.; García-Alvarez, Juan A.; Santos, Osvaldo C. B.; Rodrigues, Cleber L.; Koskinas, Marina F.; Fernández-Varea, José M.

    2018-01-01

    We measured the cross sections for Au Lα, Lβ, Lγ, Lℓ and Lη x-ray production by the impact of electrons with energies from the L3 threshold to 100 keV using a thin Au film whose mass thickness was determined by Rutherford Backscattering Spectrometry. The x-ray spectra were acquired with a Si drift detector, which allowed to separate the components of the Lγ multiplet lines. The measured Lα, Lβ, {{L}}{γ }1, L{γ }{2,3,6}, {{L}}{γ }{4,4\\prime }, {{L}}{γ }5, {{L}}{\\ell } and Lη x-ray production cross sections were then employed to derive Au L1, L2 and L3 subshell ionization cross sections with relative uncertainties of 8%, 7% and 7%, respectively; these figures include the uncertainties in the atomic relaxation parameters. The correction for the increase in electron path length inside the Au film was estimated by means of Monte Carlo simulations. The experimental ionization cross sections are about 10% above the state-of-the-art distorted-wave calculations.

  7. Comparing the UK EQ-5D-3L and English EQ-5D-5L Value Sets.

    Science.gov (United States)

    Mulhern, Brendan; Feng, Yan; Shah, Koonal; Janssen, Mathieu F; Herdman, Michael; van Hout, Ben; Devlin, Nancy

    2018-06-01

    Three EQ-5D value sets (EQ-5D-3L, crosswalk, and EQ-5D-5L) are now available for cost-utility analysis in the UK and/or England. The value sets' characteristics differ, and it is important to assess the implications of these differences. The aim of this paper is to compare the three value sets. We carried out analysis comparing the predicted values from each value set, and investigated how differences in health on the descriptive system is reflected in the utility score by assessing the value of adjacent states. We also assessed differences in values using data from patients who completed both EQ-5D-3L and EQ-5D-5L. The distribution of the value sets systematically differed. EQ-5D-5L values were higher than EQ-5D-3L/crosswalk values. The overall range and difference between adjacent states was smaller. In the patient data, the EQ-5D-5L produced higher values across all conditions and there was some evidence that the value sets rank different health conditions in a similar severity order. There are important differences between the value sets. Due to the smaller range of EQ-5D-5L values, the possible change in quality-adjusted life years (QALYs) might be reduced, but they will apply to both control and intervention groups, and will depend on whether the gain is in quality of life, survival, or both. The increased sensitivity of EQ-5D-5L may also favour QALY gains even if the changes in utility are smaller. Further work should assess the impact of the different value sets on cost effectiveness by repeating the analysis on clinical trial data.

  8. The L polymerase protein of parainfluenza virus 3 forms an oligomer and can interact with the heterologous Sendai virus L, P and C proteins

    International Nuclear Information System (INIS)

    Smallwood, Sherin; Moyer, Sue A.

    2004-01-01

    We recently showed that the L protein of Sendai virus is present as an oligomer in the active P-L polymerase complex [Smallwood et al., Virology 304 (2002) 235]. We now demonstrate using two different epitope tags that the L protein of a second respirovirus, human parainfluenza type 3 virus (PIV3), also forms an L-L complex. L oligomerization requires the coexpression of the differentially epitope tagged L proteins. By exploiting a series of C-terminal truncations the L-L binding site maps to the N-terminal half of L. There is some complex formation between the heterologous PIV3 and Sendai L and P proteins; however, the heterologous L protein does not function in transcription of either the PIV3 or Sendai template. The PIV3 C protein binds PIV3 L and inhibits RNA synthesis in vitro and in vivo. Significant homology exists between the C proteins of PIV3 and Sendai and complex formation occurs between the PIV3 and Sendai heterologous C and L proteins. In addition, the heterologous C proteins can inhibit transcription at ∼50% of the level of the homologous protein. These data suggest that while the C proteins may be functionally somewhat interchangeable, the L and P proteins are specific for each virus

  9. Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Bray Denard

    Full Text Available Doxorubicin has been shown to inhibit proliferation of cancer cells through proteolytic activation of CREB3L1 (cAMP response element binding protein 3-like 1, a transcription factor synthesized as a membrane-bound precursor. Upon doxorubicin treatment, CREB3L1 is cleaved so that the N-terminal domain of the protein can reach the nucleus where it activates transcription of genes that inhibit cell proliferation. These results suggest that the level of CREB3L1 in cancer cells may determine their sensitivity to doxorubicin.Mice transplanted with 6 lines of renal cell carcinoma (RCC were injected with doxorubicin to observe the effect of the chemotherapy on tumor growth. Immunohistochemistry and bioinformatics analyses were performed to compare CREB3L1 levels in types of cancer known to respond to doxorubicin versus those resistant to doxorubicin.Higher levels of CREB3L1 protein are correlated with increased doxorubicin sensitivity of xenograft RCC tumors (p = 0.017 by Pearson analysis. From patient tumor biopsies we analyzed, CREB3L1 was expressed in 19% of RCC, which is generally resistant to doxorubicin, but in 70% of diffuse large B-cell lymphoma that is sensitive to doxorubicin. Doxorubicin is used as the standard treatment for cancers that express the highest levels of CREB3L1 such as osteosarcoma and malignant fibrous histiocytoma but is not generally used to treat those that express the lowest levels of CREB3L1 such as RCC.Identification of CREB3L1 as the biomarker for doxorubicin sensitivity may markedly improve the doxorubicin response rate by applying doxorubicin only to patients with cancers expressing CREB3L1.

  10. Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Colette N Miller

    Full Text Available Beta-adrenergic activation stimulates uncoupling protein 1 (UCP1, enhancing metabolic rate. In vitro, most work has studied brown adipocytes, however, few have investigated more established adipocyte lines such as the murine 3T3-L1 line. To assess the effect of beta-adrenergic activation, mature 3T3-L1s were treated for 6 or 48 hours with or without isoproterenol (10 and 100 μM following standard differentiation supplemented with thyroid hormone (T3; 1 nM. The highest dose of isoproterenol increased lipid content following 48 hours of treatment. This concentration enhanced UCP1 mRNA and protein expression. The increase in UCP1 following 48 hours of isoproterenol increased oxygen consumption rate. Further, coupling efficiency of the electron transport chain was disturbed and an enhancement of glycolytic rate was measured alongside this, indicating an attempt to meet the energy demands of the cell. Lastly, markers of beige adipocytes (protein content of CD137 and gene transcript of CITED1 were also found to be upregulated at 48 hours of isoproterenol treatment. This data indicates that mature 3T3-L1 adipocytes are responsive to isoproterenol and induce UCP1 expression and activity. Further, this finding provides a model for further pharmaceutical and nutraceutical investigation of UCP1 in 3T3-L1s.

  11. Solubilities of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid in water

    Energy Technology Data Exchange (ETDEWEB)

    Mishelevich, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel); Apelblat, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel)], E-mail: apelblat@bgu.ac.il

    2008-05-15

    The solubility in water of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid was determined in the 278.15 K to 343.15 K temperature range. The solubility of these compounds served to permit the evaluation of the apparent molar enthalpies of solution.

  12. Solubilities of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid in water

    International Nuclear Information System (INIS)

    Mishelevich, Alexander; Apelblat, Alexander

    2008-01-01

    The solubility in water of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid was determined in the 278.15 K to 343.15 K temperature range. The solubility of these compounds served to permit the evaluation of the apparent molar enthalpies of solution

  13. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach.

    Directory of Open Access Journals (Sweden)

    Gregory J Crowther

    Full Text Available BACKGROUND: The increased sequencing of pathogen genomes and the subsequent availability of genome-scale functional datasets are expected to guide the experimental work necessary for target-based drug discovery. However, a major bottleneck in this has been the difficulty of capturing and integrating relevant information in an easily accessible format for identifying and prioritizing potential targets. The open-access resource TDRtargets.org facilitates drug target prioritization for major tropical disease pathogens such as the mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni. METHODOLOGY/PRINCIPAL FINDINGS: Here we present strategies to prioritize pathogen proteins based on whether their properties meet criteria considered desirable in a drug target. These criteria are based upon both sequence-derived information (e.g., molecular mass and functional data on expression, essentiality, phenotypes, metabolic pathways, assayability, and druggability. This approach also highlights the fact that data for many relevant criteria are lacking in less-studied pathogens (e.g., helminths, and we demonstrate how this can be partially overcome by mapping data from homologous genes in well-studied organisms. We also show how individual users can easily upload external datasets and integrate them with existing data in TDRtargets.org to generate highly customized ranked lists of potential targets. CONCLUSIONS/SIGNIFICANCE: Using the datasets and the tools available in TDRtargets.org, we have generated illustrative lists of potential drug targets in seven tropical disease pathogens. While these lists are broadly consistent with the research community's current interest in certain specific proteins, and suggest

  14. The quantitation of parasite-specific human IgG and IgE in sera: evaluation of solid-phase RIA and ELISA methodology

    International Nuclear Information System (INIS)

    Hamilton, R.G.; Adkinson, N.F. Jr.

    1981-01-01

    The authors have developed a non-competitive solid-phase radioimmunoassay (SPRIA) to quantitate both human IgE and IgG antibodies against soluble adult antigens of Brugia malayi (B.m.), a filarial parasite causing extensive infection throughout the tropics. Previously enzyme-linked immunosorbent assays (ELISA) had been used to detect μg/ml levels of IgG anti-B.m., but IgE antibodies were difficult to detect in this system. Since the SPRIA successfully quantitates both IgG and IgE anti-B.m., they sought to examine the reasons for the SPRIA's apparent superiority in detecting IgE anti-B.m. by extracting specific IgG from sera with high levels of IgE and IgG anti-B.m. antibodies. IgE anti-B.m. was then quantitated in these sera using both the SPRIA and ELISA methods. Results indicate that IgG anti-B.m. does not interfere with detection of specific IgE antibody in the SPRIA but does interfere in the ELISA. While ELISA permits detection of IgE anti-B.m. in the absence of competing IgG anti-B.m., as levels of specific IgG increase, the IgE is no longer detectable. These differences between SPRIA and ELISA can be explained by the SPRIA's antigen excess conditions which assure that there are sufficient antigens both to detect all anti-B.m. antibodies present in the serum and to adequately represent all antigen specificities in the crude B.m. extract. Their findings commend the use of SPRIA methods over ELISA in assessment of B.m.-specific IgE antibody in filariasis and indicate a potential role for SPRIA methods in absolute quantitation of specific serum antibodies. (Auth.)

  15. Quantitation of parasite-specific human IgG and IgE in sera: evaluation of solid-phase RIA and ELISA methodology

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, R G [Johns Hopkins Univ., Baltimore, MD (USA). Dept. of Medicine; Hussain, R; Ottesen, E A [National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA); Adkinson, Jr, N F [Johns Hopkins Univ., Baltimore, MD (USA). School of Medicine

    1981-07-17

    The authors have developed a non-competitive solid-phase radioimmunoassay (SPRIA) to quantitate both human IgE and IgG antibodies against soluble adult antigens of Brugia malayi (B.m.), a filarial parasite causing extensive infection throughout the tropics. Previously enzyme-linked immunosorbent assays (ELISA) had been used to detect ..mu..g/ml levels of IgG anti-B.m., but IgE antibodies were difficult to detect in this system. Since the SPRIA successfully quantitates both IgG and IgE anti-B.m., they sought to examine the reasons for the SPRIA's apparent superiority in detecting IgE anti-B.m. by extracting specific IgG from sera with high levels of IgE and IgG anti-B.m. antibodies. IgE anti-B.m. was then quantitated in these sera using both the SPRIA and ELISA methods. Results indicate that IgG anti-B.m. does not interfere with detection of specific IgE antibody in the SPRIA but does interfere in the ELISA. While ELISA permits detection of IgE anti-B.m. in the absence of competing IgG anti-B.m., as levels of specific IgG increase, the IgE is no longer detectable. These differences between SPRIA and ELISA can be explained by the SPRIA's antigen excess conditions which assure that there are sufficient antigens both to detect all anti-B.m. antibodies present in the serum and to adequately represent all antigen specificities in the crude B.m. extract. Their findings commend the use of SPRIA methods over ELISA in assessment of B.m.-specific IgE antibody in filariasis and indicate a potential role for SPRIA methods in absolute quantitation of specific serum antibodies.

  16. 2,3-trans-3,4-trans-3,4-Dihydroxy-L-proline: An amino acid in toxic peptides of Amanita virosa mushrooms

    Science.gov (United States)

    Buku, A.; Faulstich, H.; Wieland, T.; Dabrowski, J.

    1980-01-01

    Among the four possible stereoisomers of 3,4-dihydroxy-L-proline,2,3-trans-3,4-trans-3,4-dihydroxy-L-proline (IV) had not been found in nature previously. It has now been detected as a component of virotoxins, toxic peptides of Amanita virosa mushrooms. Because periodate failed to effect an oxidative glycol splitting reaction, the two hydroxyl groups in positions 3 and 4 were expected to be in a trans configuration. Furthermore, the formation of a 4-lactone on treatment with acids pointed to the carboxyl group and the hydroxyl group at position 4 being in a cis configuration. These results are in agreement with structure IV only. Final proof for structure IV was given by NMR spectroscopy and direct comparison with the 2,3-cis-3,4-trans-3,4-dihydroxy-L-proline isomer. PMID:16592813

  17. Results of L3 BGO calorimeter calibration using an RFQ accelerator

    CERN Document Server

    Chaturvedi, U K; Gataullin, M; Gratta, Giorgio; Kirkby, D; Lu, W; Newman, H; Shvorob, A V; Tully, C; Zhu, R

    2000-01-01

    A novel calibration system based on a radiofrequency-quadrupole (RFQ) accelerator has been installed in the L3 experiment. Radiative capture of 1.85 MeV protons from the RFQ accelerator in a lithium target produces a flux of 17.6 MeV photons which are used to calibrate 11000 crystals of the L3 BGO calorimeter. In this paper we present results of the RFQ run taken in November 1997. A calibration precision of 0.6% was reached in the barrel of the L3 BGO calorimeter, and 0.7% in the BGO endcaps. (8 refs).

  18. English L3 Learning in a Multilingual Context: The Role of Parental Education and L2 Exposure within the Living Community

    Science.gov (United States)

    De Angelis, Gessica

    2015-01-01

    The present study examines two factors in relation to English L3 proficiency development and school performance in a third language: (a) parental education and (b) second language exposure within the living community. Participants (n?=?50) are Italian L1 students with German L2 and English L3. All students (eighth grade, 14 years of age) were…

  19. Inhibitory effects of ethyl acetate-soluble fraction from morus alba on lipid accumulation in 3T3-L1 cells.

    Science.gov (United States)

    Park, Hee-Sook; Shim, Soon-Mi; Kim, Gun-Hee

    2013-11-01

    Fruits of mulberry (Morus alba) have been widely used for therapeutic purposes in Asian countries for centuries. Treatment of 3T3-L1 cells with ethanolic extracts of M. alba decreased adipocyte differentiation at 100 microg/mL by 18.6%. Treatment suppressed mRNA levels of PPARgamma and C/EBPalpha expression in 3T3-L1 cells. However, the extract did not change free glycerol release from mature adipocytes. Thus, M. alba inhibited lipid accumulation by regulating transcription factors in 3T3-L1 adipocytes without a lipolytic effect. Among the soluble- fractions, the ethyl acetate-soluble fraction had the highest antiadipogenic effects on 3T3-L1 cells. This fraction decreasing intracellular lipid accumulation by 38.5% in response to treatment with 100 microg/mL. In addition, HPLC analysis of the ethyl acetate-soluble fraction of M. alba contained 167.7 microM of protocatechulic acid in 1 mg/mL of fraction, which inhibited lipid accumulation by 44.8% in response to treatment with 100 microM. From these results, M. alba is a possible candidate for regulating lipid accumulation in obesity.

  20. Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract.

    Science.gov (United States)

    Frank, Thomas; Janssen, Marlies; Netzel, Michael; Strass, Gabriele; Kler, Adolf; Kriesl, Erwin; Bitsch, Irmgard

    2005-02-01

    Pharmacokinetic parameters of several dietary anthocyanins following consumption of Hibiscus sabdariffa L. extract were determined in 6 healthy volunteers. Subjects were given a single oral dose of 150 mL of Hibiscus sabdariffa L. extract yielding 62.6 mg of cyanidin-3-sambubioside, 81.6 mg of delphindin-3-sambubioside, and 147.4 mg of total anthocyanins (calculated as cyanidin equivalents). Within 7 hours, the urinary excretion of cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins (ie, the sum of all quantifiable anthocyanidin glycosides) was 0.016%, 0.021%, and 0.018% of the administered doses, respectively. Maximum excretion rates were determined at 1.5 to 2.0 hours after intake. The dose-normalized plasma area under the curve estimates were 0.076, 0.032, and 0.050 ng x h/mL/mg for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The dose-normalized C(max) estimates were 0.036, 0.015, and 0.023 ng/mL/mg in the same sequence. They were reached each at 1.5 hours (median) after intake. The geometric means of t1/2 were 2.18, 3.34, and 2.63 hours for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The urinary excretion of intact anthocyanins was fast and appeared to be monoexponential. To evaluate the contribution of anthocyanins to the health-protecting effects of Hibiscus sabdariffa L. extract, it will be necessary to perform further studies on both the intact glycosides and their in vivo metabolites or conjugates in human plasma and urine.

  1. Crystal and molecular structure of 2,2’-(quinoxaline-2,3-diyl)dipyridinium dinitrate (H_2L)(NO_3)_2

    International Nuclear Information System (INIS)

    Egorova, O. A.; Polyakova, I. N.; Sergienko, V. S.; Davydov, V. V.

    2016-01-01

    The crystal structure of 2,2’-(quinoxaline-2,3-diyl)dipyridinium dinitrate (H_2L)(NO_3)_2 is studied by X-ray diffraction (T = 150 K, R1 = 0.0467). The H_2L"2"+ cation is located on the twofold rotation axis and connected with two NO_3"− anions by strong N–H···O hydrogen bonds. Planar quinoxaline fragments of cations form stacks with the interplanar spacing of 3.308 Å. The structure of the diprotonated H_2L"2"+ cation is compared with those of the monoprotonated H_2L"2"+ cation and neutral L molecule.

  2. l-Cysteine supplementation increases insulin sensitivity mediated by upregulation of GSH and adiponectin in high glucose treated 3T3-L1 adipocytes.

    Science.gov (United States)

    Achari, Arunkumar E; Jain, Sushil K

    2017-09-15

    Diabetic patients have lower blood levels of l-cysteine (LC) and glutathione (GSH). This study examined the hypothesis that LC supplementation positively up regulates the effects of insulin on GSH and glucose metabolism in 3T3-L1 adipocyte model. 3T3L1 adipocytes were treated with LC (250 μM, 2 h) and/or insulin (15 or 30 nM, 2 h), and high glucose (HG, 25 mM, 20 h). Results showed that HG caused significant increase (95%) in ROS and reduction in the protein levels of DsbA-L (43%), adiponectin (64%), GCLC (20%), GCLM (21%), GSH (50%), and GLUT-4 (23%) in adipocytes. Furthermore, HG caused a reduction in total (35%) and HMW adiponectin (30%) secretion. Treatment with insulin alone significantly (p L, adiponectin, GCLC, GCLM, GSH, and GLUT-4 protein levels, glucose utilization, and improved total and HMW adiponectin secretion in HG treated adipocytes compared to HG alone. Interestingly, LC supplementation along with insulin caused greater reduction in ROS levels and significantly (p L (41% vs LC, 29% vs Insulin), adiponectin (92% Vs LC, 84% Vs insulin) protein levels and total (32% Vs LC, 22% Vs insulin) and HMW adiponectin (75% Vs LC, 39% Vs insulin) secretion compared with the either insulin or LC alone in HG-treated cells. In addition, LC supplementation along with insulin increased GCLC (21% Vs LC, 14% insulin), GCLM (28% Vs LC, 16% insulin) and GSH (25% Vs LC and insulin) levels compared with the either insulin or LC alone in HG-treated cells. Furthermore, LC and insulin increases GLUT-4 protein expression (65% Vs LC, 18% Vs Insulin), glucose utilization (57% Vs LC, 27% Vs insulin) compared with the either insulin or LC alone in HG-treated cells. Similarly, LC supplementation increased insulin action significantly in cells maintained in medium contained control glucose. To explore the beneficial effect of LC is mediated by the upregulation of GCLC, we knocked down GCLC using siRNA in adipoctyes. There was a significant decrease in DsbA-L and GLUT-4 m

  3. Contribution to the design and implementation of the trigger and acquisition system of the L3 experiment at LEP; Contribution a l`elaboration et a la mise en oeuvre du systeme de declenchement et d`acquisition de l`experience L3 au LEP

    Energy Technology Data Exchange (ETDEWEB)

    Cai, X

    1994-10-01

    The thesis is devoted to the trigger and data acquisition system of the L3 experiment at LEP. It is a large distributed system with multiple levels to trigger, collect and record events detected by the L3 detector. The three trigger levels are designed to reduce a possible first level trigger rate of 100 Hz to a few Hz. The readout and event building systems have intermediate buffering so that the only dead time is only introduced during digitization of the detector signals. The emphasis of this thesis is on the Hadron Calorimeter (one of the sub detectors) readout system, the L3 event building system and the upgraded level-3-trigger system. Both hardware and software are described. (author). 126 refs., 48 figs., 23 tabs.

  4. Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway

    International Nuclear Information System (INIS)

    Li, Taiyuan; Liu, Dongning; Lei, Xiong; Jiang, Qunguang

    2017-01-01

    Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. - Highlights: • Par3L knockout using the CRISPR/Cas system induces apoptosis in colorectal cancer cells. • Par3L interacts with Lkb1 and regulates the activity of AMPK signaling cascade. • Par3L knockout cells are more sensitive to treatment of different chemotherapy drugs and irradiation.

  5. Modeling the Global Coronal Field with Simulated Synoptic Magnetograms from Earth and the Lagrange Points L3, L4, and L5

    Science.gov (United States)

    Petrie, Gordon; Pevtsov, Alexei; Schwarz, Andrew; DeRosa, Marc

    2018-06-01

    The solar photospheric magnetic flux distribution is key to structuring the global solar corona and heliosphere. Regular full-disk photospheric magnetogram data are therefore essential to our ability to model and forecast heliospheric phenomena such as space weather. However, our spatio-temporal coverage of the photospheric field is currently limited by our single vantage point at/near Earth. In particular, the polar fields play a leading role in structuring the large-scale corona and heliosphere, but each pole is unobservable for {>} 6 months per year. Here we model the possible effect of full-disk magnetogram data from the Lagrange points L4 and L5, each extending longitude coverage by 60°. Adding data also from the more distant point L3 extends the longitudinal coverage much further. The additional vantage points also improve the visibility of the globally influential polar fields. Using a flux-transport model for the solar photospheric field, we model full-disk observations from Earth/L1, L3, L4, and L5 over a solar cycle, construct synoptic maps using a novel weighting scheme adapted for merging magnetogram data from multiple viewpoints, and compute potential-field models for the global coronal field. Each additional viewpoint brings the maps and models into closer agreement with the reference field from the flux-transport simulation, with particular improvement at polar latitudes, the main source of the fast solar wind.

  6. AVHRR Pathfinder version 5.3 level 3 collated (L3C) global 4km sea surface temperature

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The AVHRR Pathfinder Version 5.3 (PFV53) L3C Sea Surface Temperature data set is a collection of global, twice-daily (Day and Night) 4km sea surface temperature...

  7. Kinetic studies on binding of thyroid hormones (L-T3 and L-T4) to the receptors of lymphocyte cells isolated from uraemia subjects

    International Nuclear Information System (INIS)

    Al-Sultani, A.S.J.

    1989-01-01

    The levels of L-T 3 , L-T 4 and TSH in uremic sera have been measured by (RIA), and shown to have a decrease in both L-T 3 and L-T 4 levels with normal level of TSH for most specimens used in this study. Kinetics properties for binding of thyroid hormones L-T 3 and L-T 4 with nuclear receptors of human lymphocyte cells extracted from uremic patient have been studied and compared this result with control and hypothyroidism subjects and we obtained that uremic condition have a large effect on these nuclear receptors properties. Dissociation constant (K d ) and maximal binding capacity (MBC) of both L-T 3 and L-T 4 with these nuclear receptors have been determined, and we obtained that uremic condition did not affect on (K d ) values for both L-T 3 and L-T 4 but it affected on (MBC) values compared with normal subject. 8 tabs.; 25 figs.; 203 refs

  8. Application of RELAP5/MOD3.1 code to the LOFT test L3-6

    International Nuclear Information System (INIS)

    Pylev, S.S.; Roginskaja, V.L.

    1998-02-01

    A calculation of LOFT Experiment L3-6, a small break equivalent to a 4-in diameter rupture in the cold leg of a four-loop commercial pressurized water reactor, has been performed to help validate RELAP5/MOD3.1 for this application. The version of the code to be used is SCDAP/RELAP5/MOD3.1.8d0. Three calculations were carried out in order to study the sensitivity to change break nozzle superheated discharge coefficient. Conducted comparative analysis of the LOFT L3-6 experiment shows on the whole a reasonable agreement between calculated data. Some discrepancies in the system pressure do not distort a picture of the transient. 6 refs

  9. Application of RELAP5/MOD3.1 code to the LOFT test L3-6

    Energy Technology Data Exchange (ETDEWEB)

    Pylev, S.S.; Roginskaja, V.L.

    1998-02-01

    A calculation of LOFT Experiment L3-6, a small break equivalent to a 4-in diameter rupture in the cold leg of a four-loop commercial pressurized water reactor, has been performed to help validate RELAP5/MOD3.1 for this application. The version of the code to be used is SCDAP/RELAP5/MOD3.1.8d0. Three calculations were carried out in order to study the sensitivity to change break nozzle superheated discharge coefficient. Conducted comparative analysis of the LOFT L3-6 experiment shows on the whole a reasonable agreement between calculated data. Some discrepancies in the system pressure do not distort a picture of the transient. 6 refs.

  10. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Takahashi, Nobuhiko; Yoshizaki, Takayuki; Hiranaka, Natsumi; Suzuki, Takeshi; Yui, Tomoo; Akanuma, Masayoshi; Kanazawa, Kaoru; Yoshida, Mika; Naito, Sumiyoshi; Fujiya, Mikihiro; Kohgo, Yutaka; Ieko, Masahiro

    2013-01-01

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion

  11. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40, Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayoshi [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

    2013-02-01

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.

  12. The participant Coster-Kronig preceded Auger transition in the resonant L2,3-M2,3V Auger electron spectrum of Ti metal

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2008-01-01

    The L 2,3 -M 2,3 V resonant Auger electron spectroscopy (RAES) spectrum of Ti metal measured by Le Fevre et al. [P. Le Fevre, J. Danger, H. Magnan, D. Chandesris, J. Jupille, S. Bourgeois, M.-A. Arrio, R. Gotter, A. Verdini, A. Morgante, Phys. Rev. B69 (2004) 155421] is analyzed in the light of relaxation and decay of the resonantly excited L 2,3 -hole states. The relaxation time of the resonantly excited L 2,3 -hole state to the fully relaxed (screened) one is much shorter than the L 2,3 -hole Auger decay time, whereas the participant Coster-Kronig (CK) decay time of the resonantly excited L 2 -hole state to the fully relaxed L 3 -hole state at the L 2 resonance is as short as the relaxation time of the resonantly excited L 2 -hole state to the fully relaxed one. The excited electron is predominantly either rapidly decoupled from the L 2,3 -hole decay or annihilated by the participant CK decay. Thus, near the L 2,3 edges the L 2,3 -M 2,3 V RAES spectral peak appears at constant kinetic energy. The L 2,3 -M 2,3 V RAES spectrum shows a normal L 2,3 -M 2,3 V Auger decay profile not modulated by the density of empty d states probed by the resonant excitation. Not only the relaxation time but also the participant CK decay time depends on photon energy because they depend on the density of empty d states probed by the resonant excitation. As a result, the L 2,3 X-ray absorption spectroscopy spectral line broadening depends on photon energy

  13. Versatility of {l_brace}M(30-crown-10){r_brace} (M = K{sup +}, Ba{sup 2+}) as a guest in UO{sub 2}{sup 2+} complexes of 3.1.3.1 - and 3.3.3 homo-oxa-calixarenes

    Energy Technology Data Exchange (ETDEWEB)

    Masci, B. [Univ Roma La Sapienza, Dipartimento Chim, I-00185 Rome, (Italy); Thuery, P. [CEA Saclay, DSM/DRECAM/SCM, CNRS-URA 331, F-91191 Gif Sur Yvette, (France)

    2007-07-01

    The reaction between p-R-[3.1.3.1]- or [3.3.3] homo-oxa-calixarenes and uranyl salts in the presence of 30-crown-10 and the alkali or alkaline-earth metal cations K{sup +} or Ba{sup 2+} gives various supramolecular assemblages characterized by 'complex-within-complex' architectures. These can be of the simple nesting or sandwich types, as in [{l_brace}Ba(30-crown-10){r_brace}{l_brace}UO{sub 2}(L{sup 1}){r_brace}]. 2H{sub 2}O.3CHCl{sub 3} (L{sup 1}H{sub 4} p-tert-butyl[3.1.3.1] homo-oxa-calixarene) and [{l_brace}Ba(30-crown-10){r_brace}{l_brace}UO{sub 2}(L{sup 4}){r_brace}{sub 2}].2CHCl{sub 3} (L{sup 4}H{sub 3} p-bromo[3.3.3]homo-oxa-calixarene), respectively, with the cation held in the cavity of the homo-oxa-calixarene complexes in cone conformation by weak interactions, but more original structures arise when uranyl-cation bonds are present. In [{l_brace}Ba(30-crown-10){r_brace}{l_brace}UO{sub 2}(L{sup 2}){r_brace}] (L{sup 2}H{sub 4} p-phenyl[3.1.3.1] homo-oxa-calixarene), the barium ion included in the crown ether is bound to the uranyl oxo group located out of the calixarene cavity, resulting in the formation of a neutral species which self-organizes to form a columnar assembly by auto-inclusion. In [{l_brace}K(30-crown-10){r_brace}{l_brace}UO{sub 2}K(L{sup 1})(H{sub 2}O){sub 3}{r_brace}]{sub 2}.6H{sub 2}O, the nesting-type subunit dimerizes around two oxo-bound potassium ions. Finally, the use of the coordinating solvent dimethylsulfoxide leads to the neutral complex [UO{sub 2}Ba(L{sup 3})(dmso){sub 2}(MeOH)]{sub 2} (L{sup 3}H{sub 4} = p-methyl[3.1.3.1] homo-oxa-calixarene), in which the crown ether is absent and two oxo-, phenoxo- and ether-bound barium atoms ensure the dimerization of the uranyl complex. (authors)

  14. Improved l1-SPIRiT using 3D walsh transform-based sparsity basis.

    Science.gov (United States)

    Feng, Zhen; Liu, Feng; Jiang, Mingfeng; Crozier, Stuart; Guo, He; Wang, Yuxin

    2014-09-01

    l1-SPIRiT is a fast magnetic resonance imaging (MRI) method which combines parallel imaging (PI) with compressed sensing (CS) by performing a joint l1-norm and l2-norm optimization procedure. The original l1-SPIRiT method uses two-dimensional (2D) Wavelet transform to exploit the intra-coil data redundancies and a joint sparsity model to exploit the inter-coil data redundancies. In this work, we propose to stack all the coil images into a three-dimensional (3D) matrix, and then a novel 3D Walsh transform-based sparsity basis is applied to simultaneously reduce the intra-coil and inter-coil data redundancies. Both the 2D Wavelet transform-based and the proposed 3D Walsh transform-based sparsity bases were investigated in the l1-SPIRiT method. The experimental results show that the proposed 3D Walsh transform-based l1-SPIRiT method outperformed the original l1-SPIRiT in terms of image quality and computational efficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. [A study on the construction, expression and immunosterility of Lagurus laguru zona pellucida 3 DNA vaccine pVAX1-sig-LTB-lZP3-C3d3].

    Science.gov (United States)

    Li, Chen-Chen; Yu, Ji-Yun; Jiang, Min; Tu, Yi-Xian; Ma, Xiao-Lin; Zhang, Fu-Chun

    2011-09-01

    To enhance the immunocontraceptive effect of Lagurus lagurus zona pellucida 3 DNA vaccine, and to achieve the prospect of application through the pVAX1-sig-LTB-lZP3-C3d3 different immunity pathway. Two adjuvant molecules were constructed into the recombinant plasmid pVAX1-sig-LTB-lZP3-C3d3 as DNA vaccine which contains Escherichia coli heat-labile enterotoxin B subunit and the molecular adjuvant 3 copies of C3d. The results of RT-PCR and western blot showed that the DNA vaccine was expressed in mRNA and protein level. The female C57BL/6 mice were immunized by three ways: intramuscular injection, intranasal or oral route.Antibody levels and types were detected by ELISA. ELISA results showed that recombinant plasmid pVAX1-sig-LTB-lZP3-C3d3 immunization induced specific IgG, IgA levels were significantly different comparing with control (Psig-LTB-lZP3-C3d3 can induce the specific immune response efficiently and enhance the immunocontraceptive effects.

  16. The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis

    Directory of Open Access Journals (Sweden)

    Georgios Vlachogiannis

    2015-02-01

    Full Text Available A critical aspect of mammalian gametogenesis is the reprogramming of genomic DNA methylation. The catalytically inactive adaptor Dnmt3L is essential to ensuring this occurs correctly, but the mechanism by which it functions is unclear. Using gene targeting to engineer a single-amino-acid mutation, we show that the Dnmt3L histone H3 binding domain (ADD is necessary for spermatogenesis. Genome-wide single-base-resolution DNA methylome analysis of mutant germ cells revealed overall reductions in CG methylation at repetitive sequences and non-promoter CpG islands. Strikingly, we also observe an even more severe loss of non-CG methylation, suggesting an unexpected role for the ADD in this process. These epigenetic deficiencies were coupled with defects in spermatogonia, with mutant cells displaying marked changes in gene expression and reactivation of retrotransposons. Our results demonstrate that the Dnmt3L ADD is necessary for Dnmt3L function and full reproductive fitness.

  17. Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

    International Nuclear Information System (INIS)

    Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki; Takahashi, Noriko

    2013-01-01

    Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner

  18. l-3,4-Dihydroxyphenylalanine induces ptosis through a GPR143-independent mechanism in mice

    Directory of Open Access Journals (Sweden)

    Suguru Ueda

    2016-09-01

    Full Text Available Through its conversion to dopamine by aromatic l-amino acid decarboxylase (AADC, l-3,4-dihydroxyphenylalanine (l-DOPA replenishes depleted brain dopamine in Parkinson's disease patients. We recently identified GPR143 as a candidate receptor for l-DOPA. In this study, we investigated the behavioral actions of l-DOPA in wild type (wt and Gpr143-deficient mice. l-DOPA dose-dependently (10–100 mg/kg, i.p. induced ptosis under treatment with 3-hydroxybenzylhydrazine, a centrally acting AADC inhibitor. This effect was not mimicked by 3-O-methyldopa. l-DOPA-induced ptosis in Gpr143-deficient mice to a similar extent as in wt mice. These results suggest that l-DOPA induces ptosis in a GPR143-independent fashion in mice.

  19. Mutations in the Bacterial Ribosomal Protein L3 and Their Association with Antibiotic Resistance

    Science.gov (United States)

    Klitgaard, Rasmus N.; Ntokou, Eleni; Nørgaard, Katrine; Biltoft, Daniel; Hansen, Lykke H.; Trædholm, Nicolai M.; Kongsted, Jacob

    2015-01-01

    Different groups of antibiotics bind to the peptidyl transferase center (PTC) in the large subunit of the bacterial ribosome. Resistance to these groups of antibiotics has often been linked with mutations or methylations of the 23S rRNA. In recent years, there has been a rise in the number of studies where mutations have been found in the ribosomal protein L3 in bacterial strains resistant to PTC-targeting antibiotics but there is often no evidence that these mutations actually confer antibiotic resistance. In this study, a plasmid exchange system was used to replace plasmid-carried wild-type genes with mutated L3 genes in a chromosomal L3 deletion strain. In this way, the essential L3 gene is available for the bacteria while allowing replacement of the wild type with mutated L3 genes. This enables investigation of the effect of single mutations in Escherichia coli without a wild-type L3 background. Ten plasmid-carried mutated L3 genes were constructed, and their effect on growth and antibiotic susceptibility was investigated. Additionally, computational modeling of the impact of L3 mutations in E. coli was used to assess changes in 50S structure and antibiotic binding. All mutations are placed in the loops of L3 near the PTC. Growth data show that 9 of the 10 mutations were well accepted in E. coli, although some of them came with a fitness cost. Only one of the mutants exhibited reduced susceptibility to linezolid, while five exhibited reduced susceptibility to tiamulin. PMID:25845869

  20. The second level trigger of the L3 experiment. Pt. 1

    International Nuclear Information System (INIS)

    Bertsch, Y.; Blaising, J.J.; Bonnefon, H.; Chollet-Le Flour, F.; Degre, A.; Dromby, G.; Lecoq, J.; Morand, R.; Moynot, M.; Perrot, G.; Riccadonna, X.

    1993-07-01

    The second level trigger of the L3 experiment performs online background rejection and reduces the first level trigger rate to a value fitting with the third level trigger processing capability. Designed around a set of 3 bit-slice XOP microprocessors, it can process up to 500 first level triggers per second without significant dead time in the data acquisition. The system described here ensures the L3 data taking since the beginning of LEP in July 1989 and the online rejection since 1990. (authors). 24 refs., 8 figs., 3 tabs

  1. Many-body calculation of the coincidence L3 photoelectron spectroscopy main line of Ni metal

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2008-01-01

    The partial singles L 3 photoelectron spectroscopy (PES) main line of Ni metal correlated with Auger electrons emitted by the localized L 3 -VV Auger decay is calculated by a many-body theory. The partial singles L 3 PES main line of Ni metal almost coincides in both line shape and peak kinetic energy (KE) with the singles one. The former main line peak shows a KE shift of only 0.01 eV toward the lower KE and a very small asymmetric line shape change compared to the singles one. The asymmetric line shape change and the peak KE shift of the partial singles L 3 main line are very small. However, they are due to the variation with photoelectron KE in the branching ratio of the partial Auger decay width in the partial singles L 3 PES main line by the photoelectron KE dependent imaginary part of the shakeup self-energy. The L 3 PES main line of Ni metal measured in coincidence with the L 3 -VV ( 1 G) Auger electron spectroscopy (AES) main line peak is the partial singles one modulated by a spectral function R a of a fixed energy Auger electron analyzer so that it should show only a symmetric line narrowing by R a compared to the singles one. The L 3 PES main line peak of Ni metal measured in coincidence with the delocalized band-like L 3 -VV AES peak or not completely split-off (or not completely localized) L 3 -VV ( 3 F) AES peak, will show an asymmetric line narrowing and a KE shift compared to the singles one. Thus, the L 3 PES main line of Ni metal in coincidence with various parts of the L 3 -VV AES spectrum depends on which part of the L 3 -VV AES spectrum a fixed energy Auger electron analyzer is set. The experimental verification is in need

  2. MicroRNA-24 promotes 3T3-L1 adipocyte differentiation by directly targeting the MAPK7 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Min, E-mail: min_jin@zju.edu.cn [Division of Reproductive Medicine & Infertility, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88#, Jiefang Rd., Hangzhou, Zhejiang, 310009 (China); Wu, Yutao; Wang, Jing [School of Medicine, Zhejiang University, 288# Yuhangtang Rd, Hangzhou, Zhejiang, 310003 (China); Chen, Jian; Huang, Yiting; Rao, Jinpeng; Feng, Chun [Division of Reproductive Medicine & Infertility, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88#, Jiefang Rd., Hangzhou, Zhejiang, 310009 (China)

    2016-05-20

    Over the past years, MicroRNAs (miRNAs) act as a vital role in harmony with gene regulation and maintaining cellular homeostasis. It is well testified that miRNAshave been involved in numerous physiological and pathological processes, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes, and it is tightly modulated by a series of transcription factors such as peroxisome proliferator-activated receptor γ (PPAR-γ) and sterol regulatory-element binding proteins 1 (SREBP1). However, the molecular mechanisms underlying the connection between miRNAs and adipogenesis-related transcription factors remain obscure. In this study, we unveiled that miR- 24 was remarkably upregulated during 3T3-L1 adipogenesis. Overexpression of miR-24 significantly promoted 3T3-L1 adipogenesis, as evidenced by its ability to increase the expression of PPAR-γ and SREBP1, lipid droplet formation and triglyceride (TG) accumulation. Furthermore, we found that neither ectopic expression of miR-24nor miR-24 inhibitor affect cell proliferation and cell cycle progression. Finally, we demonstrated that miR-24 plays the modulational role by directly repressing MAPK7, a key number in the MAPK signaling pathway. These data indicate that miR-24 is a novel positive regulator of adipocyte differentiation by targeting MAPK7, which provides new insights into the molecular mechanism of miRNA-mediated cellular differentiation. -- Highlights: •We firstly found miR-24 was upregulated in 3T3-L1 pre-adipocytes differentiation. •miR-24 promoted 3T3-L1 pre-adipocytes differentiation while silencing the expression of miR-24 had an opposite function. •miR-24 regulated 3T3-L1 differentiation by directly targeting MAPK7 signaling pathway. •miR-24did not affect 3T3-L1 pre-adipocytes cellular proliferation.

  3. Simulation of LOFT anticipated-transient experiments L6-1, L6-2, and L6-3 using TRAC-PF1/MOD1

    International Nuclear Information System (INIS)

    Sahota, M.S.

    1984-01-01

    Anticipated-transient experiments L6-1, L6-2, and L6-3, performed at the Loss-of-fluid Test (LOFT) facility, are analyzed using the latest released version of the Transient Reactor Analysis Code (TRAC-PF1/MOD1). The results are used to assess TRAC-PF1/MOD1 trip and control capabilities, and predictions of thermal-hydraulic phenomena during slow transients. Test L6-1 simulated a loss-of-stream load in a large pressurized-water reactor (PWR), and was initiated by closing the main steam-flow control valve (MSFCV) at its maximum rate, which reduced the heat removal from the secondary-coolant system and increased the primary-coolant system pressure that initiated a reactor scram. Test L6-2 simulated a loss-of-primary coolant flow in a large PWR, and was initiated by tripping the power to the primary-coolant pumps (PCPs) allowing the pumps to coast down. The reduced primary-coolant flow caused a reactor scram. Test L6-3 simulated an excessive-load increase incident in a large PWR, and was initiated by opening the MSFCV at its maximum rate, which increased the heat removal from the secondary-coolant system and decreased the primary-coolant system pressure that initiated a reactor scram. The TRAC calculations accurately predict most test events. The test data and the calculated results for most parameters of interest also agree well

  4. The behaviour of the L3 muon chambers in a magnetic field

    International Nuclear Information System (INIS)

    Onvlee, J.

    1989-01-01

    L3 is one of the four detectors at LEP. It consists of many parts, each of which measures a specific property of the particles produced in the electron positron collisions. One of the specialities of the L3 detector is the high precision measurement of the momenta of the muons produced in the collisions. In order to curve the muon trajectories the detector is placed in a magnetic field of about 0.5 Tesla. The behaviour of the L3 muon drift chambers in this magnetic field is the main subject of this thesis. (author). 45 refs.; 47 figs.; 12 tabs

  5. Selective affinity labeling of a 27-kDa integral membrane protein in rat liver and kidney with N-bromoacetyl derivatives of L-thyroxine and 3,5,3'-triiodo-L-thyronine

    International Nuclear Information System (INIS)

    Koehrle, J.R.; Rasmussen, U.B.; Rokos, H.; Leonard, J.L.; Hesch, R.D.

    1990-01-01

    125I-Labeled N-bromoacetyl derivatives of L-thyroxine and L-triiodothyronine were used as alkylating affinity labels to identify rat liver and kidney microsomal membrane proteins which specifically bind thyroid hormones. Affinity label incorporation was analyzed by ethanol precipitation and individual affinity labeled proteins were identified by autoradiography after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Six to eight membrane proteins ranging in size from 17 to 84 kDa were affinity labeled by both bromoacetyl-L-thyroxine (BrAcT4) and bromoacetyl-L-triiodothyronine (BrAcT3). Affinity labeling was time- and temperature-dependent, and both reduced dithiols and detergents increased affinity labeling, predominantly in a 27-kDa protein(s). Up to 80% of the affinity label was associated with a 27-kDa protein (p27) under optimal conditions. Affinity labeling of p27 by 0.4 nM BrAc[125I]L-T4 was blocked by 0.1 microM of the alkylating ligands BrAcT4, BrAcT3, or 100 microM iodoacetate, by 10 microM concentrations of the non-alkylating, reversible ligands N-acetyl-L-thyroxine, 3,3',5'-triiodothyronine, 3,5-diiodosalicylate, and EMD 21388, a T4-antagonistic flavonoid. Neither 10 microM L-T4, nor 10 microM N-acetyltriiodothyronine or 10 microM L-triiodothyronine blocked affinity labeling of p27 or other affinity labeled bands. Affinity labeling of a 17-kDa band was partially inhibited by excess of the alkylating ligands BrAcT4, BrAcT3, and iodoacetate, but labeling of other minor bands was not blocked by excess of the competitors. BrAc[125I]T4 yielded higher affinity label incorporation than BrAc[125I]T3, although similar banding patterns were observed, except that BrAcT3 affinity labeled more intensely a 58,000-Da band in liver and a 53,000-55,000-Da band in kidney

  6. Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Nabilatul Hani Mohd-Radzman

    2013-01-01

    Full Text Available Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p<0.001 in normal conditions and up to 4.4 times (p<0.001 in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.

  7. Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.

    Science.gov (United States)

    Sangeetha, K N; Shilpa, K; Jyothi Kumari, P; Lakshmi, B S

    2013-02-15

    The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes. MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA. An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance. 3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent. Copyright © 2012 Elsevier GmbH. All rights reserved.

  8. Variations in CCL3L gene cluster sequence and non-specific gene copy numbers

    Directory of Open Access Journals (Sweden)

    Edberg Jeffrey C

    2010-03-01

    Full Text Available Abstract Background Copy number variations (CNVs of the gene CC chemokine ligand 3-like1 (CCL3L1 have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene. Findings Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence. Conclusions This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.

  9. Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Guoyue, E-mail: yuanguoyue@hotmail.com [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Jia, Jue; Di, Liangliang [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Zhou, Libin [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China); Dong, Sijing; Ye, Jingjing; Wang, Dong; Yang, Ling; Wang, Jifang [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Li, Lianxi [Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, 600, Yishan Road, Shanghai 200233 (China); Yang, Ying [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China); Mao, Chaoming [Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Chen, Mingdao, E-mail: mingdaochensh@yahoo.com [Ruijin Hospital, Center of Molecular Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University Medical School, 197, Ruijin Road II, Shanghai 200025 (China)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer CRP increases TNF-{alpha} and IL-6 genes expression in matured 3T3-L1 adipocytes. Black-Right-Pointing-Pointer CRP suppresses adiponectin, leptin and PPAR-{gamma} mRNA levels in matured 3T3-L1 cells. Black-Right-Pointing-Pointer Wortmannin reverses effects of CRP on adiponectin, TNF-{alpha} and leptin mRNA levels. Black-Right-Pointing-Pointer CRP may regulate IR, obesity and metabolic syndrome by this mechanism. -- Abstract: Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of adipokines that are involved in the regulation of energy metabolism, insulin resistance and metabolic syndrome. C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. A number of studies have shown that elevation of CRP concentrations is an independent predictive parameter of type 2 diabetes mellitus, which is also strongly associated with various components of the metabolic syndrome. The aim of the present study is to investigate the effects of CRP on adipokines genes expression in 3T3-L1 adipocytes. Quantitative real-time PCR analysis revealed that CRP inhibited adiponectin, leptin and peroxisome proliferator-activated receptor-gamma (PPAR-{gamma}) genes expression and raised tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) mRNA levels in matured 3T3-L1 adipocytes in a dose and time-dependent manner. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by wortmannin partially reversed the effects of CRP on adiponectin, TNF-{alpha} and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-{alpha}, leptin, IL-6 and PPAR-{gamma} genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.

  10. Effects of C-reactive protein on adipokines genes expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Yuan, Guoyue; Jia, Jue; Di, Liangliang; Zhou, Libin; Dong, Sijing; Ye, Jingjing; Wang, Dong; Yang, Ling; Wang, Jifang; Li, Lianxi; Yang, Ying; Mao, Chaoming; Chen, Mingdao

    2012-01-01

    Highlights: ► CRP increases TNF-α and IL-6 genes expression in matured 3T3-L1 adipocytes. ► CRP suppresses adiponectin, leptin and PPAR-γ mRNA levels in matured 3T3-L1 cells. ► Wortmannin reverses effects of CRP on adiponectin, TNF-α and leptin mRNA levels. ► CRP may regulate IR, obesity and metabolic syndrome by this mechanism. -- Abstract: Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of adipokines that are involved in the regulation of energy metabolism, insulin resistance and metabolic syndrome. C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. A number of studies have shown that elevation of CRP concentrations is an independent predictive parameter of type 2 diabetes mellitus, which is also strongly associated with various components of the metabolic syndrome. The aim of the present study is to investigate the effects of CRP on adipokines genes expression in 3T3-L1 adipocytes. Quantitative real-time PCR analysis revealed that CRP inhibited adiponectin, leptin and peroxisome proliferator-activated receptor-gamma (PPAR-γ) genes expression and raised tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA levels in matured 3T3-L1 adipocytes in a dose and time-dependent manner. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by wortmannin partially reversed the effects of CRP on adiponectin, TNF-α and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-α, leptin, IL-6 and PPAR-γ genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.

  11. DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription.

    Directory of Open Access Journals (Sweden)

    Natasha M Zamudio

    Full Text Available Previous studies on the epigenetic regulator DNA methyltransferase 3-Like (DNMT3L, have demonstrated it is an essential regulator of paternal imprinting and early male meiosis. Dnmt3L is also a paternal effect gene, i.e., wild type offspring of heterozygous mutant sires display abnormal phenotypes suggesting the inheritance of aberrant epigenetic marks on the paternal chromosomes. In order to reveal the mechanisms underlying these paternal effects, we have assessed X chromosome meiotic compaction, XY chromosome aneuploidy rates and global transcription in meiotic and haploid germ cells from male mice heterozygous for Dnmt3L. XY bodies from Dnmt3L heterozygous males were significantly longer than those from wild types, and were associated with a three-fold increase in XY bearing sperm. Loss of a Dnmt3L allele resulted in deregulated expression of a large number of both X-linked and autosomal genes within meiotic cells, but more prominently in haploid germ cells. Data demonstrate that similar to embryonic stem cells, DNMT3L is involved in an auto-regulatory loop in germ cells wherein the loss of a Dnmt3L allele resulted in increased transcription from the remaining wild type allele. In contrast, however, within round spermatids, this auto-regulatory loop incorporated the alternative non-coding alternative transcripts. Consistent with the mRNA data, we have localized DNMT3L within spermatids and sperm and shown that the loss of a Dnmt3L allele results in a decreased DNMT3L content within sperm. These data demonstrate previously unrecognised roles for DNMT3L in late meiosis and in the transcriptional regulation of meiotic and post-meiotic germ cells. These data provide a potential mechanism for some cases of human Klinefelter's and Turner's syndromes.

  12. ORF Alignment: NC_006833 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available malayi] ... Length = 226 ... Query: 25 ... RVLDHGFIRVVDYMGSDSAIVQAARVSYGKGTKQINQDEVLIKYLMRYHHTTPFEM...CEIK 84 ... RVLDHGFIRVVDYMGSDSAIVQAARVSYGKGTKQINQDEVLIKYLMRYHHTTPFEMCEIK Sbjct: 1 ... ... RVLDHGFIRVVDYMGSDSAIVQAARVSYGKGTKQINQDEVLIKYLMRYHHTTPFEMCEIK 60 ... Query: 145 DISKEIIDSLINDSNLVYSHYNKFIEQGLT

  13. L(3)mbt and the LINT complex safeguard cellular identity in the Drosophila ovary.

    Science.gov (United States)

    Coux, Rémi-Xavier; Teixeira, Felipe Karam; Lehmann, Ruth

    2018-04-04

    Maintenance of cellular identity is essential for tissue development and homeostasis. At the molecular level, cell identity is determined by the coordinated activation and repression of defined sets of genes. The tumor suppressor L(3)mbt has been shown to secure cellular identity in Drosophila larval brains by repressing germline-specific genes. Here, we interrogate the temporal and spatial requirements for L(3)mbt in the Drosophila ovary, and show that it safeguards the integrity of both somatic and germline tissues. l(3)mbt mutant ovaries exhibit multiple developmental defects, which we find to be largely caused by the inappropriate expression of a single gene, nanos , a key regulator of germline fate, in the somatic ovarian cells. In the female germline, we find that L(3)mbt represses testis-specific and neuronal genes. At the molecular level, we show that L(3)mbt function in the ovary is mediated through its co-factor Lint-1 but independently of the dREAM complex. Together, our work uncovers a more complex role for L(3)mbt than previously understood and demonstrates that L(3)mbt secures tissue identity by preventing the simultaneous expression of original identity markers and tissue-specific misexpression signatures. © 2018. Published by The Company of Biologists Ltd.

  14. Effects of 3,5-diiodo-L-thyronine on browning of white adipose tissue%3,5-二碘-L-甲状腺素对白色脂肪棕色化的作用

    Institute of Scientific and Technical Information of China (English)

    柯孟婷; 孙家忠; 李扬

    2016-01-01

    目的 探究3,5-二碘-L-甲状腺素(T2)诱导白色脂肪棕色化的作用.方法 3T3-LI脂肪前体细胞诱导分化并用油红O染色进行鉴定;细胞分化过程中予不同浓度梯度(1 nmol/L、10 nmol/L、100 nmol/L)的T2处理,待细胞分化成熟后,分别用实时荧光定量PCR、Western印迹检测解耦联蛋白-1(UCP-1)表达水平的变化;仅予高浓度(100 nmol/L) T2处理,Western印迹法检测其他棕色脂肪功能性基因,包括诱导细胞死亡DNA片段化因子α样效应因子A(CIDEA)、过氧化物酶体增殖物活化受体γ协同刺激因子-1α(PGC-1α)蛋白表达变化.结果 3T3-L1脂肪前体细胞呈成纤维细胞样形态,胞浆中无脂滴;诱导分化成熟后光镜下油红O染色可见细胞内大量环状脂滴.在细胞分化过程中予不同浓度T2干预后,分化成熟的脂肪细胞上UCP-1 mRNA水平均有升高(t=3.97、11.77、17.7,P均<0.05),蛋白表达水平也均有改变(t=13.31、14.55、23.62,P均<0.05),且在高浓度(100nmoL/L)下最明显.在高浓度T2(100 nmol/L)干预下,成熟脂肪细胞的棕色脂肪其他功能性基因蛋白CIDEA、PGC-1α水平表达增加(t=15.92、17.36,P均<0.05).结论 T2可诱导由3T3-L1脂肪前体细胞分化而来的成熟白色脂肪细胞表达棕色脂肪功能性基因.%Objective To explore the effects of 3,5-diiodo-L-thyronine(T2) on browning of white adipose tissue.Methods Differentiation of 3T3-L1 adipose precursor cells were induced and identified by oil red O staining.During the differentiation process,3T3-L1 were treated by different concentrations of T2 (1 nmol/L,10 nmol/L,100 nmol/L).After the maturation of 3T3-L1,the level of uncoupling protein-1 (UCP-1) mRNA and protein were detected by RT-PCR and Western blotting,respectively.Specific proteins of brown adipose tissue including cell death-inducing DNA fragmentation factor alpha like effector A (CIDEA) and peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1 α) were

  15. Alliin, a Garlic (Allium sativum Compound, Prevents LPS-Induced Inflammation in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Saray Quintero-Fabián

    2013-01-01

    Full Text Available Garlic (Allium sativum L. has been used to alleviate a variety of health problems due to its high content of organosulfur compounds and antioxidant activity. The main active component is alliin (S-allyl cysteine sulfoxide, a potent antioxidant with cardioprotective and neuroprotective actions. In addition, it helps to decrease serum levels of glucose, insulin, triglycerides, and uric acid, as well as insulin resistance, and reduces cytokine levels. However its potential anti-inflammatory effect is unknown. We examined the effects of alliin in lipopolysaccharide- (LPS- stimulated 3T3-L1 adipocytes by RT-PCR, Western blot, and microarrays analysis of 22,000 genes. Incubation of cells for 24 h with 100 μmol/L alliin prevented the increase in the expression of proinflammatory genes, IL-6, MCP-1, and Egr-1 in 3T3-L1 adipocytes exposed to 100 ng/mL LPS for 1 h. Interestingly, the phosphorylation of ERK1/2, which is involved in LPS-induced inflammation in adipocytes, was decreased following alliin treatment. Furthermore, the gene expression profile by microarrays evidentiate an upregulation of genes involved in immune response and downregulation of genes related with cancer. The present results have shown that alliin is able to suppress the LPS inflammatory signals by generating an anti-inflammatory gene expression profile and by modifying adipocyte metabolic profile.

  16. Bog bilberry (Vaccinium uliginosum L.) extract reduces cultured Hep-G2, Caco-2, and 3T3-L1 cell viability, affects cell cycle progression, and has variable effects on membrane permeability.

    Science.gov (United States)

    Liu, Jia; Zhang, Wei; Jing, Hao; Popovich, David G

    2010-04-01

    Bog bilberry (Vaccinium uliginosum L.) is a blue-pigmented edible berry related to bilberry (Vaccinium myrtillus L.) and the common blueberry (Vaccinium corymbosum). The objective of this study was to investigate the effect of a bog bilberry anthocyanin extract (BBAE) on cell growth, membrane permeability, and cell cycle of 2 malignant cancer cell lines, Caco-2 and Hep-G2, and a nonmalignant murine 3T3-L1 cell line. BBAE contained 3 identified anthocyanins. The most abundant anthocyanin was cyanidin-3-glucoside (140.9 +/- 2.6 microg/mg of dry weight), followed by malvidin-3-glucoside (10.3 +/- 0.3 microg/mg) and malvidin-3-galactoside (8.1 +/- 0.4 microg/mg). Hep-G2 LC50 was calculated to be 0.563 +/- 0.04 mg/mL, Caco-2 LC50 was 0.390 +/- 0.30 mg/mL and 0.214 +/- 0.02 mg/mL for 3T3-L1 cells. LDH release, a marker of membrane permeability, was significantly increased in Hep-G2 cells and Caco-2 cells after 48 and 72 h compared to 24 h. The increase was 21% at 48 h and 57% at 72 h in Caco-2 cells and 66% and 139% in Hep-G2 cells compared to 24 h. However, 3T3-L1 cells showed an unexpected significant lower LDH activity (P < or = 0.05) after 72 h of exposure corresponding to a 21% reduction in LDH release. BBAE treatment increased sub-G1 in all 3 cell lines without influencing cells in the G2/M phase. BBAE treatment reduced the growth and increased the accumulation of sub-G1 cells in 2 malignant and 1 nonmalignant cell line; however, the effect on membrane permeability differs considerably between the malignant and nonmalignant cells and may in part be due to differences in cellular membrane composition.

  17. Lactococcus lactis KR-050L inhibit IL-6/STAT3 activation.

    Science.gov (United States)

    Hwang, J T; Jang, H-J; Kim, J H; Park, C S; Kim, Y; Lim, C-H; Lee, S W; Rho, M-C

    2017-05-01

    The purpose of this study was to investigate IL-6/STAT3 inhibitory activity using lactic acid bacteria (LABs) isolated from Gajuknamu kimchi. Six LABs were isolated from Gajuknamu kimchi and identified through 16S rRNA sequencing. Among them, the culture broth of Lactococcus lactis KR-050L inhibited IL-6-induced STAT3 luciferase activity. Fifteen compounds were isolated from the EtOAc extract of culture broth though column chromatography and preparative high-performance liquid chromatography, and they were identified as 2,5-diketopipperazine structures by spectroscopic analyses (MS, 1 H- and 13 C-NMR). They also showed inhibitory activities on IL-6-induced STAT3 activation, and showed the different in activity according to the presence of a phenylalanine residue, hydroxyl groups and isometric structure. The six new LABs isolated from Gajuknamu kimchi, and Lc. lactis KR-050L was selected as candidate IL-6/STAT3 inhibitors. The activity levels of 15 2,5-DKPs isolated from Lc. lactis KR-050L were verified. This study constitutes the first attempt to isolate various LABs from Gajuknamu kimchi and to discover IL-6/STAT3 inhibitors in the EtOAc extract of Lc. lactis KR-050L culture broth. Moreover, our data provide useful biochemical information regarding the commercialization of Lc. lactis isolated from Gajuknamu kimchi as an approach to use functional foods for the treatment of various diseases via IL-6/STAT3 activation. © 2017 The Society for Applied Microbiology.

  18. L2 vs. L3 Initial State: A Comparative Study of the Acquisition of French DPs by Vietnamese Monolinguals and Cantonese-English Bilinguals

    Science.gov (United States)

    Leung, Yan-Kit Ingrid

    2005-01-01

    This paper compares the initial state of second language acquisition (L2A) and third language acquisition (L3A) from the generative linguistics perspective. We examine the acquisition of the Determiner Phrase (DP) by two groups of beginning French learners: an L2 group (native speakers of Vietnamese who do not speak any English) and an L3 group…

  19. Flt3/Flt3L Participates in the Process of Regulating Dendritic Cells and Regulatory T Cells in DSS-Induced Colitis

    Directory of Open Access Journals (Sweden)

    Jing-Wei Mao

    2014-01-01

    Full Text Available The immunoregulation between dendritic cells (DCs and regulatory T cells (T-regs plays an important role in the pathogenesis of ulcerative colitis (UC. Recent research showed that Fms-like tyrosine kinase 3 (Flt3 and Flt3 ligand (Flt3L were involved in the process of DCs regulating T-regs. The DSS-induced colitis model is widely used because of its simplicity and many similarities with human UC. In this study, we observe the disease activity index (DAI and histological scoring, detect the amounts of DCs and T-regs and expression of Flt3/Flt3L, and investigate Flt3/Flt3L participating in the process of DCs regulating T-regs in DSS-induced colitis. Our findings suggest that the reduction of Flt3 and Flt3L expression may possibly induce colonic immunoregulatory imbalance between CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs in DSS-induced colitis. Flt3/Flt3L participates in the process of regulating DCS and T-regs in the pathogenesis of UC, at least, in the acute stage of this disease.

  20. Experiment data report for LOFT nonnuclear test L1-3

    International Nuclear Information System (INIS)

    Millar, G.M.

    1977-04-01

    Test L1-3 was the third in a series of five nonnuclear isothermal blowdown tests conducted by the Loss of Fluid Test (LOFT) Program. For this test the LOFT Facility was configured to simulate a loss-of-coolant accident in a large pressurized water reactor resulting from a 200 percent double-ended shear break in a cold leg of the primary coolant system. A hydraulic core simulator assembly was installed in place of the nuclear core. The initial conditions in the primary coolant system intact loop were: temperature at 540 0 F, pressure at 2256 psig, and loop flow at 2.34 x 10 6 lbm/hr. During system depressurization, emergency core cooling water was specified to be injected into the lower plenum of the reactor vessel using an accumulator, a low-pressure injection system pump, and a high-pressure injection system pump to provide data on the effects of emergency core cooling on the system thermal-hydraulic response. Injection into the lower plenum was initiated from the high- and low-pressure injection systems. Injection from the accumulator, however, was not initiated because a valve was inadvertently left closed. The experiment, therefore, was not completely successful in that one of the objectives outlined in the experiment operating specification for this test was not accomplished. Test L1-3 was repeated at Test L1-3A to meet the experimental requirements. Despite these difficulties, Test L1-3 did provide very valuable data to verify experiment repeatability

  1. Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chian-Jiun Liou

    2015-01-01

    Full Text Available Ginkgolide C, isolated from Ginkgo biloba leaves, is a flavone reported to have multiple biological functions, from decreased platelet aggregation to ameliorating Alzheimer disease. The study aim was to evaluate the antiadipogenic effect of ginkgolide C in 3T3-L1 adipocytes. Ginkgolide C was used to treat differentiated 3T3-L1 cells. Cell supernatant was collected to assay glycerol release, and cells were lysed to measure protein and gene expression related to adipogenesis and lipolysis by western blot and real-time PCR, respectively. Ginkgolide C significantly suppressed lipid accumulation in differentiated adipocytes. It also decreased adipogenesis-related transcription factor expression, including peroxisome proliferator-activated receptor and CCAAT/enhancer-binding protein. Furthermore, ginkgolide C enhanced adipose triglyceride lipase and hormone-sensitive lipase production for lipolysis and increased phosphorylation of AMP-activated protein kinase (AMPK, resulting in decreased activity of acetyl-CoA carboxylase for fatty acid synthesis. In coculture with an AMPK inhibitor (compound C, ginkgolide C also improved activation of sirtuin 1 and phosphorylation of AMPK in differentiated 3T3-L1 cells. The results suggest that ginkgolide C is an effective flavone for increasing lipolysis and inhibiting adipogenesis in adipocytes through the activated AMPK pathway.

  2. Mutation of Aspergillus oryzae for improved production of 3, 4-dihydroxy phenyl-L-alanine (L-DOPA from L-tyrosine Mutação de Aspergillus orizae para produção melhorada de 3,4-dihidroxi fenil-L-alanina (L-DOPA a partir de L-tirosina

    Directory of Open Access Journals (Sweden)

    Ikram-ul Haq

    2006-03-01

    Full Text Available Aspergillus oryzae mutant strain UV-7 was further improved for the production of L-DOPA from L-tyrosine using chemical mutation. Different putative mutant strains of organism were tested for the production of L-DOPA in submerged fermentation. Among these putative mutant strains, mutant designated SI-12 gave maximum production of L-DOPA (300 mg L-DOPA.g-1 cells. The production of L-DOPA from different carbon source solutions (So= 30 g.l-1 by mutant culture was investigated at different nitrogen sources, initial pH and temperature values. At optimum pH (pHo= 5.0, and temperature (t=30ºC, 100% sugars were utilized for production and cell mass formation, corresponding to final L-DOPA product yield of 150 mg.g-1 substrate utilized, and maximum volumetric and specific productivities of 125 mg.l-1.h-1, and 150 mg.g-1 cells. h-1, respectively. There was up to 3-fold enhancement in product formation rate. This enhancement is the highest reported in literature. To explain the kinetic mechanism of L-DOPA formation and thermal inactivation of tyrosinase, the thermodynamic parameters were determined with the application of Arrhenius model: activation enthalpy and entropy for product formation, in case of mutant derivative, were 40 k j/mol and 0.076 k j/mol. K for L-DOPA production and 116 k j/mol and 0.590 k j/mol. K for thermal inactivation, respectively. The respective values for product formation were lower while those for product deactivation were higher than the respective values for the parental culture. Therefore, the mutant strain was thermodynamically more resistant to thermal denaturation.A produção de L-DOPA a partir de tirosina pela cepa mutante de Aspergillus orizae UV-7 foi melhorada através de mutação química. Diferentes cepas foram testadas quanto a produção de L-DOPA por fermentação submersa, observando-se que a cepa denominada SI-12 foi a melhor produtora (300 mg de L-DOPA por g de células. A produção de L-DOPA pela cepa

  3. The L3+C detector, a unique tool-set to study cosmic rays

    International Nuclear Information System (INIS)

    Adriani, O.; Akker, M. van den; Banerjee, S.; Baehr, J.; Betev, B.; Bourilkov, D.; Bottai, S.; Bobbink, G.; Cartacci, A.; Chemarin, M.; Chen, G.; Chen, H.S.; Chiarusi, T.; Dai, C.J.; Ding, L.K.; Duran, I.; Faber, G.; Fay, J.; Grabosch, H.J.; Groenstege, H.; Guo, Y.N.; Gupta, S.; Haller, Ch.; Hayashi, Y.; He, Z.X.; Hebbeker, T.; Hofer, H.; Hoferjun, H.; Huo, A.X.; Ito, N.; Jing, C.L.; Jones, L.; Kantserov, V.; Kawakami, S.; Kittel, W.; Koenig, A.C.; Kok, E.; Korn, A.; Kuang, H.H.; Kuijpers, J.; Ladron de Guevara, P.; Le Coultre, P.; Lei, Y.; Leich, H.; Leiste, R.; Li, D.; Li, L.; Li, Z.C.; Liu, Z.A.; Liu, H.T.; Lohmann, W.; Lu, Y.S.; Ma, X.H.; Ma, Y.Q.; Mil, A. van; Monteleoni, B.; Nahnhauer, R.; Pauss, F.; Parriaud, J.-F.; Petersen, B.; Pohl, M.; Qing, C.R.; Ramelli, R.; Ravindran, K.C.; Rewiersma, P.; Rojkov, A.; Saidi, R.; Schmitt, V.; Schoeneich, B.; Schotanus, D.J.; Shen, C.Q.; Sulanke, H.; Tang, X.W.; Timmermans, C.; Tonwar, S.; Trowitzsch, G.; Unger, M.; Verkooijen, H.; Wang, X.L.; Wang, X.W.; Wang, Z.M.; Wijk, R. van; Wijnen, Th.A.M.; Wilkens, H.; Xu, Y.P.; Xu, Z.Z.; Yang, C.G.; Yang, X.F.; Yao, Z.G.; Yu, Z.Q.; Zhang, S.; Zhu, G.Y.; Zhu, Q.Q.; Zhuang, H.L.; Zwart, A.N.M.

    2002-01-01

    The L3 detector at the CERN electron-positron collider, LEP, has been employed for the study of cosmic ray muons. The muon spectrometer of L3 consists of a set of high-precision drift chambers installed inside a magnet with a volume of about 1000 m 3 and a field of 0.5 T. Muon momenta are measured with a resolution of a few percent at 50 GeV. The detector is located under 30 m of overburden. A scintillator air shower array of 54 m by 30 m is installed on the roof of the surface hall above L3 in order to estimate the energy and the core position of the shower associated with a sample of detected muons. Thanks to the unique properties of the L3+C detector, muon research topics relevant to various current problems in cosmic ray and particle astrophysics can be studied

  4. The L3+C detector, a unique tool-set to study cosmic rays

    CERN Document Server

    Adriani, O; Banerjee, S; Bähr, J; Betev, B L; Bourilkov, D; Bottai, S; Bobbink, Gerjan J; Cartacci, A M; Chemarin, M; Chen, G; Chen He Sheng; Chiarusi, T; Dai Chang Jiang; Ding, L K

    2002-01-01

    The L3 detector at the CERN electron-positron collider, LEP, has been employed for the study of cosmic ray muons. The muon spectrometer of L3 consists of a set of high-precision drift chambers installed inside a magnet with a volume of about 1000 m**3 and a field of 0.5 T. Muon momenta are measured with a resolution of a few percent at 50 GeV. The detector is located under 30 m of overburden. A scintillator air shower array of 54 m by 30 m is installed on the roof of the surface hall above L3 in order to estimate the energy and the core position of the shower associated with a sample of detected muons. Thanks to the unique properties of the L3+C detector, muon research topics relevant to various current problems in cosmic ray and particle astrophysics can be studied.

  5. Differential effect of L3T4+ cells on recovery from total-body irradiation

    International Nuclear Information System (INIS)

    Pantel, K.; Nakeff, A.

    1990-01-01

    We have examined the importance of L3T4+ (murine equivalent to CD4+) cells for hematopoietic regulation in vivo in unperturbed mice and mice recovering from total-body irradiation (TBI) using a cytotoxic monoclonal antibody (MoAb) raised with the GK 1.5 hybridoma. Ablating L3T4+ cells in normal (unperturbed) B6D2F1 mice substantially decreased the S-phase fraction (determined by in vivo hydroxyurea suicide) of erythroid progenitor cells (erythroid colony-forming units, CFU-E) as compared to the pretreatment level (10% +/- 14.1% [day 3 following depletion] vs 79.8% +/- 15.9%, respectively) with a corresponding decrease in the marrow content of CFU-E at this time to approximately 1% of the pretreatment value. Although the S-phase fraction of CFU-GM was decreased to 2.2% +/- 3.1% 3 days after L3T4+ cell ablation from the 21.3% +/- 8.3% pretreatment value, CFU-GM cellularity showed little change over the 3 days following anti-L3T4 treatment. Anti-L3T4 MoAb treatment had little or no effect on either the S-phase fraction or the marrow content of hematopoietic stem cells (spleen colony-forming units, CFU-S) committed to myeloerythroid differentiation. Ablating L3T4+ cells prior to a single dose of 2 Gy TBI resulted in significantly reduced marrow contents of CFU-S on day 3 and granulocyte-macrophage colony-forming units (CFU-GM) on day 6 following TBI, with little or no effect on the corresponding recovery of CFU-E. The present findings provide the first in vivo evidence that L3T4+ cells are involved in: (1) maintaining the proliferative activity of CFU-E and CFU-GM in unperturbed mice and (2) supporting the restoration of CFU-S and CFU-GM following TBI-induced myelosuppression

  6. Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

    International Nuclear Information System (INIS)

    An, Lei; Pang, Yun-Wei; Gao, Hong-Mei; Tao, Li; Miao, Kai; Wu, Zhong-Hong

    2012-01-01

    Highlights: ► Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. ► fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. ► fat-1 reduces lipid deposition in 3T3-L1 adipocytes. ► The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlled experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.

  7. Synthesis, structure, luminescent, and magnetic properties of carbonato-bridged Zn(II)2Ln(III)2 complexes [(μ4-CO3)2{Zn(II)L(n)Ln(III)(NO3)}2] (Ln(III) = Gd(III), Tb(III), Dy(III); L(1) = N,N'-bis(3-methoxy-2-oxybenzylidene)-1,3-propanediaminato, L(2) = N,N'-bis(3-ethoxy-2-oxybenzylidene)-1,3-propanediaminato).

    Science.gov (United States)

    Ehama, Kiyomi; Ohmichi, Yusuke; Sakamoto, Soichiro; Fujinami, Takeshi; Matsumoto, Naohide; Mochida, Naotaka; Ishida, Takayuki; Sunatsuki, Yukinari; Tsuchimoto, Masanobu; Re, Nazzareno

    2013-11-04

    Carbonato-bridged Zn(II)2Ln(III)2 complexes [(μ4-CO3)2{Zn(II)L(n)Ln(III)(NO3)}2]·solvent were synthesized through atmospheric CO2 fixation reaction of [Zn(II)L(n)(H2O)2]·xH2O, Ln(III)(NO3)3·6H2O, and triethylamine, where Ln(III) = Gd(III), Tb(III), Dy(III); L(1) = N,N'-bis(3-methoxy-2-oxybenzylidene)-1,3-propanediaminato, L(2) = N,N'-bis(3-ethoxy-2-oxybenzylidene)-1,3-propanediaminato. Each Zn(II)2Ln(III)2 structure possessing an inversion center can be described as two di-μ-phenoxo-bridged {Zn(II)L(n)Ln(III)(NO3)} binuclear units bridged by two carbonato CO3(2-) ions. The Zn(II) ion has square pyramidal coordination geometry with N2O2 donor atoms of L(n) and one oxygen atom of a bridging carbonato ion at the axial site. Ln(III) ion is coordinated by nine oxygen atoms consisting of four from the deprotonated Schiff-base L(n), two from a chelating nitrate, and three from two carbonate groups. The temperature-dependent magnetic susceptibilities in the range 1.9-300 K, field-dependent magnetization from 0 to 5 T at 1.9 K, and alternating current magnetic susceptibilities under the direct current bias fields of 0 and 1000 Oe were measured. The magnetic properties of the Zn(II)2Ln(III)2 complexes are analyzed on the basis of the dicarbonato-bridged binuclear Ln(III)-Ln(III) structure, as the Zn(II) ion with d(10) electronic configuration is diamagnetic. ZnGd1 (L(1)) and ZnGd2 (L(2)) show a ferromagnetic Gd(III)-Gd(III) interaction with J(Gd-Gd) = +0.042 and +0.028 cm(-1), respectively, on the basis of the Hamiltonian H = -2J(Gd-Gd)ŜGd1·ŜGd2. The magnetic data of the Zn(II)2Ln(III)2 complexes (Ln(III) = Tb(III), Dy(III)) were analyzed by a spin Hamiltonian including the crystal field effect on the Ln(III) ions and the Ln(III)-Ln(III) magnetic interaction. The Stark splitting of the ground state was so evaluated, and the energy pattern indicates a strong easy axis (Ising type) anisotropy. Luminescence spectra of Zn(II)2Tb(III)2 complexes were observed, while those

  8. Effects of Methylmercury exposure in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Theresa Vertigan

    2017-02-01

    Full Text Available Mercury-containing compounds are environmental pollutants that have become increasingly consequential in the Arctic regions of North America due to processes of climate change increasing their release and availability at northern latitudes. Currently, the form of mercury known to be most detrimental to human health is methylmercury, CH3Hg+, which is found in the environment and accumulates in the tissues of piscivores, including those consumed by Alaska Natives through subsistence gathering. Much is known about the neurotoxicity of methylmercury after exposure to high concentrations, but little is known about toxicity to other tissues and cell types, particularly for long-term exposure and the lower concentrations that would occur through fish consumption. Effects of methylmercury exposure on 3T3-L1 adipocytes in culture were assessed using assays for cytotoxicity and an ELISA assay for vascular endothelial growth factor (VEGF, a signaling molecule shown to be important for maintaining metabolic status in adipose tissue. Results showed that exposure to methylmercury leads to significant toxicity in adipocytes at exposures of 100 ng/mL during later stages of differentiation, but lower methylmercury concentrations produced little to no toxicity. Results also showed that VEGF secretion is elevated in adipocytes exposed to methylmercury after the process of differentiating into mature, fat-storing cells. These results provide a basis for further exploration into metabolic consequences of methylmercury exposure on specific cell types and cell models.

  9. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Yokokawa, Takumi; Endo, Yuriko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Iwanaka, Nobumasa [Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Higashida, Kazuhiko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 (Japan); Taguchi, Sadayoshi [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  10. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-01-01

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O 2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  11. The muon filter of the L3 detector

    International Nuclear Information System (INIS)

    Adriani, O.; Bocciolini, M.; Cartacci, A.M.; Civinini, C.; D'Alessandro, R.; Gallo, E.; Landi, G.; Marchionni, A.; Meschini, M.; Monteleoni, B.; Pieri, M.; Spillantini, P.; Wang, Y.F.; Florence Univ.

    1991-01-01

    In this article we describe the outer part (Muon Filter) of the Hadron Calorimeter of the L3 detector. Construction and performance of the brass chambers, which form the sensitive part of the detector, are reviewed. We also report the results from data taken on two beam tests, at CERN. (orig.)

  12. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    International Nuclear Information System (INIS)

    Kang, Seong-Il; Ko, Hee-Chul; Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk; Lee, Nam-Ho; Kim, Se-Jae

    2011-01-01

    Highlights: → Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. → Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. → Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. → Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPARγ, C/EBPα, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

  13. Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    An, Lei, E-mail: anleim@yahoo.com.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Pang, Yun-Wei, E-mail: yunweipang@126.com [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Gao, Hong-Mei, E-mail: Gaohongmei_123@yahoo.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki-Iwama 319-0206 (Japan); Tao, Li, E-mail: Eunice8023@yahoo.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin 130118 (China); Miao, Kai, E-mail: miaokai7@163.com [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); Wu, Zhong-Hong, E-mail: wuzhh@cau.edu.cn [Ministry of Agriculture Key Laboratory of Animal Genetics, Breeding and Reproduction, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193 (China); and others

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlled experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.

  14. Increasing doses effect of L-T4 and L-T3 in the hypothalamus - hypophysis - thyroid in patients carrier of congenital and acquired hypothyroidism

    International Nuclear Information System (INIS)

    Cavaliere, H.

    1987-01-01

    The pituitary and peripheral response to L-T4 and L-T3 therapy were studied in 12 patients with congenital goitrous hypothyroidism, in 10 patients with an ectopic thyroid and onset of hypothyroidism at 3-8 years of age, and in 6 patients with adult-onset hypothyroidism, after they had had their chronic thyroid hormone replacement therapy discontinued for 30 days. They were first treated with increasing L-T4 (0.1, 0.2, and 0.4 mg daily) followed by L-T3 (0.05 and 0.2 mg daily) after stopping thyroid medication for another month. Ten normal subjects were treated identically. Since all patients received similar doses of thyroid hormones (μg/Kg of body weight) and had similar serum levels of T4 and T3 on each dose of L-T4 or L-T3, this paper concludes that congenitally hypothyroid patients have persistent pituitary resistance, but no peripheral resistance, to thyroid hormone. (author)

  15. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Wang, Zai [Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Li, Jian; Cai, Jian-Ping [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [School of Biomedical Sciences and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Pokfulam (Hong Kong); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China); Zhang, Tie-Mei, E-mail: tmzhang126@126.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China)

    2016-08-05

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

  16. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Cui, Ju; Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan; Wang, Zai; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

    2016-01-01

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

  17. TC10 is regulated by caveolin in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Dave Bridges

    Full Text Available TC10 is a small GTPase found in lipid raft microdomains of adipocytes. The protein undergoes activation in response to insulin, and plays a key role in the regulation of glucose uptake by the hormone.TC10 requires high concentrations of magnesium in order to stabilize guanine nucleotide binding. Kinetic analysis of this process revealed that magnesium acutely decreased the nucleotide release and exchange rates of TC10, suggesting that the G protein may behave as a rapidly exchanging, and therefore active protein in vivo. However, in adipocytes, the activity of TC10 is not constitutive, indicating that mechanisms must exist to maintain the G protein in a low activity state in untreated cells. Thus, we searched for proteins that might bind to and stabilize TC10 in the inactive state. We found that Caveolin interacts with TC10 only when GDP-bound and stabilizes GDP binding. Moreover, knockdown of Caveolin 1 in 3T3-L1 adipocytes increased the basal activity state of TC10.Together these data suggest that TC10 is intrinsically active in vivo, but is maintained in the inactive state by binding to Caveolin 1 in 3T3-L1 adipocytes under basal conditions, permitting its activation by insulin.

  18. Characteristics of D(-3)He fueled FRC reactor: ARTEMIS-L

    Science.gov (United States)

    Momota, H.; Motojima, O.; Okamoto, M.; Sudo, S.; Tomita, Y.; Yamaguchi, S.; Iiyoshi, A.; Onozuka, M.; Ohnishi, M.; Uenosono, C.

    1993-11-01

    The characteristics of D(-3)He fueled commercial fusion reactor ARTEMIS-L are discussed. By using favorable characteristics of a field-reversed configuration, the fusion plasma of ARTEMIS-L becomes compact and its veta-value is extremely high. Consequently, it is possible to construct an economical fusion power plant based on this concept. The life of the structural materials is found during the full reactor life (30 years) and the safety of the reactor is intrinsic to D(-3)He fuels. The amount of disposed materials is rather small and the level of the intruder dose is so low that the plant appears to be acceptable in regards to the environment.

  19. Best estimate prediction for LOFT nuclear experiment L3-2

    International Nuclear Information System (INIS)

    Kee, E.J.; Shinko, M.S.; Grush, W.H.; Condie, K.G.

    1980-02-01

    Comprehensive analyses using both the RELAP4 and the RELAP5 computer codes were performed to predict the LOFT transient thermal-hydraulic response for nuclear Loss-of-Coolant Experiment L3-2 to be performed in the Loss-of-Fluid Test (LOFT) facility. The LOFT experiment will simulate a small break in one of the cold legs of a large four-loop pressurized water reactor and will be conducted with the LOFT reactor operating at 50 MW. The break in LOCE L3-2 is sized to cause the break flow to be approximately equal to the high-pressure injection system flow at an intermediate pressure of approximately 7.6 MPa

  20. Search on charginos and neutralinos with the L3 detector at LEP; Recherche de charginos et de neutralinos avec le detecteur L3 au LEP

    Energy Technology Data Exchange (ETDEWEB)

    Chereau, Xavier [Laboratoire d`Annecy-le-vieux de physique des particules, Grenoble-1 Univ., 74 Annecy (France)

    1998-04-30

    This work presents an experimental search for supersymmetric particles, the charginos and the neutralinos, at center of mass energies {radical} 161, 172 and 183 GeV, with the L3 detector at the e{sup +}e{sup -} collider LEP. Assuming R-parity conservation, SUSY events have a large missing energy, carried by the lightest supersymmetric particle (LSP), which allow us to distinguish them from standard events. Then, for all the studied final states and all the energies, we optimized the selections in order to have the best signal-to-noise ratio. No excess of events were observed with respect to the standard model predictions. We set upper limits on the chargino and neutralino production cross sections. In the frame of the constraint MSSM, these results were combined with the results from the L3 slepton analyses to set lower limits on the chargino and neutralino masses: particularly, we exclude a neutralino {chi}{sub 1}{sup 0} bar lighter than 25.9 GeV/c{sup 2} (95% C.L.). This result plays an important role for the interpretation of the dark matter in universe. The search for events with missing energy needs a detector with a good hermeticity. At the end of 1995, a new electromagnetic calorimeter was installed in the L3 experiment. Here we present the improvements of performances and the calibration of this detector composed of 48 bricks made with lead and scintillating fibers (SPACAL) 71 refs., 104 figs., 21 tabs.

  1. Dismantling the silicon microstrip detector on L3

    CERN Multimedia

    Laurent Guiraud

    2001-01-01

    The silicon microstrip detector is located at the heart of the detector and must be kept cool to prevent thermal noise. The work shown here is the removal of the cooling system. L3 was dismantled as part of the closure of the entire LEP accelerator in 2000 to make way for the new LHC.

  2. Identification and characterization of trans-3-hydroxy-l-proline dehydratase and Δ1-pyrroline-2-carboxylate reductase involved in trans-3-hydroxy-l-proline metabolism of bacteria

    Directory of Open Access Journals (Sweden)

    Seiya Watanabe

    2014-01-01

    Full Text Available trans-4-Hydroxy-l-proline (T4LHyp and trans-3-hydroxy-l-proline (T3LHyp occur mainly in collagen. A few bacteria can convert T4LHyp to α-ketoglutarate, and we previously revealed a hypothetical pathway consisting of four enzymes at the molecular level (J Biol Chem (2007 282, 6685–6695; J Biol Chem (2012 287, 32674–32688. Here, we first found that Azospirillum brasilense has the ability to grow not only on T4LHyp but also T3LHyp as a sole carbon source. In A. brasilense cells, T3LHyp dehydratase and NAD(PH-dependent Δ1-pyrroline-2-carboxylate (Pyr2C reductase activities were induced by T3LHyp (and d-proline and d-lysine but not T4LHyp, and no effect of T3LHyp was observed on the expression of T4LHyp metabolizing enzymes: a hypothetical pathway of T3LHyp → Pyr2C → l-proline was proposed. Bacterial T3LHyp dehydratase, encoded to LhpH gene, was homologous with the mammalian enzyme. On the other hand, Pyr2C reductase encoded to LhpI gene was a novel member of ornithine cyclodeaminase/μ-crystallin superfamily, differing from known bacterial protein. Furthermore, the LhpI enzymes of A. brasilense and another bacterium showed several different properties, including substrate and coenzyme specificities. T3LHyp was converted to proline by the purified LhpH and LhpI proteins. Furthermore, disruption of LhpI gene from A. brasilense led to loss of growth on T3LHyp, d-proline and d-lysine, indicating that this gene has dual metabolic functions as a reductase for Pyr2C and Δ1-piperidine-2-carboxylate in these pathways, and that the T3LHyp pathway is not linked to T4LHyp and l-proline metabolism.

  3. The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

    2013-09-01

    The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Cusps in K{sub L}{yields}3{pi} decays

    Energy Technology Data Exchange (ETDEWEB)

    Bissegger, M. [Institute for Theoretical Physics, University of Bern, Sidlerstr. 5, CH-3012 Bern (Switzerland); Fuhrer, A. [Institute for Theoretical Physics, University of Bern, Sidlerstr. 5, CH-3012 Bern (Switzerland)], E-mail: afuhrer@itp.unibe.ch; Gasser, J. [Institute for Theoretical Physics, University of Bern, Sidlerstr. 5, CH-3012 Bern (Switzerland); Kubis, B.; Rusetsky, A. [Helmholtz-Institut fuer Strahlen- und Kernphysik, Universitaet Bonn, Nussallee 14-16, D-53115 Bonn (Germany)

    2008-01-24

    The pion mass difference generates a pronounced cusp in K{yields}3{pi} decays, the strength of which is related to the {pi}{pi} S-wave scattering lengths. We apply an effective field theory framework developed earlier to evaluate the amplitudes for K{sub L}{yields}3{pi} decays in a systematic manner, where the strictures imposed by analyticity and unitarity are respected automatically. The amplitudes for the decay {eta}{yields}3{pi} are also given.

  5. Modulation of adipogenesis and glucose uptake by Curcuma longa extract in 3T3L1 and L6 cell lines - An in vitro study

    Directory of Open Access Journals (Sweden)

    A. Prathapan

    2012-05-01

    Full Text Available Objective: To evaluate the effects of ethyl acetate extract of Curcuma longa against modulation of glucose uptake and adipogenesis in cell line models. Methods: We used 3T3L1 and L6 cells to investigate cytotoxicity, glucose uptake with 2-NBDG as probe and adipogenesis. All the analysis was done with flowcytometry. Results: The results showed that the extract did not possess any significant glucose uptake activity but it exhibited significant adipocyte differentiation potential. Conclusions: Ethyl acetate extract of Curcuma longa exhibits significant antiadipogenesis and can be used as an effective drug for the treatment of obesity and other associated complications.

  6. Genetic variants in CHI3L1 influencing YKL-40 levels

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Johansen, Julia S; Nordestgaard, Børge G

    2013-01-01

    Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.......Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population....

  7. Mango (Mangifera indica L.) peel extract fractions from different cultivars differentially affect lipid accumulation in 3T3-L1 adipocyte cells.

    Science.gov (United States)

    Taing, Meng-Wong; Pierson, Jean-Thomas; Shaw, Paul N; Dietzgen, Ralf G; Roberts-Thomson, Sarah J; Gidley, Michael J; Monteith, Gregory R

    2013-02-26

    Plant phytochemicals are increasingly recognised as sources of bioactive molecules which may have potential benefit in many health conditions. In mangoes, peel extracts from different cultivars exhibit varying effects on adipogenesis in the 3T3-L1 adipocyte cell line. In this study, the effects of preparative HPLC fractions of methanol peel extracts from Irwin, Nam Doc Mai and Kensington Pride mangoes were evaluated. Fraction 1 contained the most hydrophilic components while subsequent fractions contained increasingly more hydrophobic components. High content imaging was used to assess mango peel fraction effects on lipid accumulation, nuclei count and nuclear area in differentiating 3T3-L1 cells. For all three mango cultivars, the more hydrophilic peel fractions 1-3 inhibited lipid accumulation with greater potency than the more hydrophobic peel fractions 4. For all three cultivars, the more lipophilic fraction 4 had concentrations that enhanced lipid accumulation greater than fractions 1-3 as assessed by lipid droplet integrated intensity. The potency of this fraction 4 varied significantly between cultivars. Using mass spectrometry, five long chain free fatty acids were detected in fraction 4; these were not present in any other peel extract fractions. Total levels varied between cultivars, with Irwin fraction 4 containing the highest levels of these free fatty acids. Lipophilic components appear to be responsible for the lipid accumulation promoting effects of some mango extracts and are the likely cause of the diverse effects of peel extracts from different mango cultivars on lipid accumulation.

  8. Measurement of the masses of the electroweak gauge bosons at L3; Bestimmung der Massen der elektroschwachen Eichbosonen bei L3

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbleck, C.

    2006-10-09

    This thesis presents the measurement of the masses of the carriers of the weak force in the Standard Model of Particle Physics, the gauge bosons W and Z. The masses are determined using the kinematics of the bosons' decay products. The data were collected by the L3 experiment at the Large Electron Positron Collider (LEP) at centre-of-mass energies, {radical}(s), between 183 GeV and 209 GeV in the years 1997 to 2000. The Z-boson mass is determined to be m{sub Z}=91.272{+-}0.046 GeV. The second part of this analysis describes the measurement of the mass of the W-boson. The W-boson mass is determined to be m{sub W}=80.242{+-}0.057 GeV in this analysis. If combined with the L3 results at lower centre-of-mass energies, the final W boson mass value is m{sub W}=80.270{+-}0.055 GeV. The {rho} parameter is defined as {rho}=m{sup 2}{sub W}/(m{sup 2}{sub Z} . cos{sup 2} {theta}{sub W}). Using the value of m{sub Z} obtained in the Z resonance scan, the final value for m{sub W} and the value of {theta}{sub W}, {rho} is obtained to be {rho}=0.9937{+-}0.0024, yielding a 2.6{sigma} deviation from 1. Combining the L3 value for m{sub W} with the results of the LEP experiments ALEPH, DELPHI, and OPAL and the TEVATRON experiments CDF and DOe yields a W boson mass of m{sub W}=80.392{+-}0.029 GeV. Together with other measurements this determines the best value of the Higgs-boson mass to be m{sub H}=85{sub -28}{sup +39} GeV. (orig.)

  9. Synthesis and the crystal and molecular structures of (H3L . Cl)[CoCl4] and H2L[CuBr4] (L is 2,4,6-Tri(N,N-dimethylamino)methylphenol)

    International Nuclear Information System (INIS)

    Kovalchukova, O. V.; Stash, A. I.; Strashnova, S. B.; Romashkina, E. P.; Zaitsev, B. E.

    2010-01-01

    The complex compounds (H 3 L . Cl)[CoCl 4 ] (I) and H 2 L[CuBr 4 ] (II), where L is 2,4,6-tri(N,N-dimethylamino)methylphenol, were isolated in the crystalline state and studied by X-ray diffraction. The organic cations were found to be outer-sphere ligands. All three nitrogen atoms of the tertiary amino groups are protonated. In compound I, the H 3 L 3+ cation exists as the cis tautomer. In compound II, the H 2 L 2+ dication exists as the trans isomer. In the crystal structure, the dications are arranged in layers via hydrogen bonds.

  10. Polyphenol Stilbenes from Fenugreek (Trigonella foenum-graecum L. Seeds Improve Insulin Sensitivity and Mitochondrial Function in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Gang Li

    2018-01-01

    Full Text Available Fenugreek (Trigonella foenum-graecum L. is a well-known annual plant that is widely distributed worldwide and has possessed obvious hypoglycemic and hypercholesterolemia characteristics. In our previous study, three polyphenol stilbenes were separated from fenugreek seeds. Here, we investigated the effect of polyphenol stilbenes on adipogenesis and insulin resistance in 3T3-L1 adipocytes. Oil Red O staining and triglyceride assays showed that polyphenol stilbenes differently reduced lipid accumulation by suppressing the expression of adipocyte-specific proteins. In addition, polyphenol stilbenes improved the uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-ylamino-2-deoxyglucose (2-NBDG by promoting the phosphorylation of protein kinase B (AKT and AMP-activated protein kinase (AMPK. In present studies, it was found that polyphenol stilbenes had the ability to scavenge reactive oxygen species (ROS. Results from adenosine triphosphate (ATP production and mitochondrial membrane potentials suggested that mitochondria play a critical role in insulin resistance and related signaling activation, such as AKT and AMPK. Rhaponticin, one of the stilbenes from fenugreek, had the strongest activity among the three compounds in vitro. Future studies will focus on mitochondrial biogenesis and function.

  11. Search for Higgs bosons using the L3 detector at LEP

    International Nuclear Information System (INIS)

    Kopp, A.

    2000-02-01

    This thesis is devoted to the search for Higgs bosons predicted by various theoretical models. By the introduction of these particles into the theory, the masses of bosons and fermions can be explained. The search is performed in experimentally related channels, which are characterised by charged leptons in the final state. The analysis uses data taken during the years 1996-1998 with the L3 detector at the large electron positron collider LEP. The observed candidates are consistent with the expectation from standard model background processes. Evidence for Higgs boson production could not be found. New mass limits were determined superseding previous mass limits established by L3 and other experiments. In the search for the Higgs boson of the standard model the channels hZ → b anti bl + l - (l = e,μ,τ) and hZ → τ + τ - q anti q were analysed at centre-of-mass energies between 183 and 189 GeV. A lower mass limit of m h > 87.5 GeV is derived at the 95% confidence level. (orig.)

  12. Measurement of L3 subshell absorption jump ratios and jump factors for high Z elements using EDXRF technique

    International Nuclear Information System (INIS)

    Kaçal, M.R.

    2014-01-01

    Energy dispersive X-ray fluorescence technique (EDXRF) has been employed for measuring L 3 -subshell absorption jump ratios, r L 3 and jump factors, J L 3 for high Z elements. Jump factors and jump ratios for these elements have been determined by measuring L 3 subshell fluorescence parameters such as L 3 subshell X-ray production cross section σ L 3 , L 3 subshell fluorescence yield, ω L 3 , total L 3 subshell and higher subshells photoionization cross section σ L T . Measurements were performed using a Cd-109 radioactive point source and an Si(Li) detector in direct excitation experimental geometry. Measured values for jump factors and jump ratios have been compared with theoretically calculated and other experimental values. - Highlights: • This paper regards L 3 subshell absorption jump ratios and jump factors using the EDXRF method. • These parameters were measured using a new method. • This method is more useful than other methods which require much effort. • Results are in good agreement with theoretical and experimental values

  13. Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation

    International Nuclear Information System (INIS)

    Chen, Ching-Chu; Chuang, Wei-Ting; Lin, Ai-Hsuan; Tsai, Chia-Wen; Huang, Chin-Shiu; Chen, Yun-Ting; Chen, Haw-Wen; Lii, Chong-Kuei

    2016-01-01

    Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0–15 μM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPβ mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48 h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPβ expression. In addition, ERK and GSK3β-dependent C/EBPβ phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression. - Highlights: • Andrographolide is a diterpenoid phytochemical.

  14. Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ching-Chu [Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan (China); Division of Endocrinology and Metabolism, Department of Chinese Medicine, China Medical University, China Medical University, Taichung, Taiwan (China); Chuang, Wei-Ting; Lin, Ai-Hsuan; Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Chen, Yun-Ting [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Chen, Haw-Wen, E-mail: chenhw@mail.cmu.edu.tw [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei, E-mail: cklii@mail.cmu.edu.tw [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

    2016-09-15

    Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0–15 μM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPβ mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48 h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPβ expression. In addition, ERK and GSK3β-dependent C/EBPβ phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression. - Highlights: • Andrographolide is a diterpenoid phytochemical.

  15. Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yu-Kyoung [Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of); Lee, Tae-Yoon [Department of Microbiology, College of Medicine, Yeungnam University, 170 Hyunchung-Ro, Nam-gu, Daegu 705-717 (Korea, Republic of); Choi, Jong-Soon [Division of Life Science, Korea Basic Science Institute, 169-148 Gwahakro, Yuseong-gu, Daejeon 305-333 (Korea, Republic of); Hong, Victor Sukbong [Department of Chemistry, College of Natural Sciences, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of); Lee, Jinho, E-mail: jinho@gw.kmu.ac.kr [Department of Chemistry, College of Natural Sciences, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of); Park, Jong-Wook, E-mail: j303nih@dsmc.or.kr [Department of Immunology, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of); Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr [Department of Molecular Medicine, College of Medicine, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 704-701 (Korea, Republic of)

    2014-10-03

    Highlights: • Compound 7b, a meridianin C derivative, inhibits adipogenesis. • Compound 7b inhibits C/EBP-α, PPAR-γ, FAS, STAT-3, and STAT-5 in 3T3-L1 adipocytes. • Compound 7b inhibits leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Compound 7b thus may have therapeutic potential against obesity. - Abstract: Meridianin C, a marine alkaloid, is a potent protein kinase inhibitor and has anti-cancer activity. We have recently developed a series of meridianin C derivatives (compound 7a–7j) and reported their proviral integration Moloney Murine Leukemia Virus (pim) kinases’ inhibitory and anti-proliferative effects on human leukemia cells. Here we investigated the effect of these meridianin C derivatives on adipogenesis. Strikingly, among the derivatives tested, compound 7b most strongly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. However, meridianin C treatment was largely cytotoxic to 3T3-L1 adipocytes. On mechanistic levels, compound 7b reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during adipocyte differentiation. Moreover, compound 7b repressed leptin, but not adiponectin, expression during adipocyte differentiation. Collectively, these findings demonstrate that a meridianin C derivative inhibits adipogenesis by down-regulating expressions and/or phosphorylations of C/EBP-α, PPAR-γ, FAS, STAT-3 and STAT-5.

  16. Characterization of dissimilar welding: carbon steel E309L-E308L-ERNiCr3-ENiCrFe3 alloy 600; Caracterizacion de la soldadura disimilar: acero al carbono E309L-E308L-ERNiCr3-ENiCrFe3 aleacion 600

    Energy Technology Data Exchange (ETDEWEB)

    Mucino G, O.

    2015-07-01

    Most BWR type reactors have internal support components, which need to be attached to the inner surface by welding. Specifically, in these joints two materials interact, such as stainless steel and nickel base alloys. Nickel base alloys such as alloy 82 (ERNiCr3) and alloy 182 (ENiCrFe-3) are used for the joining of both dissimilar materials. For joints made with both nickel base alloys, the alloy 182 is prone to stress corrosion cracking (SCC); so it is essential to carry out studies related to this contribution material. In the nuclear industry any study related to this alloy is of importance because experience is gained in its behavior when is part of a system of an operation reactor. This work presents the characterization of the weld deposit of a stainless steel coating (with electrodes E309L and E308L) on a carbon steel plate type A36 and the joining with an Inconel 600 plate, simulating the joining of the internal coating of vessel and the heel of the support leg of the envelope of a BWR reactor. In this work, the mechanical and micro-structural characterization of the alloy deposit 182 was performed. (Author)

  17. N-[(2S-4-Chloro-2-(l-menthyloxy-5-oxo-2,5-dihydro-3-furyl]-l-alanine

    Directory of Open Access Journals (Sweden)

    Kai Yang

    2009-05-01

    Full Text Available The title compound, C17H26ClNO5, was prepared via a tandem asymmetric Michael addition–elimination reaction of (5S-3,4-dichloro-5-(l-menthyloxyfuran-2(5H-one and l-alanine in the presence of potassium hydroxide. The five-membered furanone ring is approximately planar while the six-membered menthyloxy ring adopts a chair conformation. The crystal packing is stabilized by intermolecular O—H...O and N—H...O hydrogen bonds.

  18. Triiodothyronine increases mRNA and protein leptin levels in short time in 3T3-L1 adipocytes by PI3K pathway activation.

    Directory of Open Access Journals (Sweden)

    Miriane de Oliveira

    Full Text Available The present study aimed to examine the effects of thyroid hormone (TH, more precisely triiodothyronine (T3, on the modulation of leptin mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K signaling pathway in adipocytes, 3T3-L1, cell culture. We examined the involvement of this pathway in mediating TH effects by treating 3T3-L1 adipocytes with physiological (P=10nM or supraphysiological (SI=100 nM T3 dose during one hour (short time, in the absence or the presence of PI3K inhibitor (LY294002. The absence of any treatment was considered the control group (C. RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey's test was used at 5% significance. T3 increased leptin mRNA expression in P (2.26 ± 0.36, p 0.001. These results demonstrate that the activation of the PI3K signaling pathway has a role in TH-mediated direct and indirect leptin gene expression in 3T3-L1 adipocytes.

  19. Is a volume of 3.6 mL better than 1.8 mL for inferior alveolar nerve blocks in patients with symptomatic irreversible pulpitis?

    Science.gov (United States)

    Fowler, Sara; Reader, Al

    2013-08-01

    The purpose of this retrospective study was to determine the success of the inferior alveolar nerve (IAN) block using either 3.6 mL or 1.8 mL 2% lidocaine with 1:100,000 epinephrine in patients presenting with symptomatic irreversible pulpitis. As part of 7 previously published studies, 319 emergency patients presenting with symptomatic irreversible pulpitis received either a 1.8-mL volume or 3.6-mL volume of 2% lidocaine with 1:100,000 epinephrine in an IAN block. One hundred ninety patients received a 1.8-mL volume, and 129 received a 3.6-mL volume. Endodontic emergency treatment was completed on each subject. Success was defined as the ability to access and instrument the tooth without pain (visual analog scale score of 0) or mild pain (VAS rating ≤54 mm). Success of the 1.8-mL volume was 28%, and for the 3.6-mL volume it was 39%. There was no statistically significant difference between the 2 volumes. In conclusion, for patients presenting with irreversible pulpitis, success was not significantly different between a 3.6-mL volume and a 1.8-mL volume of 2% lidocaine with 1:100,000 epinephrine. The success rates (28%-39%) with either volume were not high enough to ensure complete pulpal anesthesia. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. The Bilingual Advantage in L3 Learning: A Developmental Study of Rhotic Sounds

    Science.gov (United States)

    Kopecková, Romana

    2016-01-01

    Facilitative effects of bilingualism on general aspects of third language (L3) proficiency have been demonstrated in numerous studies conducted in bilingual communities and classrooms around the world. When it comes to L3 phonology, however, empirical evidence has been scarce and inconclusive in respect to the question of whether and/or how…

  1. Search for scalar leptons at LEP with the L3 detector

    CERN Document Server

    Xia, Lei

    2002-01-01

    In this thesis, I present a search for scalar leptons in e+e- annihilation using the L3 detector at LEP. Data collected in 1999 and 2000, at center-of-mass energies between 192 GeV and 208 GeV, was used in this analysis. This work covered the scalar lepton searches in both SUGRA and GMSB models. To achieve this analysis, a parametrized selection was developed to handle the different event signatures in SUGRA models. Improvement of the L3 simulation and reconstruction program packages was carried out so that one can simulated the scalar leptons in GMSB models correctly. The simulation of the L3 Time Expansion Chamber (TEC) dE/dx measurement was rewritten to facilitate the analysis for a stable slepton signal, which is relevant in some parts of the parameter space in GMSB models. In this analysis, we didn't abserve any significant indication of scalar lepton production of any type. We achieved the following mass exclusion limits for scalar leptons in SUGRA models, for large dM: M(scalar e) > 97 GeV (expected 97...

  2. Correction to: Comparing the UK EQ-5D-3L and English EQ-5D-5L Value Sets

    NARCIS (Netherlands)

    B. Mulhern (Brendan); Feng, Y. (Yan); K.K. Shah (Koonal); M.F. Janssen (Bas); M. Herdman (Michael); van Hout, B. (Ben); N. Devlin (Nancy)

    2018-01-01

    textabstractThe article Comparing the UK EQ-5D-3L and English EQ-5D-5L Value Sets, written by Brendan Mulhern, Yan Feng, Koonal Shah, Mathieu F. Janssen, Michael Herdman, Ben van Hout, Nancy Devlin was originally published electronically on the publisher’s internet portal (currently SpringerLink) on

  3. The first 3':5'-cyclic nucleotide-amino acid complex: L-His-cIMP.

    Science.gov (United States)

    Slepokura, Katarzyna

    2012-08-01

    In the crystal structure of the L-His-cIMP complex, i.e. L-histidinium inosine 3':5'-cyclic phosphate [systematic name: 5-(2-amino-2-carboxyethyl)-1H-imidazol-3-ium 7-hydroxy-2-oxo-6-(6-oxo-6,9-dihydro-1H-purin-9-yl)-4a,6,7,7a-tetrahydro-4H-1,3,5,2λ(5)-furo[3,2-d][1,3,2λ(5)]dioxaphosphinin-2-olate], C(6)H(10)N(3)O(2)(+)·C(10)H(10)N(4)O(7)P(-), the Hoogsteen edge of the hypoxanthine (Hyp) base of cIMP and the Hyp face are engaged in specific amino acid-nucleotide (His···cIMP) recognition, i.e. by abutting edge-to-edge and by π-π stacking, respectively. The Watson-Crick edge of Hyp and the cIMP phosphate group play a role in nonspecific His···cIMP contacts. The interactions between the cIMP anions (anti/C3'-endo/trans-gauche/chair conformers) are realized mainly between riboses and phosphate groups. The results for this L-His-cIMP complex, compared with those for the previously reported solvated L-His-IMP crystal structure, indicate a different nature of amino acid-nucleotide recognition and interactions upon the 3':5'-cyclization of the nucleotide phosphate group.

  4. L3 physics at the Z resonance and a search for the Higgs particle

    International Nuclear Information System (INIS)

    Coan, T.A.; Kinnison, W.W.; Kapustinsky, J.; Shukla, J.

    1997-01-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory. Electroweak interactions were studied using the L3 Detector on the Large Electron-Positron Collider (LEP) at the European Center for Nuclear Study (CERN). The specific physics studied utilized the Silicon Microvertex Detector (SMD) of L3, which Los Alamos had previously played a major role in proposing, designing, constructing, and commissioning. This detector enabled L3 to investigate short-lived mesons containing b-quarks

  5. Pyrazole complexes of rhenium. Synthesis and crystal structure of trans-[Re(O)(OMe)L4]Br2 · L · 4H2O (L - 3,5-dimethylpyrazole)

    International Nuclear Information System (INIS)

    Sokolov, M.N.; Fedorova, N.Eh.; Fedorov, V.E.; Virovets, A.V.; Nun'es, P.

    2002-01-01

    The first rhenium (V) mononuclear complex featuring composition [Re(O)(OMe)L 4 ]Br 2 (L = 3,5-dimethylpyrazole), which is resistant to hydrolysis in neutral aqueous solution, along with its molecular adduct of the composition [Re(O)(OMe)L 4 ]Br 2 · L · 4H 2 O were synthesized. The reaction products were characterized by the methods of elementary analysis, absorption spectroscopy in visible, UV and IR ranges, mass spectrometry. Besides, the adduct structure was studied by the method of X-ray diffraction analysis. It was ascertained that the adduct is crystallized in tetragonal crystal system with unit cell parameters as follows: a = 14.912 (3), c = 17.108 (4) A, sp. gr. I4/m, Z = 4. In the complex molecule linear grouping Re(O)(OMe)] 2+ (Re-O-C angle being equal to 180 deg) is coordinated by four L ligand molecules [ru

  6. Genetic Interactions Between the Meiosis-Specific Cohesin Components, STAG3, REC8, and RAD21L.

    Science.gov (United States)

    Ward, Ayobami; Hopkins, Jessica; Mckay, Matthew; Murray, Steve; Jordan, Philip W

    2016-06-01

    Cohesin is an essential structural component of chromosomes that ensures accurate chromosome segregation during mitosis and meiosis. Previous studies have shown that there are cohesin complexes specific to meiosis, required to mediate homologous chromosome pairing, synapsis, recombination, and segregation. Meiosis-specific cohesin complexes consist of two structural maintenance of chromosomes proteins (SMC1α/SMC1β and SMC3), an α-kleisin protein (RAD21, RAD21L, or REC8), and a stromal antigen protein (STAG1, 2, or 3). STAG3 is exclusively expressed during meiosis, and is the predominant STAG protein component of cohesin complexes in primary spermatocytes from mouse, interacting directly with each α-kleisin subunit. REC8 and RAD21L are also meiosis-specific cohesin components. Stag3 mutant spermatocytes arrest in early prophase ("zygotene-like" stage), displaying failed homolog synapsis and persistent DNA damage, as a result of unstable loading of cohesin onto the chromosome axes. Interestingly, Rec8, Rad21L double mutants resulted in an earlier "leptotene-like" arrest, accompanied by complete absence of STAG3 loading. To assess genetic interactions between STAG3 and α-kleisin subunits RAD21L and REC8, our lab generated Stag3, Rad21L, and Stag3, Rec8 double knockout mice, and compared them to the Rec8, Rad21L double mutant. These double mutants are phenotypically distinct from one another, and more severe than each single knockout mutant with regards to chromosome axis formation, cohesin loading, and sister chromatid cohesion. The Stag3, Rad21L, and Stag3, Rec8 double mutants both progress further into prophase I than the Rec8, Rad21L double mutant. Our genetic analysis demonstrates that cohesins containing STAG3 and REC8 are the main complex required for centromeric cohesion, and RAD21L cohesins are required for normal clustering of pericentromeric heterochromatin. Furthermore, the STAG3/REC8 and STAG3/RAD21L cohesins are the primary cohesins required for

  7. Proton induced L{sub 1}, L{sub 2}, L{sub 3}-sub-shell X-ray production cross sections of Hf and Au

    Energy Technology Data Exchange (ETDEWEB)

    Bertol, A.P.L., E-mail: anapaula.bertol@gmail.com [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Hinrichs, R. [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Geociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Vasconcellos, M.A.Z. [Programa de Pós-graduação em Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2015-11-15

    Experimental data for proton induced X-ray production cross sections of L-sub-shells of Hf and Au were obtained, in order to contribute to the existing data sets and to support refinements of the ECPSSR theory. X-ray emissions of mono-elemental 10 nm films of Hf and Au were excited with 0.7–1.5 MeV protons. The measured L-line spectra were fitted assuming Gaussian shapes and constraining peak positions and line widths. The transition energy values used to establish peak positions were based on values proposed in the literature, while the line widths were matched to the detector resolution, obtained independently. The intensity of each line was obtained from the adjusted areas, without the use of emission rates. The line intensities were summed in α, β, γ, and ℓ groups to validate the measurements by comparison with existing data, and in L{sub 1}, L{sub 2}, L{sub 3}-sub-shells for comparison with ECPSSR-UA theory. Ratios of the emission rates of lines of the same sub-shell were obtained and compared with the data from the literature.

  8. EPR investigation of gamma-irradiated L-citrulline, α-methyl-DL-serine, 3-fluoro-DL-valine and N-acetyl-L-cysteine

    Science.gov (United States)

    Osmanoğlu, Y. Emre; Sütçü, Kerem; Başkan, M. Halim

    2017-02-01

    The spectroscopic parameters of the paramagnetic species produced in gamma-irradiated L-citrulline, α-methyl-DL-serine, 3-fluoro-DL-valine and N-acetyl-L-cysteine were investigated at room temperature at a dose of 20 kGy by using EPR technique. The paramagnetic species were attributed to NH2CONH(CH2)3ĊNH2COOH, HOCH2ĊCH3COOH and HOĊHCCH3NH2COOH, CH3CH3ĊCHNH2COOH and SHCH2ĊNHCOCH3COOH radicals, respectively. EPR data of the unpaired electron with the environmental protons and 14N nucleus were used to characterize the contributing radicals produced in gamma irradiated compounds. In this paper, the stability of these compounds at room temperature after irradiation was also studied.

  9. The magnetic field of cloud 3 in L204

    Energy Technology Data Exchange (ETDEWEB)

    Cashman, Lauren R.; Clemens, D. P., E-mail: lcashman@bu.edu, E-mail: clemens@bu.edu [Institute for Astrophysical Research, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States)

    2014-10-01

    The L204 dark cloud complex is a nearby filamentary structure in Ophiuchus North that has no signs of active star formation. Past studies show that L204 is interacting with the nearby runaway O star, ζ Oph, and hosts a magnetic field that is coherent across parsec-length scales. Near-infrared H-band (1.6 μm) linear polarization measurements were obtained for 3896 background stars across a 1° × 1.°5 region centered on the dense Cloud 3 in L204, using the Mimir near-infrared instrument on the 1.8 m Perkins Telescope. Analysis of these observations reveals both large-scale properties and small-scale changes in the magnetic field direction in Cloud 3. In the northern and western ζ Oph facing regions of the cloud, the magnetic field appears to be pushed up against the face of the cloud. This may indicate that the UV flux from ζ Oph has compressed the magnetic field on the western edge of L204. The plane-of-sky magnetic field strength is estimated to be ∼11-26 μG using the Chandrasekhar-Fermi method. The polarimetry data also reveal that the polarization efficiency (PE ≡ P {sub H}/A {sub V}) steadily decreases with distance from ζ Oph (–0.09% ± 0.03% mag{sup –1} pc{sup –1}). Additionally, power-law fits of PE versus A {sub V} for localized samples of probe stars show steeper negative indices with distance from ζ Oph. Both findings highlight the importance of external illumination, here from ζ Oph, in aligning dust grains to embedded magnetic fields.

  10. Characteristics of D-3He fueled frc reactor: ARTEMIS-L

    International Nuclear Information System (INIS)

    Momota, H.; Motojima, O.; Okamoto, M.; Sudo, S.; Tomita, Y.; Yamaguchi, S.; Iiyoshi, A.; Onozuka, M.; Ohnishi, M.; Uenosono, C.

    1993-11-01

    The paper introduces briefly the scenario and discuss the attractive characteristics of D-3He fueled commercial fusion reactor ARTEMIS-L. By using favorable characteristics of a field-reversed configuration, the fusion plasma of ARTEMIS-L is compact and its beta-value is extremely high. One find consequently a possibility of constructing an economical fusion power power plant on this prospect. The life of the structural materials is sound during the full reactor life (30 years) and the safety of the reactor is intrinsic to D-3He fuels. The amount of disposed materials is rather small and the level of these intruder dose is so low that the plant appears to be acceptable in view of the environment. (author)

  11. Crystal and molecular structure of 2,2’-(quinoxaline-2,3-diyl)dipyridinium dinitrate (H{sub 2}L)(NO{sub 3}){sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Egorova, O. A. [People’s Friendship University of Russia (Russian Federation); Polyakova, I. N., E-mail: polyakova@igic.ras.ru; Sergienko, V. S. [Russian Academy of Sciences, Kurnakov Institute of General and Inorganic Chemistry (Russian Federation); Davydov, V. V. [People’s Friendship University of Russia (Russian Federation)

    2016-07-15

    The crystal structure of 2,2’-(quinoxaline-2,3-diyl)dipyridinium dinitrate (H{sub 2}L)(NO{sub 3}){sub 2} is studied by X-ray diffraction (T = 150 K, R1 = 0.0467). The H{sub 2}L{sup 2+} cation is located on the twofold rotation axis and connected with two NO{sub 3}{sup −} anions by strong N–H···O hydrogen bonds. Planar quinoxaline fragments of cations form stacks with the interplanar spacing of 3.308 Å. The structure of the diprotonated H{sub 2}L{sup 2+} cation is compared with those of the monoprotonated H{sub 2}L{sup 2+} cation and neutral L molecule.

  12. Reexamination of M2,3 atomic level widths and L1M2,3 transition energies of elements 69≤Z≤95

    Science.gov (United States)

    Fennane, K.; Berset, M.; Dousse, J.-Cl.; Hoszowska, J.; Raboud, P.-A.; Campbell, J. L.

    2013-11-01

    We report on high-resolution measurements of the photoinduced L1M2 and L1M3 x-ray emission lines of 69Tm, 70Yb, 71Lu, 73Ta, 74W, 75Re, 77Ir, 81Tl, 83Bi, and 95Am. From the linewidths of the measured transitions an accurate set of M2 and M3 level widths is determined assuming for the L1 level widths the values reported by Raboud [P.-A. Raboud et al., Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.65.022512 65, 022512 (2002)]. Furthermore, the present experimental M2,3 data set is extended to 80Hg, 90Th, and 92U, using former L1M2,3 high-resolution x-ray emission spectroscopy measurements performed by our group. A detailed comparison of the M2 and M3 level widths determined in the present work with those recommended by Campbell and Papp [J. L. Campbell and T. Papp, At. Data Nucl. Data TablesADNDAT0092-640X10.1006/adnd.2000.0848 77, 1 (2001)] and other available experimental data as well as theoretical predictions is done. The observed abrupt changes of the M2,3 level widths versus atomic number Z can be explained satisfactorily by the cutoffs and onsets of the M2M4N1, respectively M3M4N3,4,5 and M3M5N2,3 Coster-Kronig transitions deduced from the semiempirical (Z+1) approximation. As a spin-off result of this study, precise L1M2 and L1M3 transition energies are obtained for the investigated elements. A very good agreement with transition energies calculated within the many-body perturbation theory is found.

  13. Exploring the Mental Lexicon of the Multilingual: Vocabulary Size, Cognate Recognition and Lexical Access in the L1, L2 and L3

    OpenAIRE

    Szabo, Cz.

    2016-01-01

    Recent empirical findings in the field of Multilingualism have shown that the mental lexicon of a language learner does not consist of separate entities, but rather of an intertwined system where languages can interact with each other (e.g. Cenoz, 2013; Szubko-Sitarek, 2015). Accordingly, multilingual language learners have been considered differently to second language learners in a growing number of studies, however studies on the variation in learners’ vocabulary size both in the L2 and L3...

  14. l-2-Nitrimino-1,3-diazepane-4-carboxylic acid

    Directory of Open Access Journals (Sweden)

    Harutyun A. Karapetyan

    2008-05-01

    Full Text Available The cyclic form of l-nitroarginine, C6H10N4O4, crystallizes with two independent molecules in the asymmetric unit. According to the geometrical parameters, similar in both molecules, the structure corresponds to that of l-2-nitrimino-1,3-diazepane-4-carboxylic acid; there are, however, conformational differences between the independent molecules, one of them being close to a twisted chair while the other might be described as a rather flattened boat. All six active H atoms in the two molecules are involved in hydrogen bonds, two of which are intramolecular and four intermolecular, forming an infinite chain of molecules along the b axis.

  15. Proteomic approaches for the study of tissue specific effects of 3,5,3’-triiodo-L-thyronine and 3,5-diiodo-L-thyronine in conditions of altered energy metabolism.

    Directory of Open Access Journals (Sweden)

    Elena eSilvestri

    2014-12-01

    Full Text Available In vertebrates and, specifically, in mammals, energy homeostasis is achieved by the integration of metabolic and neuroendocrine signals linked to one another in an intricate network hierarchically responding to the tight modulating action of hormones among which thyroid hormones (THs play a central role. At the cellular level, 3,5,3’-triiodo-L-thyronine (T3 acts mainly by binding to specific nuclear receptors (TRs but actually it is becoming more and more evident that some T3- actions are independent of TRs and that other iodothyronines, such as 3,5-diiodo-L-thyronine (T2, affect energy metabolism and adiposity. In the postgenomic era, clinical and basic biological researches are increasingly benefiting from the recently developed new omics approaches including, among the others, proteomics. Considering the recognized value of proteins as excellent targets in physiology, the functional and simultaneous analysis of the expression level and the cellular localization of multiple proteins can actually be considered fundamental in the understanding of complex mechanisms such as those involved in thyroid control of metabolism. Here, we will discuss new leads (i.e. target proteins and metabolic pathways emerging in applying proteomics to the actions of T3 and T2 in conditions of altered energy metabolism in animal tissues having a central role in the control of energy balance.

  16. L-Cysteine supplementation increases adiponectin synthesis and secretion, and GLUT4 and glucose utilization by upregulating disulfide bond A-like protein expression mediated by MCP-1 inhibition in 3T3-L1 adipocytes exposed to high glucose.

    Science.gov (United States)

    Achari, Arunkumar Elumalai; Jain, Sushil K

    2016-03-01

    Adiponectin is an anti-diabetic and anti-atherogenic adipokine; its plasma levels are decreased in obesity, insulin resistance, and type 2 diabetes. An adiponectin-interacting protein named disulfide bond A-like protein (DsbA-L) plays an important role in the assembly of adiponectin. This study examined the hypothesis that L-cysteine (LC) regulates glucose homeostasis through the DsbA-L upregulation and synthesis and secretion of adiponectin in diabetes. 3T3L1 adipocytes were treated with LC (250 and 500 µM, 2 h) and high glucose (HG, 25 mM, 20 h). Results showed that LC supplementation significantly (p L, adiponectin, and GLUT-4 protein expression and glucose utilization in HG-treated adipocytes. LC supplementation significantly (p L expression and adiponectin levels in 3T3-L1 cells. Treatment with LC prevented the decrease in DsbA-L, adiponectin, and GLUT-4 expression in 3T3L1 adipocyte cells exposed to MCP-1. Thus, this study demonstrates that DsbA-L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP-1 secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes.

  17. Modelling thermodynamic properties of lanthanide (LnL)3+ and actinide (AnL)3+ complexes with tridentate planar nitrogen ligands (L)

    International Nuclear Information System (INIS)

    Ionova, G.; Rabbe, C.; Charbonnel, M.C.; Hill, C.; Guillaumont, D.; Guillaumont, R.; Ionov, S.; Madic, C.

    2004-01-01

    We report here the results obtained from a systematic theoretical study on the thermodynamic properties of trivalent lanthanide (Ln) and actinide (An) complexes with chelating nitrogen tridentate ligands. The mechanism of chelation has been investigated and the role of cation dissolution is investigated through a comparison of the thermodynamic properties of solvated cations and complexes. The difference in thermodynamic properties of LnL and AnL complexes is analyzed. (authors)

  18. CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3

    Directory of Open Access Journals (Sweden)

    Lucía Sanjurjo

    2018-03-01

    Full Text Available CD5L (CD5 molecule-like is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.

  19. Safety analysis report for packaging (onsite) L3-181 N basin cask

    International Nuclear Information System (INIS)

    Adkins, H.E. Jr.

    1996-01-01

    Purpose of this Safety Analysis Report (SARP) is to authorize the onsite transfer of a Type B, Fissile Excepted, non-highway route controlled quantity in the L3-181 packaging from the N Basin to a storage/disposal facility within 200 West Area. This SARP provides the evaluation necessary to demonstrate that the L3-181 meets the requirements of the 'Hazardous Material Packaging and Shipping', WHC- CM-2-14, by meeting the applicable performance requirements for normal conditions of transport

  20. Activation of liver X receptors prevents statin-induced death of 3T3-L1 preadipocytes

    DEFF Research Database (Denmark)

    Madsen, Lise; Petersen, Rasmus K; Steffensen, Knut R

    2008-01-01

    The biological functions of liver X receptors (LXRs) alpha and beta have primarily been linked to pathways involved in fatty acid and cholesterol homeostasis. Here we report a novel role of LXR activation in protecting cells from statin-induced death. When 3T3-L1 preadipocytes were induced...

  1. L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Xiang-Zhu Xie

    2016-01-01

    Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

  2. DOT1L and H3K79 Methylation in Transcription and Genomic Stability.

    Science.gov (United States)

    Wood, Katherine; Tellier, Michael; Murphy, Shona

    2018-02-27

    The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.

  3. DOT1L and H3K79 Methylation in Transcription and Genomic Stability

    Directory of Open Access Journals (Sweden)

    Katherine Wood

    2018-02-01

    Full Text Available The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79. H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.

  4. EQ-5D-3L as a health measure of Brazilian adult population.

    Science.gov (United States)

    Menezes, Renata de Miranda; Andrade, Mônica Viegas; Noronha, Kenya Valéria Micaela de Souza; Kind, Paul

    2015-11-01

    This study explores the use of EQ-5D-3L as a measure of population health status in a Brazilian region with significant socioeconomic, demographic, and epidemiological heterogeneity. Data came from a study of 3363 literate individuals aged between 18 and 64 years living in urban areas of the state of Minas Gerais. Descriptive analysis and logistic and OLS regression models were performed to analyze the relationship between EQ-5D-3L (descriptive system and EQ VAS) and other health (self-assessed health status and 8 self-reported diagnosed chronic diseases), socioeconomic (educational level and economic class), and demographic (gender and age) measures. Additionally, a grade of membership (GoM) analysis was performed to identify multidimensional health profiles. A total of 76 health statuses were identified in the Brazilian population. The most prevalent one is full health (44 % of the sample). Elderly people, women, and individuals with poor health and lower socioeconomic conditions generally report more health problems in the EQ-5D-3L dimensions. The GoM analysis demonstrated that health status of older individuals is associated with the socioeconomic condition. Arthritis exhibited the strongest association with the EQ-5D-3L instrument. The results indicate that EQ-5D-3L is a good measure of health status for the Brazilian population. The instrument has a good discriminatory capacity in terms of demographic, socioeconomic, and health measures. The high prevalence of individuals with full health may indicate the presence of ceiling effect. However, this prevalence is smaller than that in other countries.

  5. In vivo CHI3L1 (YKL-40 expression in astrocytes in acute and chronic neurological diseases

    Directory of Open Access Journals (Sweden)

    Hamilton Ronald L

    2010-06-01

    Full Text Available Abstract Background CHI3L1 (YKL-40 is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes. Methods In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases. Results ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS patients as well as mild elevation with aging. In situ hybridization (ISH showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts. Conclusions Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells.

  6. L'assignació de metadades a llibres digitals en el format EPUB3. Primera part. Les metadades en les especificacions de l'EPUB3

    Directory of Open Access Journals (Sweden)

    Centelles Velilla, Miquel

    2015-12-01

    Full Text Available Objectius: descriure els mecanismes i la funció de les metadades internes i descriptives en el format EPUB3 segons els estàndards vigents i les bones pràctiques difoses per la indústria editorial, i identificar un conjunt de recomanacions especialment orientades a petits editors o autors que s'autoediten les obres. -- Metodologia: l'article és descriptiu i instructiu, ja que a partir de l'explicació de l'estructura interna d'un llibre en format EPUB3 s'expliquen els diferents elements de metadades, els estàndards corresponents, la seva estructura i els possibles valors. El conjunt de propostes s'exemplifica a partir d'un cas d'estudi. -- Resultats: el format EPUB disposa de mecanismes de descripció del context, el contingut i l’estructura dels llibres que emulen, en origen, els instruments específicament orientats a la catalogació, una mostra de la consolidació del model de metadades en origen. Els autors recomanen especialment la inclusió dels cinc elements de metadades obligatoris, tres dels quals (identificador, títol i idioma dins l'esquema Dublin Core i dos segons un esquema propi, per descriure la data de la darrera modificació i la durada dels mitjans audiovisuals inclosos.Objetivos: describir los mecanismos y la función de los metadatos internos y descriptivos en el formato EPUB3 según los estándares vigentes y las buenas prácticas difundidas por la industria editorial, e identificar un conjunto de recomendaciones especialmente orientadas a pequeños editores o autores que se autoeditan las obras. Metodología: el artículo es descriptivo e instructivo, ya que a partir de la explicación de la estructura interna de un libro en formato EPUB3 se explican los diferentes elementos de metadatos, los estándares correspondientes, su estructura y los posibles valores. El conjunto de propuestas se ejemplifica a partir de un caso de estudio. Resultados: el formato EPUB dispone de mecanismos de descripción del contexto, el

  7. Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

    Science.gov (United States)

    Obanda, Diana N; Zhao, Peng; Richard, Allison J; Ribnicky, David; Cefalu, William T; Stephens, Jacqueline M

    2016-01-01

    Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

  8. LOFT/L3-, Loss of Fluid Test, 7. NRC L3 Small Break LOCA Experiment

    International Nuclear Information System (INIS)

    1992-01-01

    1 - Description of test facility: The LOFT Integral Test Facility is a scale model of a LPWR. The intent of the facility is to model the nuclear, thermal-hydraulic phenomena which would take place in a LPWR during a LOCA. The general philosophy in scaling coolant volumes and flow areas in LOFT was to use the ratio of the LOFT core [50 MW(t)] to a typical LPWR core [3000 MW(t)]. For some components, this factor is not applied; however, it is used as extensively as practical. In general, components used in LOFT are similar in design to those of a LPWR. Because of scaling and component design, the LOFT LOCA is expected to closely model a LPWR LOCA. 2 - Description of test: This was the seventh in the NRC L3 Series of small-break LOCA experiments. A 2.5-cm (10-in.) cold-leg non-communicative-break LOCA was simulated. The experiment was conducted on 20 June 1980

  9. Washout of tritium from 3R-3(3H)-L-aspartate in the aspartase reaction

    International Nuclear Information System (INIS)

    Katz, B.M.; Cook, P.F.

    1987-01-01

    Bacterial aspartase catalyzes the reversible conversion of L-aspartate to fumarate and ammonia. Recent studies that made use of deuterium and 15 N isotope effects suggested a carbanion intermediate mechanism in which C-N bond cleavage is rate determining. This could result in removal of a proton from the 3R position of aspartate at a rate of faster than the elimination of ammonia. 3R-3( 3 H)-Aspartate was prepared enzymatically using aspartase from fumarate, ammonia and 3 H 2 O and aspartate isolated via chromatography on Dowex 50W x 8 at pH 1, eluting with 2N pyridine. The rate of 3 H washout from this aspartate was then measured as a function of aspartate concentration and compared to the rate of production of fumarate. Tritium does washout of aspartate at a rate faster than fumarate is formed but the proton is apparently not rapidly equilibrated with solvent. The tritium washout experiments were supplemented using 3R-3( 2 H)-aspartate prepared as above with 2 H 2 O replacing 3 H 2 O and monitoring the appearance of 3R-3( 1 H)-aspartate via 1 H-NMR. Results confirm the tritium washout results. Data are discussed in terms of the carbanion mechanism

  10. VLBI-simulations for the estimation of degree-three Love and Shida numbers h3 and l3

    Science.gov (United States)

    Mendes Cerveira, P. J.; Boehm, J.; Wresnik, J.; Spicakova, H.; Schuh, H.

    2007-12-01

    For the displacement due to solid Earth tides, the IERS Conventions 2003 recommend several corrections to nominal values. One of these corrections is the in-phase contribution by using the real Love and Shida numbers h3 and l3 at all degree-3 tides, where only the contribution of the moon is relevant. The maximum predicted radial displacement is in the order of 1.7 mm. The nominal values are 0.292 for h3, and 0.015 for l3, respectively. Using realistic station and source catalogues, we simulated VLBI (Very Long Baseline Interferometry) group time delays, with a white noise going up to 2 cm, and taking into account the solid Earth tides displacement. Goal of this study was to investigate whether degree-3 Love and Shida numbers can be unambiguously determined from VLBI observations. Therefore, several setups w.r.t., e.g., station constellation, cutoff angle, time span, sampling interval, and different levels of white noise were tested. Attention was put into the separability and correlation between the degree-2 and degree-3 Love and Shida numbers.

  11. A lead-scintillating fiber calorimeter to increase L3 hermeticity

    CERN Document Server

    Basti, G

    1997-01-01

    A lead-scintillating fiber calorimeter has been built to fill the gap between endcap and barrel of the L3 BGO electromagnetic calorimeter. We report details of the construction, as well as results from test-beam and simulation.

  12. Reliability and validity of the EQ-5D-3L for Kashin-Beck disease in China.

    Science.gov (United States)

    Fang, Hua; Farooq, Umer; Wang, Dimiao; Yu, Fangfang; Younus, Mohammad Imran; Guo, Xiong

    2016-01-01

    Kashin-Beck Disease (KBD) is an endemic osteoarthropathy in areas which extend from the North-East to the South-West of China. Most of the patients with KBD suffer multiple dysfunctions in major joints causing decreased health status. However because of their low education level and unique living habits, it is hard to find tools to measure the health-related quality of life (HRQOL). European quality of life (EQ-5D-3L) patient-reported instrument is widely used to measure HRQOL. This study aimed to establish the validity and reliability of the Chinese version of the EQ-5D-3L for evaluating HRQOL of KBD individuals in rural area. 368 individuals who were suffering from KBD were recruited through stratified multistage random sampling from Shaanxi province, China. The EQ-5D-3L and the WHOQOL-BREF were administrated in each individual by face to face interview. Test-retest reliability was assessed at 10-14 days intervals. The test-retest reliability was measured by calculating the Kappa coefficients for EQ-5D-3L five dimensions. For the EQ VAS, the intraclass correlation coefficient (ICC) was computed. Convergent and divergent analysis, construct validity was established using Spearman's rank correlation between the EQ-5D-3L and the WHOQOL-BREF. Known groups' validity was examined by comparing groups with a priori expected differences in health-related quality of life (HRQOL). For 362 individuals (98%), comprehensive data of all the EQ-5D-3L dimensions were available. Kappa values of the EQ-5D-3L five items ranged from 0.324 to 0.554. ICC of the EQ VAS was 0.497. For convergent validity, the three items (self-care, usual activity, and mobility) of EQ-5D-3L, index scores, and VAS showed moderate correlations with the physical health domain of the WHOQOL-BREF (r absolute value ranged from 0.339 to 0.475). For divergent validity, the 5 items of EQ-5D-3L showed weak or no correlations with environment and social relationship domains of WHOQOL-BREF. The Chinese EQ-5D-3L

  13. Characterization of dissimilar welding: carbon steel E309L-E308L-ERNiCr3-ENiCrFe3 alloy 600

    International Nuclear Information System (INIS)

    Mucino G, O.

    2015-01-01

    Most BWR type reactors have internal support components, which need to be attached to the inner surface by welding. Specifically, in these joints two materials interact, such as stainless steel and nickel base alloys. Nickel base alloys such as alloy 82 (ERNiCr3) and alloy 182 (ENiCrFe-3) are used for the joining of both dissimilar materials. For joints made with both nickel base alloys, the alloy 182 is prone to stress corrosion cracking (SCC); so it is essential to carry out studies related to this contribution material. In the nuclear industry any study related to this alloy is of importance because experience is gained in its behavior when is part of a system of an operation reactor. This work presents the characterization of the weld deposit of a stainless steel coating (with electrodes E309L and E308L) on a carbon steel plate type A36 and the joining with an Inconel 600 plate, simulating the joining of the internal coating of vessel and the heel of the support leg of the envelope of a BWR reactor. In this work, the mechanical and micro-structural characterization of the alloy deposit 182 was performed. (Author)

  14. Photoactivation of GLUT4 translocation promotes glucose uptake via PI3-K/Akt2 signaling in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2014-05-01

    Full Text Available Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes. Dysfunction of PI-3K/Akt signaling was involved in insulin resistance. Glucose transporter 4 (GLUT4 is a key factor for glucose uptake in muscle and adipose tissues, which is closely regulated by PI-3K/Akt signaling in response to insulin treatment. Low-power laser irradiation (LPLI has been shown to regulate various physiological processes and induce the synthesis or release of multiple molecules such as growth factors, which (especially red and near infrared light is mainly through the activation of mitochondrial respiratory chain and the initiation of intracellular signaling pathways. Nevertheless, it is unclear whether LPLI could promote glucose uptake through activation of PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes. In this study, we investigated how LPLI promoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling pathway. Here, we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm to cytomembrane upon LPLI treatment in 3T3L-1 adipocytes, which enhanced glucose uptake. Moreover, we found that glucose uptake was mediated by the PI3-K/Akt2 signaling, but not Akt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors. Collectively, our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators for improvement of glucose uptake under LPLI treatment in 3T3L-1 adipocytes. More importantly, our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provide guidance in practical applications for promotion of glucose uptake in insulin-resistant adipose tissue.

  15. L-3,4-Dihydroxyphenylalanine (l-DOPA) induces neuroendocrinological, physiological, and immunological regulation in white shrimp, Litopenaeus vannamei.

    Science.gov (United States)

    Mapanao, Ratchaneegorn; Kuo, Hsin-Wei; Chang, Chin-Chuan; Liu, Kuan-Fu; Cheng, Winton

    2018-03-01

    L-3,4-Dihydroxyphenylalanine (l-DOPA) is a precursor for dopamine (DA) synthesis. Assessments were conducted to analyze the effects of l-DOPA on mediating regulation of neuroendocrinological, immunological, and physiological parameters in the shrimp, Litopenaeus vannamei when they were individually injected with 0.01 N HCl or l-DOPA at 0.5 or 1.0 μmol shrimp -1 for 60, 120, and 240 min. For catecholamine synthesis evaluation, tyrosine hydroxylase (TH) and DA beta hydroxylase (DBH) activities, l-DOPA, DA, and norepinephrine (NE) levels in hemolymph were determined. The total hemocyte count (THC), differential hemocyte count (DHC), phenoloxidase (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, phagocytic activity, and clearance efficiency in response to the pathogen, Vibrio alginolyticus were assessed for immune responses, and plasma glucose and lactate levels were for physiological response. Results showed that the TH activity, THC, hyaline cells (HCs), and semigranular cells (SGCs) at 120 min, DA levels at 60-240 min, PO activity in hemocytes per 50 μL of hemolymph at 60-120 min, and PO activity per granulocyte (granular cells (GCs) + SGCs) at 60 min significantly increased, but TH activity, l-DOPA levels, GCs, SGCs, and respiratory bursts in hemocytes per 10 μL of hemolymph at 60 min, respiratory bursts per hemocyte and SOD activity at 120 min, phagocytic activity at 60-240 min, and the clearance efficiency at 60-120 min significantly decreased in shrimp injected with l-DOPA at 1.0 μmol shrimp -1 . In another experiment, 60 min after shrimp had received l-DOPA at 0.5 or 1.0 μmol shrimp -1 , they were challenged with an injection of V. alginolyticus at 2 × 10 5  colony-forming units (cfu) shrimp -1 . The injection of l-DOPA at 1.0 μmol shrimp -1 also significantly increased the cumulative mortality of shrimp by 16.7%, compared to the HCl-challenged control after 120 h. These results suggest

  16. Dark Matter Limits From a 2L C3F8 Filled Bubble Chamber

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Alan Edward [Univ. of Chicago, IL (United States)

    2015-12-01

    The PICO-2L C3F8 bubble chamber search forWeakly Interacting Massive Particle (WIMP) dark matter was operated in the SNOLAB underground laboratory at the same location as the previous CF3I lled COUPP-4kg detector. Neutron calibrations using photoneutron sources in C3F8 and CF3I lled calibration bubble chambers were performed to verify the sensitivity of these target uids to dark matter scattering. This data was combined with similar measurements using a low-energy neutron beam at the University of Montreal and in situ calibrations of the PICO-2L and COUPP-4kg detectors. C3F8 provides much greater sensitivity to WIMP-proton scattering than CF3I in bubble chamber detectors. PICO-2L searched for dark matter recoils with energy thresholds below 10 keV. Radiopurity assays of detector materials were performed and the expected neutron recoil background was evaluated to be 1.6+0:3

  17. High-resolution parallel electron energy-loss spectroscopy of MnL2,3-edges in inorganic manganese compounds

    International Nuclear Information System (INIS)

    Garvie, L.A.J.; Craven, A.J.

    1994-01-01

    Parallel electron energy-loss spectroscopy (PEELS) in a scanning transmission electron microscope (STEM) was used to record the Mn L 2,3 -edges from a range of natural and synthetic manganese containing materials, covering valences 0, II, III, IV and VII, with an energy resolution of ca. 0.5 eV. The Mn L 2,3 electron-loss near-edge structure (ELNES) of these edges provided a sensitive fingerprint of its valence. The Mn 2+ L 2,3 -edges show little sensitivity to the local site symmetry of the ligands surrounding the manganese. This is illustrated by comparing the Mn L 2,3 -edges from 4-, 6-and 8-fold coordinated Mn 2+ . In contrast, the Mn L 3 -edges from Mn 3+ and Mn 4+ containing minerals exhibited ELNES that are interpreted in terms of a crystals-field splitting of the 3d electrons, governed by the symmetry of the surrounding ligands. The Mn L 3 -edges for octahedrally coordinated Mn 2+ , Mn 3+ and Mn 4+ showed variations in their ELNES that were sensitive to the crystal-field strength. The crystal-field strength (10Q) was measured from these edges and compared very well with published optically determinted values. The magnitude of 10Dq measured from the Mn L 3 -edges and their O K-edge prepeaks of the manganese oxides were almost identical. This further confirms that the value of 10Dq measured at the Mn L 3 -edge is correct. Selected spectra are compared with theoretical 2p atomic multiplet spectra and the differences and similarities are explained in terms of the covalency and site symmetry of the manganese. The Mn L 3 -edges allow the valence of the manganese to be ascertained, even in multivalent state materials, and can also be used to dtermin 10Dq. (orig.)

  18. Crystal and molecular structure of the coordination compounds of Er3+ with 1-(methoxydiphenylphosphoryl)-2-diphenylphosphorylbenzene [ErL21(NO3)2]2[Er(NO3)2(H2O)5]0.333(NO3)2.333 · 2.833H2O and its ethyl substituted derivative [ErL22(NO3)2][Er(NO3)5]0.5 · 0.5H2O

    International Nuclear Information System (INIS)

    Polyakova, I. N.; Baulin, V. E.; Ivanova, I. S.; Pyatova, E. N.; Sergienko, V. S.; Tsivadze, A. Yu.

    2015-01-01

    The coordination compounds of Er 3+ with 1-(methoxydiphenylphosphoryl)-2-diphenylphosphorylbenzene [ErL 2 1 (NO 3 ) 2 ] 2 [Er(NO 3 ) 2 (H 2 O) 5 ] 0.333 (NO 3 ) 2.333 · 2.833H 2 O (I) and its ethyl substituted derivative [ErL 2 2 (NO 3 ) 2 ][Er(NO 3 ) 5 ] 0.5 · 0.5H 2 O (II) are synthesized and their crystal structures are studied. I and II contain [ErL 2 (NO 3 ) 2 ] + complex cations of identical composition and close structure. The eight-vertex polyhedron of the Er atom in the shape of a distorted octahedron with two split trans vertices is formed by the O atoms of the phosphoryl groups of L ligands and nitrate anions. L ligands close nine-membered metallocycles. The structures contain spacious channels which are populated differently, namely, by disordered [Er(NO 3 ) 2 (H 2 O) 5 ] + complex cations, NO 3 − anions, and crystallization water molecules in I and disordered [Er(NO 3 ) 5 ] 2− complex anions and crystallization water molecules in II. The IR spectra of I and II are studied

  19. Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1 Expression by Orphan Nuclear Receptor Nr4a1

    Directory of Open Access Journals (Sweden)

    Michael P. Greenwood

    2017-12-01

    Full Text Available Cyclic AMP (cAMP inducible transcription factor cAMP responsive element binding protein 3 like 1 (Creb3l1 is strongly activated in the hypothalamus in response to hyperosmotic cues such as dehydration (DH. We have recently shown that Creb3l1 expression is upregulated by cAMP pathways in vitro, however the exact mechanisms are not known. Here we show that increasing Creb3l1 transcription by raising cAMP levels in mouse pituitary AtT20 cells automatically initiates cleavage of Creb3l1, leading to a greater abundance of the transcriptionally active N-terminal portion. Inhibiting protein synthesis indicated that de novo protein synthesis of an intermediary transcription factor was required for Creb3l1 induction. Strategic mining of our microarray data from dehydrated rodent hypothalamus revealed four candidates, reduced to two by analysis of acute hyperosmotic-induced transcriptional activation profiles in the hypothalamus, and one, orphan nuclear receptor Nr4a1, by direct shRNA mediated silencing in AtT20 cells. We show that activation of Creb3l1 transcription by Nr4a1 involves interaction with a single NBRE site in the promoter region. The ability to activate Creb3l1 transcription by this pathway in vitro is dictated by the level of methylation of a CpG island within the proximal promoter/5′UTR of this gene. We thus identify a novel cAMP-Nr4a1-Creb3l1 transcriptional pathway in AtT20 cells and also, our evidence would suggest, in the hypothalamus.

  20. C2C12 myotubes inhibit the proliferation and differentiation of 3T3-L1 preadipocytes by reducing the expression of glucocorticoid receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Weiwei; Wei, Wei; Yu, Shigang; Han, Haiyin; Shi, Xiaoli [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Sun, Wenxing [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); College of Public Health, Nantong University, Nantong 226019 (China); Gao, Ying [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Zhang, Lifan [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Chen, Jie, E-mail: jiechen@njau.edu.cn [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China)

    2016-03-25

    Obesity is a well-established risk factor to health for its relationship with insulin resistance, diabetes and metabolic syndrome. Myocyte-adipocyte crosstalk model plays a significant role in studying the interaction of muscle and adipose development. Previous related studies mainly focus on the effects of adipocytes on the myocytes activity, however, the influence of myotubes on the preadipocytes development remains unclear. The present study was carried out to settle this issue. Firstly, the co-culture experiment showed that the proliferation, cell cycle, and differentiation of 3T3-L1 preadipocytes were arrested, and the apoptosis was induced, by differentiated C2C12 myotubes. Next, the sensitivity of 3T3-L1 preadipocytes to glucocorticoids (GCs), which was well known as cell proliferation, differentiation, apoptosis factor, was decreased after co-cultured with C2C12 myotubes. What's more, our results showed that C2C12 myotubes suppressed the mRNA and protein expression of glucocorticoid receptor (GR) in 3T3-L1 preadipocytes, indicating the potential mechanism of GCs sensitivity reduction. Taken together, we conclude that C2C12 myotubes inhibited 3T3-L1 preadipocytes proliferation and differentiation by reducing the expression of GR. These data suggest that decreasing GR by administration of myokines may be a promising therapy for treating patients with obesity or diabetes. - Highlights: • C2C12 myotubes inhibited proliferation and differentiation of 3T3-L1 preadipocytes. • C2C12 myotubes arrested cell cycle of 3T3-L1 preadipocytes. • C2C12 myotubes induced apoptosis of 3T3-L1 preadipocytes. • C2C12 inhibit 3T3-L1 cells by reducing the expression of glucocorticoid receptor gene.

  1. Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    International Nuclear Information System (INIS)

    Jang, Byeong-Churl

    2016-01-01

    Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra S. Moore and has been shown to possess anti-inflammatory and anti-cancerous activities. In this study, the effect of tetrandrine on adipogenesis in 3T3-L1 preadipocytes was investigated. Tetrandrine at 10 μM concentration strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, tetrandrine reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 adipocyte differentiation. Tetrandrine also reduced the mRNA expression of leptin, but not adiponectin, during 3T3-L1 adipocyte differentiation. Collectively, these findings show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. - Highlights: • Tetrandrine, a bisbenzylisoquinoline alkaloid, inhibits adipogenesis. • Tetrandrine inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. • Tetrandrine reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Tetrandrine may thus have therapeutic potential against obesity.

  2. Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr

    2016-08-05

    Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra S. Moore and has been shown to possess anti-inflammatory and anti-cancerous activities. In this study, the effect of tetrandrine on adipogenesis in 3T3-L1 preadipocytes was investigated. Tetrandrine at 10 μM concentration strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, tetrandrine reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during 3T3-L1 adipocyte differentiation. Tetrandrine also reduced the mRNA expression of leptin, but not adiponectin, during 3T3-L1 adipocyte differentiation. Collectively, these findings show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. - Highlights: • Tetrandrine, a bisbenzylisoquinoline alkaloid, inhibits adipogenesis. • Tetrandrine inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. • Tetrandrine reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Tetrandrine may thus have therapeutic potential against obesity.

  3. Replacing Alpha-Fetoprotein With Alpha-Fetoprotein-L3 Increases the Sensitivity of Prenatal Screening for Trisomy 21.

    Science.gov (United States)

    Huai, Lei; Leng, Jianhang; Ma, Shenglin; Huang, Fang; Shen, Junya; Ding, Yu

    This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.

  4. Synthesis of 1- and 3-11C-labelled L-lactic acid using multi-enzyme catalysis

    International Nuclear Information System (INIS)

    Bjurling, P.; Laangstroem, B.

    1990-01-01

    The synthesis of 1- and 3- 11 C-labelled L-lactic acid from the corresponding racemic 1- or 3- 11 C-labelled alanine using a multi-enzymatic reaction route, is presented. DL-[1- 11 C]Alanine was synthesised by reacting sodium 1-hydroxy-ethyl sulfite with hydrogen [ 11 C]cyanide, obtained from [ 11 C]carbon dioxide, and ammonia followed by acid hydrolysis. DL-[3- 11 C]-Alanine was synthesised by a methylation of a glycine derivative, N-(diphenylmethylene)-glycine tert-butyl ester, with [ 11 C]methyl iodide, obtained from [ 11 C]carbon dioxide, and subsequent hydrolysis. The racemic 1- or 3- 11 C-labelled alanine was then converted to pyruvic acid, by D-amino acid oxidase/catalase and glutamic-pyruvic transaminase, which was directly reduced to L-lactic acid by L-lactic dehydrogenase in a one-pot procedure. The total synthesis time was 40 minutes, counted from release of [ 11 C]carbon dioxide. The decay corrected radiochemical yields were ca. 80% for L-[1- 11 C]lactic acid, based on hydrogen cyanide, and ca. 60% for L-[3- 11 C]lactic acid, based on carbon dioxide. The radiochemical purities were higher than 99% analysed by HPLC. (author)

  5. 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

    DEFF Research Database (Denmark)

    Nygaard, Birte

    2012-01-01

    . Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues...

  6. Free Fatty Acids Activate Renin-Angiotensin System in 3T3-L1 Adipocytes through Nuclear Factor-kappa B Pathway

    Directory of Open Access Journals (Sweden)

    Jia Sun

    2016-01-01

    Full Text Available The activity of a local renin-angiotensin system (RAS in the adipose tissue is closely associated with obesity-related diseases. However, the mechanism of RAS activation in adipose tissue is still unknown. In the current study, we found that palmitic acid (PA, one kind of free fatty acid, induced the activity of RAS in 3T3-L1 adipocytes. In the presence of fetuin A (Fet A, PA upregulated the expression of angiotensinogen (AGT and angiotensin type 1 receptor (AT1R and stimulated the secretion of angiotensin II (ANG II in 3T3-L1 adipocytes. Moreover, the activation of RAS in 3T3-L1 adipocytes was blocked when we blocked Toll-like receptor 4 (TLR4 signaling pathway using TAK242 or NF-κB signaling pathway using BAY117082. Together, our results have identified critical molecular mechanisms linking PA/TLR4/NF-κB signaling pathway to the activity of the local renin-angiotensin system in adipose tissue.

  7. Role of lipids in the transmission of the infective stage (L3) of Strongylus vulgaris (Nematoda: Strongylida).

    Science.gov (United States)

    Medica, D L; Sukhdeo, M V

    1997-10-01

    Infective larvae (L3) of Strongylus vulgaris have limited energy stores for host finding and for infection. For transmission to occur, the larvae must have sufficient energy to (a) migrate onto grass, where they are ingested by their equine host (host finding), and (b) penetrate into the host gut. This study is designed to test the hypothesis that L3 larvae of S. vulgaris partition their energy stores between locomotory activity (used in host finding) and infection activity (penetration). Chronic locomotory activity was stimulated by incubating S. vulgaris L3 larvae at a constant temperature (38 C). After 8 days of treatment, locomotory activity ceased (exhaustion). Exhausted L3 larvae had significantly decreased total lipid when compared to controls (P vulgaris L3 larvae are comprised of 9 fatty acids, some of which are depleted in exhausted worms (14:0, 14:1, 16:0, 16:1, 18:1, 18:2), whereas others (18:0, 20:4, 24:0) remain unchanged. These data suggest that specific fatty acids provide the energy source for locomotory activity in S. vulgaris. Exhausted L3 larvae were also less able to penetrate host cecal tissue in in vitro penetration assays when compared to controls (P vulgaris L3 larvae partition their energy stores between host-finding and infection activities. A comparison of lipid storage profiles in the L3 larvae of 4 nematode species with similar transmission strategies (S. vulgaris, Strongylus edentatus, Strongylus equinus, and Haemonchus contortus) revealed similarities in the fatty acid composition of these species. These data suggest a relationship between transmission patterns and energy storage strategies in the L3 larvae of nematode parasites of vertebrates.

  8. Stinging Nettle (Urtica dioica L. Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Diana N Obanda

    Full Text Available Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle improves insulin action, yet the precise mechanism(s are not known. Hence, we examined the effects of Urtica dioica L. (UT on adipocytes.We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined.As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation.In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

  9. Excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in experimental approaches of Parkinsonism.

    Science.gov (United States)

    Fernández-Espejo, Emilio; Bis-Humbert, Cristian

    2018-06-06

    3-iodo-l-tyrosine might play a role in Parkinson's disease since this molecule is able, at high concentration, to inhibit tyrosine-hydroxylase activity, the rate-limiting enzyme in dopamine biosynthesis. The possible Parkinson-like effects of 3-iodo-l-tyrosine were tested on three experimental approaches in mice: cultured substantia nigra neurons, the enteric nervous system of the jejunum after intra-peritoneal infusions, and the nigrostriatal system following unilateral intrabrain injections. 3-iodo-l-tyrosine, a physiological molecule, was used at concentrations higher than its serum levels in humans. Parkinson-like signs were evaluated through abnormal aggregation of α-synuclein and tyrosine-hydroxylase, loss of tyrosine-hydroxylase-expressing and striatum-projecting neurons and fibers, reduced tyrosine-hydroxylase density, and Parkinson-like motor and non-motor deficits. The retrograde tracer FluoroGold was used in the brain model. The findings revealed that excess amounts of 3-iodo-l-tyrosine induce Parkinson-like effects in the three experimental approaches. Thus, culture neurons of substantia nigra show, after 3-iodo-l-tyrosine exposure, intracytoplasmic inclusions that express α-synuclein and tyrosine-hydroxylase. Intra-peritoneal infusions of 3-iodo-l-tyrosine cause, in the long-term, α-synuclein aggregation, thicker α-synuclein-positive fibers, and loss of tyrosine-hydroxylase-positive cells and fibers in intramural plexuses and ganglia of the jejunum. Infusion of 3-iodo-l-tyrosine into the left dorsal striata of mice damages the nigrostriatal system, as revealed through lower striatal tyrosine-hydroxylase density, reduced number of tyrosine-hydroxylase-expressing and striatum-projecting neurons in the left substantia nigra, as well as the emergence of Parkinson-like behavioral deficits such as akinesia, bradykinesia, motor disbalance, and locomotion directional bias. In conclusion, excess amounts of 3-iodo-l-tyrosine induce Parkinson-like features in

  10. E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox

    Directory of Open Access Journals (Sweden)

    Asisa Volz

    2018-01-01

    Full Text Available The highly attenuated Modified Vaccinia virus Ankara (MVA lacks most of the known vaccinia virus (VACV virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

  11. Artesunate inhibits adipogeneis in 3T3-L1 preadipocytes by reducing the expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Byeong-Churl, E-mail: jangbc123@gw.kmu.ac.kr

    2016-05-20

    Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. However, excessive adipogenesis is closely linked to the development of obesity. Artesunate, one of artemisinin-type sesquiterpene lactones from Artemisia annua L., is known for anti-malarial and anti-cancerous activities. In this study, we investigated the effect of artesunate on adipogenesis in 3T3-L1 preadipocytes. Artesunate strongly inhibited lipid accumulation and triglyceride (TG) synthesis during the differentiation of 3T3-L1 preadipocytes into adipocytes at 5 μM concentration. Artesunate at 5 μM also reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during adipocyte differentiation. Moreover, artesunate at 5 μM reduced leptin, but not adiponectin, mRNA expression during adipocyte differentiation. Taken together, these findings demonstrate that artesunate inhibits adipogenesis in 3T3-L1 preadipoytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. -- Highlights: •Artesunate, an artemisinin derivative, inhibits adipogenesis. •Artesunate inhibits C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3 in 3T3-L1 adipocytes. •Artesunate reduces leptin, but not adiponectin, expression in 3T3-L1 adipocytes. •Artesunate thus may have therapeutic potential against obesity.

  12. HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway

    Directory of Open Access Journals (Sweden)

    Yi Liu

    2018-01-01

    Full Text Available Here, we show that HEMATOLOGICAL AND NEUROLOGICAL EXPRESSED 1-LIKE (HN1L is a targetable breast cancer stem cell (BCSC gene that is altered in 25% of whole breast cancer and significantly correlated with shorter overall or relapse-free survival in triple-negative breast cancer (TNBC patients. HN1L silencing reduced the population of BCSCs, inhibited tumor initiation, resensitized chemoresistant tumors to docetaxel, and hindered cancer progression in multiple TNBC cell line-derived xenografts. Additionally, gene signatures associated with HN1L correlated with shorter disease-free survival of TNBC patients. We defined HN1L as a BCSC transcription regulator for genes involved in the LEPR-STAT3 signaling axis as HN1L binds to a putative consensus upstream sequence of STAT3, LEPTIN RECEPTOR, and MIR-150. Our data reveal that BCSCs in TNBC depend on the transcription regulator HN1L for the sustained activation of the LEPR-STAT3 pathway, which makes it a potentially important target for both prognosis and BCSC therapy.

  13. Decoy receptor 3 suppresses FasL-induced apoptosis via ERK1/2 activation in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi; Li, Dechun; Zhao, Xin; Song, Shiduo; Zhang, Lifeng; Zhu, Dongming [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Wang, Zhenxin [Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China); Chen, Xiaochen [Department of Pathology, The Obstetrics & Gynecology Hospital of Fudan University, Shanghai 200090 (China); Zhou, Jian, E-mail: zhoujian20150602@126.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006 (China)

    2015-08-07

    Resistance to Fas Ligand (FasL) mediated apoptosis plays an important role in tumorigenesis. Decoy receptor 3 (DcR3) is reported to interact with FasL and is overexpressed in some malignant tumors. We sought to investigate the role of DcR3 in resistance to FasL in pancreatic cancer. We compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. We explored the impact of siRNA knockdown of, or exogenous supplementation with, DcR3 on FasL-induced cell growth inhibition in pancreatic cancer cell lines and expression of proteins involved in apoptotic signaling. We assessed the level of DcR3 protein and ERK1/2 phosphorylation in tumor and non-tumor tissue samples of 66 patients with pancreatic carcinoma. RNAi knockdown of DcR3 expression in SW1990 cells reduced resistance to FasL-induced apoptosis, and supplementation of Patu8988 with rDcR3 had the opposite effect. RNAi knockdown of DcR3 in SW1990 cells elevated expression of caspase 3, 8 and 9, and reduced ERK1/2 phosphorylation (P < 0.05), but did not alter phosphorylated-Akt expression. 47 tumor tissue specimens, but only 15 matched non-tumor specimens stained for DcR3 (χ{sup 2} = 31.1447, P < 0.001). The proliferation index of DcR3 positive specimens (14.26  ±  2.67%) was significantly higher than that of DcR3 negative specimens (43.58  ±  7.88%, P < 0.01). DcR3 expression positively correlated with p-ERK1/2 expression in pancreatic cancer tissues (r = 0.607, P < 0.001). DcR3 enhances ERK1/2 phosphorylation and opposes FasL signaling in pancreatic cancer cells. - Highlights: • We investigated the role of DcR3 in FasL resistance in pancreatic cancer. • Knockdown of DcR3 in SW1990 cells reduced resistance to FasL-induced apoptosis. • DcR3 knockdown also elevated caspase expression, and reduced ERK1/2 phosphorylation. • Tumor and non-tumor tissues were collected from 66 pancreatic carcinoma patients

  14. Hydroxyframoside B, a secoiridoid of Fraxinus rhynchophylla, inhibits adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Choi, Kyeong-Mi; Shin, Eunjin; Liu, Qing; Yoo, Hwan-Soo; Kim, Young Choong; Sung, Sang Hyun; Hwang, Bang Yeon; Lee, Mi Kyeong

    2011-07-01

    Fraxinus rhynchophylla showed significant inhibitory activity on adipocyte differentiation in the 3T3-L1 preadipocyte cell line as assessed by measuring fat accumulation using Oil Red O staining. Further fractionation led to the isolation of two secoiridoids, oleuropein and hydroxyframoside B. Hydroxyframoside B significantly reduced fat accumulation and triglyceride content in differentiated 3T3-L1 cells without affecting cell viability, whereas oleuropein showed little effect. Further studies with interval treatment demonstrated that hydroxyframoside B exerted inhibitory activity on adipocyte differentiation when treated within 2 days (days 0-2) after differentiation induction. In addition, hydroxyframoside B significantly blocked the induction of adipogenic transcription factors such as C/EBP α, C/EBP β, and PPAR γ. Taken together, these results suggest that hydroxyframoside B inhibited early/middle stage of adipogenic differentiation, in part, via inhibition of C/EBP α, C/EBP β, and PPAR γ-dependent pathways. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Characteristics of D-{sup 3}He fueled frc reactor: ARTEMIS-L

    Energy Technology Data Exchange (ETDEWEB)

    Momota, H.; Motojima, O.; Okamoto, M.; Sudo, S.; Tomita, Y.; Yamaguchi, S.; Iiyoshi, A.; Onozuka, M.; Ohnishi, M.; Uenosono, C.

    1993-11-01

    The paper introduces briefly the scenario and discuss the attractive characteristics of D-3He fueled commercial fusion reactor ARTEMIS-L. By using favorable characteristics of a field-reversed configuration, the fusion plasma of ARTEMIS-L is compact and its beta-value is extremely high. One find consequently a possibility of constructing an economical fusion power power plant on this prospect. The life of the structural materials is sound during the full reactor life (30 years) and the safety of the reactor is intrinsic to D-3He fuels. The amount of disposed materials is rather small and the level of these intruder dose is so low that the plant appears to be acceptable in view of the environment. (author).

  16. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    Science.gov (United States)

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Estimating an exchange rate between the EQ-5D-3L and ASCOT.

    Science.gov (United States)

    Stevens, Katherine; Brazier, John; Rowen, Donna

    2018-06-01

    The aim was to estimate an exchange rate between EQ-5D-3L and the Adult Social Care Outcome Tool (ASCOT) using preference-based mapping via common time trade-off (TTO) valuations. EQ-5D and ASCOT are useful for examining cost-effectiveness within the health and social care sectors, respectively, but there is a policy need to understand overall benefits and compare across sectors to assess relative value for money. Standard statistical mapping is unsuitable since it relies on conceptual overlap of the measures but EQ-5D and ASCOT have different conceptualisations of quality of life. We use a preference-based mapping approach to estimate the exchange rate using common TTO valuations for both measures. A sample of health states from each measure was valued using TTO by 200 members of the UK adult general population. Regression analyses are used to generate separate equations between EQ-5D-3L and ASCOT values using their original value set and TTO values elicited here. These are solved as simultaneous equations to estimate the relationship between EQ-5D-3L and ASCOT. The relationship for moving from ASCOT to EQ-5D-3L is a linear transformation with an intercept of -0.0488 and gradient of 0.978. This enables QALY gains generated by ASCOT and EQ-5D to be compared across different interventions. This paper estimated an exchange rate between ASCOT and EQ-5D-3L using a preference-based mapping approach that does not compromise the descriptive systems of the two measures. This contributes to the development of preference-based mapping through the use of TTO as the common metric used to estimate the exchange rate between measures.

  18. 3D-LIN: A Configurable Low-Latency Interconnect for Multi-Core Clusters with 3D Stacked L1 Memory

    OpenAIRE

    Beanato, Giulia; Loi, Igor; De Micheli, Giovanni; Leblebici, Yusuf; Benini, Luca

    2012-01-01

    Shared L1 memories are of interest for tightly- coupled processor clusters in programmable accelerators as they provide a convenient shared memory abstraction while avoiding cache coherence overheads. The performance of a shared-L1 memory critically depends on the architecture of the low-latency interconnect between processors and memory banks, which needs to provide ultra-fast access to the largest possible L1 working set. The advent of 3D technology provides new opportunities to improve the...

  19. An L319F mutation in transmembrane region 3 (TM3) selectively reduces sensitivity to okaramine B of the Bombyx mori l-glutamate-gated chloride channel.

    Science.gov (United States)

    Furutani, Shogo; Okuhara, Daiki; Hashimoto, Anju; Ihara, Makoto; Kai, Kenji; Hayashi, Hideo; Sattelle, David B; Matsuda, Kazuhiko

    2017-10-01

    Okaramines produced by Penicillium simplicissimum AK-40 activate l-glutamate-gated chloride channels (GluCls) and thus paralyze insects. However, the okaramine binding site on insect GluCls is poorly understood. Sequence alignment shows that the equivalent of residue Leucine319 of the okaramine B sensitive Bombyx mori (B. mori) GluCl is a phenylalanine in the okaramine B insensitive B. mori γ-aminobutyric acid-gated chloride channel of the same species. This residue is located in the third transmembrane (TM3) region, a location which in a nematode GluCl is close to the ivermectin binding site. The B. mori GluCl containing the L319F mutation retained its sensitivity to l-glutamate, but responses to ivermectin were reduced and those to okaramine B were completely blocked.

  20. Power density investigation on the press-pack IGBT 3L-HB-VSCs applied to large wind turbine

    DEFF Research Database (Denmark)

    Senturk, Osman Selcuk; Munk-Nielsen, Stig; Teodorescu, Remus

    2011-01-01

    capabilities, DC capacitor sizes, converter cabinet volumes of the three 3LHB- VSCs utilizing press-pack IGBTs are investigated in order to quantify and compare the power densities of the 3L-HB-VSCs employed as grid-side converters. Also, the suitable transformer types for the 3L-HB-VSCs are determined......With three different DC-side and AC-side connections, the three-level H-bridge voltage source converters (3L-HB-VSCs) are alternatives to 3L neutral-point-clamped VSCs (3L-NPC-VSCs) for interfacing large wind turbines with electricity grids. In order to assess their feasibility for large wind...... turbines, they should be investigated in terms of power density, which is one of the most important design criteria for wind turbine converters due to turbine nacelle space limitation. In this study, by means of the converter electro-thermal models based on the converter characteristics, the power...

  1. Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3′ Uridylated Intermediates Degraded by DIS3L2

    Directory of Open Access Journals (Sweden)

    Marshall P. Thomas

    2015-05-01

    Full Text Available Apoptosis is a tightly coordinated cell death program that damages mitochondria, DNA, proteins, and membrane lipids. Little is known about the fate of RNA as cells die. Here, we show that mRNAs, but not noncoding RNAs, are rapidly and globally degraded during apoptosis. mRNA decay is triggered early in apoptosis, preceding membrane lipid scrambling, genomic DNA fragmentation, and apoptotic changes to translation initiation factors. mRNA decay depends on mitochondrial outer membrane permeabilization and is amplified by caspase activation. 3′ truncated mRNA decay intermediates with nontemplated uridylate-rich tails are generated during apoptosis. These tails are added by the terminal uridylyl transferases (TUTases ZCCHC6 and ZCCHC11, and the uridylated transcript intermediates are degraded by the 3′ to 5′ exonuclease DIS3L2. Knockdown of DIS3L2 or the TUTases inhibits apoptotic mRNA decay, translation arrest, and cell death, whereas DIS3L2 overexpression enhances cell death. Our results suggest that global mRNA decay is an overlooked hallmark of apoptosis.

  2. Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

    Directory of Open Access Journals (Sweden)

    Sassi, A.,

    2017-10-01

    Full Text Available Trichosanthes cucumerina (Cucurbitaceae commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001 increased glycerol release levels (75.34±3.69 μg/ml during adipolysis. The extracts also significantly (p<0.001 promoted the uptake of glucose into the cells (2636.22±91.33 Bq in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001 in adiponectin concentrations (3593.1±225.25 ng/mL and a decrease in leptin concentrations (23870±5066.07 pg/mL. The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

  3. The muon spectrometer of the L3 detector at LEP

    International Nuclear Information System (INIS)

    Peng, Y.

    1988-01-01

    In this thesis the construction of the muon spectrometer of the L3 detector is described, one of the four detectors presently being prepared for experimentation at LEP. This accelerator is built at CERN, Geneva, and is due to start operation in July 1989. One of the unique features of the L3 experiment is the measurement of the momentum of the muons produced in the e + e - collisions iwht an independent muon spectrometer. This makes it possible to study final states involving muons, with high accuracy (δP/P = 2% at 45 GeV). The muon spectrometer consists of 80 large drift chambers, arranged in 16 modules or 'octants', that fill a cylindrical volume of 12 m in length, 5 m inner diameter and 12 m outer diameter. The design of the drift chambers, the construction, the alignment procedure and the test results for the complete octants are described. 51 refs.; 57 figs.; 16 tabs

  4. AV3V lesions reduce the pressor response to L-glutamate into the RVLM.

    Science.gov (United States)

    Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; Colombari, Débora Simões de Almeida; Menani, José V

    2006-05-01

    Neurons from the rostral ventrolateral medulla (RVLM) directly activate sympathetic pre-ganglionic neurons in the spinal cord. Hypertensive responses and sympathetic activation produced by different stimuli are strongly affected by lesions of the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V region). Therefore, in the present study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the AV3V region on the pressor responses produced by injections of the excitatory amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the RVLM were used. The pressor responses produced by injections of L-glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39 +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6, 39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2 and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in sham or AV3V-lesioned rats produced no significant change in the heart rate (HR). Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium nitroprusside, respectively, and the pressor and bradycardic responses to chemoreflex activation with iv potassium cyanide were not modified by AV3V lesions. The results suggest that signals from the AV3V region are important for sympathetic activation induced by L-glutamate into the RVLM.

  5. Monoterpene limonene induces brown fat-like phenotype in 3T3-L1 white adipocytes.

    Science.gov (United States)

    Lone, Jameel; Yun, Jong Won

    2016-05-15

    Several dietary compounds that are able to induce the brown fat-like phenotype in white adipocytes have been considered for treatment of obesity due to their ability to increase energy expenditure. Here, we report that limonene induces the brown fat-like phenotype in 3T3-L1 adipocytes by increasing expression of brown adipocyte-specific genes and proteins. Limonene-induced browning in white adipocytes was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR, immunoblot analysis, and immunocytochemical staining. Limonene enhanced mitochondrial biogenesis, as evidenced by increased mitochondrial content and immunofluorescent intensity. Limonene also significantly elevated protein levels of HSL, PLIN, p-AMPK, p-ACC, ACO, COX4, CPT1, and CYT C, suggesting its possible role in enhancement of lipolysis and lipid catabolism. Increased expression of PRDM16, UCP1, C/EBPβ, and other brown fat-specific markers by limonene was possibly mediated by activation of β3-adnergenic receptor (β3-AR), as inhibition of β3-AR inhibited up-regulation of brown fat-specific markers. Similarly, limonene-mediated activation of ERK and up-regulation of key brown adipocyte specific markers were eliminated by treatment with ERK antagonist. Taken together, these results suggest that limonene induces browning of 3T3-L1 adipocytes via activation of β3-AR and the ERK signaling pathway. In conclusion, our findings suggest that limonene plays a dual modulatory role in induction of the brown adipocyte-like phenotype as well as promotion of lipid metabolism and thus may have potential therapeutic implications for treatment of obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The direct l-type resonance spectrum of CF3CCH in the vibrational state ν 10 = 2

    International Nuclear Information System (INIS)

    Woetzel, Ulf; Maeder, Heinrich; Harder, Hauke; Pracna, Petr; Sarka, Kamil

    2005-01-01

    The direct l-type resonance spectrum of CF 3 CCH in the vibrational state ν 10 = 2 has been measured by means of waveguide microwave Fourier transform spectroscopy in the range 8-26 GHz. Two types of direct l-type resonance transitions induced by the (Δk = ±2, Δl = ±2) interaction could be observed: 262 transitions following the ΔJ = 0, Δk = Δl = 2 selection rule covering values of J = 17-64 and G vertical bar k - l vertical bar from 2 to 15, and 75 transitions following the ΔJ = 0, Δk = Δl = 4 selection rule covering values of J = 44-70 and G up to 3. The strong (2, 2) resonance furthermore allowed the observation of A 1 -A 2 splittings of the k = l = ±2 states from J = 63-70. The transitions with G = 3 showed splittings due to the (4, -2) and (0, 6) interactions. The corresponding energy level systems and part of the Hamiltonian matrix are discussed. Strong perturbations due to Δ(k - l) = 3 interactions coupling the states k = ±1, l = ±2 and k = ±4, l ±2 made possible the observation of perturbation-allowed transitions with selection rule k = ±1, l =± 2 ↔ k = 0, l = ±2. Additionally, the J = 2-1 and 3-2 rotational transitions have been measured. A multiple fitting analysis has been performed in which the experimental data have been fitted using five reduced forms of the effective Hamiltonian as proposed by Sarka and Harder [J. Mol. Spectrosc. 197 (1999) 254]. Parameters up to sixth order have been determined including the axial rotational constant A for both values of vertical bar l vertical bar and the unitary equivalence of the determined parameter sets has been demonstrated

  7. [Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

    Science.gov (United States)

    Lin, Juan-Na; Kuang, Qiao-Ting; Ye, Kai-He; Ye, Chun-Ling; Huang, Yi; Zhang, Xiao-Qi; Ye, Wen-Cai

    2013-08-01

    To investigate the influences of triterpenoid from Psidium guajava Leaves (ursolic acid) on the proliferation, differentiation of 3T3-L1 preadipocyte, and its possible mechanism treat for insulin resistance. 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h, the cell viability was tested by MTT assay. Induced for 6 days, the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARgamma and PTP1B in insulin resistant adipocyte were measured by Western Blotting. Compared with medium control group, 30, 100 micromol/L ursolic acid could increase its proliferation and differentiation significantly (P 0.05). Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte, enhance cellular glucose uptake, inhibit the production of FFA, promote the secretion of adiponectin insulin resistant adipocyte, its mechanism may be related to upregulating the expression of PPARgamma protein.

  8. LOFT/L3-6, Loss of Fluid Test, 6. NRC L3 Small Break LOCA Experiment

    International Nuclear Information System (INIS)

    1992-01-01

    1 - Description of test facility: The LOFT Integral Test Facility is a scale model of a LPWR. The intent of the facility is to model the nuclear, thermal-hydraulic phenomena which would take place in a LPWR during a LOCA. The general philosophy in scaling coolant volumes and flow areas in LOFT was to use the ratio of the LOFT core [50 MW(t)] to a typical LPWR core [3000 MW(t)]. For some components, this factor is not applied; however, it is used as extensively as practical. In general, components used in LOFT are similar in design to those of a LPWR. Because of scaling and component design, the LOFT LOCA is expected to closely model a LPWR LOCA. 2 - Description of test: This was the sixth in the NRC L3 Series of small-break LOCA experiments. A 10-cm (2.5-in.) cold-leg non-communicative-break LOCA was simulated. Pumps were running. The experiment was conducted on 10 December 1980

  9. LOFT/L3-5, Loss of Fluid Test, 5. NRC L3 Small Break LOCA Experiment

    International Nuclear Information System (INIS)

    1991-01-01

    1 - Description of test facility: The LOFT Integral Test Facility is a scale model of a LPWR. The intent of the facility is to model the nuclear, thermal-hydraulic phenomena which would take place in a LPWR during a LOCA. The general philosophy in scaling coolant volumes and flow areas in LOFT was to use the ratio of the LOFT core [50 MW(t)] to a typical LPWR core [3000 MW(t)]. For some components, this factor is not applied; however, it is used as extensively as practical. In general, components used in LOFT are similar in design to those of a LPWR. Because of scaling and component design, the LOFT LOCA is expected to closely model a LPWR LOCA. 2 - Description of test: This was the fifth in the NRC L3 Series of small-break LOCA experiments. A 10-cm (2.5-in.) cold-leg non-communicative-break LOCA was simulated. Pumps were shut off. The experiment was conducted on 29 September 1980

  10. T-odd correlation in the $K_{l3} \\gamma$ decay

    CERN Document Server

    Braguta, V V; Chalov, A E

    2002-01-01

    The dependence of the K/sup +/ to pi /sup 0/l/sup +/ nu /sub l/ gamma decay rate on the T-odd kinematical variable xi = q . Ýp/sub l/ * p /sub pi /¿/m/sub K//sup 3/ is investigated in the tree and one-loop approximations of the Standard Model (SM). It is shown that the partial width of the decay on the tree level is an even function of the variable, whereas the odd component is generated by the electromagnetic final-state interaction and determined by the imaginary parts of one-loop diagrams. The xi -odd components of the partial widths of the K/sup +/ to pi /sup 0/e/sup +/ nu /sub e/ gamma and K/sup +/ to pi /sup 0/ mu /sup +/ nu /sub mu / gamma decays calculated in the one-loop approximation are smaller by four orders of magnitude than the even components evaluated from the tree-level SM diagrams. (11 refs).

  11. Search on charginos and neutralinos with the L3 detector at LEP

    International Nuclear Information System (INIS)

    Chereau, Xavier

    1998-01-01

    This work presents an experimental search for supersymmetric particles, the charginos and the neutralinos, at center of mass energies √ 161, 172 and 183 GeV, with the L3 detector at the e + e - collider LEP. Assuming R-parity conservation, SUSY events have a large missing energy, carried by the lightest supersymmetric particle (LSP), which allow us to distinguish them from standard events. Then, for all the studied final states and all the energies, we optimized the selections in order to have the best signal-to-noise ratio. No excess of events were observed with respect to the standard model predictions. We set upper limits on the chargino and neutralino production cross sections. In the frame of the constraint MSSM, these results were combined with the results from the L3 slepton analyses to set lower limits on the chargino and neutralino masses: particularly, we exclude a neutralino χ 1 0 bar lighter than 25.9 GeV/c 2 (95% C.L.). This result plays an important role for the interpretation of the dark matter in universe. The search for events with missing energy needs a detector with a good hermeticity. At the end of 1995, a new electromagnetic calorimeter was installed in the L3 experiment. Here we present the improvements of performances and the calibration of this detector composed of 48 bricks made with lead and scintillating fibers (SPACAL)

  12. Determination of the masses of electrical weak gauge bosons with L3

    CERN Document Server

    Rosenbleck, Christian

    2006-01-01

    This thesis presents the measurement of the masses of the carriers of the weak force in the Standard Model of Particle Physics, the gauge bosons W and Z. The masses are determined using the kinematics of the bosons' decay products. The data were collected by the L3 experiment at the Large Electron Positron Collider (LEP) at centre-of-mass energies, sqrt(s), between 183 GeV and 209 GeV in the years 1997 to 2000. The mass of the Z-boson, mZ, is already known very precisely: The L3 collaboration determined it to be mZ = 91.1898 +- 0.0031 GeV from a scan of the Z resonance. Therefore the main aim of this analysis is not the determination of the numerical value of mZ; instead the analysis is used to cross-check the measurement of the W boson mass since the methods are similar. Alternatively, the analysis can be used to measure the mean centre-of-mass energy at the L3 interaction point. The Z-boson mass is determined to be mZ = 91.272 +- 0.046 GeV. If interpreted as measurement of the centre-of-mass energy, this va...

  13. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Kusunoki, Chisato; Yang, Liu; Yoshizaki, Takeshi; Nakagawa, Fumiyuki; Ishikado, Atsushi; Kondo, Motoyuki; Morino, Katsutaro; Sekine, Osamu; Ugi, Satoshi; Nishio, Yoshihiko; Kashiwagi, Atsunori; Maegawa, Hiroshi

    2013-01-01

    Highlights: ► Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. ► EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. ► Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. ► Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid (ω3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of ω3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with ω3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). ω3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with ω3-PUFA prevented H 2 O 2 -induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.

  14. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3T3-L1 cells

    International Nuclear Information System (INIS)

    Hsu, Hsin-Fen; Tsou, Tsui-Chun; Chao, How-Ran; Kuo, Ya-Ting; Tsai, Feng-Yuan; Yeh, Szu-Ching

    2010-01-01

    Dioxin exposure has been positively associated with human type II diabetes. Because lipophilic dioxins accumulate mainly in adipose tissue, this study aimed to determine if dioxins induce metabolic dysfunction in fat cells. Using 3T3-L1 cells as an in vitro model, we analyzed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model dioxin, on adipogenic differentiation, glucose uptake, and lipolysis. TCDD inhibited adipogenic differentiation, as determined by using oil droplet formation and adipogenic marker gene expression, including PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer-binding protein α), and Glut4 (glucose transporter type 4). Effects of TCDD on glucose uptake were evaluated using fully differentiated 3T3-L1 adipocytes, revealing that TCDD significantly attenuated insulin-induced glucose uptake dose dependently. Inhibition of aryl hydrocarbon receptor (AhR) by α-naphthoflavone (α-NF), an AhR inhibitor, did not prevent the inhibitory effect of TCDD on glucose uptake, suggesting that TCDD attenuates insulin-induced glucose uptake in an AhR-independent manner. Effects of TCDD on lipolysis were determined using glycerol release assay. We found that TCDD had no marked effect on isoproterenol-induced glycerol release in fully differentiated 3T3-L1 adipocytes. These results provide in vitro evidence of TCDD's effects on fat cell metabolism, suggesting dioxin exposure in development of insulin resistance and type II diabetes.

  15. Association of low race performance with mtDNA haplogroup L3b of Australian thoroughbred horses.

    Science.gov (United States)

    Lin, Xiang; Zheng, Hong-Xiang; Davie, Allan; Zhou, Shi; Wen, Li; Meng, Jun; Zhang, Yong; Aladaer, Qimude; Liu, Bin; Liu, Wu-Jun; Yao, Xin-Kui

    2018-03-01

    Mitochondrial DNA (mtDNA) encodes the genes for respiratory chain sub-units that determine the efficiency of oxidative phosphorylation in mitochondria. The aim of this study was to determine if there were any haplogroups and variants in mtDNA that could be associated with athletic performance of Thoroughbred horses. The whole mitochondrial genomes of 53 maternally unrelated Australian Thoroughbred horses were sequenced and an association study was performed with the competition histories of 1123 horses within their maternal lineages. A horse mtDNA phylogenetic tree was constructed based on a total of 195 sequences (including 142 from previous reports). The association analysis showed that the sample groups with poor racing performance history were enriched in haplogroup L3b (p = .0003) and its sub-haplogroup L3b1a (p = .0007), while those that had elite performance appeared to be not significantly associated with haplogroups G2 and L3a1a1a (p > .05). Haplogroup L3b and L3b1a bear two and five specific variants of which variant T1458C (site 345 in 16s rRNA) is the only potential functional variant. Furthermore, secondary reconstruction of 16s RNA showed considerable differences between two types of 16s RNA molecules (with and without T1458C), indicating a potential functional effect. The results suggested that haplogroup L3b, could have a negative association with elite performance. The T1458C mutation harboured in haplogroup L3b could have a functional effect that is related to poor athletic performance.

  16. Exploring the role of CHI3L1 in pre-metastatic lungs of mammary tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Stephania eLibreros

    2013-12-01

    Full Text Available Elevated levels of chitinase-3-like-1 (CHI3L1 are associated with poor prognosis, shorter recurrence-free intervals and low survival in breast cancer patients. Breast cancer often metastasizes to the lung. We hypothesized that molecules expressed in the pre-metastatic lung microenvironment could support the newly immigrant tumor cells by providing growth and angiogenic factors. Macrophages are known to play an important role in tumor growth by releasing pro-angiogenic molecules. Using mouse mammary tumor models, we have previously shown that during neoplastic progression both the mammary tumor cells and splenic macrophages from tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice. However, the role of CHI3L1 in inducing angiogenesis by macrophages at the pulmonary microenvironment to support newly arriving breast cancer cells is not yet known. In this study, we determined the expression of CHI3L1 in bronchoalveolar lavage macrophages and interstitial macrophages in regulating angiogenesis that could support the growth of newly immigrant mammary tumor cells into the lung. Here we show that in vitro treatment of pulmonary macrophages with recombinant murine CHI3L1 resulted in enhanced expression of pro-angiogenic molecules including CCL2, CXCL2 and MMP-9. We and others have previously shown that inhibition of CHI3L1 decreases the production of angiogenic molecules. In this study, we explored if in vivo administration of chitin microparticles has an effect on the expression of CHI3L1 and pro-angiogenic molecules in the lungs of mammary tumor-bearing mice. We show that treatment with chitin microparticles decreases the expression of CHI3L1 and pro-angiogenic molecules in the metastatic lung. These studies suggest that targeting CHI3L1 may serve as a potential therapeutic agent to inhibit angiogenesis and thus possibly tumor growth and metastasis.

  17. Synergistic Effect of L-Methionine and KI on Copper Corrosion Inhibition in HNO3 (1M

    Directory of Open Access Journals (Sweden)

    Amel SEDIK

    2014-05-01

    Full Text Available L-Methionine (L-Met efficiency as a non-toxic corrosion inhibitor for copper in 1M HNO3 has been studied by using electrochemical impedance spectroscopy (EIS and potentiodynamic polarization. Copper corrosion rate significant decrease was observed in the presence of L-Met at 10-4M. The Obtained Results from potentiodynamic polarization and impedance measurements are in good agreement. L-Methionine adsorption on copper surface follows Langmuir isotherm. L-Met free energy adsorption on copper (-30 KJ mol-1 reveals an inhibition strong physical adsorption on copper surface. In order to evaluate the L-Met effect, L-Met and iodide ion’synergistic effect was used to prevent copper corrosion in nitric acid. It was found that inhibitor efficiency (IE reached 98.27 % in 1M solution containing 10-4M L-Met and 10- 3 M KI. The synergistic effect was attributed to iodide ions adsorption on copper surface, which facilitated the L-Met adsorption and an inhibitive film formation.

  18. Through analysis of LOFT L2-3 by THYDE-P code

    International Nuclear Information System (INIS)

    Hirano, Masashi

    1981-10-01

    A through calculation of Experiment L2-3 of the Loss-of-Fluid Test (LOFT) Facility Power Ascension Series (Experiment Series L2) was performed with the THYDE-P code. The specific objectives of Experiment L2-3 were to determine the thermal-hydraulic behavior of the nuclear core and the thermal-mechanical response of the fuel rod cladding with a maximum linear heat generation rate of 39.4 kW/m. The THYDE-P code is a computer code to analyze both the blowdown and refill-reflood phases of loss-of-coolant accidents (LOCAs) of pressurized water reactors (PWRs) without a change in the methods and the models and is now under verification study and modification. The present calculation was performed by best estimate (BE) options as Sample Calculation Run 40, which is a portion of a series of THYDE-P sample calculations. The calculation was carried out from test initiation until complete submersion of the core volume with subcooled water, i.e. about 60 sec. The trend of the calculated cladding surface temperature was in good agreement with that of the experimental results. (author)

  19. Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway.

    Directory of Open Access Journals (Sweden)

    Yonghan He

    Full Text Available BACKGROUND: Ursolic acid (UA is a triterpenoid compound with multiple biological functions. This compound has recently been reported to possess an anti-obesity effect; however, the mechanisms are less understood. OBJECTIVE: As adipogenesis plays a critical role in obesity, the present study was conducted to investigate the effect of UA on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes. METHODS AND RESULTS: The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of UA for 6 days. The cells were determined for proliferation, differentiation, fat accumulation as well as the protein expressions of molecular targets that regulate or are involved in fatty acid synthesis and oxidation. The results demonstrated that ursolic acid at concentrations ranging from 2.5 µM to 10 µM dose-dependently attenuated adipogenesis, accompanied by reduced protein expression of CCAAT element binding protein β (C/EBPβ, peroxisome proliferator-activated receptor γ (PPARγ, CCAAT element binding protein α (C/EBPα and sterol regulatory element binding protein 1c (SREBP-1c, respectively. Ursolic acid increased the phosphorylation of acetyl-CoA carboxylase (ACC and protein expression of carnitine palmitoyltransferase 1 (CPT1, but decreased protein expression of fatty acid synthase (FAS and fatty acid-binding protein 4 (FABP4. Ursolic acid increased the phosphorylation of AMP-activated protein kinase (AMPK and protein expression of (silent mating type information regulation 2, homolog 1 (Sirt1. Further studies demonstrated that the anti-adipogenic effect of UA was reversed by the AMPK siRNA, but not by the Sirt1 inhibitor nicotinamide. Liver kinase B1 (LKB1, the upstream kinase of AMPK, was upregulated by UA. When LKB1 was silenced with siRNA or the inhibitor radicicol, the effect of UA on AMPK activation was diminished. CONCLUSIONS: Ursolic acid inhibited 3T3-L1 preadipocyte differentiation and adipogenesis through the LKB1/AMPK

  20. Simulation Experiment Description Markup Language (SED-ML Level 1 Version 3 (L1V3

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T.

    2018-03-01

    Full Text Available The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML is an XML-based format that encodes, for a given simulation experiment, (i which models to use; (ii which modifications to apply to models before simulation; (iii which simulation procedures to run on each model; (iv how to post-process the data; and (v how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1 implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

  1. Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 3 (L1V3).

    Science.gov (United States)

    Bergmann, Frank T; Cooper, Jonathan; König, Matthias; Moraru, Ion; Nickerson, David; Le Novère, Nicolas; Olivier, Brett G; Sahle, Sven; Smith, Lucian; Waltemath, Dagmar

    2018-03-19

    The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML) describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML) is an XML-based format that encodes, for a given simulation experiment, (i) which models to use; (ii) which modifications to apply to models before simulation; (iii) which simulation procedures to run on each model; (iv) how to post-process the data; and (v) how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1) implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

  2. Orientación de láminas delgadas de (Pb, CaTiO3

    Directory of Open Access Journals (Sweden)

    Mendiola, J.

    1999-06-01

    Full Text Available Calcium modified PbTiO3 thin films have been prepared on platinized Si, MgO and SrTiO3 substrates. The films were deposited from a sol-gel solution with a concentration of 0.3 M and with a 10% excess of PbO. Two deposits of this solution on the substrates were made by spin-coating, crystallizing each of them by a Rapid Thermal Processing. The resulting films present a single (Pb,CaTiO3 perovskite phase. All the films are textured, but the films deposited on MgO and SrTiO3 show a preferred orientation in the polar direction of the perovskite. As a result of this orientation, pyroelectric coefficients were measured, without any poling, for the films on MgO and SrTiO3. Pyroelectric measurements indicate the application of these films in infrarred sensors.Se han preparado láminas delgadas de PbTiO3 modificado con calcio sobre substratos de Si, MgO y SrTiO3 electrodados con Pt. Las películas se depositaron a partir de una solución sintetizada por sol-gel, con concentración 0.3 M y con un 10 % en exceso de PbO. En cada lámina se hicieron dos depósitos de la solución sobre el substrato mediante la técnica de “spin-coating”, cristalizando cada uno de ellos con un tratamiento térmico rápido. Todas las láminas resultantes presentaban como única fase cristalina la perovskita de (Pb,CaTiO3. Las láminas presentaron una cierta textura, observándose una orientación preferente en la dirección polar en el caso de las películas depositas sobre MgO y SrTiO3. Como resultado de esta orientación, se midieron coeficientes piroeléctricos, sin polarización previa, en las láminas sobre MgO y SrTiO3. Las medidas piroeléctricas de estos materiales evidencian su utilidad en dispositivos para sensores de infrarrojo.

  3. BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L).

    Science.gov (United States)

    Maiuri, Maria Chiara; Criollo, Alfredo; Tasdemir, Ezgi; Vicencio, José Miguel; Tajeddine, Nicolas; Hickman, John A; Geneste, Olivier; Kroemer, Guido

    2007-01-01

    Beclin 1 has recently been identified as novel BH3-only protein, meaning that it carries one Bcl-2-homology-3 (BH3) domain. As other BH3-only proteins, Beclin 1 interacts with anti-apoptotic multidomain proteins of the Bcl-2 family (in particular Bcl-2 and its homologue Bcl-X(L)) by virtue of its BH3 domain, an amphipathic alpha-helix that binds to the hydrophobic cleft of Bcl-2/Bcl-X(L). The BH3 domains of other BH3-only proteins such as Bad, as well as BH3-mimetic compounds such as ABT737, competitively disrupt the inhibitory interaction between Beclin 1 and Bcl-2/Bcl-X(L). This causes autophagy of mitochondria (mitophagy) but not of the endoplasmic reticulum (reticulophagy). Only ER-targeted (not mitochondrion-targeted) Bcl-2/Bcl-X(L) can inhibit autophagy induced by Beclin 1, and only Beclin 1-Bcl-2/Bcl-X(L) complexes present in the ER (but not those present on heavy membrane fractions enriched in mitochondria) are disrupted by ABT737. These findings suggest that the Beclin 1-Bcl-2/Bcl-X(L) complexes that normally inhibit autophagy are specifically located in the ER and point to an organelle-specific regulation of autophagy. Furthermore, these data suggest a spatial organization of autophagy and apoptosis control in which BH3-only proteins exert two independent functions. On the one hand, they can induce apoptosis, by (directly or indirectly) activating the mitochondrion-permeabilizing function of pro-apoptotic multidomain proteins from the Bcl-2 family. On the other hand, they can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-X(L) at the level of the endoplasmic reticulum.

  4. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

    Science.gov (United States)

    Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-04-24

    Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

  5. Reexamination of $L_{3}$ and $M_{1}$ atomic-level widths of elements 54 $\\le$ Z $\\le$ 77

    CERN Document Server

    Mauron, O; Baechler, S; Berset, M; Maillard, Y P; Raboud, P A; Hoszowska, J

    2003-01-01

    High-resolution measurements of the photoinduced L/sub 3/-M/sub 1/ and L/sub 3/-M/sub 4,5/ X-ray emission lines were performed with a reflection-type bent-crystal spectrometer for a variety of elements ranging from xenon (Z=54) to iridium (Z=77). The measurements were performed at the European Synchrotron Radiation Facility in Grenoble, France. From the observed linewidths of the L/sub 3/-M/sub 1/ x-ray transitions, the widths of the M/sub 1/ levels were determined using the L/sub 3/ level widths extracted from the measured L/sub 3/-M/sub 5/ transitions, and assuming for the M/sub 5/ levels the widths reported recently by Campbell and Papp ÝAt. Data Nucl. Data Tables 77, 1 (2001)¿. In the rare-earth region a Z-dependent broadening of the M/sub 1/ level was observed. (51 refs).

  6. Power density investigations for the large wind turbines' grid-side press-pack IGBT 3L-NPC-VSCs

    DEFF Research Database (Denmark)

    Senturk, Osman Selcuk; Helle, Lars; Munk-Nielsen, Stig

    2012-01-01

    -thermal models are required to be derived, implemented, and utilized. In this study, employed as a grid-side medium voltage full-scale voltage source converters (VSCs) in a multi-MW wind turbine, press-pack IGBT three-level neutral-point-clamped VSC (3L-NPC-VSC), 3L active NPC-VSC (3L-ANPC-VSC), and 3L neutral......Power density is the important design criterion in wind turbine converter design provided that satisfactory converter performance is guaranteed. In order to assess a converter in terms of power density, which is dependent on converter electrical and thermal behaviors, converter electro......-point-piloted VSC (3L-NPP-VSC) are characterized in terms of converter operating principles, physical structure, power loss, and DC bus capacitor size for establishing the basis for converter electro-thermal modeling. Via the practical implementations of the converter electro-thermal models in a computation...

  7. Exonuclease hDIS3L2 specifies an exosome-independent 3'-5' degradation pathway of human cytoplasmic mRNA

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Damgaard, Christian Kroun; Tomecki, Rafal

    2013-01-01

    Turnover of mRNA in the cytoplasm of human cells is thought to be redundantly conducted by the monomeric 5'-3' exoribonuclease hXRN1 and the 3'-5' exoribonucleolytic RNA exosome complex. However, in addition to the exosome-associated 3'-5' exonucleases hDIS3 and hDIS3L, the human genome encodes...

  8. The roles of the catalytic and noncatalytic activities of Rpd3L and Rpd3S in the regulation of gene transcription in yeast.

    Directory of Open Access Journals (Sweden)

    Daniella Yeheskely-Hayon

    Full Text Available In budding yeasts, the histone deacetylase Rpd3 resides in two different complexes called Rpd3L (large and Rpd3S (small that exert opposing effects on the transcription of meiosis-specific genes. By introducing mutations that disrupt the integrity and function of either Rpd3L or Rpd3S, we show here that Rpd3 function is determined by its association with either of these complexes. Specifically, the catalytic activity of Rpd3S activates the transcription of the two major positive regulators of meiosis, IME1 and IME2, under all growth conditions and activates the transcription of NDT80 only during vegetative growth. In contrast, the effects of Rpd3L depends on nutrients; it represses or activates transcription in the presence or absence of a nitrogen source, respectively. Further, we show that transcriptional activation does not correlate with histone H4 deacetylation, suggesting an effect on a nonhistone protein. Comparison of rpd3-null and catalytic-site point mutants revealed an inhibitory activity that is independent of either the catalytic activity of Rpd3 or the integrity of Rpd3L and Rpd3S.

  9. The Roles of the Catalytic and Noncatalytic Activities of Rpd3L and Rpd3S in the Regulation of Gene Transcription in Yeast

    Science.gov (United States)

    Yeheskely-Hayon, Daniella; Kotler, Anat; Stark, Michal; Hashimshony, Tamar; Sagee, Shira; Kassir, Yona

    2013-01-01

    In budding yeasts, the histone deacetylase Rpd3 resides in two different complexes called Rpd3L (large) and Rpd3S (small) that exert opposing effects on the transcription of meiosis-specific genes. By introducing mutations that disrupt the integrity and function of either Rpd3L or Rpd3S, we show here that Rpd3 function is determined by its association with either of these complexes. Specifically, the catalytic activity of Rpd3S activates the transcription of the two major positive regulators of meiosis, IME1 and IME2, under all growth conditions and activates the transcription of NDT80 only during vegetative growth. In contrast, the effects of Rpd3L depends on nutrients; it represses or activates transcription in the presence or absence of a nitrogen source, respectively. Further, we show that transcriptional activation does not correlate with histone H4 deacetylation, suggesting an effect on a nonhistone protein. Comparison of rpd3-null and catalytic-site point mutants revealed an inhibitory activity that is independent of either the catalytic activity of Rpd3 or the integrity of Rpd3L and Rpd3S. PMID:24358376

  10. Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    He, Yonghan [Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China); Li, Ying [Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China); Zhang, Shuocheng [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Perry, Ben [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3 (Canada); Zhao, Tiantian [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Department of Psychology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada M1C 1A4 (Canada); Wang, Yanwen, E-mail: yanwen.wang@nrc.ca [Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada); Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3 (Canada); Sun, Changhao, E-mail: sun2002changhao@yahoo.com [Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China)

    2013-06-28

    Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- Abstract: Heat shock protein 90 (Hsp90) is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. As adipocyte differentiation plays a critical role in obesity development, the present study investigated the effect of an Hsp90 inhibitor radicicol on the differentiation of 3T3-L1 preadipocytes and potential mechanisms. The cells were treated with different concentrations of radicicol during the first 8 days of cell differentiation. Adipogenesis, the expression of adipogenic transcriptional factors, differentiation makers and cell cycle were determined. It was found that radicicol dose-dependently decreased intracellular fat accumulation through down-regulating the expression of peroxisome proliferator-activated receptor γ (PPAR{sub γ}) and CCAAT element binding protein α (C/EBP{sub α}), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Flow cytometry analysis revealed that radicicol blocked cell cycle at G1-S phase. Radicicol redcued the phosphorylation of Akt while showing no effect on β-catenin expression. Radicicol decreased the phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). The results suggest that radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway and subsequent inhibition of mitotic clonal expansion and the expression/activity of adipogenic transcriptional factors and their downstream adipogenic proteins.

  11. Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes

    International Nuclear Information System (INIS)

    He, Yonghan; Li, Ying; Zhang, Shuocheng; Perry, Ben; Zhao, Tiantian; Wang, Yanwen; Sun, Changhao

    2013-01-01

    Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- Abstract: Heat shock protein 90 (Hsp90) is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. As adipocyte differentiation plays a critical role in obesity development, the present study investigated the effect of an Hsp90 inhibitor radicicol on the differentiation of 3T3-L1 preadipocytes and potential mechanisms. The cells were treated with different concentrations of radicicol during the first 8 days of cell differentiation. Adipogenesis, the expression of adipogenic transcriptional factors, differentiation makers and cell cycle were determined. It was found that radicicol dose-dependently decreased intracellular fat accumulation through down-regulating the expression of peroxisome proliferator-activated receptor γ (PPAR γ ) and CCAAT element binding protein α (C/EBP α ), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Flow cytometry analysis revealed that radicicol blocked cell cycle at G1-S phase. Radicicol redcued the phosphorylation of Akt while showing no effect on β-catenin expression. Radicicol decreased the phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). The results suggest that radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway and subsequent inhibition of mitotic clonal expansion and the expression/activity of adipogenic transcriptional factors and their downstream adipogenic proteins

  12. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics.

    Science.gov (United States)

    Pakula, Kevin K; Hansen, Lykke H; Vester, Birte

    2017-09-01

    Several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics also occurs through methylation of 23S rRNA at position A2503 by the methyltransferase Cfr. The mutations in L3 and the cfr gene have been found together in clinical isolates, raising the question of whether they have a combined effect on antibiotic resistance or growth. We transformed a plasmid-borne cfr gene into a uL3-depleted Escherichia coli strain containing either wild-type L3 or L3 with one of seven mutations, G147R, Q148F, N149S, N149D, N149R, Q150L, or T151P, expressed from plasmid-carried rplC genes. The L3 mutations are well tolerated, with small to moderate growth rate decreases. The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were seen. This study underscores the complex interplay between various resistance mechanisms and cross-resistance, even from antibiotics with overlapping binding sites. Copyright © 2017 American Society for Microbiology.

  13. Regulation of the beta-adrenergic receptor-adenylate cyclase complex of 3T3-L1 fibroblasts by sodium butyrate

    International Nuclear Information System (INIS)

    Stadel, J.M.; Poksay, K.S.; Nakada, M.T.; Crooke, S.T.

    1986-01-01

    Mouse 3T3-L1 fibroblasts contain beta-adrenergic receptors (BAR), predominantly of the B 1 subtype. Incubation of these cells with 2-10 mM sodium butyrate (SB) for 24-48 hr results in a switch in the BAR subtype from B 1 to B 2 and promotes a 1.5 to 2.5 fold increase in total BAR number. Other short chain acids were not as effective as SB in promoting changes in BAR. BAR were assayed in membranes prepared from the 3T3-L1 cells using the radiolabeled antagonist [ 125 I]-cyanopindolol and the B 2 selective antagonist ICI 118.551. BAR subtype switch was confirmed functionally by measuring cellular cAMP accumulation in response to agonists. The structure and amount of the alpha subunits of the guanine nucleotide regulatory proteins N/sub s/ and N/sub i/ were determined by ADP-ribosylation using 32 P-NAD and either cholera toxin or pertussis toxin for labeling of the respective subunits. Preincubation of cells with 5 mM SB for 48 hr resulted in a 2-3 fold increase in the labeling of the alpha subunits of both N/sub s/ and N/sub i/. A protein of M/sub r/ = 44,000 showed enhanced labeling by cholera toxin following SB treatment of the cells. These data indicate SB concomitantly regulates expression of BAR subtype and components of the adenylate cyclase in 3T3-L1 cells

  14. TES/Aura L3 H2O Monthly Gridded V004

    Data.gov (United States)

    National Aeronautics and Space Administration — The TES Aura L3 H2O data consist of daily atmospheric temperature and VMR for the atmospheric species. Data are provided at 2 degree latitude X 4 degree longitude...

  15. Bilingual Education and L3 Learning: Metalinguistic Advantage or Not?

    Science.gov (United States)

    Rutgers, Dieuwerke; Evans, Michael

    2017-01-01

    Metalinguistic skills are highlighted in the literature as providing bilinguals with an advantage in additional language (L3) learning. The extent to which this may apply to bilingual education and content-and-language-integrated-learning settings, however, is as yet little understood. This article reports on a study exploring and comparing the…

  16. Omega-3 polyunsaturated fatty acid has an anti-oxidant effect via the Nrf-2/HO-1 pathway in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kusunoki, Chisato, E-mail: yosizaki@belle.shiga-med.ac.jp [Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192 (Japan); Yang, Liu; Yoshizaki, Takeshi; Nakagawa, Fumiyuki; Ishikado, Atsushi; Kondo, Motoyuki; Morino, Katsutaro; Sekine, Osamu; Ugi, Satoshi [Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192 (Japan); Nishio, Yoshihiko [Division of Diabetes, Metabolism and Endocrinology, Department of Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kashiwagi, Atsunori; Maegawa, Hiroshi [Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa-Cho, Otsu, Shiga 520-2192 (Japan)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Omega-3 PUFA has a direct anti-oxidant effect in adipocytes. Black-Right-Pointing-Pointer EPA and DHA induce HO-1 expression in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer Omega-3 PUFA and its end-product, 4-HHE, activates the Nrf-2/HO-1 pathway. Black-Right-Pointing-Pointer Omega-3 PUFA protects against oxidative stress-induced cytotoxicity. -- Abstract: Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid ({omega}3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of {omega}3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with {omega}3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). {omega}3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with {omega}3-PUFA prevented H{sub 2}O{sub 2}-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress.

  17. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Hsin-Fen [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan (China); Tsou, Tsui-Chun, E-mail: tctsou@nhri.org.tw [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan (China); Chao, How-Ran [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan (China); Kuo, Ya-Ting; Tsai, Feng-Yuan; Yeh, Szu-Ching [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan (China)

    2010-10-15

    Dioxin exposure has been positively associated with human type II diabetes. Because lipophilic dioxins accumulate mainly in adipose tissue, this study aimed to determine if dioxins induce metabolic dysfunction in fat cells. Using 3T3-L1 cells as an in vitro model, we analyzed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model dioxin, on adipogenic differentiation, glucose uptake, and lipolysis. TCDD inhibited adipogenic differentiation, as determined by using oil droplet formation and adipogenic marker gene expression, including PPAR{gamma} (peroxisome proliferator-activated receptor {gamma}), C/EBP{alpha} (CCAAT/enhancer-binding protein {alpha}), and Glut4 (glucose transporter type 4). Effects of TCDD on glucose uptake were evaluated using fully differentiated 3T3-L1 adipocytes, revealing that TCDD significantly attenuated insulin-induced glucose uptake dose dependently. Inhibition of aryl hydrocarbon receptor (AhR) by {alpha}-naphthoflavone ({alpha}-NF), an AhR inhibitor, did not prevent the inhibitory effect of TCDD on glucose uptake, suggesting that TCDD attenuates insulin-induced glucose uptake in an AhR-independent manner. Effects of TCDD on lipolysis were determined using glycerol release assay. We found that TCDD had no marked effect on isoproterenol-induced glycerol release in fully differentiated 3T3-L1 adipocytes. These results provide in vitro evidence of TCDD's effects on fat cell metabolism, suggesting dioxin exposure in development of insulin resistance and type II diabetes.

  18. 3D modelling of the pathogenic Leptospira protein LipL32: A bioinformatics approach.

    Science.gov (United States)

    Kumaran, Sharmilah Kumari; Bakar, Mohd Faizal Abu; Mohd-Padil, Hirzahida; Mat-Sharani, Shuhaila; Sakinah, S; Poorani, K; Alsaeedy, Hiba; Peli, Amira; Wei, Teh Seoh; Ling, Mok Pooi; Hamat, Rukman Awang; Neela, Vasantha Kumari; Higuchi, Akon; Alarfaj, Abdullah A; Rajan, Mariappan; Benelli, Giovanni; Arulselvan, Palanisamy; Kumar, S Suresh

    2017-12-01

    Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. A luminosity measurement at LEP using the L3 detector

    Energy Technology Data Exchange (ETDEWEB)

    Koffeman, E.N.

    1996-06-25

    To perform high precision measurements at particle colliders it is crucial to know the exact intensity of the colliding beams. In particle physics this quantity is generally referred to as the luminosity. The determination of the luminosity in one of the experiments (L3) is the topic of this thesis. The implementation and the use of a silicon strip detector in L3, will be described in detail. In chapter one the most important parameters measured at LEP are discussed, preceded by a short introduction to the Standard Model. The process generally used for luminosity measurements in electron positron colliders is small angle Bhabha scattering. This process is discussed at the end of chapter one. In chapter two the characteristics of the collider and the L3 experiment are given. Together with the signature of the small angle Bhabha scattering, these experimental conditions determine the specifications for the design of the luminosity monitor. The general features of silicon strip detectors for their application in high energy physics are presented in chapter three. Some special attention is given to the behaviour of the sensors used for the tracking detector in the luminosity monitor. The more specific design details of the luminosity monitor are constricted to chapter four. In chapter five the conversion from detector signals into ccordinates relevant for the analysis is explained. The selection of the small angle Bhabha scattering events and the subsequent determination of the luminosity, are presented in chapter six. Systematic uncertainties are carefully studied. Important for a good understanding of the Bhabha selection are the events where a photon is produced in the scattering process. These events are separately studied. In chapter seven a comparison is presented between the radiative events observed in the data and their modelling in the Bhlumi Monte Carlo programme. (orig.).

  20. A luminosity measurement at LEP using the L3 detector

    International Nuclear Information System (INIS)

    Koffeman, E.N.

    1996-01-01

    To perform high precision measurements at particle colliders it is crucial to know the exact intensity of the colliding beams. In particle physics this quantity is generally referred to as the luminosity. The determination of the luminosity in one of the experiments (L3) is the topic of this thesis. The implementation and the use of a silicon strip detector in L3, will be described in detail. In chapter one the most important parameters measured at LEP are discussed, preceded by a short introduction to the Standard Model. The process generally used for luminosity measurements in electron positron colliders is small angle Bhabha scattering. This process is discussed at the end of chapter one. In chapter two the characteristics of the collider and the L3 experiment are given. Together with the signature of the small angle Bhabha scattering, these experimental conditions determine the specifications for the design of the luminosity monitor. The general features of silicon strip detectors for their application in high energy physics are presented in chapter three. Some special attention is given to the behaviour of the sensors used for the tracking detector in the luminosity monitor. The more specific design details of the luminosity monitor are constricted to chapter four. In chapter five the conversion from detector signals into ccordinates relevant for the analysis is explained. The selection of the small angle Bhabha scattering events and the subsequent determination of the luminosity, are presented in chapter six. Systematic uncertainties are carefully studied. Important for a good understanding of the Bhabha selection are the events where a photon is produced in the scattering process. These events are separately studied. In chapter seven a comparison is presented between the radiative events observed in the data and their modelling in the Bhlumi Monte Carlo programme. (orig.)

  1. 5-Acetamido-3,5-dideoxy-L-glycero-L-manno-non-2-ulosonic acid-containing O-polysaccharide from marine bacterium Pseudomonas glareae KMM 9500T.

    Science.gov (United States)

    Kokoulin, Maxim S; Kalinovsky, Anatoly I; Romanenko, Lyudmila A; Mikhailov, Valery V

    2018-05-22

    The O-polysaccharide was isolated from the lipopolysaccharide of a marine bacterium Pseudomonas glareae KMM 9500 T and studied by chemical methods along with 1D and 2D 1 H and 13 C NMR spectroscopy including 1 H, 1 H-TOCSY, 1 H, 1 H-COSY, 1 H, 1 H-ROESY, 1 H, 13 C-HSQC and 1 H, 13 C-HMBC experiments. The O-polysaccharide was found to consist of linear tetrasaccharide repeating units constituted by D-glucuronic acid (D-GlcA), L-rhamnose (L-Rha), D-glucose (D-Glc) and 5-acetamido-7,9-O-[(S)-1-carboxyethylidene]-3,5-dideoxy-L-glycero-L-manno-non-2-ulosonic acid (Sug7,9(S-Pyr)), partially O-acetylated at position 8 (∼70%): →4)-α-D-GlcpA-(1→3)-β-L-Rhap-(1→4)-β-D-Glcp-(1→4)-β-Sugp8Ac(∼70%)7,9(S-Pyr)-(2→. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Co-administration of recombinant major envelope proteins (rA27L and rH3L) of buffalopox virus provides enhanced immunogenicity and protective efficacy in animal models.

    Science.gov (United States)

    Kumar, Amit; Yogisharadhya, Revanaiah; Venkatesan, Gnanavel; Bhanuprakash, Veerakyathappa; Pandey, Awadh Bihari; Shivachandra, Sathish Bhadravati

    2017-05-01

    Buffalopox virus (BPXV) and other vaccinia-like viruses (VLVs) are causing an emerging/re-emerging zoonosis affecting buffaloes, cattle and humans in India and other countries. A27L and H3L are immuno-dominant major envelope proteins of intracellular mature virion (IMV) of orthopoxviruses (OPVs) and are highly conserved with an ability to elicit neutralizing antibodies. In the present study, two recombinant proteins namely; rA27L ( 21 S to E 110 ; ∼30 kDa) and rH3L( 1 M to I 280 ; ∼50 kDa) of BPXV-Vij/96 produced from Escherichia coli were used in vaccine formulation. A combined recombinant subunit vaccine comprising rA27L and rH3L antigens (10 μg of each) was used for active immunization of adult mice (20μg/dose/mice) with or without adjuvant (FCA/FIA) by intramuscular route. Immune responses revealed a gradual increase in antigen specific serum IgG as well as neutralizing antibody titers measured by using indirect-ELISA and serum neutralization test (SNT) respectively, which were higher as compared to that elicited by individual antigens. Suckling mice passively administered with combined anti-A27L and anti-H3L sera showed a complete (100%) pre-exposure protection upon challenge with virulent BPXV. Conclusively, this study highlights the potential utility of rA27L and rH3L proteins as safer candidate prophylactic antigens in combined recombinant subunit vaccine for buffalopox as well as passive protective efficacy of combined sera in employing better pre-exposure protection against virulent BPXV. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The MLL1-H3K4me3 Axis-Mediated PD-L1 Expression and Pancreatic Cancer Immune Evasion.

    Science.gov (United States)

    Lu, Chunwan; Paschall, Amy V; Shi, Huidong; Savage, Natasha; Waller, Jennifer L; Sabbatini, Maria E; Oberlies, Nicholas H; Pearce, Cedric; Liu, Kebin

    2017-01-01

    Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion. Histone methyltransferase inhibitors, RNAi, and overexpression were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation. All statistical tests were two-sided. PD-L1 is expressed in 60% to 90% of tumor cells in human pancreatic carcinomas and in nine of 10 human pancreatic cancer cell lines. PD-1 is expressed in 51.2% to 52.1% of pancreatic tumor-infiltrating cytotoxic T lymphocytes (CTLs). Tumors grow statistically significantly faster in FasL-deficient mice than in wild-type mice (P = .03-.001) and when CTLs are neutralized (P = .03-evasion. Targeting the MLL1-H3K4me3 axis is an effective approach to enhance the efficacy of checkpoint immunotherapy against pancreatic cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. MODIS/Terra Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Day V006

    Data.gov (United States)

    National Aeronautics and Space Administration — MODIS/Terra Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Day (MOD21A1D.006). A new suite of MODIS Land Surface Temperature (LST) and...

  5. MODIS/Aqua Land Surface Temperature/3-Band Emissivity 8-Day L3 Global 1km SIN Grid V006

    Data.gov (United States)

    National Aeronautics and Space Administration — MODIS/Aqua Land Surface Temperature/3-Band Emissivity 8-Day L3 Global 1km SIN Grid (MYD21A2.006). A new suite of MODIS Land Surface Temperature (LST) and Emissivity...

  6. MODIS/Aqua Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Day V006

    Data.gov (United States)

    National Aeronautics and Space Administration — MODIS/Aqua Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Day (MYD21A1D.006). A new suite of MODIS Land Surface Temperature (LST) and...

  7. MODIS/Terra Land Surface Temperature/3-Band Emissivity 8-Day L3 Global 1km SIN Grid V006

    Data.gov (United States)

    National Aeronautics and Space Administration — MODIS/Terra Land Surface Temperature/3-Band Emissivity 8-Day L3 Global 1km SIN Grid (MOD21A2.006). A new suite of MODIS Land Surface Temperature (LST) and Emissivity...

  8. MODIS/Terra Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Night V006

    Data.gov (United States)

    National Aeronautics and Space Administration — MODIS/Terra Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Night (MOD21A1N.006). A new suite of MODIS Land Surface Temperature (LST) and...

  9. MODIS/Aqua Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Night V006

    Data.gov (United States)

    National Aeronautics and Space Administration — MODIS/Aqua Land Surface Temperature/3-Band Emissivity Daily L3 Global 1km SIN Grid Night (MYD21A1N.006). A new suite of MODIS Land Surface Temperature (LST) and...

  10. Vibrational spectroscopic and theoretical study of 3,5-dimethyl-1-thiocarboxamide pyrazole (L) and the complexes Co2L2Cl4, Cu2L2Cl4 and Cu2L2Br2

    International Nuclear Information System (INIS)

    Nemcsok, Denes; Kovacs, Attila; Szecsenyi, Katalin Meszaros; Leovac, Vukadin M.

    2006-01-01

    In the present paper we report a joint experimental and theoretical study of 3,5-dimethyl-1-thiocarboxamide pyrazole (L) and its complexes Co 2 L 2 Cl 4 , Cu 2 L 2 Cl 4 and Cu 2 L 2 Br 2 . DFT computations were used to model the structural and bonding properties of the title compounds as well as to derive a reliable force field for the normal coordinate analysis of L. The computations indicated the importance of hydrogen bonding interactions in stabilising the global minimum structures on the potential energy surfaces. In contrast to the S-bridged binuclear Cu 2 L 2 Br 2 complex found in the crystal, our computations predicted the formation of (CuLBr) 2 dimers in the isolated state stabilized by very strong (53 kJ/mol) N-H...Br hydrogen bonding interactions. On the basis of FT-IR and FT-Raman experiments and the DFT-derived scaled quantum mechanical force field we carried out a complete normal coordinate analysis of L. The FT-IR spectra of the three complexes were interpreted using the present assignment of L, literature data and computed results

  11. Target molecules in 3T3-L1 adipocytes differentiation are regulated by maslinic acid, a natural triterpene from Olea europaea.

    Science.gov (United States)

    Pérez-Jiménez, Amalia; Rufino-Palomares, Eva E; Fernández-Gallego, Nieves; Ortuño-Costela, M Carmen; Reyes-Zurita, Fernando J; Peragón, Juan; García-Salguero, Leticia; Mokhtari, Khalida; Medina, Pedro P; Lupiáñez, José A

    2016-11-15

    Metabolic syndrome is a set of pathologies among which stand out the obesity, which is related to the lipid droplet accumulation and changes to cellular morphology regulated by several molecules and transcription factors. Maslinic acid (MA) is a natural product with demonstrated pharmacological functions including anti-inflammation, anti-tumor and anti-oxidation, among others. Here we report the effects of MA on the adipogenesis process in 3T3-L1 cells. Cell viability, glucose uptake, cytoplasmic triglyceride droplets, triglycerides quantification, gene transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte fatty acid-binding protein (aP2) and intracellular Ca 2+ levels were determined in pre-adipocytes and adipocytes of 3T3-L1 cells. MA increased glucose uptake. MA also decreased lipid droplets and triglyceride levels, which is in concordance with the down-regulation of PPARγ and aP2. Finally, MA increased the intracellular Ca 2+ concentration, which could also be involved in the demonstrated antiadipogenic effect of this triterpene. MA has been demonstrated as potential antiadipogenic compound in 3T3-L1 cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Assessment of RELAP5/MOD3.1 using LOFT L2-3 experiment data

    International Nuclear Information System (INIS)

    Lee, Sang Yong; Ban, Chang Hwan; Chung, Bob Dong

    1994-06-01

    The capability of RELAP5/MOD3.1 to predict overall LOCA thermal hydraulic phenomena was assessed utilizing the data of LOFT L2-3 experiment. Loop behaviors such as mass flow rate, water density, momentum flux, and the heating-up and rewetting of the fuel rod cladding during blowdown were well calculated. Reflood heat-up of the fuel rod cladding at the high power region of the core was reasonably predicted. But in the upper part of the core, cladding heat-up was calculated incorrectly since present code has no capability to calculate the top-down quenching which of highly multi-dimensional behavior. (Author) 10 refs., 46 figs., 2 tabs

  13. Mn L2,3-edge X-ray absorption spectroscopic studies on charge-discharge mechanism of Li2MnO3

    International Nuclear Information System (INIS)

    Kubobuchi, Kei; Mogi, Masato; Imai, Hideto; Ikeno, Hidekazu; Tanaka, Isao; Mizoguchi, Teruyasu

    2014-01-01

    The redox reaction of Mn in Li 2 MnO 3 was studied by X-ray absorption spectroscopy and ab initio multiplet calculation. Associated with the de-intercalation of Li-ion, small but clear spectral changes were observed in Mn-L 2,3 X-ray absorption near edge structure (XANES). The systematic ab initio multiplet calculations of Mn-L 2,3 XANES revealed that the spectral changes in the experiment could not simply be ascribed to the change of the valency from Mn 4+ to Mn 5+ but can be explained well by the changes of local atomic structures around Mn 4+ due to the Li de-intercalation. Our results suggest that the electronic state of oxygen should change during charging in Li 2 MnO 3

  14. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

    Science.gov (United States)

    Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

    2014-02-01

    Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

  15. High specific activity N-Acetyl-3H-α-Aspartyl- L-Glutamic at micro mole scale

    International Nuclear Information System (INIS)

    Suarez, C.

    1984-01-01

    High specific activity N-Acetyl-3 H - α -Aspartyl-I-Glutamic acid at micro mole scale in prepared acetylating L- α -Aspartyl-L-glutamic with 3 H -acetic anhydride in re distilled toluene. The product le purified through cationic and anionic columns. The radiochemical purity as determined by thin-layer chromatography is greater then 99% at the time preparation. (Author) 5 refs

  16. Short-Chain Fatty Acids Enhance the Lipid Accumulation of 3T3-L1 Cells by Modulating the Expression of Enzymes of Fatty Acid Metabolism.

    Science.gov (United States)

    Yu, Haining; Li, Ran; Huang, Haiyong; Yao, Ru; Shen, Shengrong

    2018-01-01

    Short-chain fatty acids (SCFA) such as acetic acid, propionic acid, and butyric acid are produced by fermentation by gut microbiota. In this paper, we investigate the effects of SCFA on 3T3-L1 cells and the underlying molecular mechanisms. The cells were treated with acetic acid, propionic acid, or butyric acid when cells were induced to differentiate into adipocytes. MTT assay was employed to detect the viability of 3T3-L1 cells. Oil Red O staining was used to visualize the lipid content in 3T3-L1 cells. A triglyceride assay kit was used to detect the triacylglycerol content in 3T3-L1 cells. qRT-PCR and Western blot were used to evaluate the expression of metabolic enzymes. MTT results showed that safe concentrations of acetic acid, propionic acid, and butyric acid were less than 6.4, 3.2, and 0.8 mM, respectively. Oil Red O staining and triacylglycerols detection results showed that treatment with acetic acid, propionic acid, and butyric acid accelerated the 3T3-L1 adipocyte differentiation. qRT-PCR and Western blot results showed that the expressions of lipoprotein lipase (LPL), adipocyte fatty acid binding protein 4 (FABP4), fatty acid transporter protein 4 (FATP4), and fatty acid synthase (FAS) were significantly increased by acetic acid, propionic acid, and butyric acid treatment during adipose differentiation (p fatty acid metabolism. © 2018 AOCS.

  17. Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.

    Science.gov (United States)

    Diep, Duy Trong Vien; Hong, Kyungki; Khun, Triyeng; Zheng, Mei; Ul-Haq, Asad; Jun, Hee-Sook; Kim, Young-Bum; Chun, Kwang-Hoon

    2018-02-06

    Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK's activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent.

  18. Effect of UBE2L3 genotype on regulation of the linear ubiquitin chain assembly complex in systemic lupus erythematosus.

    Science.gov (United States)

    Lewis, Myles; Vyse, Simon; Shields, Adrian; Boeltz, Sebastian; Gordon, Patrick; Spector, Timothy; Lehner, Paul; Walczak, Henning; Vyse, Timothy

    2015-02-26

    A single risk haplotype across UBE2L3 is strongly associated with systemic lupus erythematosus (SLE) and many other autoimmune diseases. UBE2L3 is an E2 ubiquitin-conjugating enzyme with specificity for RING-in-between-RING E3 ligases, including HOIL-1 and HOIP, components of the linear ubiquitin chain assembly complex (LUBAC), which has a pivotal role in inflammation, through crucial regulation of NF-κB. We aimed to determine whether UBE2L3 regulates LUBAC-mediated activation of NF-κB, and determine the effect of UBE2L3 genotype on NF-κB activation and B-cell differentiation. UBE2L3 genotype data from SLE genome-wide association studies was imputed by use of 1000 Genomes data. UBE2L3 function was studied in a HEK293-NF-κB reporter cell line with standard molecular biology techniques. p65 NF-κB translocation in ex-vivo B cells and monocytes from genotyped healthy individuals was quantified by imaging flow cytometry. B-cell subsets from healthy individuals and patients with SLE, stratified by UBE2L3 genotype, were determined by multicolour flow cytometry. rs140490, located at -270 base pairs of the UBE2L3 promoter, was identified as the most strongly associated single nucleotide polymorphism (p=8·6 × 10(-14), odds ratio 1·30, 95% CI 1·21-1·39). The rs140490 risk allele increased UBE2L3 expression in B cells and monocytes. Marked upregulation of NF-κB was observed with combined overexpression of UBE2L3 and LUBAC, but abolished by dominant-negative mutant UBE2L3 (C86S), or UBE2L3 silencing. The rs140490 genotype correlated with basal NF-κB activation in ex-vivo human B cells and monocytes, as well as NF-κB sensitivity to CD40 or tumour necrosis factor (TNF) stimulation. UBE2L3 expression was 3-4 times higher in circulating plasmablasts and plasma cells than in other B-cell subsets, with higher levels in patients with SLE than in controls. The rs140490 genotype correlated with increasing plasmablast and plasma cell differentiation in patients with SLE

  19. Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis—Experience from two prospective cohorts

    DEFF Research Database (Denmark)

    Kornblit, Brian; Hellemann, Dorthe; Munthe-Fog, Lea

    2013-01-01

    YKL-40, derived from the CHI3L1 gene, has been associated with outcome of infectious and inflammatory diseases. We hypothesized that plasma YKL-40 concentrations and CHI3L1 genotype could be used as prognostic biomarkers in the assessment of systemic inflammatory response syndrome (SIRS) and sepsis....... The objective of the study was to assess the prognostic value of plasma YKL-40 and CHI3L1 genotype in patients with SIRS and sepsis. Plasma YKL-40 and CHI3L1 genotype (rs4950928) were analyzed at time of admission to intensive care units (ICU), in two prospective cohorts of consecutive SIRS patients (cohort 1...

  20. Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Elmarie Myburgh

    Full Text Available Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals.

  1. Microcell-mediated chromosome transfer identifies EPB41L3 as a functional suppressor of epithelial ovarian cancers

    DEFF Research Database (Denmark)

    Dafou, Dimitra; Grun, Barbara; Sinclair, John

    2010-01-01

    lines. Using immunohistochemistry, 66% of 794 invasive ovarian tumors showed no EPB41L3 expression compared with only 24% of benign ovarian tumors and 0% of normal ovarian epithelial tissues. EPB41L3 was extensively methylated in ovarian cancer cell lines and primary ovarian tumors compared with normal...... (erythrocyte membrane protein band 4.1-like 3, alternative names DAL-1 and 4.1B) was a candidate ovarian cancer-suppressor gene. Immunoblot analysis showed that EPB41L3 was activated in TOV21G(+18) hybrids, expressed in normal ovarian epithelial cell lines, but was absent in 15 (78%) of 19 ovarian cancer cell...... tissues (P = .00004), suggesting this may be the mechanism of gene inactivation in ovarian cancers. Constitutive reexpression of EPB41L3 in a three-dimensional multicellular spheroid model of ovarian cancer caused significant growth suppression and induced apoptosis. Transmission and scanning electron...

  2. The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells

    Digital Repository Service at National Institute of Oceanography (India)

    Nita-Lazar, M.; Mancini, J.; Feng, C.; Gonzalez-Montalban, N.; Ravindran, C.; Jackson, S.; Heras-Sanchez, A.D.L.; Giomarelli, B.; Ahmed, H.; Haslam, S.M.; Wu, G.; Dell, A.; Ammayappan, A.; Vakharia, V.N.; Vasta, G.R.

    galectin-3 (Drgal3-L1) in IHNV adhesion to epithelial cells. Our results suggest that the extracellular Drgal1-L2 and Drgal3-L1 interact directly and in a carbohydrate-dependent manner with the IHNV glycosylated envelope and glycans on the epithelial cell...

  3. Cardiovascular responses to microinjection of L-glutamate into the NTS in AV3V-lesioned rats.

    Science.gov (United States)

    Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; de Almeida Colombari, Débora Simões; Menani, José V

    2004-10-29

    The excitatory amino acid L-glutamate injected into the nucleus of the solitary tract (NTS) in unanesthetized rats similar to peripheral chemoreceptor activation increases mean arterial pressure (MAP) and reduces heart rate. In this study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the preoptic-periventricular tissue surrounding the anteroventral third ventricle (AV3V region) on the pressor and bradycardic responses induced by injections of L-glutamate into the NTS or peripheral chemoreceptor activation in unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the NTS were used. Differently from the pressor responses (28+/-3 mm Hg) produced by injections into the NTS of sham-lesioned rats, L-glutamate (5 nmol/100 nl) injected into the NTS reduced MAP (-26+/-8 mm Hg) or produced no effect (2+/-7 mm Hg) in acute and chronic AV3V-lesioned rats, respectively. The bradycardia to l-glutamate into the NTS and the cardiovascular responses to chemoreflex activation with intravenous potassium cyanide or to baroreflex activation with intravenous phenylephrine or sodium nitroprusside were not modified by AV3V lesions. The results show that the integrity of the AV3V region is essential for the pressor responses to L-glutamate into the NTS but not for the pressor responses to chemoreflex activation, suggesting dissociation between the central mechanisms involved in these responses.

  4. Diffusion of aluminium during the transformation UAl{sub 3} - UAl{sub 4} in the solid state; Diffusion de l'aluminium dans la transformation UAl{sub 3} - UAl{sub 4} a l'etat solide

    Energy Technology Data Exchange (ETDEWEB)

    Boucher, R [Commissariat a l' Energie Atomique, Fontenay aux Roses (France).Centre d' Etudes Nucleaires

    1959-07-01

    The alloys studied which contain 40 % uranium, are quenched from the region liquid + UAl{sub 3} so as to obtain pure crystals of UAl{sub 3}. These samples are then heat treated at 600 deg. C (at which point Al and UAl{sub 4} are in equilibrium) for varying durations in order to permit the transformation of UAl{sub 3} to UA{sub 4}. This transformation presumably takes place by the diffusion of aluminium through the UAl{sub 4}. The evolution of the transformation UAl{sub 3} {yields} UAl{sub 4} is followed micro-graphically. The compounds are distinguished by: - colour; - examination under polarised light; - microhardness measurements. The kinetics of the transformation are strongly influenced by the presence of elements such as silicon in relatively small quantities. In the absence of silicon UAl{sub 3}, crystals are transformed to UAl{sub 4} in approximately one hour. For low silicon contents (0,1% by weight) the transformation takes ten times longer. Silicon concentrations of 0,6 practically stop the transformation. After a hundred hours a slight transformation is observed, but this transformation is no further advanced even after 1000 hours. (author) [French] Les alliages etudies, de teneur en uranium egale a 40 % en poids, sont trempes a partir du domaine 'liquide + UAl{sub 3}'; pour obtenir des cristaux UAl{sub 3} purs. Ces echantillons sont ensuite traites a 500 deg. C dans le domaine 'AI + UAl{sub 4}' pendant des temps varies pour transformer UAl{sub 3} en UAl{sub 4}. Cette transformation se fait vraisemblablement par diffusion de l'aluminium a travers UAl{sub 4}. On suit l'evolution UAl{sub 3} {yields} UAl{sub 4} principalement par methode micrographique. L'identification et la distinction des composes se font a l'aide: - de colorations; - d'examens en lumiere polarisee; - de mesures de microduretes. La cinetique de la transformation est fortement influencee par la presence d'elements tels que le silicium - en quantite relativement faible. Sans silicium, les

  5. A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Masubuchi

    Full Text Available BACKGROUND: Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells. METHODOLOGY/PRINCIPAL FINDINGS: In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6. The α subunits of Gs (Gαs and G14 (Gα14 but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects. CONCLUSIONS: 3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism.

  6. The second level trigger of the L3 experiment. Pt. 1

    International Nuclear Information System (INIS)

    Bertsch, Y.; Blaising, J.J.; Bonnefon, H.; Chollet-Leflour, F.; Degre, A.; Dromby, G.; Lecoq, J.; Morand, R.; Moynot, M.; Perrot, G.; Riccadonna, X.

    1994-01-01

    The second level trigger of the L3 experiment performs online background rejection and reduces the first level trigger rate to a value fitting with the third level trigger processing capability. Designed around a set of three bit-slice XOP microprocessors, it can process up to 500 first level triggers per second without significant dead time in the data acquisition. At each LEP beam crossing (45/90 kHz) the complete trigger information (5 kbytes) is memorized in a 1.4 gigabyte bandwidth real dual port memory. The XOP processor builds up the trigger block in less than 400 μs, and signs the background or physics origin of the current event in less than 3 ms. These very high performances rely essentially on the association of parallelism with high speed ECL technology, provided by dedicated processors fully integrated in Fastbus. Emphasis is given here to the specific hardware developed, to its operation and technical aspects of its installation and integration. The system described here ensures the L3 data taking since the beginning of LEP in July 1989 and the online rejection since 1990. (orig.)

  7. 3'-L-monoiodothyronine: development of a radioimmunoassay and demonstration of in vivo conversion from 3',5'-diiodothyronine

    International Nuclear Information System (INIS)

    Smallridge, R.C.; Wartofsky, L.; Green, B.J.; Miller, F.C.; Burman, K.D.

    1979-01-01

    A sensitive, reproducible RIA for the measurement of 3'-L-monoiodothyronine (3'T 1 ) is described. Mean intra- and interassay coefficients of variation were 2.4% and 22.5%, respectively. Cross-reactivity with other iodothyronines was negligible, except for 3,3'-L-diiodothyronine (3,3'T 2 ) which started to demonstrate cross-reactivity when 3,3'T 2 levels were elevated above 35 ng/dl. Fifty percent displacement occurred when 500 pg 3,3'T 2 were added to the 3'T 1 assay. Employing this assay, 11 normal subjects and 7 pregnant women had serum 3'T 1 levels below the limits of detectability of the assay ( 1 , with the mean (+-SD) values being 6.5 +- 3.0 ng/dl. Serum 3'T 1 levels were present in all cord sera measured (7.3 +- 2.3 ng/dl; n = 19), and the highest levels of 3'T 1 observed were in 38- to 40-week gestation amniotic fluid specimens (15.4 +- 8.4 ng/dl; n = 20). Compared to other iodothyronines, it seems that a relatively low proportion of 3'T 1 is bound to circulating proteins, as the mean percentage of dialyzable 3'T 1 in 12 normal subjects was 5.7 +- 1.2%. An oral dose of 3'T 1 (120 μg) given to 2 euthyroid individuals resulted in peak serum levels of 28 ng/dl 2 h after ingestion. After iv administration of 3'5'T 2 to 2 athyreotic patients (1 hypothyroid and the other euthyroid on replacement T 4 ), 3'T 1 levels rose from undetectable levels to 20 ng/dl. It was concluded that 3'T 1 is routinely detectable in the serum of hyperthyroid but not normal individuals, and even higher levels are present in cord sera and amniotic fluid. Moreover, the study demonstrates that in vivo conversion of 3',5'T 2 to 3'T 1 may occur

  8. Sea cucumber and blue mussel: new sources of phospholipid enriched omega-3 fatty acids with a potential role in 3T3-L1 adipocyte metabolism.

    Science.gov (United States)

    Vaidya, Hitesh; Cheema, Sukhinder K

    2014-12-01

    Omega (n)-3 polyunsaturated fatty acids (PUFA), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to reduce the risk of insulin resistance and ameliorate obesity-associated disorders. DHA and EPA structured in the phospholipid form possess superior biological effects compared to the triglyceride form available in fish oil. In this study, we have found that sea cucumber (SC) and blue mussel (BM) from Newfoundland and Labrador are rich sources of n-3 PUFA structured in the phospholipid form. Treatment with SC and BM methanolic extracts (250 and 100 μg mL(-1), respectively) significantly (p triglyceride accumulation in 3T3-L1 adipocytes, along with an increase in the mRNA expression of the peroxisome proliferator-activated receptor-γ (37 and 39%, respectively) and adiponectin (57 and 56%, respectively) compared with control cells (p triglyceride accumulation in 3T3-L1 cells as opposed to an increase in triglyceride accumulation at lower concentrations. This was due to inhibition of acetyl-CoA carboxylase-1 and SREBP-1 mRNA expression compared to control cells (p triglyceride accumulation at higher concentrations is not due to breakdown and release of fat. This is the first report to show that SC and BM are new sources of phospholipid bonded n-3 PUFA, with the potential to target insulin resistance and obesity.

  9. Thermodynamic and spectroscopic study of Al3+ interaction with glycine, l-cysteine and tranexamic acid in aqueous solution.

    Science.gov (United States)

    Cardiano, Paola; Giacobello, Fausta; Giuffrè, Ottavia; Sammartano, Silvio

    2017-11-01

    In this paper a thermodynamic and spectroscopic study on the interaction between Al 3+ and glycine (Gly), l-cysteine (Cys), tranexamic acid (Tranex) is reported. Speciation models have been obtained by processing potentiometric titration data to determine stability constants of the species formed in aqueous solution at T=298.15K, 0.15≤I/molL -1 ≤1 in NaCl. Thermodynamic formation parameters have been obtained from calorimetric titration data, at T=298.15K, I=0.15molL -1 using NaCl as ionic medium. Al 3+ -Cys system was also investigated by spectrophotometric and 1 H NMR measurements. 1 H NMR experiments were performed on Al 3+ -Tranex system as well. Different speciation models have been observed for the three systems. The results showed the formation of MLH, ML and M 2 L 2 (OH) 2 species for Gly, ML, M 2 L and MLOH for Cys, MLH and MLOH for Tranex. The formed species are quite stable, i.e. for ML, logβ=7.18, 11.91 for Gly and Cys, respectively, at I=0.15molL -1 and T=298.15K. For all the systems the dependence of formation constants on ionic strength over the range 0.1-1molL -1 is reported. The sequestering ability of the ligands under study was also evaluated by pL 0.5 empiric parameter. For Gly, Cys and Tranex, pL 0.5 =2.51, 3.74, 3.91 respectively, at pH=5, I=0.15molL -1 and T=298.15K. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L

    Science.gov (United States)

    Arivazhagan, Roshini; Lee, Jaesuk; Bayarsaikhan, Delger; Kwak, Peter; Son, Myeongjoo; Byun, Kyunghee; Salekdeh, Ghasem Hosseini; Lee, Bonghee

    2018-01-01

    DNA Directed Polymerase Zeta Catalytic Subunit (REV3L) has recently emerged as an important oncogene. Although the expressions of REV3L are similar in normal and cancer cells, several mutations in REV3L have been shown to play important roles in cancer. These mutations cause proteins misfolding and mislocalization, which in turn alters their interactions and biological functions. miRNAs play important regulatory roles during the progression and metastasis of several human cancers. This study was undertaken to determine how changes in the location and interactions of REV3L regulate colon cancer progression. REV3L protein mislocalization confirmed from the immunostaining results and the known interactions of REV3L was found to be broken as seen from the PLA assay results. The mislocalized REV3L might interact with new proteins partners in the cytoplasm which in turn may play role in regulating colon cancer progression. hsa-miR-340 (miR-340), a microRNA down-regulated in colon cancer, was used to bind to and downregulate REV3L, and found to control the proliferation and induce the apoptosis of colon cancer cells (HCT-116 and DLD-1) via the MAPK pathway. Furthermore, this down-regulation of REV3L also diminished colon cancer cell migration, and down-regulated MMP-2 and MMP-9. Combined treatment of colon cancer cells with miR-340 and 5-FU enhanced the inhibitory effects of 5-FU. In addition, in vivo experiments conducted on nude mice revealed tumor sizes were smaller in a HCT-116-miR-340 injected group than in a HCT-116-pCMV injected group. Our findings suggest mutations in REV3L causes protein mislocalization to the cytoplasm, breaking its interaction and is believed to form new protein interactions in cytoplasm contributing to colon cancer progression. Accordingly, microRNA-340 appears to be a good candidate for colon cancer therapy. PMID:29435169

  11. Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Kazuaki Kajimoto

    2014-01-01

    Full Text Available The fatty acid binding protein 4 (FABP4, one of the most abundant proteins in adipocytes, has been reported to have a proinflammatory function in macrophages. However, the physiological role of FABP4, which is constitutively expressed in adipocytes, has not been fully elucidated. Previously, we demonstrated that FABP4 was involved in the regulation of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF production in 3T3-L1 adipocytes. In this study, we examined the effects of FABP4 silencing on the oxidative and endoplasmic reticulum (ER stress in 3T3-L1 adipocytes. We found that the cellular reactive oxygen species (ROS and 8-nitro-cyclic GMP levels were significantly elevated in the differentiated 3T3-L1 adipocytes transfected with a small interfering RNA (siRNA against Fabp4, although the intracellular levels or enzyme activities of antioxidants including reduced glutathione (GSH, superoxide dismutase (SOD and glutathione S-transferase A4 (GSTA4 were not altered. An in vitro evaluation using the recombinant protein revealed that FABP4 itself functions as a scavenger protein against hydrogen peroxide (H2O2. FABP4-knockdown resulted in a significant lowering of cell viability of 3T3-L1 adipocytes against H2O2 treatment. Moreover, four kinds of markers related to the ER stress response including the endoplasmic reticulum to nucleus signaling 1 (Ern1, the signal sequence receptor α (Ssr1, the ORM1-like 3 (Ormdl3, and the spliced X-box binding protein 1 (Xbp1s, were all elevated as the result of the knockdown of FABP4. Consequently, FABP4 might have a new role as an antioxidant protein against H2O2 and contribute to cytoprotection against oxidative and ER stress in adipocytes.

  12. Temperature Dependent Rate Coefficients for the Gas-Phase Reaction of the OH Radical with Linear (L2, L3) and Cyclic (D3, D4) Permethylsiloxanes.

    Science.gov (United States)

    Bernard, François; Papanastasiou, Dimitrios K; Papadimitriou, Vassileios C; Burkholder, James B

    2018-04-19

    Permethylsiloxanes are emitted into the atmosphere during production and use as personal care products, lubricants, and cleaning agents. The predominate atmospheric loss process for permethylsiloxanes is expected to be via gas-phase reaction with the OH radical. In this study, rate coefficients, k(T), for the OH radical gas-phase reaction with the two simplest linear and cyclic permethylsiloxanes were measured using a pulsed laser photolysis-laser induced fluorescence technique over the temperature range of 240-370 K and a relative rate method at 294 K: hexamethyldisiloxane ((CH 3 ) 3 SiOSi(CH 3 ) 3 , L 2 ), k 1 ; octamethyltrisiloxane ([(CH 3 ) 3 SiO] 2 Si(CH 3 ) 2 , L 3 ), k 2 ; hexamethylcyclotrisiloxane ([-Si(CH 3 ) 2 O-] 3 , D 3 ), k 3 ; and octamethylcyclotetrasiloxane ([-Si(CH 3 ) 2 O-] 4 , D 4 ), k 4 . The obtained k(294 K) values and temperature-dependence expressions for the 240-370 K temperature range are (cm 3 molecule -1 s -1 , 2σ absolute uncertainties): k 1 (294 K) = (1.28 ± 0.08) × 10 -12 , k 1 ( T) = (1.87 ± 0.18) × 10 -11 exp(-(791 ± 27)/ T); k 2 (294 K) = (1.72 ± 0.10) × 10 -12 , k 2 ( T) = 1.96 × 10 -13 (T/298) 4.34 exp(657/ T); k 3 (294 K) = (0.82 ± 0.05) × 10 -12 , k 3 ( T) = (1.29 ± 0.19) × 10 -11 exp(-(805 ± 43)/ T); and k 4 (294 K) = (1.12 ± 0.10) × 10 -12 , k 4 ( T) = (1.80 ± 0.26) × 10 -11 exp(-(816 ± 43)/ T). The cyclic molecules were found to be less reactive than the analogous linear molecule with the same number of -CH 3 groups, while the linear and cyclic permethylsiloxane reactivity both increase with the increasing number of CH 3 - groups. The present results are compared with previous rate coefficient determinations where available. The permethylsiloxanes included in this study are atmospherically short-lived compounds with estimated atmospheric lifetimes of 11, 8, 17, and 13 days, respectively.

  13. EX1004L3 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1004L3: Exploration Indonesia - Bitung...

  14. EX1502L3 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1502L3: Caribbean Exploration (ROV)...

  15. A new diarylheptanoid from Alpinia officinarum promotes the differentiation of 3T3-L1 preadipocytes.

    Science.gov (United States)

    Zhang, Xuguang; Zhang, Xiaopo; Wang, Yong; Chen, Feng; Li, Youbin; Li, Yonghui; Tan, Yinfeng; Gong, Jingwen; Zhong, Xia; Li, Hailong; Zhang, Junqing

    2018-03-01

    A new diarylheptanoid, namely trans-(4R,5S)-epoxy-1,7-diphenyl-3-heptanone (1), and a new natural product, 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-hepta-4E,6E-dien-3-one (2), were obtained from the aqueous extract of Alpinia officinarum Hance, together with three other diarylheptanoids, 5-hydroxy-1,7-diphenyl-3-heptanone (3), 1,7-diphenyl-4E-en-3-heptanone (4) and 5-methoxy-1,7-diphenyl-3-heptanone (5). The structures were characterised mainly by analysing their physical data including IR, NMR and HRMS. This study highlights that the 4,5-epoxy moiety in 1 is rarely seen in diarylheptanoids. In addition, the five isolates were tested for their differentiation activity of 3T3-L1 preadipocytes. The results showed that these compounds could dose-dependently promote adipocyte differentiation without cytotoxicity (IC 50  > 100 μM).

  16. L'assignació de metadades a llibres digitals en el format EPUB3. Segona part. Ús i explotació de metadades de l'EPUB3

    Directory of Open Access Journals (Sweden)

    Centelles Velilla, Miquel

    2016-06-01

    Full Text Available Objectiu: analitzar i valorar les tendències actuals pel que fa a l'ús i explotació de les metadades en els mecanismes de cerca i organització dels llibres digitals, a les plataformes de distribució i en els dispositius o aplicacions de lectura. A partir de l'ús observat, extreure'n recomanacions per a l'assignació de metadades en el marc de l'estàndard de metadades EPUB3 però amb una visió pràctica i aplicada. -- Metodologia: es revisen manualment les dades incorporades en les plataformes Amazon, iTunes Stores i Projecte Gutenberg. També es revisen manualment les dades usades en les aplicacions de lectura Adobe Digital Editions, Apple iBooks, Azardi, Calibre i Readium, tant els sistemes d'exploració com els sistemes de recuperació de llibres per paraules clau per ítem i per col·lecció (biblioteques personals o externes. -- Resultat: les plataformes de distribució no tenen en compte les metadades previstes per l'estàndard EPUB3 incloses en el mateix document per tal d'alimentar la descripció del producte en la seva incorporació. Les aplicacions de lectura, en canvi, sí que importen aquestes dades, però en fan un ús mínim en la cerca i organització dels llibres. Com a conseqüència d'això es recomana als autors i editors incorporar les metadades obligatòries segons l'estàndard EPUB3 per permetre la validació de publicacions, però evitar els mecanismes d'enriquiment i assignar valors únics a cada element.Objetivo: analizar y valorar las tendencias actuales en relación al uso y explotación de los metadatos en los mecanismos de búsqueda y organización de los libros digitales, en las plataformas de distribución y en los dispositivos o aplicaciones de lectura. A partir del uso observado, derivar recomendaciones para la asignación de metadatos en el marco del estándar de metadatos EPUB3 pero con una visión práctica y aplicada. -- Metodología: se revisan manualmente los datos incorporados en las plataformas

  17. Strong theoretical support for the assignment of B11244 to l-C{sub 3}H{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Botschwina, P.; Stein, C.; Sebald, P.; Schröder, B.; Oswald, R. [Institut für Physikalische Chemie, Georg-August-Universität Göttingen, Tammannstraße 6, D-37077 Göttingen (Germany)

    2014-05-20

    Highly accurate quantum chemical calculations beyond CCSD(T) have been used to study the molecular cation l-C{sub 3}H{sup +} which is the carrier of harmonically related radio lines observed in the Horsehead photodissociation region and toward Sgr B2(N). Excellent agreement with spectroscopic and radioastronomical measurements is obtained for the rotational constant, with the calculated value of B {sub 0} = 11246.4 MHz only 1.5 MHz or 0.01% above the experimental value. The unusually large ratio of centrifugal distortion constants D {sub 0}(exp.)/D{sub e}(theor.) = 1.80 is attributed to the shallow CCC bending potential of l-C{sub 3}H{sup +} and is quantitatively reproduced by variational calculations within a pseudo-triatomic model. A comparative study of centrifugal distortion constants in a series of four linear interstellar molecules (C{sub 3}N{sup –}, C{sub 3}O, l-C{sub 3}H{sup +}, and C{sub 3}) is made and some general conclusions are drawn.

  18. Structural study of glasses in the binary system NaPO{sub 3}-MoO{sub 3} by X-ray absorption spectroscopy at the Mo K and L{sub 3} edges

    Energy Technology Data Exchange (ETDEWEB)

    Poirier, Gael, E-mail: gael@unifal-mg.edu.br [Department of Science and Technology, UNIFAL-MG, Rua Corumba 72, CEP 37701-100, Pocos de Caldas, MG (Brazil); Cassanjes, Fabia C. [Department of Science and Technology, UNIFAL-MG, Rua Corumba 72, CEP 37701-100, Pocos de Caldas, MG (Brazil)

    2010-04-15

    Glasses were prepared in the binary system (100 - x)NaPO{sub 3}-xMoO{sub 3} with x varying from 0 to 50 mol%. An increase in the MoO{sub 3} concentration promotes a strong absorption in the visible and near infrared attributed to Mo reduction during glass synthesis. X-ray absorption measurements were performed at the Mo K and L{sub 3} edges to investigate both the coordination number and oxidation state of Mo in these glasses. The evolution of the pre-peak observed at the K edge suggests that Mo atoms are six-fold coordinated in these glasses. This hypothesis was confirmed by data obtained at the Mo-L{sub 3}-absorption edge. Since the final electronic states at the L{sub 3}-absorption edge are mostly orbitals of d-character which are splitted by the ligand field, the amplitude of the d-orbital splitting could be estimated and the related coordination number of Mo obtained. Finally, the oxidation state of Mo could be related with a change of the white line intensity at the Mo-L{sub 3} edge. These results confirm that the optical absorption in the visible is due to Mo reduction and that transparent samples prepared by slow cooling contain less reduced Mo species.

  19. Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on fetal hypothyroidism in primates

    International Nuclear Information System (INIS)

    Bachrach, L.K.; Dibattista, D.; Burrow, G.N.; Holland, F.J.

    1983-01-01

    Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of the DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus

  20. EX0909L3 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX0909L3: Mapping Field Trials - Hawaiian...

  1. EX1202L3 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1202L3: Gulf of Mexico Exploration...

  2. Progesterone dose-dependently modulates hepatocyte growth factor production in 3T3-L1 mouse preadipocytes.

    Science.gov (United States)

    Ito, Tomoki; Yamaji, Daisuke; Kamikawa, Akihiro; Abd Eldaim, Mabrouk Attia; Okamatsu-Ogura, Yuko; Terao, Akira; Saito, Masayuki; Kimura, Kazuhiro

    2017-08-30

    It is well documented that estrogen is predominant inducer of hepatocyte growth factor (HGF) in a variety of cell types. However, the effect of progesterone (P) remains to be elusive. Thus, in the present study, we examined the effect of P and combined effect of P and 17β-estradiol (E2) on HGF expression and production in 3T3-L1 fibroblastic preadipocytes and mature adipocytes, as a model of stromal cells. Northern blot analysis showed that hgf mRNA expressed in preadipocytes was notably higher than that of mature adipocytes, and increased by treatment of preadipocytes with E2 or 10 nM P, but not with 1,000 nM P. The E2-induced hgf mRNA expression was enhanced by 10 nM P, but suppressed by 1,000 nM P. Western blot analysis revealed that biological active forms of HGF protein was found in the preadipocyte culture medium, while the lesser amount of HGF precursor protein was detected in the mature adipocyte culture medium. The amounts of HGF were changed dependently on the hgf mRNA expression levels. These results indicate that HGF production is intricately regulated by E2 and P at the transcriptional levels in 3T3-L1 cells, and may explain the changes in the HGF production during the mammary gland development, especially decrease in HGF expression during pregnancy when P concentration is high.

  3. Isolation of L-3-phenyllactyl-Phe-Lys-Ala-NH2 (Antho-KAamide), a novel neuropeptide from sea anemones

    DEFF Research Database (Denmark)

    Nothacker, H P; Rinehart, K L; Grimmelikhuijzen, C J

    1991-01-01

    sea anemones. We propose that the L-3-phenyllactyl residue renders Antho-KAamide resistant to nonspecific aminopeptidases, thereby increasing the stability of the neuropeptide after neuronal release. The existence of the L-3-phenyllactyl residue in 3 neuropeptides isolated so far suggests...

  4. Synthesis, crystal structure and properties of [Co(L2](ClO42 (L=1,3-bis(1H-benzimidazol-2-yl-2-oxapropane

    Directory of Open Access Journals (Sweden)

    Tavman Aydin

    2015-01-01

    Full Text Available The reaction of 1,3-bis(1H-benzimidazol-2-yl-2-oxapropane (L with Co(ClO42•6H2O in absolute ethanol produces di[1,3-bis(1H-benzimidazol-2-yl-2-oxapropane-k2N,N’]cobalt(IIdiperchlorate chelate complex ([Co(L2](ClO42, 1. The complex 1 was characterized by elemental analysis, magnetic moment, molar conductivity, thermogravimetric analysis, FT-IR, UV-visible, mass spectrometry, and its solid state structure was determined by single crystal X-ray diffraction. According to the thermogravimetric analysis data, there is no any water coordinated or uncoordinated in 1 as well as elemental analysis. The complex 1 has 1:2 M:L ionic characteristic according to the molar conductivity. In the complex, the distances between the cobalt and the ethereal oxygen atoms (Co1-O2: 2.805(3; Co2-O1: 2.752(2 Å show the semi-coordination bonding and the Co(II ion is six-coordinated with a N4O2 ligand set, resulting in a distorted octahedron.

  5. T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Masubuchi

    Full Text Available We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A. In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules. Sweetener-induced microtubule disassembly was accompanied by activation of RhoA and Rho-associated kinase (ROCK. This was attenuated with by knockdown of GEF-H1, a microtubule-localized guanine nucleotide exchange factor for Rho GTPase. Furthermore, overexpression of the dominant-negative mutant of RhoA (RhoA-T19N blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. These results suggest that the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.

  6. EX1504L3 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1504L3: CAPSTONE Leg III: Main Hawaiian...

  7. The second level trigger of the L3 experiment. Pt. 2

    International Nuclear Information System (INIS)

    Beingessner, S.P.; Blaising, J.J.; Chollet-Le Flour, F.; Degre, A.; Dromby, G.; Goy, C.; Lecoq, J.; Morand, R.; Moynot, M.; Perrot, G.; Rosier-Lees, S.; Forconi, G.

    1993-07-01

    The events recorded by the L3 Data Acquisition System are selected by three levels of trigger. The event filtering performed by software at the second trigger level is described. First coded offline in FORTRAN, the filtering software is microcoded for online execution in a farm of 3 XOP processors operating in a round robin mode. It identifies and rejects background events. Depending on running conditions and trigger type, rejection factors ranging from 45% to 80% are obtained on first level energy, muon and tec triggers. Selection efficiencies greater than 99.95% are achieved. (authors). 14 refs., 3 figs., 2 tabs

  8. Precise measurement of muon momenta at LEP using the L3 detector

    International Nuclear Information System (INIS)

    Gonzalez Romero, E.M.

    1990-01-01

    In this PhD report the author presents the studies and methods developed to achieve the optimization of the resolution in the momentum measurement of the L3 moun detector. Chapters 1 and 2 show the motivations to build a precision muon detector for the LEP e + e - collider. Special emphasis is applied to the study of the Higgs scalar boson search and identification and the guiding principles used to design the L3 muon detector are outlined. Chapter 3 is devoted to the description of the drift chambers. They are located in three concentric octagonal cylinders inside one solenoidal magnet, around the interaction point and coaxial with the beams. These chambers are the measuring elements of the detector. The chapter includes the description or the different tests applied to the chambers to obtain their resolution and calibration. In chapter 4 the alignment system of this chambers is described. This system is a key element to the precision of the detector, that being 12 meters long and of 12 meters of diameter has to measure the particles trajectories with precisions of just a few micrometers. Chapter 5 describes the third key piece for the detector precision, the monitoring and control system. It allows to know continually the precise values of the critical parameters of the detector. Finally in chapter 6 the author presents the results of the many test applied to the detector using cosmic rays, UV lasers and even the actual muons produced in the e + e - interactions. These tests prove that the L3 muon detector is the most precise measuring system for muon momenta installed at present in one e + e - collider ring. (Author)

  9. Dicty_cDB: Contig-U07003-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available aegypti infected with Brugia Mal... 50 0.090 1 ( DV278108 ) NAAF224TF Aedes aegypti - Fat Bodies Normalized ...(... 50 0.090 1 ( DV276715 ) NAAHF49TR Aedes aegypti - Fat Bodies Normalized (...

  10. EX1402L3 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1402L3: Gulf of Mexico Mapping and ROV...

  11. JNK1 Controls Dendritic Field Size in L2/3 and L5 of the Motor Cortex, Constrains Soma Size and Influences Fine Motor Coordination

    Directory of Open Access Journals (Sweden)

    Emilia eKomulainen

    2014-09-01

    Full Text Available Genetic anomalies on the JNK pathway confer susceptibility to autism spectrum disorders, schizophrenia and intellectual disability. The mechanism whereby a gain or loss of function in JNK signaling predisposes to these prevalent dendrite disorders, with associated motor dysfunction, remains unclear. Here we find that JNK1 regulates the dendritic field of L2/3 and L5 pyramidal neurons of the mouse motor cortex (M1, the main excitatory pathway controlling voluntary movement. In Jnk1-/- mice, basal dendrite branching of L5 pyramidal neurons is increased in M1, as is cell soma size, whereas in L2/3, dendritic arborization is decreased. We show that JNK1 phosphorylates rat HMW-MAP2 on T1619, T1622 and T1625 (Uniprot P15146 corresponding to mouse T1617, T1620, T1623, to create a binding motif, that is critical for MAP2 interaction with and stabilization of microtubules, and dendrite growth control. Targeted expression in M1 of GFP-HMW-MAP2 that is pseudo-phosphorylated on T1619, T1622 and T1625 increases dendrite complexity in L2/3 indicating that JNK1 phosphorylation of HMW-MAP2 regulates the dendritic field. Consistent with the morphological changes observed in L2/3 and L5, Jnk1-/- mice exhibit deficits in limb placement and motor coordination, while stride length is reduced in older animals. In summary, JNK1 phosphorylates HMW-MAP2 to increase its stabilization of microtubules while at the same time controlling dendritic fields in the main excitatory pathway of M1. Moreover, JNK1 contributes to normal functioning of fine motor coordination. We report for the first time, a quantitative sholl analysis of dendrite architecture, and of motor behavior in Jnk1-/- mice. Our results illustrate the molecular and behavioral consequences of interrupted JNK1 signaling and provide new ground for mechanistic understanding of those prevalent neuropyschiatric disorders where genetic disruption of the JNK pathway is central.

  12. Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation.

    Science.gov (United States)

    Guntur, Anyonya R; Gerencser, Akos A; Le, Phuong T; DeMambro, Victoria E; Bornstein, Sheila A; Mookerjee, Shona A; Maridas, David E; Clemmons, David E; Brand, Martin D; Rosen, Clifford J

    2018-06-01

    Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research. © 2018 American Society for Bone and Mineral Research.

  13. Analyze and Improve Lifetime in 3L-NPC Inverter from Power Cycle and Thermal Balance

    DEFF Research Database (Denmark)

    Chen, Quan; Chen, Zhe; Wang, Qunjing

    2014-01-01

    Three-level Neutral-point-clamped (3L-NPC) topology is becoming a realistic alternative to the conventional one in high-voltage and high-power application. Studies show that the power cycling mean time to failure (MTTF) of the semiconductor bond wire in 3L-NPC inverter system may be very short...... under some common conditions. Firstly, this paper shows the impact of some key parameters on power electronic system lifetime according the analysis of semiconductor failure mechanism. Secondly, a switching frequency reduction method based on the position relationship between the flowing current...... and load voltage is applied to reduce power cycle and switching losses. And then, three-level active neutral point-clamped topology is taken into account to wake the most thermo stressed device. In order to validate the improve lifetime method in this paper, a 2MW 3L-NPC converter used in wind energy has...

  14. Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model

    Directory of Open Access Journals (Sweden)

    Claudio Laurido

    2012-01-01

    Full Text Available N-methyl-D-aspartic acid receptor (NMDAr activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR. D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS and L-erythro-3-hydroxyaspartate (LEHA, among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μg/10 μL and LEHA (100 μg/10 μL in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μg/10 μL of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain.

  15. Asymmetric synthesis of L-[3-11C]phenylalanine using chiral hydrogenation catalysts

    International Nuclear Information System (INIS)

    Halldin, C.; Langstroem, B.

    1984-01-01

    The seven-step synthesis of L-[3- 11 C]phenylalanine using chiral diphosphines as ligands in rhodium catalysts is reported. [ 11 C]Benzaldehyde, prepared in a three-step reaction from [ 11 C]carbon dioxide, as reported elsewhere, was reacted with 2-phenyl-5-oxazolone or 2-(4-chloro)phenyl-5-oxazolone in the presence of the tertiary amine diazabicyclooctane (DABCO). The resultant [α- 11 C]-4-arylene-2-atyl-5-oxazolones were hydrogenated after ring opening, using the chiral rhodium complex of (R)-1,2-bis(diphenylphosphino)propane [(R)-PROPHOS] or (+)-2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane [(+)-DIOP]. After removal of the amino protecting group, the labelled amino acid was obtained on purification by preparative LC in 10-15% radiochemical yield, and radiochemical purity higher than 95% from [ 11 C]carbon dioxide within 60 min. The optical purity of the products determined by the tRNA method and capillary GC, was 80 and 60% e.e., respectively (i.e. L/D=90/10 and 80/20). (author)

  16. Real-time monitoring of inflammation status in 3T3-L1 adipocytes possessing a secretory Gaussia luciferase gene under the control of nuclear factor-kappa B response element

    Energy Technology Data Exchange (ETDEWEB)

    Nagasaki, Haruka; Yoshimura, Takeshi [Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507 (Japan); Aoki, Naohito, E-mail: n-aoki@bio.mie-u.ac.jp [Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507 (Japan)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Inflammation status in adipocytes can be monitored by the new assay system. Black-Right-Pointing-Pointer Only an aliquot of conditioned medium is required without cell lysis. Black-Right-Pointing-Pointer Inflammation-attenuating compounds can be screened more conveniently. -- Abstract: We have established 3T3-L1 cells possessing a secretory Gaussia luciferase (GLuc) gene under the control of nuclear factor-kappa B (NF-{kappa}B) response element. The 3T3-L1 cells named 3T3-L1-NF-{kappa}B-RE-GLuc could differentiate into adipocyte as comparably as parental 3T3-L1 cells. Inflammatory cytokines such as tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-1{beta} induced GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes in a concentration- and time-dependent manner. GLuc secretion of 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes was also induced when cultured with RAW264.7 macrophages and was dramatically enhanced by lipopolysaccharide (LPS)-activated macrophages. An NF-{kappa}B activation inhibitor BAY-11-7085 and an antioxidant N-acetyl cysteine significantly suppressed GLuc secretion induced by macrophages. Finally, we found that rosemary-derived carnosic acid strongly suppressed GLuc secretion induced by macrophages and on the contrary up-regulated adiponectin secretion. Collectively, by using 3T3-L1-NF-{kappa}B-RE-GLuc adipocytes, inflammation status can be monitored in real time and inflammation-attenuating compounds can be screened more conveniently.

  17. Regulation of myosin light chain kinase during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Shelly Woody

    Full Text Available Myosin II (MyoII is required for insulin-responsive glucose transporter 4 (GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Our previous studies have shown that insulin signaling stimulates phosphorylation of the regulatory light chain (RLC of MyoIIA via myosin light chain kinase (MLCK. The experiments described here delineate upstream regulators of MLCK during insulin-stimulated glucose uptake. Since 3T3-L1 adipocytes express two MyoII isoforms, we wanted to determine which isoform was required for insulin-stimulated glucose uptake. Using a siRNA approach, we demonstrate that a 60% decrease in MyoIIA protein expression resulted in a 40% inhibition of insulin-stimulated glucose uptake. We also show that insulin signaling stimulates the phosphorylation of MLCK. We further show that MLCK can be activated by calcium as well as signaling pathways. We demonstrate that adipocytes treated with the calcium chelating agent, 1,2-b (iso-aminophenoxy ethane-N,N,N',N'-tetra acetic acid, (BAPTA (in the presence of insulin impaired the insulin-induced phosphorylation of MLCK by 52% and the RLC of MyoIIA by 45% as well as impairing the recruitment of MyoIIA to the plasma membrane when compared to cells treated with insulin alone. We further show that the calcium ionophore, A23187 alone stimulated the phosphorylation of MLCK and the RLC associated with MyoIIA to the same extent as insulin. To identify signaling pathways that might regulate MLCK, we examined ERK and CaMKII. Inhibition of ERK2 impaired phosphorylation of MLCK and insulin-stimulated glucose uptake. In contrast, while inhibition of CaMKII did inhibit phosphorylation of the RLC associated with MyoIIA, inhibition of CAMKIIδ did not impair MLCK phosphorylation or translocation to the plasma membrane or glucose uptake. Collectively, our results are the first to delineate a role for calcium and ERK in the activation of MLCK and thus MyoIIA during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

  18. Changes in natural Foxp3(+Treg but not mucosally-imprinted CD62L(negCD38(+Foxp3(+Treg in the circulation of celiac disease patients.

    Directory of Open Access Journals (Sweden)

    Marieke A van Leeuwen

    Full Text Available BACKGROUND: Celiac disease (CD is an intestinal inflammation driven by gluten-reactive CD4(+ T cells. Due to lack of selective markers it has not been determined whether defects in inducible regulatory T cell (Treg differentiation are associated with CD. This is of importance as changes in numbers of induced Treg could be indicative of defects in mucosal tolerance development in CD. Recently, we have shown that, after encounter of retinoic acid during differentiation, circulating gut-imprinted T cells express CD62L(negCD38(+. Using this new phenotype, we now determined whether alterations occur in the frequency of natural CD62L(+Foxp3(+ Treg or mucosally-imprinted CD62L(negCD38(+Foxp3(+ Treg in peripheral blood of CD patients. In particular, we compared pediatric CD, aiming to select for disease at onset, with adult CD. METHODS: Cell surface markers, intracellular Foxp3 and Helios were determined by flow cytometry. Foxp3 expression was also detected by immunohistochemistry in duodenal tissue of CD patients. RESULTS: In children, the percentages of peripheral blood CD4(+Foxp3(+ Treg were comparable between CD patients and healthy age-matched controls. Differentiation between natural and mucosally-imprinted Treg on the basis of CD62L and CD38 did not uncover differences in Foxp3. In adult patients on gluten-free diet and in refractory CD increased percentages of circulating natural CD62L(+Foxp3(+ Treg, but normal mucosally-imprinted CD62L(negCD38(+Foxp3(+ Treg frequencies were observed. CONCLUSIONS: Our data exclude that significant numeric deficiency of mucosally-imprinted or natural Foxp3(+ Treg explains exuberant effector responses in CD. Changes in natural Foxp3(+ Treg occur in a subset of adult patients on a gluten-free diet and in refractory CD patients.

  19. Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways.

    Science.gov (United States)

    Jang, Yeon Jeong; Koo, Hyun Jung; Sohn, Eun-Hwa; Kang, Se Chan; Rhee, Dong-Kwon; Pyo, Suhkneung

    2015-07-01

    Obesity is characterized by hypertrophy and/or by the differentiation or adipogenesis of pre-existing adipocytes. In this study, we investigated the inhibitory effects of theobromine, a type of alkaloid in cocoa, on adipocyte differentiation of 3T3-L1 preadipocytes and its mechanisms of action. Theobromine inhibited the accumulation of lipid droplets, the expression of PPARγ and C/EBPα, and the mRNA expression of aP2 and leptin. The inhibition of adipogenic differentiation by theobromine occurred primarily in the early stages of differentiation. In addition, theobromine arrested the cell cycle at the G0/G1 phase and regulated the expressions of CDK2, p27, and p21. Theobromine treatment increased AMPK phosphorylation and knockdown of AMPKα1/α2 prevented the ability of theobromine to inhibit PPARγ expression in the differentiating 3T3-L1 cells. Theobromine reduced the phosphorylation of ERK and JNK. Moreover, the secretion and the mRNA level of TNF-α and IL-6 were inhibited by theobromine treatment. These data suggest that theobromine inhibits adipocyte differentiation during the early stages of adipogenesis by regulating the expression of PPARγ and C/EBPα through the AMPK and ERK/JNK signaling pathways in 3T3-L1 preadipocytes.

  20. Theoretical and experimental study of resonant 3d X-ray photoemission and resonant L3M45M45 Auger transition of PdO

    International Nuclear Information System (INIS)

    Uozumi, Takayuki; Kotani, Akio

    2000-01-01

    The observed 3d X-ray photoemission spectra (XPS), resonant 3dXPS (RXPS) at the L 3 edge and resonant L 3 M 45 M 45 Auger electron spectra (RAES) of 4d transition metal oxide PdO are successfully analyzed by means of an impurity Anderson model. The importance of Pd 4d-O 2p hybridization effect is especially emphasized in the interpretation of observed spectra. It causes charge transfer satellites in 3dXPS and L 3 M 45 M 45 RAES and mainly determines the structure of resonance enhancements in 3dRXPS. From the analysis of spectra, 4d-2p charge transfer energy Δ, 4d correlation energy U dd and 4d-2p transfer integral pdσ are estimated to be 5.5 eV, 4.5 eV and 2.1 eV, respectively. The character of the insulating energy gap PdO is also theoretically investigated: PdO is classified as an intermediate-type insulator due to the strong 4d-2p hybridization. (author)

  1. YKL-40 and genetic status of CHI3L1 in a large group of asthmatics

    DEFF Research Database (Denmark)

    Hansen, Jakob W; Thomsen, Simon F; Porsbjerg, Celeste

    2015-01-01

    BACKGROUND: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40...... to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1....

  2. Position of coordination of the lithium ion determines the regioselectivity of demethylations of 3,4-dimethoxymorphinans with L-selectride.

    Science.gov (United States)

    Wu, Huifang; Thatcher, Linn N; Bernard, Denzil; Parrish, Damon A; Deschamps, Jeffrey R; Rice, Kenner C; MacKerell, Alexander D; Coop, Andrew

    2005-06-23

    [reaction: see text] L-Selectride is an efficient agent for the 3-O-demethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-demethylation, rather than cleavage of the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion.

  3. 3D FT-IR imaging spectroscopy of phase-separation in a poly(3-hydroxybutyrate)/poly(L-lactic acid) blend

    Science.gov (United States)

    Miriam Unger; Julia Sedlmair; Heinz W. Siesler; Carol Hirschmugl; Barbara Illman

    2014-01-01

    In the present study, 3D FT-IR spectroscopic imaging measurements were applied to study the phase separation of a poly(3-hydroxybutyrate) (PHB)/poly(L-lactic acid) (PLA) (50:50 wt.%) polymer blend film. While in 2D projection imaging the z-dependent information is overlapped, thereby complicating the analysis, FT-IR spectro-micro-tomography,...

  4. A Back-to-Back 2L-3L Grid Integration of a Marine Current Energy Converter

    Directory of Open Access Journals (Sweden)

    Senad Apelfröjd

    2015-01-01

    Full Text Available The paper proposes a back-to-back 2L-3L grid connection topology for a marine current energy converter. A prototype marine current energy converter has been deployed by a research group at Uppsala University. The concept behind the prototype revolves around a fixed pitch vertical axis turbine directly connected to a permanent magnet synchronous generator (PMSG. The proposed grid connection system utilizes a well known and proven two level voltage source converter generator-side combined with a three-level cascaded H-bridge (CHB multilevel converter grid-side. The multilevel converter brings benefits in terms of efficiency, power quality and DC-link utilization. The system is here presented for a single marine current energy converter but can easily be scaled up for clusters of marine current energy converters. Control schemes for both grid-side and generator-side voltage source converters are presented. The start-up, steady state and dynamic performance of the marine current energy converter are investigated and simulation results are presented in this paper.

  5. Nikkaji Dictionary: 3-アミノ-L-チロシン [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term 3-アミノ-L-チロシン 名詞 一般 * * * * 3-アミノ-L-チロシン... ... Nikkaji J221.623J 200906062358760920 C CA06 UNKNOWN_2 3 - アミ ノ - L - チロシン

  6. Nikkaji Dictionary: 3-ヨード-L-チロシン [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term 3-ヨード-L-チロシン 名詞 一般 * * * * 3-ヨード-L-チロシン... ... Nikkaji J4.880A 200906077910378804 C CA06 UNKNOWN_2 3 - ヨード - L - チロシン

  7. Bixin regulates mRNA expression involved in adipogenesis and enhances insulin sensitivity in 3T3-L1 adipocytes through PPAR{gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuyuki; Goto, Tsuyoshi; Taimatsu, Aki; Egawa, Kahori; Katoh, Sota; Kusudo, Tatsuya; Sakamoto, Tomoya; Ohyane, Chie; Lee, Joo-Young; Kim, Young-il; Uemura, Taku; Hirai, Shizuka [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011 (Japan)

    2009-12-25

    Insulin resistance is partly due to suppression of insulin-induced glucose uptake into adipocytes. The uptake is dependent on adipocyte differentiation, which is controlled at mRNA transcription level. The peroxisome proliferator-activated receptor (PPAR), a ligand-regulated nuclear receptor, is involved in the differentiation. Many food-derived compounds serve as ligands to activate or inactivate PPAR. In this study, we demonstrated that bixin and norbixin (annatto extracts) activate PPAR{gamma} by luciferase reporter assay using GAL4-PPAR chimera proteins. To examine the effects of bixin on adipocytes, 3T3-L1 adipocytes were treated with bixin or norbixin. The treatment induced mRNA expression of PPAR{gamma} target genes such as adipocyte-specific fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and adiponectin in differentiated 3T3-L1 adipocytes and enhanced insulin-dependent glucose uptake. The observations indicate that bixin acts as an agonist of PPAR{gamma} and enhances insulin sensitivity in 3T3-L1 adipocytes, suggesting that bixin is a valuable food-derived compound as a PPAR ligand to regulate lipid metabolism and to ameliorate metabolic syndrome.

  8. The Expansion of mtDNA Haplogroup L3 within and out of Africa

    Czech Academy of Sciences Publication Activity Database

    Soares, P.; Alshamali, F.; Pereira, J. B.; Fernandes, V.; Silva, N. M.; Afonso, C.; Costa, M. D.; Musilová, E.; Macaulay, V.; Richards, M. B.; Černý, Viktor; Pereira, L.

    2012-01-01

    Roč. 29, č. 3 (2012), s. 915-927 ISSN 0737-4038 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA * complete genomes * haplogroup L3 * out of Africa * modern human expansions Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 10.353, year: 2012

  9. Radiosynthesis and biological evaluation of 5-(3-[18F]Fluoropropyloxy)-L-tryptophan for tumor PET imaging

    International Nuclear Information System (INIS)

    He, Shanzhen; Tang, Ganghua; Hu, Kongzhen; Wang, Hongliang; Wang, Shuxia; Huang, Tingting; Liang, Xiang; Tang, Xiaolan

    2013-01-01

    Introduction: [ 18 F]FDG PET has difficulty distinguishing tumor from inflammation in the clinic because of the same high uptake in nonmalignant and inflammatory tissue. In contrast, amino acid tracers do not accumulate in inflamed tissues and thus provide an excellent opportunity for their use in clinical cancer imaging. In this study, we developed a new amino acid tracer 5-(3-[ 18 F]Fluoropropyloxy)-L-tryptophan ([ 18 F]-L-FPTP) by two-step reactions and performed its biologic evaluation. Methods: [ 18 F]-L-FPTP was prepared by [ 18 F]fluoropropylation of 5-hydroxy-L-tryptophan disodium salt and purification on C18 cartridges. The biodistribution of [ 18 F]-L-FPTP was determined in normal mice and the incorporation of [ 18 F]-L-FPTP into tissue proteins was investigated. In vitro competitive inhibition experiments were performed with Hepa1-6 hepatoma cell lines. [ 18 F]-L-FPTP PET imaging was performed on tumor-bearing and inflammation mice and compared with [ 18 F]-L-FEHTP PET. Results: The overall uncorrected radiochemical yield of [ 18 F]-L-FPTP was 21.1 ± 4.4% with a synthesis time of 60 min, the radiochemical purity was more than 99%. Biodistribution studies demonstrate high uptake of [ 18 F]-L-FPTP in liver, kidney, pancreas, and blood at the early phase, and fast clearance in most tissues over the whole observed time. The uptake studies in Hepa1-6 cells suggest that [ 18 F]-L-FPTP is transported by the amino acid transport system B 0,+ , LAT2 and ASC. [ 18 F]-L-FPTP displays good stability and is not incorporated into proteins in vitro. PET imaging shows that [ 18 F]-L-FPTP can be a better potential PET tracer for differentiating tumor from inflammation than [ 18 F]FDG and 5-(3-[ 18 F]fluoroethyloxy)-L-tryptophan ([ 18 F]-L-FEHTP), with high [ 18 F]-L-FPTP uptake ratio (2.53) of tumor to inflammation at 60 min postinjection. Conclusions: Using [ 18 F]fluoropropyl derivatives as intermediates, the new tracer [ 18 F]-L-FPTP was achieved with good yield and

  10. Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: Zinc-dependent 3,3',5-triiodo-l-thyronine binding.

    Science.gov (United States)

    Suzuki, Shunsuke; Kasai, Kentaro; Yamauchi, Kiyoshi

    2015-01-01

    Transthyretin (TTR) diverged from an ancestral 5-hydroxyisourate hydrolase (HIUHase) by gene duplication at some early stage of chordate evolution. To clarify how TTR had participated in the thyroid system as an extracellular thyroid hormone (TH) binding protein, TH binding properties of recombinant little skate Leucoraja erinacea TTR was investigated. At the amino acid level, skate TTR showed 37-46% identities with the other vertebrate TTRs. Because the skate TTR had a unique histidine-rich segment in the N-terminal region, it could be purified by Ni-affinity chromatography. The skate TTR was a 46-kDa homotetramer of 14.5kDa subunits, and had one order of magnitude higher affinity for 3,3',5-triiodo-l-thyronine (T3) and some halogenated phenols than for l-thyroxine. However, the skate TTR had no HIUHase activity. Ethylenediaminetetraacetic acid (EDTA) treatment inhibited [(125)I]T3 binding activity whereas the addition of Zn(2+) to the EDTA-treated TTR recovered [(125)I]T3 binding activity in a Zn(2+) concentration-dependent manner. Scatchard analysis revealed the presence of two classes of binding site for T3, with dissociation constants of 0.24 and 17nM. However, the high-affinity sites were completely abolished with 1mM EDTA, whereas the remaining low-affinity sites decreased binding capacity. The number of zinc per TTR was quantified to be 4.5-6.3. Our results suggest that skate TTR has tight Zn(2+)-binding sites, which are essential for T3 binding to at least the high-affinity sites. Zn(2+) binding to the N-terminal histidine-rich segment may play an important role in acquisition or reinforcement of TH binding ability during early evolution of TTR. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication.

    Science.gov (United States)

    Morais, Ana Ts; Terzian, Ana Cb; Duarte, Danilo Vb; Bronzoni, Roberta Vm; Madrid, Maria Cfs; Gavioli, Arieli F; Gil, Laura Hvg; Oliveira, Amanda G; Zanelli, Cleslei F; Valentini, Sandro R; Rahal, Paula; Nogueira, Mauricio L

    2013-06-22

    Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication. To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference. In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L with YFV NS5 may play a role

  12. Evaluating Vaccine Candidates for Filariasis

    Science.gov (United States)

    2013-04-16

    causative agents of lymphatic filariasis, W. bancrofti, B. malayi, or B. timori, and that the worldwide prevalence of genital disease or lymphedema...St. Louis, Missouri: Saundeers Elsevier 71. Johnson MH, Orihel TC, Beaver PC. 1974. Dipetalonema viteae in the experimentally infected jird

  13. Measurement of alignment parameter for photon induced $L_{3}$ vacancies in the elements 59

    CERN Document Server

    Ertugrul, M; Sahin, Y

    2002-01-01

    The alignment parameter was measured using the L/sub alpha //L/sub l/ intensity ratio. For this measurement. the Kamiya et al. ÝPhys. Rev. A 20, 820 (1979)¿ equation was used. The L/sub l/ and L/sub alpha / X-rays of the elements were measured with a Si (Li) detector at a direction of 90 degrees to the projectile. The L/sub 3/ edges of the elements were excited with the selected ionising energies. (13 refs).

  14. Effect of high hydrostatic pressure extract of fresh ginseng on adipogenesis in 3T3-L1 adipocytes.

    Science.gov (United States)

    Lee, Mak-Soon; Jung, Sunyoon; Oh, Soojung; Shin, Yoonjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2015-09-01

    Red ginseng is produced by steaming and drying fresh ginseng. Through this processing, chemical compounds are modified, and then biological activities are changed. In the food-processing industry, high hydrostatic pressure (HHP) has become an alternative to heat processing to make maximum use of bioactive compounds in food materials. This study comparatively investigated the anti-adipogenic effects of water extract of red ginseng (WRG) and high hydrostatic pressure extract of fresh ginseng (HPG) in 3T3-L1 adipocytes. Both WRG and HPG inhibited the accumulation of intracellular lipids and triglycerides, and the activity of glycerol-3-phosphate dehydrogenase (GPDH), a key enzyme in triglyceride biosynthesis. Intracellular lipid content and GPDH activity were significantly lower in the HPG group compared to the WRG group. In addition, mRNA expression of adipogenic genes, including CEBP-α, SREBP-1c and aP2, were lower in HPG-treated cells compared to WRG-treated cells. HPG significantly increased the activity of AMPK, and WRG did not. Results suggested that HPG may have superior beneficial effects on the inhibition of adipogenesis compared with WRG. The anti-adipogenic effects of HPG were partially associated with the inhibition of GPDH activity, suppression of adipogenic gene expression and activation of AMPK in 3T3-L1 adipocytes. © 2014 Society of Chemical Industry.

  15. Ultra-Low Inductance Design for a GaN HEMT Based 3L-ANPC Inverter

    DEFF Research Database (Denmark)

    Gurpinar, Emre; Castellazzi, Alberto; Iannuzzo, Francesco

    2016-01-01

    contributors to voltage overshoots and increase of switching losses, are discussed. The ultra-low inductance power cell design based on a four layer PCB with the aim to maximise the switching performance of GaN HEMTs is explained. Gate driver design for GaN HEMT devices is presented. Common-mode behaviours......In this paper, an ultra-low inductance power cell design for a 3L-ANPC based on 650 V GaN HEMT devices is presented. The 3L-ANPC topology with GaN HEMT devices and the selected modulation scheme suitable for wide-bandgap (WBG) devices are presented. The commutation loops, which are the main...

  16. Triiodothyronine Acutely Stimulates Glucose Transport into L6 Muscle Cells Without Increasing Surface GLUT4, GLUT1, or GLUT3

    Science.gov (United States)

    Teixeira, Silvania Silva; Tamrakar, Akhilesh K.; Goulart-Silva, Francemilson; Serrano-Nascimento, Caroline; Klip, Amira

    2012-01-01

    Background Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T3) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T3 and insulin action. Methods Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T3, Tx plus insulin, and Tx plus insulin and T3. Results Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T3 treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T3 treatment; however, in these cells glucose transport was not stimulated by T3. In wild-type L6 cells, although T3 treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T3 stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T3 plus insulin. Conclusions These data reveal that T3 rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T3 effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT. PMID:22663547

  17. Anti-adipogenic effects of extracts of Ficus deltoidea var. deltoidea and var. angustifolia on 3T3-L1 adipocytes.

    Science.gov (United States)

    Woon, Shiau Mei; Seng, Yew Wei; Ling, Anna Pick Kiong; Chye, Soi Moi; Koh, Rhun Yian

    2014-03-01

    This study examined the anti-adipogenic effects of extracts of Ficus deltoidea var. deltoidia and var. angustifolia, a natural slimming aid, on 3T3-L1 adipocytes. Methanol and water extracts of leaves of the F. deltoidea varieties were analyzed to determine their total flavonoid content (TFC) and total phenolic content (TPC), respectively. The study was initiated by determining the maximum non-toxic dose (MNTD) of the methanol and water extracts for 3T3-L1 preadipocytes. Possible anti-adipogenic effects were then examined by treating 2-d post confluent 3T3-L1 preadipocytes with either methanol extract or water extract at MNTD and half MNTD (½MNTD), after which the preadipocytces were induced to form mature adipocytes. Visualisation and quantification of lipid content in mature adipocytes were carried out through oil red O staining and measurement of optical density (OD) at 520 nm, respectively. The TFCs of the methanol extracts were 1.36 and 1.97 g quercetin equivalents (QE)/100 g dry weight (DW), while the TPCs of the water extracts were 5.61 and 2.73 g gallic acid equivalents (GAE)/100 g DW for var. deltoidea and var. angustilofia, respectively. The MNTDs determined for methanol and water extracts were (300.0 ± 28.3) and (225.0 ± 21.2) µg/ml, respectively, for var. deltoidea, while much lower MNTDs [(60.0 ± 2.0) µg/ml for methanol extracts and (8.0 ± 1.0) µg/ml for water extracts] were recorded for var. angustifolia. Studies revealed that the methanol extracts of both varieties and the water extracts of var. angustifolia at either MNTD or ½MNTD significantly inhibited the maturation of preadipocytes. The inhibition of the formation of mature adipocytes indicated that leaf extracts of F. deltoidea could have potential anti-obesity effects.

  18. Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells.

    Science.gov (United States)

    Sasidharan Nair, Varun; Toor, Salman M; Ali, Bassam R; Elkord, Eyad

    2018-05-02

    Breast cancer is the most commonly diagnosed cancer, and it is a leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) constitutes 15% of breast cancer and shows distinct metastasis profiles with poor prognosis. Strong PD-L1 expression has been observed in some tumors, supporting their escape from immune surveillance. Targeting PD-L1 could be a promising therapeutic approach in breast cancer patients. We investigated potential molecular mechanisms for constitutive expression of PD-L1 by inhibiting upstream STAT1 and STAT3 signals. PD-L1 expression in three breast cancer cell lines was measured using quantitative PCR and western blotting. Activation of STAT1 and STAT3 was blocked using pharmacological inhibitors and siRNA. The mechanism underlying the constitutive expression of PD-L1 was investigated using ChIP and co-immunoprecipitation assays. We found that individual inhibition of STAT1 and STAT3 activation partially downregulated PD-L1, while combined inhibition completely downregulated PD-L1 expression. Moreover, our results suggest that pSTAT1-pSTAT3 dimerize in cytosol and translocate to the nucleus, where they bind to PD-L1 promoter and induce PD-L1 expression. These findings provide a rationale for combined targeting of STAT1 and STAT3 for the development of immune-based cancer therapies for down regulation of PD-L1 expression.

  19. Differentiation to adipocytes in accompanied by an increase in the amounts of Gi- and Go-proteins in 3T3-L1 cells

    International Nuclear Information System (INIS)

    Watkins, D.C.; Northup, J.K.; Malbon, C.C.

    1986-01-01

    Treatment of cultures of 3T3-L1 cells with methylisobutyl-xanthine and dexamethasone has been shown to result in accumulation of lipid and conversion to the morphology of adipocytes in more than 90% of the cells. The status of the stimulatory (Gs), inhibitory (Gi) and Go-proteins during the course of 3T3-L1 differentiation was examined. The amount of alpha subunit of Gs (αGs), assayed by radiolabeling in the presence of cholera toxin and [ 32 P]NAD + , increased upon differentiation as previously described by others. The amounts of αGi and αGo assayed by radiolabeling in the presence of pertussis toxin and [ 32 P]NAD + increased 3-fold upon differentiation. Immunoblots of cell membranes subjected to gel electrophoresis in sodium dodecyl sulfate were probed with two rabbit antisera raised against bovine brain αGo and with one raised against theβ-subunit of the bovine rod-outer-segment G-protein, referred to as transducin. The immunoblotting data confirm the increase upon differentiation of αGo and also demonstrate an increase in the amount of the β-subunit. Thus differentiation of 3T3-L1 cells is accompanied by dramatic changes in the complexion of G-proteins in the membranes

  20. Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains▿ †

    OpenAIRE

    Bellot, Grégory; Garcia-Medina, Raquel; Gounon, Pierre; Chiche, Johanna; Roux, Danièle; Pouysségur, Jacques; Mazure, Nathalie M.

    2009-01-01

    While hypoxia-inducible factor (HIF) is a major actor in the cell survival response to hypoxia, HIF also is associated with cell death. Several studies implicate the HIF-induced putative BH3-only proapoptotic genes bnip3 and bnip3l in hypoxia-mediated cell death. We, like others, do not support this assertion. Here, we clearly demonstrate that the hypoxic microenvironment contributes to survival rather than cell death by inducing autophagy. The ablation of Beclin1, a major actor of autophagy,...

  1. The Electronic Properties and L3 XANES of Au and Nano-Au

    International Nuclear Information System (INIS)

    Yiu, Y.M.; Zhang, P.; Sham, T.K.

    2004-01-01

    The electronic properties of Au crystal and nano Au have been investigated by theory and experiment. Molecularly capped nano-Au was synthesized using the two-phase method. Au nano-particles have been characterized by X-Ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). They retain the fcc crystal structure. Their sizes have been determined to be in a range from 5.5 nm to 1.7 nm. The L3 X-ray Absorption Near Edge Structure (XANES) of nano-Au and Au foil have been recorded using synchrotron radiation, and examined by theoretical calculation based on the first principles. Both theory and experiment show that the nano-Au particles have essentially all the Au L3 XANES features of bulk Au in the near edge region with less pronounced resonance peaks. It is also shown that nano Au exhibits lower 4f binding energy than bulk Au in good agreement with quantum confined Au systems reported previously.

  2. Effet de la substitution du cuivre par du lithium sur les proprietes de l'oxyde spinelle lithium(x)cuivre(y-x)cobalt(3-y)oxygen(4) etudie pour l'electrocatalyse de la reaction de degagement de l'oxygene en milieu alcalin

    Science.gov (United States)

    Fatih, Khalid

    L'electrolyse de l'eau demeure la seule technologie industrielle de generation de l'hydrogene et de l'oxygene tres purs sans rejet de CO2 dans l'atmosphere, ce qui le rend tres attrayant par rapport a la combustion de carburants fossiles qui provoque presentement de serieux problemes environnementaux. Dans le but d'ameliorer le rendement de ce procede, nous avons developpe de nouveaux materiaux d'anode peu couteux, a base de l'oxyde mixte CuyCo3-yO 4, qui possedent une cinetique rapide pour la reaction de degagement de l'oxygene (RDO). Cette reaction suscite un interet particulier en raison de la surtension d'activation relativement elevee a l'anode qui cause la principale perte de rendement du procede. Une etude systematique a ete effectuee sur la substitution du Cu par du Li (0 a 40%), afin d'elucider les proprietes electrocatalytiques des oxydes LixCuy-xCo3-yO4. Ces oxydes, prepares sous forme de poudres par decomposition thermique des nitrates precurseurs entre 300 et 500°C, ont montre (DRX et FTIR) une structure spinelle inverse non-stcechiometrique avec une diminution du volume de la maille cristalline. La surface specifique par BET est d'environ 6 m2 g-1. Le pcn, obtenu par titrage acido-basique, a indique une diminution de la force du lien M-OH avec le taux du Li dans l'oxyde. Les analyses par XPS, realisees sur des films d'oxyde prepares par nebulisation reactive sur un substrat lisse de nickel, revelent un enrichissement de la surface en Cu a partir de 30% Li, et la presence des cations de surface Co2+, Co3+, Cu +, Cu2+ et Cu3+. La concentration de ce dernier montre un maximum a 10 et 20% Li. Suite a la substitution du Cu par du Li, la compensation de la charge serait assuree principalement par la formation d'especes Cu3+ pour les oxydes contenant jusqu'a 20% Li, et par la formation d'especes Co3+ aux taux de substitution superieurs. Les micrographies MEB montrent une morphologie hemispherique des particules d'oxyde reparties uniformement sur le substrat

  3. Differential uptake of [18F]FET and [3H]L-methionine in focal cortical ischemia

    International Nuclear Information System (INIS)

    Salber, Dagmar; Stoffels, Gabriele; Pauleit, Dirk; Reifenberger, Guido; Sabel, Michael; Shah, Nadim Jon; Hamacher, Kurt; Coenen, Heinz H.; Langen, Karl-Josef

    2006-01-01

    Amino acids such as [ 11 C-methyl]L-methionine are particularly useful in brain tumor diagnosis, but unspecific uptake (e.g., in cerebral ischemia) has been reported. O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) shows a clinical potential similar to that of L-methionine (MET) in brain tumor diagnosis but is applicable on a wider clinical scale. The aim of this study was to evaluate the uptake of [ 18 F]FET and [ 3 H]MET in focal cortical ischemia in rats by dual-tracer autoradiography. Methods: Focal cortical ischemia was induced in 25 CDF rats using the photothrombosis (PT) model. At different time points up to 6 weeks after the induction of PT, [ 18 F]FET and [ 3 H]MET were injected intravenously. Additionally, contrast-enhanced magnetic resonance imaging (MRI) was performed in 10 animals. One hour after tracer injection, brains were cut in coronal sections and evaluated by dual-tracer autoradiography. Lesion-to-brain (L/B) ratios were calculated by dividing the maximal uptake in the lesion by the mean uptake in the brain. An L/B ratio of >2.0 was considered indicative of pathological uptake. Histological slices were stained by cresyl violet and supplemented by immunostainings for glial fibrillary acidic protein (GFAP) and CD68 in selected cases. Results: A variably increased uptake of both tracers was observed in the PT lesion and its demarcation zone up to 7 days after PT for [ 18 F]FET and up to 6 weeks for [ 3 H]MET. The cutoff level of 2.0 was exceeded in 12/25 animals for [ 18 F]FET and in 18/25 animals for [ 3 H]MET. Focally increased tracer uptake matched contrast enhancement in MRI in 3/10 cases for [ 18 F]FET and in 5/10 cases for [ 3 H]MET. Immunohistochemical staining in lesions with differential uptake of [ 18 F]FET and [ 3 H]MET revealed that selective uptake of [ 18 F]FET was associated with GFAP-positive astrogliosis while selective [ 3 H]MET uptake correlated with CD68-positive macrophage infiltration. Conclusions: [ 18 F]FET, like [ 3 H

  4. Quantification of vitamin D3 and its hydroxylated metabolites in waxy leaf nightshade (Solanum glaucophyllum Desf.), tomato (Solanum lycopersicum L.) and bell pepper (Capsicum annuum L.)

    DEFF Research Database (Denmark)

    Jäpelt, Rie Bak; Silvestro, Daniele; Smedsgaard, Jørn

    2013-01-01

    Changes in vitamin D3 and its metabolites were investigated following UVB- and heat-treatment in the leaves of Solanum glaucophyllum Desf., Solanum lycopersicum L. and Capsicum annuum L. The analytical method used was a sensitive and selective liquid chromatography electrospray ionisation tandem ...

  5. Spectroscopic Constants and Vibrational Frequencies for l-C3H+ and Isotopologues from Highly-Accurate Quartic Force Fields: The Detection of l-C3H+ in the Horsehead Nebula PDR Questioned

    Science.gov (United States)

    Huang, Xinchuan; Fortenberry, Ryan Clifton; Lee, Timothy J.

    2013-01-01

    Very recently, molecular rotational transitions observed in the photon-dominated region of the Horsehead nebula have been attributed to l-C3H+. In an effort to corroborate this finding, we employed state-of-the art and proven high-accuracy quantum chemical techniques to compute spectroscopic constants for this cation and its isotopologues. Even though the B rotational constant from the fit of the observed spectrum and our computations agree to within 20 MHz, a typical level of accuracy, the D rotational constant differs by more than 40%, while the H rotational constant differs by three orders of magnitude. With the likely errors in the rotational transition energies resulting from this difference in D on the order of 1 MHz for the lowest observed transition (J = 4 yields 3) and growing as J increases, the assignment of the observed rotational lines from the Horsehead nebula to l-C3H+ is questionable.

  6. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-01-01

    INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

  7. Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development.

    Science.gov (United States)

    Puckette, Michael; Clark, Benjamin A; Smith, Justin D; Turecek, Traci; Martel, Erica; Gabbert, Lindsay; Pisano, Melia; Hurtle, William; Pacheco, Juan M; Barrera, José; Neilan, John G; Rasmussen, Max

    2017-11-15

    The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production. Copyright © 2017 Puckette et al.

  8. Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP-α and PPAR-γ Expression in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Thi Tuyet Nhung Nguyen

    2017-01-01

    Full Text Available Many studies have comprehensively examined the venom of Ophiophagus hannah snake. Its venom comprises different compounds exhibiting a wide range of pharmacological activities. In this investigation, four peptide fractions (PFs, ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O. hannah were separated by HPLC and investigated for their inhibitory activity on adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two peptides on 3T3-L1 adipocytes, it was revealed that, at 10 μg/mL, pOh2 was able to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without affecting cell viability. Furthermore, the pOh2 downregulated the gene expression of important transcription factors C/EBP-α and PPAR-γ. In addition, aP2 and GPDH adipocyte-specific markers were also significantly reduced compared to untreated differentiated cells. Taken together, pOh2 inhibited the expression of key transcription factors C/EBP-α and PPAR-γ and their target genes, aP2 and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this novel class of peptide might have potential for in vivo antiobesity effects.

  9. Microarray evaluation of EP4 receptor-mediated prostaglandin E2 suppression of 3T3-L1 adipocyte differentiation

    International Nuclear Information System (INIS)

    Sugimoto, Yukihiko; Tsuboi, Hiroaki; Okuno, Yasushi; Tamba, Shigero; Tsuchiya, Soken; Tsujimoto, Gozo; Ichikawa, Atsushi

    2004-01-01

    Prostaglandin E 2 (PGE 2 ) has been shown to negatively regulate adipogenesis. To explore to what extent PGE 2 inhibits the differentiation of cells to adipocytes and to examine whether its effect could be due to EP4 receptor signaling, we used microarrays to analyze the gene expression profiles of 3T3-L1 cells exposed to a differentiation cocktail supplemented with PGE 2 , AE1-329 (an EP4 agonist), or vehicle. The differentiation-associated responses in genes such as adipocytokines and enzymes related to lipid metabolism were largely weakened upon PGE 2 treatment. In particular, the expression of peroxisome proliferator activated receptor-γ and CCAAT/enhancer binding protein-α, genes playing a central role in adipogenesis, was greatly suppressed. PGE 2 appears to be ineffective to a subclass of insulin target genes such as hexokinase 2 and phosphofructokinase. Similar responses were produced in the differentiation-associated genes upon AE1-329 treatment. These results suggest that PGE 2 inhibits a crucial step of the adipocyte differentiation process by acting on the EP4 receptor in 3T3-L1 cells

  10. Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang ZG

    2015-12-01

    Full Text Available Zhiguo Zhang,1 Yanying Zhang,2 Yeying Wang,1 Lingling Xu,3 Wanju Xu3 1Department of Clinical Laboratory, Zhangqiu Maternity and Child Care Hospital, Zhangqiu, 2Department of Clinical Laboratory, Zaozhuang City Wangkai Infection Hospital, Zaozhuang, 3Department of Clinical Laboratory, Qianfoshan Hospital, Jinan, People’s Republic of China Abstract: Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP-negative hepatocellular carcinoma (HCC. Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73 as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use

  11. Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics

    DEFF Research Database (Denmark)

    Pakula, Kevin K; Hansen, Lykke H; Vester, Birte

    2017-01-01

    . The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects...... of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were...

  12. Predicting yield-stress anomalies in L12 alloys: Ni3Ge-Fe3Ge pseudo-binaries

    International Nuclear Information System (INIS)

    Liu, J.B.; Johnson, D.D.; Smirnov, A.V.

    2005-01-01

    The L1 2 -based pseudo-binary (Ni 1-c Fe c ) 3 Ge is an ideal system to study yield-strength anomaly and its origin as it has a solid-solution phase vs. c and Ni 3 Ge exhibits an anomaly while Fe 3 Ge does not. Using two ab initio electronic-structure techniques, we calculate the planar-fault energies on the γ-surface, i.e., antiphase boundaries (APB) and stacking faults, both complex and superlattice intrinsic (SISF), for (Ni 1-c Fe c ) 3 Ge as a function of c. Generally, we use the fault energies combined with elasticity theory to predict occurrence/loss of the yield-strength anomaly and show that the loss of anomaly occurs due to APB(1 1 1)-to-SISF(1 1 1) instability. Assessing the stability of APB(1 1 1) on the γ-surface within linear elasticity theory, we predict the transition from anomalous to normal temperature dependence of yield strength for c ∼≥ 0.35 (or 26 at.% Fe), as is observed, after which type-II, rather than type-I, dissociation is energetically favorable. Hence, first-principles calculations can predict reliably the existence/loss of anomalous yield-strength. Finally, we show that (0 0 1) and (1 1 1) APB energies of the binaries and pseudo-binaries agree quantitatively with measured values when chemical antisite disorder, intrinsic to the samples characterized, is included, whereas they are too large by a factor of two in perfect L1 2 . We investigate three types of disorder: thermal and off-stoichiometric antisites, as well as chemical disorder vs. Fe-content in pseudo-binaries

  13. Recovery after fracture dislocation of L3/L4 ASIA B: Case report

    Directory of Open Access Journals (Sweden)

    Gustavo Caldera

    2016-02-01

    Full Text Available In fracture dislocations of the lumbar region, two anatomical facts can help preserve neurological damage in patients, when compared with trauma in the cervical or thoracic region. Firstly, the spinal cord in adults extends only to the lower edge of the first lumbar vertebra, and secondly, the large vertebral space in this region gives ample space for the roots of the cauda equine. As a result, the nerve injury may be minimal, because the nerve roots in this region are accommodated in a larger area, with less content and space. This study presents the case of a 48-year-old male, a construction worker, who suffered a fall from a height of approximately 15 meters, directly hitting the lumbar region against a beam, and presenting pain and inability to move the legs. The patient was brought to the emergency room 1 hour after the accident, clinically assessed, submitted to x-rays and a CT scan, and diagnosed as having an ASIA B L3-L4 fracture dislocation. Three hours after the accident, reduction was performed via posterior transpedicular fixation. One week later, an anterior approach was performed. The patient progressed to ASIA C 24 hours after the first surgery. Three months later, the patient was functional with ASIA D and good sphincter control. The author's purpose is to show the results obtained by an intervention in the initial hours of the trauma, which helped promote the evolution from a nonfunctional injury to a functional one, with near-total recovery. Keywords: Spine fracture, Recovery, Neurological deficit, Asia scale, Dislocation

  14. Cytotoxic effects in 3T3-L1 mouse and WI-38 human fibroblasts following 72 hour and 7 day exposures to commercial silica nanoparticles

    International Nuclear Information System (INIS)

    Stępnik, Maciej; Arkusz, Joanna; Smok-Pieniążek, Anna; Bratek-Skicki, Anna; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A.; Gromadzińska, Jolanta; De Jong, Wim H.; Rydzyński, Konrad

    2012-01-01

    The potential toxic effects in murine (3T3-L1) and human (WI-38) fibroblast cell lines of commercially available silica nanoparticles (NPs), Ludox CL (nominal size 21 nm) and CL-X (nominal size of 30 nm) were investigated with particular attention to the effect over long exposure times (the tests were run after 72 h exposure up to 7 days). These two formulations differed in physico-chemical properties and showed different stabilities in the cell culture medium used for the experiments. Ludox CL silica NPs were found to be cytotoxic only at the higher concentrations to the WI-38 cells (WST-1 and LDH assays) but not to the 3T3-L1 cells, whereas the Ludox CL-X silica NPs, which were less stable over the 72 h exposure, were cytotoxic to both cell lines in both assays. In the clonogenic assay both silica NPs induced a concentration dependent decrease in the surviving fraction of 3T3-L1 cells, with the Ludox CL-X silica NPs being more cytotoxic. Cell cycle analysis showed a trend indicating alterations in both cell lines at different phases with both silica NPs tested. Buthionine sulfoximine (γ-glutamylcysteine synthetase inhibitor) combined with Ludox CL-X was found to induce a strong decrease in 3T3-L1 cell viability which was not observed for the WI-38 cell line. This study clearly indicates that longer exposure studies may give important insights on the impact of nanomaterials on cells. However, and especially when investigating nanoparticle effects after such long exposure, it is fundamental to include a detailed physico-chemical characterization of the nanoparticles and their dispersions over the time scale of the experiment, in order to be able to interpret eventual impacts on cells. -- Highlights: ► Ludox CL silica NPs are cytotoxic to WI-38 fibroblasts but not to 3T3-L1 fibroblasts. ► Ludox CL-X silica NPs are cytotoxic to both cell lines. ► In clonogenic assay both silica NPs induce cytotoxicity, higher for CL-X silica. ► Cell cycle analysis shows

  15. The Audi 3.0l TFSI - the new top-of-the-range V6 engine; Der Audi 3,0l TFSI - die neue V6 Spitzenmotorisierung

    Energy Technology Data Exchange (ETDEWEB)

    Fitzen, M.; Hatz, W.; Eiser, A.; Heiduk, T.; Riegner, J. [Audi AG, Ingolstadt (Germany)

    2008-07-01

    The 3.0l TFSI represents the new top-of-the-range V6 engine from Audi. In its basic form this engine design delivers 213 kW (290 bhp) and 420 Nm. The fundamental design of the engine has been adopted from the naturally aspirated V6 engines as revised in 2006, including the measures to reduce frictional losses. An entirely new development is the supercharger module, with integrated Roots blower, bypass regulation and charge air intercooling. All the components are accommodated inside the V. As a result of the extremely compact dimensions it has also been possible to adopt the arrangement of the inlet and exhaust systems directly from the naturally aspirated engines without any changes. In conjunction with direct injection, this sets new standards in terms of responsiveness, efficiency and noise levels. The new Audi V6 3.0l TFSI combines excellent torque and power output with outstanding responsiveness, along with the package and exhaust-related benefits of a naturally aspirated engine. That makes it ideally suitable for a wide range of applications within the Audi model portfolio. The initial launch of the engine will be in the new A6 for the autumn of 2008. (orig.)

  16. Chondroitin Sulfate Inhibits Monocyte Chemoattractant Protein-1 Release From 3T3-L1 Adipocytes: A New Treatment Opportunity for Obesity-Related Inflammation?

    Directory of Open Access Journals (Sweden)

    Thomas V Stabler

    2017-08-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1 overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adipocytes using an established protocol. Adipocytes were treated with lipopolysaccharide (LPS to induce inflammation and thus MCP-1 release. At the same time, varying concentrations of chondroitin sulfate (CS were added in a physiologically relevant range (10-200 µg/mL to determine its impact on MCP-1 release. Chondroitin sulfate, a natural glycosaminoglycan of connective tissue including the cartilage extracellular matrix, was chosen on the basis of our previous studies demonstrating its anti-inflammatory effect on macrophages. Because the main action of MCP-1 is to induce monocyte migration, cultured THP-1 monocytes were used to test whether CS at the highest physiologically relevant concentration could inhibit cell migration induced by human recombinant MCP-1. Chondroitin sulfate (100-200 µg/mL inhibited MCP-1 release from inflamed adipocytes in a dose-dependent manner ( P  < .01, 95% confidence interval [CI]: −5.89 to −3.858 at 100 µg/mL and P  < .001, 95% CI: −6.028 to −3.996 at 200 µg/mL but had no effect on MCP-1–driven chemotaxis of THP-1 monocytes. In summary, CS could be expected to reduce macrophage infiltration into adipose tissue by reduction in adipocyte expression and release of MCP-1 and as such might reduce adipose tissue inflammation in response to pro-inflammatory stimuli such as LPS, now increasingly recognized to be relevant in vivo.

  17. Proteomic analysis of cAMP-mediated signaling during differentiation of 3 T3-L1 preadipocytes

    DEFF Research Database (Denmark)

    Borkowski, Kamil; Wrzesinski, Krzysztow; Rogowska-Wrzesinska, Adelina

    2014-01-01

    Initiation of adipocyte differentiation is promoted by the synergistic action of insulin/insulin-like growth factor, glucocorticoids, and agents activating cAMP-dependent signaling. The action of cAMP is mediated via PKA and Epac, where at least part of the PKA function relates to strong repression...... a comprehensive evaluation of Epac-mediated processes and their interplay with PKA during the initiation of 3 T3-L1 preadipocyte differentiation using a combination of proteomics, molecular approaches, and bioinformatics. Proteomic analyses revealed 7 proteins specifically regulated in response to Epac activation......-dependent signaling thereby adding a novel facet to our understanding of cAMP-mediated potentiation of adipocyte differentiation....

  18. Identification of epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) and amino acid profiles in various tea (Camellia sinensis L.) cultivars.

    Science.gov (United States)

    Ji, Hyang-Gi; Lee, Yeong-Ran; Lee, Min-Seuk; Hwang, Kyeng Hwan; Kim, Eun-Hee; Park, Jun Seong; Hong, Young-Shick

    2017-10-01

    This article includes experimental data on the identification of epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3''Me) by 2-dimensional (2D) proton ( 1 H) NMR analysis and on the information of amino acid and catechin compound profiles by HPLC analysis in leaf extracts of various tea cultivars. These data are related to the research article " Metabolic phenotyping of various tea (Camellia sinensis L.) cultivars and understanding of their intrinsic metabolism " (Ji et al., 2017) [1]. The assignment for EGCG3x''Me by 1 H NMR analysis was also confirmed with spiking experiment of its pure chemical.

  19. Potential role of marine algae extract on 3T3-L1 cell proliferation and differentiation: an in vitro approach

    Directory of Open Access Journals (Sweden)

    Soundharrajan Ilavenil

    Full Text Available BACKGROUND: From ancient times, marine algae have emerged as alternative medicine and foods, contains the rich source of natural products like proteins, vitamins, and secondary metabolites, especially Chlorella vulgaris (C. vulgaris contains numerous anti-inflammatory, antioxidants and wound healing substances. Type 2 diabetes mellitus is closely associated with adipogenesis and their factors. Hence, we aimed to investigate the chemical constituents and adipo-genic modulatory properties of C. vulgaris in 3T3-L1 pre-adipocytes. RESULTS: We analysed chemical constituents in ethanolic extract of C. vulgaris (EECV by LC-MS. Results revealed that the EECV contains few triterpenoids and saponin compounds. Further, the effect of EECV on lipid accumulation along with genes and proteins expressions which are associated with adipogenesis and lipogenesis were evaluated using oil red O staining, qPCR and western blot techniques. The data indicated that that EECV treatment increased differentiation and lipid accumulation in 3T3-L1 cells, which indicates positive regulation of adipogenic and lipogenic activity. These increases were associated with up-regulation of PPAR-γ2, C/EBP-α, adiponectin, FAS, and leptin mRNA and protein expressions. Also, EECV treatments increased the concentration of glycerol releases as compared with control cells. Troglitazone is a PPAR-γ agonist that stimulates the PPAR-y2, adiponectin, and GLUT-4 expressions. Similarly, EECV treatments significantly upregulated PPAR-γ2, adiponectin, GLUT-4 expressions and glucose utilization. Further, EECV treatment decreased AMPK-α expression as compared with control and metformin treated cells. CONCLUSION: The present research findings confirmed that the EECV effectively modulates the lipid accumulation and differentiation in 3T3-L1 cells through AMPK-α mediated signalling pathway.

  20. A crystallographic constitutive model for Ni3Al (L12) intermetallics

    International Nuclear Information System (INIS)

    Choi, Y.S.; Dimiduk, D.M.; Uchic, M.D.; Parthasarathy, T.A.

    2005-01-01

    A constitutive model was developed in order to capture the unique thermo-mechanical flow behavior of L1 2 -structured Ni 3 (Al, X) alloys. This model utilized a framework for flow-stress partitioning, which was previously proposed by Ezz and Hirsch, and incorporated a model for exhaustion hardening proposed by Caillard. The simulation results well represent the major aspects of the thermo-mechanical flow behavior of Ni 3 (Al, X) alloys, such as a flow-stress anomaly, its strain dependence and a work-hardening rate anomaly. Selected limitations are discussed along with our current efforts toward extending the present model

  1. Municipal wastewater affects adipose deposition in male mice and increases 3T3-L1 cell differentiation

    International Nuclear Information System (INIS)

    Biasiotto, Giorgio; Zanella, Isabella; Masserdotti, Alice; Pedrazzani, Roberta; Papa, Matteo; Caimi, Luigi; Di Lorenzo, Diego

    2016-01-01

    Trace concentration of EDs (endocrine disrupting compounds) in water bodies caused by wastewater treatment plant effluents is a recognized problem for the health of aquatic organisms and their potential to affect human health. In this paper we show that continuous exposure of male mice from early development to the adult life (140 days) to unrestricted drinking of wastewater collected from a municipal sewage treatment plant, is associated with an increased adipose deposition and weight gain during adulthood because of altered body homeostasis. In parallel, bisphenol A (BPA) at the administration dose of 5 μg/kg/body weight, shows an increasing effect on total body weight and fat mass. In vitro, a solid phase extract (SPE) of the wastewater (eTW), caused stimulation of 3T3-L1 adipocyte differentiation at dilutions of 0.4 and 1 % in the final culture medium which contained a concentration of BPA of 40 nM and 90 nM respectively. Pure BPA also promoted adipocytes differentiation at the concentration of 50 and 80 μM. BPA effect in 3T3-L1 cells was associated to the specific activation of the estrogen receptor alpha (ERα) in undifferentiated cells and the estrogen receptor beta (ERβ) in differentiated cells. BPA also activated the Peroxisome Proliferator Activated Receptor gamma (PPARγ) upregulating a minimal 3XPPARE luciferase reporter and the PPARγ-target promoter of the aP2 gene in adipose cells, while it was not effective in preadipocytes. The pure estrogen receptor agonist diethylstilbestrol (DES) played an opposite action to that of BPA inhibiting PPARγ activity in adipocytes, preventing cell differentiation, activating ERα in preadipocytes and inhibiting ERα and ERβ regulation in adipocytes. The results of this work show that the drinking of chemically-contaminated wastewater promotes fat deposition in male mice and that EDs present in sewage are likely responsible for this effect through a nuclear receptor-mediated mechanism. - Highlights: • Sewage

  2. Municipal wastewater affects adipose deposition in male mice and increases 3T3-L1 cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Biasiotto, Giorgio; Zanella, Isabella [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Masserdotti, Alice [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy); Pedrazzani, Roberta [DIMI Department of Mechanical and Industrial Engineering, University of Brescia, via Branze 38, I-25123 Brescia (Italy); Papa, Matteo [DICATAM Department of Civil, Environmental, Architectural Engineering and Mathematics, University of Brescia, via Branze 43, I-25123 Brescia (Italy); Caimi, Luigi [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Di Lorenzo, Diego, E-mail: diego.dilorenzo@yahoo.it [Laboratory of Biotechnology, Civic Hospital of Brescia, Brescia (Italy)

    2016-04-15

    Trace concentration of EDs (endocrine disrupting compounds) in water bodies caused by wastewater treatment plant effluents is a recognized problem for the health of aquatic organisms and their potential to affect human health. In this paper we show that continuous exposure of male mice from early development to the adult life (140 days) to unrestricted drinking of wastewater collected from a municipal sewage treatment plant, is associated with an increased adipose deposition and weight gain during adulthood because of altered body homeostasis. In parallel, bisphenol A (BPA) at the administration dose of 5 μg/kg/body weight, shows an increasing effect on total body weight and fat mass. In vitro, a solid phase extract (SPE) of the wastewater (eTW), caused stimulation of 3T3-L1 adipocyte differentiation at dilutions of 0.4 and 1 % in the final culture medium which contained a concentration of BPA of 40 nM and 90 nM respectively. Pure BPA also promoted adipocytes differentiation at the concentration of 50 and 80 μM. BPA effect in 3T3-L1 cells was associated to the specific activation of the estrogen receptor alpha (ERα) in undifferentiated cells and the estrogen receptor beta (ERβ) in differentiated cells. BPA also activated the Peroxisome Proliferator Activated Receptor gamma (PPARγ) upregulating a minimal 3XPPARE luciferase reporter and the PPARγ-target promoter of the aP2 gene in adipose cells, while it was not effective in preadipocytes. The pure estrogen receptor agonist diethylstilbestrol (DES) played an opposite action to that of BPA inhibiting PPARγ activity in adipocytes, preventing cell differentiation, activating ERα in preadipocytes and inhibiting ERα and ERβ regulation in adipocytes. The results of this work show that the drinking of chemically-contaminated wastewater promotes fat deposition in male mice and that EDs present in sewage are likely responsible for this effect through a nuclear receptor-mediated mechanism. - Highlights: • Sewage

  3. Verification and Validation of the k-kL Turbulence Model in FUN3D and CFL3D Codes

    Science.gov (United States)

    Abdol-Hamid, Khaled S.; Carlson, Jan-Renee; Rumsey, Christopher L.

    2015-01-01

    The implementation of the k-kL turbulence model using multiple computational uid dy- namics (CFD) codes is reported herein. The k-kL model is a two-equation turbulence model based on Abdol-Hamid's closure and Menter's modi cation to Rotta's two-equation model. Rotta shows that a reliable transport equation can be formed from the turbulent length scale L, and the turbulent kinetic energy k. Rotta's equation is well suited for term-by-term mod- eling and displays useful features compared to other two-equation models. An important di erence is that this formulation leads to the inclusion of higher-order velocity derivatives in the source terms of the scale equations. This can enhance the ability of the Reynolds- averaged Navier-Stokes (RANS) solvers to simulate unsteady ows. The present report documents the formulation of the model as implemented in the CFD codes Fun3D and CFL3D. Methodology, veri cation and validation examples are shown. Attached and sepa- rated ow cases are documented and compared with experimental data. The results show generally very good comparisons with canonical and experimental data, as well as matching results code-to-code. The results from this formulation are similar or better than results using the SST turbulence model.

  4. Magnetic Fe3O4@MCM-41 core-shell nanoparticles functionalized with thiol silane for efficient l-asparaginase immobilization.

    Science.gov (United States)

    Ulu, Ahmet; Noma, Samir Abbas Ali; Koytepe, Suleyman; Ates, Burhan

    2018-06-06

    l-Asparaginase (l-ASNase) is a vital enzyme for medical treatment and food industry. Here, we assessed the use of Fe 3 O 4 @Mobil Composition of Matter No. 41 (MCM-41) magnetic nanoparticles as carrier matrix for l-ASNase immobilization. In addition, surface of Fe 3 O 4 @MCM-41 magnetic nanoparticles was functionalized with 3-mercaptopropyltrimethoxysilane (MPTMS) to enhance stability of l-ASNase. The chemical structure, thermal properties, magnetic profile and morphology of the thiol-functionalized Fe 3 O 4 @MCM-41 magnetic nanoparticles were characterized with Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential thermal analysis (DTA), differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM), scanning electron microscope (SEM), energy dispersive X-ray (EDX) spectroscopy and zeta-potential measurement. l-ASNase was covalently immobilized onto the thiol-functionalized Fe 3 O 4 @MCM-41 magnetic nanoparticles. The properties of the immobilized enzyme, including optimum pH, temperature, kinetic parameters, thermal stability, reusability and storage stability were investigated and compared to free one. Immobilized enzyme was found to be stable over a wide range of pH and temperature range than free enzyme. The immobilized l-ASNase also showed higher thermal stability after 180 min incubation at 50 °C. The immobilized enzyme still retained 63% of its original activity after 16 times of reuse. The Km value for the immobilized enzyme was 1.15-fold lower than the free enzyme, which indicates increased affinity for the substrate. Additionally, the immobilized enzyme was active over 65% and 53% after 30 days of storage at 4 °C and room temperature (∼25 °C), respectively. Thereby, the results confirmed that thiol-functionalized Fe 3 O 4 @MCM-41 magnetic nanoparticles had high efficiency for l-ASNase immobilization and improved stability of L-ASNase.

  5. Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-α-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Seok-Woo Hong

    2014-12-01

    Full Text Available BackgroundTumor necrosis factor (TNF-α and AMP-activated protein kinase (AMPK are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated.MethodsThe key factors and mechanism of action of TNF-α and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK/eukaryotic initiation factor 2 α (eIF2α by Western blot and an immunofluorescence assay in 24-hour TNF-α-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation.ResultsEnhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR suppressed TNF-α-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-α and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2α, a component of the unfolded protein response signaling pathway, was observed in TNF-α or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-α-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2α.ConclusionThese data indicated that AICAR-induced AMPK activation attenuates TNF-α-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2α activity is a novel mechanism of the anti-lipolytic effect of AICAR.

  6. Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Takahashi, Nobuhiko; Yoshizaki, Takayuki; Hiranaka, Natsumi; Suzuki, Takeshi; Yui, Tomoo; Akanuma, Masayasu; Oka, Kazuya; Kanazawa, Kaoru; Yoshida, Mika; Naito, Sumiyoshi; Fujiya, Mikihiro; Kohgo, Yutaka; Ieko, Masahiro

    2011-01-01

    Highlights: ► Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. ► Adipose lipin-1 expression is reduced in obesity. ► Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. ► Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-κB activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

  7. Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayasu; Oka, Kazuya [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. Black-Right-Pointing-Pointer Adipose lipin-1 expression is reduced in obesity. Black-Right-Pointing-Pointer Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. Black-Right-Pointing-Pointer Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-{kappa}B activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

  8. Diagnostic value of Joint Detection of GP73 and AFP-L3 in Primary Hepatic Carcinoma with Low Concentration of AFP

    Directory of Open Access Journals (Sweden)

    Lei CAI

    2015-03-01

    Full Text Available Objective: To explore the applicative value of serum Golgi protein (GP73 and alpha-proteinvariant (AFP-L3 in the diagnosis of patients with primary hepatic carcinoma (PHC. Methods:Totally 110 patients were enrolled, including 60 PHC patients with low concentration of AFP ((1.1-108.0 μg/L and 50 patients with non-PHC digestive system diseases (20 cases of patients with chronic hepatitis, 15 patients with liver cirrhosis, 4 patients with bile duct cancer, 4 patients with gastric cancer, 4 patients with rectal cancer and 3 patients with colon cancer. In addition, 42 healthy people were selected as control group. GP73 was detected by enzyme-linked immunosorbent assay (ELISA trace centrifugal column method was adopted for separation of AFP-L3. Luo's chemiluminescence method was used to determine the total content of AFP and AFP-L3 in eluent for calculating the ratio of AFP-L3/ AFP. Results: The levels of serum GP73 and AFP-L3(% in PHC group were significantly higher than the other 2 groups (P<0.01 and the level of serum GP73 and AFP-L3 (% in Non-PHC group were higher than those in healthy group (P<0.01. ROC analysis showed that the area under ROC curve of single GP73 and AFP-L3(% in diagnosis of PHC and non-PHC were 0.887 and 0.860, respectively. Additionally, the ROC analysis also showed that critical value of GP73 and AFP-L3 for the diagnosis of HPC were 83.78 μg/L and 13.87%, respectively. The sensitivity of joint detection of serum GP73 or AFP-L3 was higher than detection of them alone (90.0 vs. 71.7 and 60.0, P<0.05 but the specificity was similar between single detection and joint detection (P>0.05. The positive predictive value and negative predictive value of joint detection of them was higher than single detections of them and there was significant differences in negative predictive value (P<0.05 but no difference in positive predictive value (P>0.05. The overall response rate of joint detection of GP73 and AFP-L3 was higher

  9. The Vaporization of B2O3(l) to B2O3(g) and B2O2(g)

    Science.gov (United States)

    Jacobson, Nathan S.; Myers, Dwight L.

    2011-01-01

    The vaporization of B2O3 in a reducing environment leads to formation of both B2O3(g) and B2O2(g). While formation of B2O3(g) is well understood, many questions about the formation of B2O2(g) remain. Previous studies using B(s) + B2O3(l) have led to inconsistent thermodynamic data. In this study, it was found that after heating, B(s) and B2O3(l) appear to separate and variations in contact area likely led to the inconsistent vapor pressures of B2O2(g). To circumvent this problem, an activity of boron is fixed with a two-phase mixture of FeB and Fe2B. Both second and third law enthalpies of formation were measured for B2O2(g) and B2O3(g). From these the enthalpies of formation at 298.15 K are calculated to be -479.9 +/- 41.5 kJ/mol for B2O2(g) and -833.4 +/- 13.1 kJ/mol for B2O3(g). Ab initio calculations to determine the enthalpies of formation of B2O2(g) and B2O3(g) were conducted using the W1BD composite method and show good agreement with the experimental values.

  10. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-11-01

    The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

  11. Biochemical characterization of an autoradiographic method for studying excitatory amino acid receptors using L-[3H]glutamate

    International Nuclear Information System (INIS)

    Cincotta, M.; Summers, R.J.; Beart, P.M.

    1989-01-01

    A method was developed for radiolabeling excitatory amino acid receptors of rat brain with L-[ 3 H]glutamate. Effective labeling of glutamate receptors in slide-mounted 10-microns sections was obtained using a low incubation volume (0.15 ml) and rapid washing: a procedure where high ligand concentrations were achieved with minimal waste. Saturation experiments using [ 3 H]glutamate revealed a single binding site of micromolar affinity. The Bmax was trebled in the presence of Ca2+ (2.5 mM) and Cl- (20 mM) with no change in the Kd. Binding was rapid, saturable, stereospecific, and sensitive to glutamate receptor agonists. The proportions of [ 3 H]glutamate binding sensitive to N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were 34, 54, and 51%, respectively. NMDA inhibited binding at a distinct subset of L-[ 3 H]glutamate sites, whereas AMPA and kainate competed for some common sites. Labeling of sections with L-[ 3 H]glutamate in the presence of the selective agonists allowed autoradiographic visualization of glutamate receptor subtypes in brain tissue

  12. Measurements of Vcb, form factors and branching fractions in the decays B0 -> D*+l-νl and B0 -> D+l-νl

    Science.gov (United States)

    Buskulic, D.; de Bonis, I.; Decamp, D.; Ghez, P.; Goy, C.; Lees, J.-P.; Lucotte, A.; Minard, M.-N.; Nief, J.-Y.; Odier, P.; Pietrzyk, B.; Casado, M. P.; Chmeissani, M.; Comas, P.; Crespo, J. M.; Delfino, M.; Efthymiopoulos, I.; Fernandez, E.; Fernandez-Bosman, M.; Garrido, Ll.; Juste, A.; Martinez, M.; Orteu, S.; Padilla, C.; Park, I. C.; Pascual, A.; Perlas, J. A.; Riu, I.; Sanchez, F.; Teubert, F.; Colaleo, A.; Creanza, D.; de Palma, M.; Gelao, G.; Girone, M.; Iaselli, G.; Maggi, G.; Maggi, M.; Marinelli, N.; Nuzzo, S.; Ranieri, A.; Raso, G.; Ruggieri, F.; Selvaggi, G.; Silvestris, L.; Tempesta, P.; Tricomi, A.; Zito, G.; Huang, X.; Lin, J.; Ouyang, Q.; Wang, T.; Xie, Y.; Xu, R.; Xue, S.; Zhang, J.; Zhang, L.; Zhao, W.; Abbaneo, D.; Alemany, R.; Bazarko, A. O.; Bright-Thomas, P.; Cattaneo, M.; Cerutti, F.; Coyle, P.; Drevermann, H.; Forty, R. W.; Frank, M.; Hagelberg, R.; Harvey, J.; Janot, P.; Jost, B.; Kneringer, E.; Knobloch, J.; Lehraus, I.; Lutters, G.; Mato, P.; Minten, A.; Miquel, R.; Mir, Ll. M.; Moneta, L.; Oest, T.; Pacheco, A.; Pusztaszeri, J.-F.; Ranjard, F.; Rensing, P.; Rizzo, G.; Rolandi, L.; Schlatter, D.; Schmelling, M.; Schmitt, M.; Schneider, O.; Tejessy, W.; Tomalin, I. R.; Venturi, A.; Wachsmuth, H.; Wagner, A.; Ajaltouni, Z.; Barrès, A.; Boyer, C.; Falvard, A.; Gay, P.; Guicheney, C.; Henrard, P.; Jousset, J.; Michel, B.; Monteil, S.; Montret, J.-C.; Pallin, D.; Perret, P.; Podlyski, F.; Proriol, J.; Rosnet, P.; Rossignol, J.-M.; Fearnley, T.; Hansen, J. B.; Hansen, J. D.; Hansen, J. R.; Hansen, P. H.; Nilsson, B. S.; Rensch, B.; Wäänänen, A.; Kyriakis, A.; Markou, C.; Simopoulou, E.; Siotis, I.; Vayaki, A.; Zachariadou, K.; Blondel, A.; Bonneaud, G.; Brient, J. C.; Bourdon, P.; Rougé, A.; Rumpf, M.; Valassi, A.; Verderi, M.; Videau, H.; Candlin, D. J.; Parsons, M. I.; Focardi, E.; Parrini, G.; Corden, M.; Georgiopoulos, C.; Jaffe, D. E.; Antonelli, A.; Bencivenni, G.; Bologna, G.; Bossi, F.; Campana, P.; Capon, G.; Casper, D.; Chiarella, V.; Felici, G.; Laurelli, P.; Mannocchi, G.; Murtas, F.; Murtas, G. P.; Passalacqua, L.; Pepe-Altarelli, M.; Curtis, L.; Dorris, S. J.; Halley, A. W.; Knowles, I. G.; Lynch, J. G.; O'Shea, V.; Raine, C.; Scarr, J. M.; Smith, K.; Teixeira-Dias, P.; Thompson, A. S.; Thomson, E.; Thomson, F.; Turnbull, R. M.; Becker, U.; Geweniger, C.; Graefe, G.; Hanke, P.; Hansper, G.; Hepp, V.; Kluge, E. E.; Putzer, A.; Schmidt, M.; Sommer, J.; Stenzel, H.; Tittel, K.; Werner, S.; Wunsch, M.; Beuselinck, R.; Binnie, D. M.; Cameron, W.; Dornan, P. J.; Martin, E. B.; Moutoussi, A.; Nash, J.; Sedgbeer, J. K.; Stacey, A. M.; Williams, M. D.; Dissertori, G.; Girtler, P.; Kuhn, D.; Rudolph, G.; Betteridge, A. P.; Bowdery, C. K.; Colrain, P.; Crawford, G.; Finch, A. J.; Foster, F.; Hughes, G.; Sloan, T.; Williams, M. I.; Galla, A.; Giehl, I.; Greene, A. M.; Hoffmann, C.; Jakobs, K.; Kleinknecht, K.; Quast, G.; Renk, B.; Rohne, E.; Sander, H.-G.; van Gemmeren, P.; Zeitnitz, C.; Aubert, J. J.; Bencheikh, A. M.; Benchouk, C.; Bonissent, A.; Bujosa, G.; Calvet, D.; Carr, J.; Diaconu, C.; Etienne, F.; Konstantinidis, N.; Payre, P.; Rousseau, D.; Talby, M.; Sadouki, A.; Thulasidas, M.; Trabelsi, K.; Aleppo, M.; Ragusa, F.; Berlich, R.; Blum, W.; Büscher, V.; Dietl, H.; Dydak, F.; Ganis, G.; Gotzhein, C.; Kroha, H.; Lütjens, G.; Lutz, G.; Männer, W.; Moser, H.-G.; Richter, R.; Rosado-Schlosser, A.; Schael, S.; Settles, R.; Seywerd, H.; St. Denis, R.; Stenzel, H.; Wiedenmann, W.; Wolf, G.; Boucrot, J.; Callot, O.; Choi, Y.; Cordier, A.; Davier, M.; Duflot, L.; Grivaz, J.-F.; Heusse, Ph.; Höcker, A.; Jacholkowska, A.; Jacquet, M.; Kim, D. W.; Le Diberder, F.; Lefrançois, J.; Lutz, A.-M.; Nikolic, I.; Park, H. J.; Schune, M.-H.; Simion, S.; Veillet, J.-J.; Videau, I.; Zerwas, D.; Azzurri, P.; Bagliesi, G.; Batignani, G.; Bettarini, S.; Bozzi, C.; Calderini, G.; Carpinelli, M.; Ciocci, M. A.; Ciulli, V.; dell'Orso, R.; Fantechi, R.; Ferrante, I.; Foà, L.; Forti, F.; Giassi, A.; Giorgi, M. A.; Gregorio, A.; Ligabue, F.; Lusiani, A.; Marrocchesi, P. S.; Messineo, A.; Palla, F.; Sanguinetti, G.; Sciabà, A.; Spagnolo, P.; Steinberger, J.; Tenchini, R.; Tonelli, G.; Vannini, C.; Verdini, P. G.; Blair, G. A.; Bryant, L. M.; Chambers, J. T.; Gao, Y.; Green, M. G.; Medcalf, T.; Perrodo, P.; Strong, J. A.; von Wimmersperg-Toeller, J. H.; Botterill, D. R.; Clifft, R. W.; Edgecock, T. R.; Haywood, S.; Maley, P.; Norton, P. R.; Thompson, J. C.; Wright, A. E.; Bloch-Devaux, B.; Colas, P.; Emery, S.; Kozanecki, W.; Lançon, E.; Lemaire, M. C.; Locci, E.; Perez, P.; Rander, J.; Renardy, J.-F.; Roussarie, A.; Schuller, J.-P.; Schwindling, J.; Trabelsi, A.; Vallage, B.; Black, S. N.; Dann, J. H.; Johnson, R. P.; Kim, H. Y.; Litke, A. M.; McNeil, M. A.; Taylor, G.; Booth, C. N.; Boswell, R.; Brew, C. A. J.; Cartwright, S.; Combley, F.; Koksal, A.; Letho, M.; Newton, W. M.; Reeve, J.; Thompson, L. F.; Böhrer, A.; Brandt, S.; Cowan, G.; Grupen, C.; Minguet-Rodriguez, J.; Rivera, F.; Saraiva, P.; Smolik, L.; Stephan, F.; Apollonio, M.; Bosisio, L.; della Marina, R.; Giannini, G.; Gobbo, B.; Musolino, G.; Rothberg, J.; Wasserbaech, S.; Armstrong, S. R.; Elmer, P.; Feng, Z.; Ferguson, D. P. S.; Gao, Y. S.; González, S.; Grahl, J.; Greening, T. C.; Hayes, O. J.; Hu, H.; McNamara, P. A.; Nachtman, J. M.; Orejudos, W.; Pan, Y. B.; Saadi, Y.; Scott, I. J.; Walsh, A. M.; Walsh, J.; Sau, Lan Wu; Wu, X.; Yamartino, J. M.; Zheng, M.; Zobernig, G.

    1997-02-01

    Two samples of exclusive semileptonic decays, 579 B0 -> D*+l-νl events and 261 B0 -> D+l-νl events, are selected from approximately 3.9 million hadronic Z decays collected by the ALEPH detector at LEP. From the reconstructed differential decay rate of each sample, the product of the hadronic form factor F(ω) at zero recoil of the D(*)+ meson and the CKM matrix element Vcb are measured to be FD*+ (1) Vcb = (31.9 +/- 1.8stat +/- 1.9syst) × 10-3,FD+ (1) Vcb = (27.8 +/- 6.8stat +/- 6.5syst) × 10-3. The ratio of the form factorsFD+ (1) and FD*+ (1) is measured to beFD+ (1)/FD*+ (1) = 0.87 +/- 0.22stat +/- 0.21syst. A value of Vcb is extracted from the two samples, using theoretical constraints on the slope and curvature of the hadronic form factors and their normalization at zero recoil, with the result Vcb = (34.4 +/- 1.6stat +/- 2.3syst +/- 1.4th) × 10-3. The branching fractions are measured from the two integrated spectra to be Br(B0 -> D*+l-νl) = (5.53 +/- 0.26stat +/- 0.52syst) %, Br(B0 -> D+l-νl) = (2.35 +/- 0.20stat +/- 0.44syst) %.

  13. 3D High Resolution l1-SPIRiT Reconstruction on Gadgetron based Cloud

    DEFF Research Database (Denmark)

    Xue, Hui; Kelmann, Peter; Inati, Souheil

    framework to support distributed computing in a cloud environment. This extension is named GT-Plus. A cloud version of 3D l1-SPIRiT was implemented on the GT-Plus framework. We demonstrate that a 3mins reconstruction could be achieved for 1mm3 isotropic resolution neuro scans with significantly improved......Applying non-linear reconstruction to high resolution 3D MRI is challenging because of the lengthy computing time needed for those iterative algorithms. To achieve practical processing duration to enable clinical usage of non-linear reconstruction, we have extended previously published Gadgetron...

  14. Neutrinoless double beta decay in an SU(3)L x U(1)N model

    International Nuclear Information System (INIS)

    Pleitez, V.; Tonasse, M.D.

    1993-01-01

    A model for the electroweak interactions with SU (3) L x U(1) N gauge symmetry is considered. It is shown that, it is the conservation of F = L + B which forbids massive neutrinos and the neutrinoless double beta decay, (β β) On u. Explicit and spontaneous breaking of F imply that the neutrinos have an arbitrary mass and (β β) On u proceeds also with some contributions that do not depend explicitly on the neutrino mass. (author)

  15. The CSIRO Mk3L climate system model version 1.0 – Part 1: Description and evaluation

    Directory of Open Access Journals (Sweden)

    S. J. Phipps

    2011-06-01

    Full Text Available The CSIRO Mk3L climate system model is a coupled general circulation model, designed primarily for millennial-scale climate simulations and palaeoclimate research. Mk3L includes components which describe the atmosphere, ocean, sea ice and land surface, and combines computational efficiency with a stable and realistic control climatology. This paper describes the model physics and software, analyses the control climatology, and evaluates the ability of the model to simulate the modern climate.

    Mk3L incorporates a spectral atmospheric general circulation model, a z-coordinate ocean general circulation model, a dynamic-thermodynamic sea ice model and a land surface scheme with static vegetation. The source code is highly portable, and has no dependence upon proprietary software. The model distribution is freely available to the research community. A 1000-yr climate simulation can be completed in around one-and-a-half months on a typical desktop computer, with greater throughput being possible on high-performance computing facilities.

    Mk3L produces realistic simulations of the larger-scale features of the modern climate, although with some biases on the regional scale. The model also produces reasonable representations of the leading modes of internal climate variability in both the tropics and extratropics. The control state of the model exhibits a high degree of stability, with only a weak cooling trend on millennial timescales. Ongoing development work aims to improve the model climatology and transform Mk3L into a comprehensive earth system model.

  16. Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity

    NARCIS (Netherlands)

    Bazuine, Merlijn; Ouwens, D. Margriet; Gomes de Mesquita, Daan S.; Maassen, J. Antonie

    2003-01-01

    The protein-modifying agent arsenite stimulates glucose uptake in 3T3-L1 adipocytes. In the current study we have analysed the signalling pathways that contribute to this response. By subcellular fractionation we observed that arsenite, like insulin, induces translocation of the GLUT1 and GLUT4

  17. IMPORTANT NEMATODE INFECTIONS IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Sri Oemijati

    2012-09-01

    Full Text Available At least 13 species of intestinal nematodes and 4 species of blood and tissue nematodes have been reported infecting man in Indonesia. Five species of intestinal nematodes are very common and highly prevalent, especially in the rural areas and slums of the big cities. Those species are Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Trichuris trichiura and Oxyuris vermicularis, while Strongyloides stercoralis is disappearing. The prevalence of the soil transmitted helminths differs from place to place, depending on many factors such as the type of soil, human behaviour etc. Three species of lymph dwelling filarial worms are known to be endemic, the urban Wuchereria bancrofti is low endemic in Jakarta and a few other cities along the north coast of Java, with Culex incriminated as vector, high endemicity is found in Irian Jaya, where Anopheline mosquitoes act as vectors. Brugia malayi is widely distributed and is still highly endemic in many areas. The zoonotic type is mainly endemic in swampy areas, and has many species of Mansonia mosquitoes as vectors. B.timori so far has been found only in the south eastern part of the archipelago and has Anopheles barbirostris as vector. Human infections with animal parasites have been diagnosed properly only when adult stages were found either in autopsies or removed tissues. Cases of infections with A. caninum, A.braziliense, A.ceylanicum, Trichostrongylus colubriformis, T.axei and Oesophagostomum apiostomum have been desribed from autopsies, while infections with Gnathostoma spiningerum have been reported from removed tissues. Infections with the larval stages such as VLM, eosinophylic meningitis, occult filanasis and other could only be suspected, since the diagnosis was extremely difficult and based on the finding and identification of the parasite. Many cases of creeping eruption which might be caused by the larval stages of A.caninum and A.braziliense and Strongyloides stercoralis

  18. Precontrol observations on lymphatic filariasis & geo-helminthiases in two coastal districts of rural Orrisa.

    Science.gov (United States)

    Chhotray, G P; Ranjit, M R; Khuntia, H K; Acharya, A S

    2005-11-01

    Lymphatic filariasis (LF) is a major public health problem in India, accounting for 40 per cent of the global burden. The World Health Organization has launched a global programme to eliminate LF by 2020 and India is a signatory to it. Orissa, an eastern Indian State has long been known to be endemic for LF. Prior to implementation of mass drug administration programme it is important to collect baseline data on filariasis and geo-helminthiases in the State. The present cross-sectional survey was therefore carried out between February and December 2001 to obtain baseline information on both LF and geo-helminthiases before application of the control measures. The study was carried out in rural areas of Puri and Ganjam districts in two phases. In phase I, the distribution of microfilaraemia in two district was mapped out in randomly selected primary health centres (PHCs), and 12 microfilaraemic villages were identified in each district by cluster analysis for the phase II study. In phase II, detailed clinical and parasitological survey for LF and geo-helminthiases was carried out following the standard procedures. Wuchereria bancrofti was found to be widely prevalent in Puri district with certain pockets of Brugia malayi while W. bancrofti was the only species in Ganjam district. The microfilaraemia (Mf) rate was found to be 9.5 and 11.1 per cent; and circulating filarial antigenaemia (CFA) was 16.8 and 17.8 per cent in Puri and Ganjam respectively. The geometric mean intensity (GMI) of Mf per ml of blood among positive individuals was 387 in Puri and 454 in Ganjam. The overall disease rate in Puri was 7.9 and 8.9 per cent in Ganjam. The prevalence of chronic manifestations was found to be significantly higher (PGanjam; and the heavy infection was found to be significantly higher (PGanjam compared to Puri district. The present study identified LF and geo-helminthiases as widely distributed health problem in rural areas of coastal Orissa which warrants intervention

  19. Dicty_cDB: Contig-U05658-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ted with Brugia Mala... 44 2.4 1 ( DV286265 ) NAAI621TR Aedes aegypti - Fat Bodie...s Normalized (... 44 2.4 1 ( DV286264 ) NAAI621TF Aedes aegypti - Fat Bodies Normalized (... 44 2.4 1 ( CP00

  20. Phenyllactic Acid from Lactobacillus plantarum PromotesAdipogenic Activity in 3T3-L1 Adipocyte via Up-Regulationof PPAR-γ2

    Directory of Open Access Journals (Sweden)

    Soundharrajan Ilavenil

    2015-08-01

    Full Text Available Synthetic drugs are commonly used to cure various human ailments at present. However, the uses of synthetic drugs are strictly regulated because of their adverse effects. Thus, naturally occurring molecules may be more suitable for curing disease without unfavorable effects. Therefore, we investigated phenyllactic acid (PLA from Lactobacillus plantarum with respect to its effects on adipogenic genes and their protein expression in 3T3-L1 pre-adipocytes by qPCR and western blot techniques. PLA enhanced differentiation and lipid accumulation in 3T3-L1 cells at the concentrations of 25, 50, and 100 μM. Maximum differentiation and lipid accumulation were observed at a concentration of 100 μM of PLA, as compared with control adipocytes (p < 0.05. The mRNA and protein expression of PPAR-γ2, C/EBP‑α, adiponectin, fatty acid synthase (FAS, and SREBP-1 were increased by PLA treatment as compared with control adipocytes (p < 0.05. PLA stimulates PPAR-γ mRNA expression in a concentration dependent manner, but this expression was lesser than agonist (2.83 ± 0.014 fold of PPAR-γ2. Moreover, PLA supplementation enhances glucose uptake in 3T3-L1 pre-adipocytes (11.81 ± 0.17 mM compared to control adipocytes, but this glucose uptake was lesser than that induced by troglitazone (13.75 ± 0.95 mM and insulin treatment (15.49 ± 0.20 mM. Hence, we conclude that PLA treatment enhances adipocyte differentiation and glucose uptake via activation of PPAR-γ2, and PLA may thus be the potential candidate for preventing Type 2 Diabetes Mellitus (T2DM.