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Sample records for altered selenoprotein synthesis

  1. Exposure to monomethylarsonous acid (MMA(III)) leads to altered selenoprotein synthesis in a primary human lung cell model.

    Science.gov (United States)

    Meno, Sarah R; Nelson, Rebecca; Hintze, Korry J; Self, William T

    2009-09-01

    Monomethylarsonous acid (MMA(III)), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMA(III) is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMA(III) on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMA(III) resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMA(III) treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMA(III), as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMA(III) induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMA(III) alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element.

  2. Reduced macrophage selenoprotein expression alters oxidized lipid metabolite biosynthesis from arachidonic and linoleic acid.

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    Mattmiller, Sarah A; Carlson, Bradley A; Gandy, Jeff C; Sordillo, Lorraine M

    2014-06-01

    Uncontrolled inflammation is an underlying etiology for multiple diseases and macrophages orchestrate inflammation largely through the production of oxidized fatty acids known as oxylipids. Previous studies showed that selenium (Se) status altered the expression of oxylipids and magnitude of inflammatory responses. Although selenoproteins are thought to mediate many of the biological effects of Se, the direct effect of selenoproteins on the production of oxylipids is unknown. Therefore, the role of decreased selenoprotein activity in modulating the production of biologically active oxylipids from macrophages was investigated. Thioglycollate-elicited peritoneal macrophages were collected from wild-type and myeloid-cell-specific selenoprotein knockout mice to analyze oxylipid production by liquid chromatography/mass spectrometry as well as oxylipid biosynthetic enzyme and inflammatory marker gene expression by quantitative real-time polymerase chain reaction. Decreased selenoprotein activity resulted in the accumulation of reactive oxygen species, enhanced cyclooxygenase and lipoxygenase expression and decreased oxylipids with known anti-inflammatory properties such as arachidonic acid-derived lipoxin A₄ (LXA₄) and linoleic acid-derived 9-​oxo-octadecadienoic acid (9-oxoODE). Treating RAW 264.7 macrophages with LXA₄ or 9-oxoODE diminished oxidant-induced macrophage inflammatory response as indicated by decreased production of TNFα. The results show for the first time that selenoproteins are important for the balanced biosynthesis of pro- and anti-inflammatory oxylipids during inflammation. A better understanding of the Se-dependent control mechanisms governing oxylipid biosynthesis may uncover nutritional intervention strategies to counteract the harmful effects of uncontrolled inflammation due to oxylipids. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Exposure to silver nanoparticles inhibits selenoprotein synthesis and the activity of thioredoxin reductase.

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    Srivastava, Milan; Singh, Sanjay; Self, William T

    2012-01-01

    Silver nanoparticles (AgNPs) and silver (Ag)-based materials are increasingly being incorporated into consumer products, and although humans have been exposed to colloidal Ag in many forms for decades, this rise in the use of Ag materials has spurred interest into their toxicology. Recent reports have shown that exposure to AgNPs or Ag ions leads to oxidative stress, endoplasmic reticulum stress, and reduced cell proliferation. Previous studies have shown that Ag accumulates in tissues as silver sulfides (Ag2S) and silver selenide (Ag2Se). In this study we investigated whether exposure of cells in culture to AgNPs or Ag ions at subtoxic doses would alter the effective metabolism of selenium, that is, the incorporation of selenium into selenoproteins. For these studies we used a keratinocyte cell model (HaCat) and a lung cell model (A549). We also tested (in vitro, both cellular and chemical) whether Ag ions could inhibit the activity of a key selenoenzyme, thioredoxin reductase (TrxR). We found that exposure to AgNPs or far lower levels of Ag ions led to a dose-dependent inhibition of selenium metabolism in both cell models. The synthesis of protein was not altered under these conditions. Exposure to nanomolar levels of Ag ions effectively blocked selenium metabolism, suggesting that Ag ion leaching was likely the mechanism underlying observed changes during AgNP exposure. Exposure likewise inhibited TrxR activity in cultured cells, and Ag ions were potent inhibitors of purified rat TrxR isoform 1 (cytosolic) (TrxR1) enzyme. Exposure to AgNPs leads to the inhibition of selenoprotein synthesis and inhibition of TrxR1. Further, we propose these two sites of action comprise the likely mechanism underlying increases in oxidative stress, increases endoplasmic reticulum stress, and reduced cell proliferation during exposure to Ag.

  4. Selenoprotein-Transgenic Chlamydomonas reinhardtii

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    Jiazuan Ni

    2013-02-01

    Full Text Available Selenium (Se deficiency is associated with the occurrence of many diseases. However, excessive Se supplementation, especially with inorganic Se, can result in toxicity. Selenoproteins are the major forms of Se in vivo to exert its biological function. Expression of those selenoproteins, especially with the application of a newly developed system, is thus very important for studying the mechanism of Se in nutrition. The use of Chlamydomonas reinhardtii (C. reinhardtii as a biological vector to express an heterogeneous protein is still at the initial stages of development. In order to investigate the possibility of using this system to express selenoproteins, human 15-KDa selenoprotein (Sep15, a small but widely distributed selenoprotein in mammals, was chosen for the expression platform test. Apart from the wild-type human Sep15 gene fragment, two Sep15 recombinants were constructed containing Sep15 open reading frame (ORF and the selenocysteine insertion sequence (SECIS element from either human Sep15 or C. reinhardtii selenoprotein W1, a highly expressed selenoprotein in this alga. Those Sep15-containing plasmids were transformed into C. reinhardtii CC-849 cells. Results showed that Sep15 fragments were successfully inserted into the nuclear genome and expressed Sep15 protein in the cells. The transgenic and wild-type algae demonstrated similar growth curves in low Se culture medium. To our knowledge, this is the first report on expressing human selenoprotein in green alga.

  5. Selenoprotein P is the essential selenium transporter for bones.

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    Pietschmann, Nicole; Rijntjes, Eddy; Hoeg, Antonia; Stoedter, Mette; Schweizer, Ulrich; Seemann, Petra; Schomburg, Lutz

    2014-05-01

    Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations.

  6. Thyroid hormones regulate selenoprotein expression and selenium status in mice.

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    Jens Mittag

    Full Text Available Impaired expression of selenium-containing proteins leads to perturbed thyroid hormone (TH levels, indicating the central importance of selenium for TH homeostasis. Moreover, critically ill patients with declining serum selenium develop a syndrome of low circulating TH and a central downregulation of the hypothalamus-pituitary-thyroid axis. This prompted us to test the reciprocal effect, i.e., if TH status would also regulate selenoprotein expression and selenium levels. To investigate the TH dependency of selenium metabolism, we analyzed mice expressing a mutant TH receptor α1 (TRα1+m that confers a receptor-mediated hypothyroidism. Serum selenium was reduced in these animals, which was a direct consequence of the mutant TRα1 and not related to their metabolic alterations. Accordingly, hyperthyroidism, genetically caused by the inactivation of TRβ or by oral TH treatment of adult mice, increased serum selenium levels in TRα1+m and controls, thus demonstrating a novel and specific role for TRα1 in selenium metabolism. Furthermore, TH affected the mRNA levels for several enzymes involved in selenoprotein biosynthesis as well as serum selenoprotein P concentrations and the expression of other antioxidative selenoproteins. Taken together, our results show that TH positively affects the serum selenium status and regulates the expression of several selenoproteins. This demonstrates that selenium and TH metabolism are interconnected through a feed-forward regulation, which can in part explain the rapid parallel downregulation of both systems in critical illness.

  7. Evolution of selenoproteins in the metazoan

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    Jiang Liang

    2012-09-01

    Full Text Available Abstract Background The selenocysteine (Sec containing proteins, selenoproteins, are an important group of proteins present throughout all 3 kingdoms of life. With the rapid progression of selenoprotein research in the post-genomic era, application of bioinformatics methods to the identification of selenoproteins in newly sequenced species has become increasingly important. Although selenoproteins in human and other vertebrates have been investigated, studies of primitive invertebrate selenoproteomes are rarely reported outside of insects and nematodes. Result A more integrated view of selenoprotein evolution was constructed using several representative species from different evolutionary eras. Using a SelGenAmic-based selenoprotein identification method, 178 selenoprotein genes were identified in 6 invertebrates: Amphimedon queenslandica, Trichoplax adhaerens, Nematostella vectensis, Lottia gigantean, Capitella teleta, and Branchiostoma floridae. Amphioxus was found to have the most abundant and variant selenoproteins of any animal currently characterized, including a special selenoprotein P (SelP possessing 3 repeated Trx-like domains and Sec residues in the N-terminal and 2 Sec residues in the C-terminal. This gene structure suggests the existence of two different strategies for extension of Sec numbers in SelP for the preservation and transportation of selenium. In addition, novel eukaryotic AphC-like selenoproteins were identified in sponges. Conclusion Comparison of various animal species suggests that even the most primitive animals possess a selenoproteome range and variety similar to humans. During evolutionary history, only a few new selenoproteins have emerged and few were lost. Furthermore, the massive loss of selenoproteins in nematodes and insects likely occurred independently in isolated partial evolutionary branches.

  8. Effects of acclimation salinity on the expression of selenoproteins in the tilapia, Oreochromis mossambicus

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    Seale, Lucia A.; Gilman, Christy L.; Moorman, Benjamin P.; Berry, Marla J.; Grau, E. Gordon; Seale, Andre P.

    2014-01-01

    Selenoproteins are ubiquitously expressed, act on a variety of physiological redox-related processes, and are mostly regulated by selenium levels in animals. To date, the expression of most selenoproteins has not been verified in euryhaline fish models. The Mozambique tilapia, Oreochromis mossambicus, a euryhaline cichlid fish, has a high tolerance for changes in salinity and survives in fresh water (FW) and seawater (SW) environments which differ greatly in selenium availability. In the present study, we searched EST databases for cichlid selenoprotein mRNAs and screened for their differential expression in FW and SW-acclimated tilapia. The expression of mRNAs encoding iodothyronine deiodinases 1, 2 and 3 (Dio1, Dio2, Dio3), Fep15, glutathione peroxidase 2, selenoproteins J, K, L, M, P, S, and W, was measured in the brain, eye, gill, kidney, liver, pituitary, muscle, and intraperitoneal white adipose tissue. Gene expression of selenophosphate synthetase 1, Secp43, and selenocysteine lyase, factors involved in selenoprotein synthesis or in selenium metabolism, were also measured. The highest variation in selenoprotein and synthesis factor mRNA expression between FW- and SW-acclimated fish was found in gill and kidney. While the branchial expression of Dio3 was increased upon transferring tilapia from SW to FW, the inverse effect was observed when fish were transferred from FW to SW. Protein content of Dio3 was higher in fish acclimated to FW than in those acclimated to SW. Together, these results outline tissue distribution of selenoproteins in FW and SW-acclimated tilapia, and indicate that at least Dio3 expression is regulated by environmental salinity. PMID:24854764

  9. Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

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    Tarek, Marwa; Louka, Manal Louis; Khairy, Eman; Ali-Labib, Randa; Zakaria Zaky, Doaa; Montasser, Iman F

    2017-05-01

    There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

  10. Analysis of Conserved Structural Features of Selenoprotein K | Al ...

    African Journals Online (AJOL)

    Selenium plays important roles in human health and these roles may be exerted through its presence in selenoproteins. Among the 25 selenoproteins in human is selenoprotein K (SelK) whose exact function is still unclear. Here, we investigated the conserved structural features of SelK using bioinformatics as an approach ...

  11. Selenoprotein P in colitis-associated carcinoma

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    Short, Sarah P.; Whitten-Barrett, Caitlyn; Williams, Christopher S.

    2016-01-01

    ABSTRACT Patients with inflammatory bowel disease are often deficient in micronutrients such as selenium and have an increased risk of colon cancer. We tested whether the selenium transport protein, selenoprotein P, could modify colitis-associated cancer. Our results indicate that global SEPP1 haploinsufficiency augments tumorigenesis and mediates oxidative damage in the intestine. PMID:27314080

  12. Relaxation of selective constraints causes independent selenoprotein extinction in insect genomes.

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    Charles E Chapple

    Full Text Available BACKGROUND: Selenoproteins are a diverse family of proteins notable for the presence of the 21st amino acid, selenocysteine. Until very recently, all metazoan genomes investigated encoded selenoproteins, and these proteins had therefore been believed to be essential for animal life. Challenging this assumption, recent comparative analyses of insect genomes have revealed that some insect genomes appear to have lost selenoprotein genes. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we investigate in detail the fate of selenoproteins, and that of selenoprotein factors, in all available arthropod genomes. We use a variety of in silico comparative genomics approaches to look for known selenoprotein genes and factors involved in selenoprotein biosynthesis. We have found that five insect species have completely lost the ability to encode selenoproteins and that selenoprotein loss in these species, although so far confined to the Endopterygota infraclass, cannot be attributed to a single evolutionary event, but rather to multiple, independent events. Loss of selenoproteins and selenoprotein factors is usually coupled to the deletion of the entire no-longer functional genomic region, rather than to sequence degradation and consequent pseudogenisation. Such dynamics of gene extinction are consistent with the high rate of genome rearrangements observed in Drosophila. We have also found that, while many selenoprotein factors are concomitantly lost with the selenoproteins, others are present and conserved in all investigated genomes, irrespective of whether they code for selenoproteins or not, suggesting that they are involved in additional, non-selenoprotein related functions. CONCLUSIONS/SIGNIFICANCE: Selenoproteins have been independently lost in several insect species, possibly as a consequence of the relaxation in insects of the selective constraints acting across metazoans to maintain selenoproteins. The dispensability of selenoproteins in insects may

  13. Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

    International Nuclear Information System (INIS)

    Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

    1985-01-01

    Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1- 14 C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis

  14. Disruption and complementation of the selenocysteine biosynthesis pathway reveals a hierarchy of selenoprotein gene expression in the archaeon Methanococcus maripaludis.

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    Stock, Tilmann; Selzer, Mirjam; Connery, Sarah; Seyhan, Deniz; Resch, Armin; Rother, Michael

    2011-11-01

    Proteins containing selenocysteine are found in members of all three domains of life, Bacteria, Eukarya and Archaea. A dedicated tRNA (tRNA(sec)) serves as a scaffold for selenocysteine synthesis. However, sequence and secondary structures differ in tRNA(sec) from the different domains. An Escherichia coli strain lacking the gene for tRNA(sec) could only be complemented with the homologue from Methanococcus maripaludis when a single base in the anticodon loop was exchanged demonstrating that this base is a crucial determinant for archaeal tRNA(sec) to function in E. coli. Complementation in trans of M. maripaludis JJ mutants lacking tRNA(sec) , O-phosphoseryl-tRNA(sec) kinase or O-phosphoseryl-tRNA(sec) :selenocysteine synthase with the corresponding genes from M. maripaludis S2 restored the mutant's ability to synthesize selenoproteins. However, only partial restoration of the wild-type selenoproteome was observed as only selenocysteine-containing formate dehydrogenase was synthesized. Quantification of transcripts showed that disrupting the pathway of selenocysteine synthesis leads to downregulation of selenoprotein gene expression, concomitant with upregulation of a selenium-independent backup system, which is not re-adjusted upon complementation. This transcriptional arrest was independent of selenophosphate but depended on the 'history' of the mutants and was inheritable, which suggests that a stable genetic switch may cause the resulting hierarchy of selenoproteins synthesized. © 2011 Blackwell Publishing Ltd.

  15. Mutants of Cercospora kikuchii altered in cercosporin synthesis and pathogenicity

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    Upchurch, R.G.; Walker, D.C.; Rollins, J.A.; Ehrenshaft, M.; Daub, M.E. (North Carolina State Univ., Raleigh (United States))

    1991-10-01

    The authors have obtained spontaneous and UV-induced stable mutants, altered in the synthesis of cercosporin, of the fungal soybean pathogen Cercospora kikuchii. The mutants were isolated on the basis of colony color on minimal medium. The UV-induced mutants accumulated, at most, 2% of wild-type cercosporin levels on all media tested. In contrast, cercosporin accumulation by the spontaneous mutants was strongly medium regulated, occurring only on potato dextrose medium but at concentrations comparable to those produced by the wild-type strain. UV-induced mutants unable to synthesize cercosporin on any medium were unable to incite lesions when inoculated onto the soybean host. Cercosporin was reproducibly isolated from all inoculated leaves showing lesions. Although cercosporin involvement in disease has been indirectly suggested by many previous studies, this is the first report in which mutants blocked in cercosporin synthesis have been used to demonstrate that cercosporin is a crucial pathogenicity factor for this fungal genus.

  16. Selenium deficiency mainly influences the gene expressions of antioxidative selenoproteins in chicken muscles.

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    Yao, Haidong; Zhao, Wenchao; Zhao, Xia; Fan, Ruifeng; Khoso, Pervez Ahmed; Zhang, Ziwei; Liu, Wei; Xu, Shiwen

    2014-12-01

    Dietary selenium (Se) deficiency induces muscular dystrophy in chicken, but the molecular mechanism remains unclear. The aim of the present study was to investigate the effect of dietary Se deficiency on the expressions of 25 selenoproteins. One-day-old broiler chickens were fed either an Se deficiency diet (0.033 mg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or a diet supplemented with Se (as sodium selenite) at 0.2 mg/kg for 55 days. Then, the mRNA levels of 25 selenoproteins in chicken muscles were examined, and the principal component was further analyzed. The results showed that antioxidative selenoproteins especially Gpxs and Sepw1 were highly and extensively expressed than other types of selenoproteins in chicken muscles. In 25 selenoproteins, Gpxs, Txnrd2, Txnrd 3, Dio1, Dio 3, Selk, Sels, Sepw1, Selh, Sep15, Selu, Selpb, Sepp1, Selo, Sepx1, and SPS2 were downregulated (P  0.05). Se deficiency decreased the expressions of 19 selenoproteins (P muscles. However, compared with these antioxidative selenoproteins, some other lower expressed selenoproteins (Dio1, Selu, Selpb, Sepp1) were excessively decreased (more than 60 %, P muscles. And, antioxidative selenoproteins especially Gpxs and Sepw1 may play a crucial role in chicken muscles. Thus, it helps us focus on some specific selenoproteins when studying the role of Se in chicken muscles.

  17. Serum selenium and selenoprotein P status in adult Danes-8-year followup

    DEFF Research Database (Denmark)

    Rasmussen, Lone Banke; Hollenbach, B.; Laurberg, P.

    2009-01-01

    subjects had filled in a food frequency questionnaire (FFQ) and a questionnaire with information about smoking habits, alcohol consumption and exercise habits. Mean serum selenium level was 98.7+/-19.8microg/L and median selenoprotein P level was 2.72 (2.18-3.49)mg/L. Serum selenium and selenoprotein P...

  18. Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal cancer.

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    Martha L Slattery

    Full Text Available BACKGROUND: Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. METHODS: We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls and rectal (n = 754 cases, 959 controls cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH, SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. RESULTS: After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208. Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300. Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR and rectal cancer (SepX1 increased HRR. CONCLUSIONS: Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is

  19. Dimethyl sulfoxide alterations of macromolecular synthesis by chick limb mesenchymal cells in vitro

    International Nuclear Information System (INIS)

    Major, F.W.; Parker, C.L.; Patterson, R.M.

    1986-01-01

    Earlier the authors reported that dimethyl sulfoxide (DMSO) inhibited the chondrogenesis of chick limb cells in vitro at concentrations of 30 mg/ml or greater. The present study was undertaken to determine if inhibition by DMSO might be due to an alteration in protein and/or DNA synthesis by the treated cells. Micromass cultures were prepared from stage 23-25 chick limb mesenchyme. The cells were treated with either 30 or 40 mg of DMSO/ml of culture medium for 24, 48, and 72 hr. After each treatment, protein and DNA synthesis were analyzed by the incorporation of [ 3 H]-leucine and [ 3 H]-thymidine, respectively. Cell cultures exposed to 40 mg DMSO/ml for 24 hr showed a significant decrease in protein synthesis, while there was no decrease in protein synthesis for cells treated with 30 mg DMSO/ml. At both 48 and 72 hr treatment with 30 mg of DMSO, there was a decrease in [ 3 H]-leucine incorporation. The thymidine studies indicated that there was a significant decrease in DNA synthesis as early as 24 hr for both DMSO concentrations. These findings suggest that the inhibition of chondrogenesis following DMSO treatment may be related to alterations in macromolecular synthesis possibly including extracellular cartilage matrix production

  20. Dimethyl sulfoxide alterations of macromolecular synthesis by chick limb mesenchymal cells in vitro

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    Major, F.W.; Parker, C.L.; Patterson, R.M.

    1986-03-01

    Earlier the authors reported that dimethyl sulfoxide (DMSO) inhibited the chondrogenesis of chick limb cells in vitro at concentrations of 30 mg/ml or greater. The present study was undertaken to determine if inhibition by DMSO might be due to an alteration in protein and/or DNA synthesis by the treated cells. Micromass cultures were prepared from stage 23-25 chick limb mesenchyme. The cells were treated with either 30 or 40 mg of DMSO/ml of culture medium for 24, 48, and 72 hr. After each treatment, protein and DNA synthesis were analyzed by the incorporation of (/sup 3/H)-leucine and (/sup 3/H)-thymidine, respectively. Cell cultures exposed to 40 mg DMSO/ml for 24 hr showed a significant decrease in protein synthesis, while there was no decrease in protein synthesis for cells treated with 30 mg DMSO/ml. At both 48 and 72 hr treatment with 30 mg of DMSO, there was a decrease in (/sup 3/H)-leucine incorporation. The thymidine studies indicated that there was a significant decrease in DNA synthesis as early as 24 hr for both DMSO concentrations. These findings suggest that the inhibition of chondrogenesis following DMSO treatment may be related to alterations in macromolecular synthesis possibly including extracellular cartilage matrix production.

  1. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

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    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  2. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  3. Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern

    DEFF Research Database (Denmark)

    Petit, Nathalie; Lescure, Alain; Rederstorff, Mathieu

    2003-01-01

    of an endoplasmic reticulum-addressing and -retention signal within the N-terminus. SEPN1 is present at a high level in several human fetal tissues and at a lower level in adult ones, including skeletal muscle. Its high expression in cultured myoblasts is also down-regulated in differentiating myotubes, suggesting......Rigid spine muscular dystrophy and the classical form of multiminicore disease are caused by mutations in SEPN1 gene, leading to a new clinical entity referred to as SEPN1-related myopathy. SEPN1 codes for selenoprotein N, a new member of the selenoprotein family, the function of which is still...

  4. Cloning, Sequencing, and Expression of Selenoprotein Transcripts in the Turkey (Meleagris gallopavo.

    Directory of Open Access Journals (Sweden)

    Roger A Sunde

    Full Text Available The minimum Se requirement for male turkey poults is 0.3 μg Se/g--three times higher than requirements found in rodents--based on liver and gizzard glutathione peroxidase-4 (GPX4 and GPX1 activities. In addition, turkey liver GPX4 activity is 10-fold higher and GPX1 activity is 10-fold lower than in rats, and both GPX1 and GPX4 mRNA levels are dramatically down-regulated by Se deficiency. Currently, the sequences of all annotated turkey selenoprotein transcripts and proteins in the NCBI database are only "predicted." Thus we initiated cloning and sequencing of the full turkey selenoprotein transcriptome to demonstrate expression of selenoprotein transcripts in the turkey, and to develop tools to investigate Se regulation of the full selenoproteome. Total RNA was isolated from six tissues of Se-adequate adult tom turkeys, and used to prepare reverse-transcription cDNA libraries. PCR primers were designed, based initially on chicken, rodent, porcine, bovine and human sequences and later on turkey shotgun cloning sequences. We report here the cloning of full transcript sequences for 9 selenoproteins, and 3'UTR portions for 15 additional selenoproteins, which include SECIS elements in 22 3'UTRs, and in-frame Sec (UGA codons within coding regions of 19 selenoproteins, including 12 Sec codons in SEPP1. In addition, we sequenced the gap between two contigs from the shotgun cloning of the turkey genome, and found the missing sequence for the turkey Sec-tRNA. RTPCR was used to determine the relative transcript expression in 6 tissues. GPX3 expression was high in all tissues except kidney, GPX1 expression was high in kidney, SEPW1 expression was high in heart, gizzard and muscle, and SELU expression was high in liver. SEPP2, a selenoprotein not found in mammals, was highly expressed in liver but not in other tissues. In summary, transcripts for 24 selenoproteins are expressed in the turkey, not just predicted.

  5. Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States

    Science.gov (United States)

    Chen, Richard J.; Zhang, Guofeng; Garfield, Susan H.; Shi, Yi-Jun; Chen, Kevin G.; Robey, Pamela G.; Leapman, Richard D.

    2015-01-01

    Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions. PMID:26565809

  6. Selenoprotein S expression in reactive astrocytes following brain injury.

    Science.gov (United States)

    Fradejas, Noelia; Serrano-Pérez, Maria Del Carmen; Tranque, Pedro; Calvo, Soledad

    2011-06-01

    Selenoprotein S (SelS) is an endoplasmic reticulum (ER)-resident protein involved in the unfolded protein response. Besides reducing ER-stress, SelS attenuates inflammation by decreasing pro-inflammatory cytokines. We have recently shown that SelS is responsive to ischemia in cultured astrocytes. To check the possible association of SelS with astrocyte activation, here we investigate the expression of SelS in two models of brain injury: kainic acid (KA) induced excitotoxicity and cortical mechanical lesion. The regulation of SelS and its functional consequences for neuroinflammation, ER-stress, and cell survival were further analyzed using cultured astrocytes from mouse and human. According to our immunofluorescence analysis, SelS expression is prominent in neurons and hardly detectable in astrocytes from control mice. However, brain injury intensely upregulates SelS, specifically in reactive astrocytes. SelS induction by KA was evident at 12 h and faded out after reaching maximum levels at 3-4 days. Analysis of mRNA and protein expression in cultured astrocytes showed SelS upregulation by inflammatory stimuli as well as ER-stress inducers. In turn, siRNA-mediated SelS silencing combined with adenoviral overexpression assays demonstrated that SelS reduces ER-stress markers CHOP and spliced XBP-1, as well as inflammatory cytokines IL-1β and IL-6 in stimulated astrocytes. SelS overexpression increased astrocyte resistance to ER-stress and inflammatory stimuli. Conversely, SelS suppression compromised astrocyte viability. In summary, our results reveal the upregulation of SelS expression in reactive astrocytes, as well as a new protective role for SelS against inflammation and ER-stress that can be relevant to astrocyte function in the context of inflammatory neuropathologies. Copyright © 2011 Wiley-Liss, Inc.

  7. Determination of selenoprotein P in human plasma by solid phase extraction and inductively coupled plasma mass spectrometry

    DEFF Research Database (Denmark)

    Bendahl, L.; Sidenius, U.; Gammelgaard, Bente

    2000-01-01

    A method based on solid phase extraction was developed for the determination of selenoprotein P as selenium in human plasma. Separation of selenoprotein P from other selenium-containing proteins was accomplished by immobilized metal-ion affinity chromatography. The selenium content was subsequently...... measured by inductively coupled plasma mass spectrometry (ICP-MS) monitoring the Se-82 isotope. Linear response was observed in the concentration range 0.3-70.8 mu g/l selenium as selenoprotein P with a correlation coefficient of 0.9994. The precision expressed as relative standard deviation was better...

  8. Overexpression of Human Selenoprotein H in Neuronal Cells Ameliorates Ultraviolet Irradiation Induced Damage by Modulating Cell Signaling Pathways

    OpenAIRE

    Mendelev, Natalia; Witherspoon, Sam; Li, P. Andy

    2009-01-01

    Selenoprotein H (SelH) is one of the 25 so far identified selenoproteins. Selenoproteins may function as antioxidants, heavy metal antidotes, and neural survival factors. Previous studies have shown that overexpression of SelH in HT22 cells protected the cells from UVB irradiation-induced death by reducing superoxide formation. The objective of this study was to determine the effects of SelH on cell signaling pathways after UVB irradiation. We exposed both human SelH- and vector-transfected H...

  9. Selenium, selenoproteins and the thyroid gland: interactions in health and disease.

    Science.gov (United States)

    Schomburg, Lutz

    2011-10-18

    The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases, enzymes involved in thyroid hormone metabolism, regulation of redox state and protection from oxidative damage. Selenium content in selenium-sensitive tissues such as the liver, kidney or muscle and expression of nonessential selenoproteins, such as the glutathione peroxidases GPx1 and GPx3, is controlled by nutritional supply. The thyroid gland is, however, largely independent from dietary selenium intake and thyroid selenoproteins are preferentially expressed. As a consequence, no explicit effects on thyroid hormone profiles are observed in healthy individuals undergoing selenium supplementation. However, low selenium status correlates with risk of goiter and multiple nodules in European women. Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined. The baseline selenium status of an individual could constitute the most important parameter modifying the outcome of selenium supplementation, which might primarily disrupt self-amplifying cycles of the endocrine-immune system interface rectifying the interaction of lymphocytes with thyroid autoantigens. Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction.

  10. A tale of two toxicities: malformed selenoproteins and oxidative stress both contribute to selenium stress in plants.

    Science.gov (United States)

    Van Hoewyk, Doug

    2013-10-01

    Despite selenium's toxicity in plants at higher levels, crops supply most of the essential dietary selenium in humans. In plants, inorganic selenium can be assimilated into selenocysteine, which can replace cysteine in proteins. Selenium toxicity in plants has been attributed to the formation of non-specific selenoproteins. However, this paradigm can be challenged now that there is increasingly abundant evidence suggesting that selenium-induced oxidative stress also contributes to toxicity in plants. This Botanical Briefing summarizes the evidence indicating that selenium toxicity in plants is attributable to both the accumulation of non-specific selenoproteins and selenium-induced oxidative stress. Evidence is also presented to substantiate the claim that inadvertent selenocysteine replacement probably impairs or misfolds proteins, which supports the malformed selenoprotein hypothesis. The possible physiological ramifications of selenoproteins and selenium-induced oxidative stress are discussed. Malformed selenoproteins and oxidative stress are two distinct types of stress that drive selenium toxicity in plants and could impact cellular processes in plants that have yet to be thoroughly explored. Although challenging, deciphering whether the extent of selenium toxicity in plants is imparted by selenoproteins or oxidative stress could be helpful in the development of crops with fortified levels of selenium.

  11. Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern

    DEFF Research Database (Denmark)

    Petit, Nathalie; Lescure, Alain; Rederstorff, Mathieu

    2003-01-01

    . Subcellular fractionation experiments and endoglycosidase H sensitivity indicate that SEPN1 is a glycoprotein-localized within the endoplasmic reticulum. Immunofluorescence analyses confirm this subcellular localization and green fluorescent protein fusion experiments demonstrate the presence...... unknown. In a previous study, two isoforms were deduced from SEPN1 transcript analyses. Using polyclonal antibodies directed against SEPN1 and cDNA constructs encoding for the two isoforms, we show that the main SEPN1 gene product corresponds to a 70 kDa protein, containing a single selenocysteine residue......Rigid spine muscular dystrophy and the classical form of multiminicore disease are caused by mutations in SEPN1 gene, leading to a new clinical entity referred to as SEPN1-related myopathy. SEPN1 codes for selenoprotein N, a new member of the selenoprotein family, the function of which is still...

  12. Maternal reproductive health: Expression patterns of antioxidant enzyme selenoproteins of post-implantation embryos conceived by ethanol-treated murine mothers supplemented with α-tocopherol

    Directory of Open Access Journals (Sweden)

    Gliceria B Ramos

    2017-01-01

    Full Text Available Objective: To investigate if the protective effect of α-tocopherol against the impact of ethanol on brain morphogenesis involved the activity of the selenoproteins phospholipid hydroperoxide glutathione peroxidase (PHGPx; GPx4 and selenoprotein P (SelPP that have roles against oxidative stress. Methods: Forty female mice were randomly assigned into natural control (CON, positive control (ETOH, low-, medium-, and high-α-tocopherolsupplemented- ethanol groups (LTOC, MTOC, HTOC, respectively. CON received drinking water without ethanol while ETOH, LTOC, MTOC and HTOC groups received 20% ethanol in drinking water. The supplemented groups were given respective dosages of α-tocopherol, 0.410, 0.819, and 1.640 mg/g body weight, at day 14 before mating onwards to the day 9 of gestation. At 10.5 ED of gestation (1 100 h, the pregnant females were sacrificed by cervical dislocation and the embryos were harvested. Total RNA were extracted, cDNA synthesis and qRT- PCR analyses were carried out. Results: The level of expression of PHGPx in the positive control was significantly lower than that of the natural control. Among the three α- tocopherol-supplemented groups, only the medium dose- group was significantly higher than the positive control. The level of expression of SelPP in the positive control was significantly lower than those of the natural control, the low- and medium- dose α-tocopherol supplemented groups. In the high dose-α-tocopherol supplemented group, the level of expression was not significantly different from the positive control but significantly lower than the natural control. Conclusions: The activity of the selenoproteins PHGPx and SelPP are involved in the internetwork of antioxidative enzymes with vitamin E when given up to a medium dose only and is one of the possible pathways of shielding embryonic development against the impact of ethanol on brain morphogenesis. This study strengthens the impact of dietaryα-tocopherol and

  13. Determination of selenoprotein P in human plasma by solid phase extraction and inductively coupled plasma mass spectrometry

    DEFF Research Database (Denmark)

    Bendahl, L.; Sidenius, U.; Gammelgaard, Bente

    2000-01-01

    A method based on solid phase extraction was developed for the determination of selenoprotein P as selenium in human plasma. Separation of selenoprotein P from other selenium-containing proteins was accomplished by immobilized metal-ion affinity chromatography. The selenium content was subsequent...... than 2% in this range. The estimated limit of detection was 2 mu g/l and the experimentally verified quantification limit was 5 mu g/l, giving a relative standard deviation less than 2%. (C) 2000 Elsevier Science B.V. All rights reserved......A method based on solid phase extraction was developed for the determination of selenoprotein P as selenium in human plasma. Separation of selenoprotein P from other selenium-containing proteins was accomplished by immobilized metal-ion affinity chromatography. The selenium content was subsequently...... measured by inductively coupled plasma mass spectrometry (ICP-MS) monitoring the Se-82 isotope. Linear response was observed in the concentration range 0.3-70.8 mu g/l selenium as selenoprotein P with a correlation coefficient of 0.9994. The precision expressed as relative standard deviation was better...

  14. Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass

    Energy Technology Data Exchange (ETDEWEB)

    Martyniuk, Christopher J. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Sanchez, Brian C. [Department of Forestry and Natural Resources and School of Civil Engineering, 195 Marsteller St., Purdue University, West Lafayette, IN 47907 (United States); Szabo, Nancy J.; Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Sepulveda, Maria S., E-mail: mssepulv@purdue.edu [Department of Forestry and Natural Resources and School of Civil Engineering, 195 Marsteller St., Purdue University, West Lafayette, IN 47907 (United States)

    2009-10-19

    Many aquatic contaminants potentially affect the central nervous system, however the underlying mechanisms of how toxicants alter normal brain function are not well understood. The objectives of this study were to compare the effects of emerging and prevalent environmental contaminants on the expression of brain transcripts with a role in neurotransmitter synthesis and reproduction. Adult male largemouth bass (Micropterus salmoides) were injected once for a 96 h duration with control (water or oil) or with one of two doses of a single chemical to achieve the following body burdens ({mu}g/g): atrazine (0.3 and 3.0), toxaphene (10 and 100), cadmium (CdCl{sub 2}) (0.000067 and 0.00067), polychlorinated biphenyl (PCB) 126 (0.25 and 2.5), and phenanthrene (5 and 50). Partial largemouth bass gene segments were cloned for enzymes involved in neurotransmitter (glutamic acid decarboxylase 65, GAD65; tyrosine hydroxylase) and estrogen (brain aromatase; CYP19b) synthesis for real-time PCR assays. In addition, neuropeptides regulating feeding (neuropeptide Y) and reproduction (chicken GnRH-II, cGnRH-II; salmon GnRH, sGnRH) were also investigated. Of the chemicals tested, only cadmium, PCB 126, and phenanthrene showed any significant effects on the genes tested, while atrazine and toxaphene did not. Cadmium (0.000067 {mu}g/g) significantly increased cGnRH-II mRNA while PCB 126 (0.25 {mu}g/g) decreased GAD65 mRNA. Phenanthrene decreased GAD65 and tyrosine hydroxylase mRNA levels at the highest dose (50 {mu}g/g) but increased cGnRH-II mRNA at the lowest dose (5 {mu}g/g). CYP19b, NPY, and sGnRH mRNA levels were unaffected by any of the treatments. A hierarchical clustering dendrogram grouped PCB 126 and phenanthrene more closely than other chemicals with respect to the genes tested. This study demonstrates that brain transcripts important for neurotransmitter synthesis neuroendocrine function are potential targets for emerging and prevalent aquatic contaminants.

  15. Comparison of different transition metal ions for immobilized metal affinity chromatography of selenoprotein P from human plasma

    DEFF Research Database (Denmark)

    Sidenius, U; Farver, O; Jøns, O

    1999-01-01

    Cu2+, Ni2+, Zn2+, Co2+ and Cd2+ were evaluated in metal ion affinity chromatography for enrichment of selenoprotein P, and immobilized Co2+ affinity chromatography was found to be the most selective chromatographic method. The chromatography was performed by fast protein liquid chromatography...... and the fractionation was followed by analysis of the collected fractions for selenium by inductively coupled plasma mass spectrometry. By the combination of immobilized Co2+ affinity chromatography and heparin affinity chromatography a simple method was developed yielding a 14,800-fold enrichment of selenoprotein P...

  16. Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer’s Disease Brain

    OpenAIRE

    Rueli, Rachel H.L.H.; Parubrub, Arlene C.; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane H.; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

    2015-01-01

    Subjects with Alzheimer’s disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in compar...

  17. Direct determination of selenoproteins in polyvinylidene difluoride membranes by electrothermal atomic absorption spectrometry

    DEFF Research Database (Denmark)

    Sidenius, U; Gammelgaard, Bente

    2000-01-01

    A method for the direct determination of selenoproteins in plastic membranes after protein separation by gel electrophoresis was developed. Quantification was based on the determination of the selenium content of the proteins by electrothermal atomic absorption spectrometry (ET-AAS) after manual...... were excised and chemical modifier was added on top of the excised membrane prior to atomic absorption measurement. Acceptable linearity was achieved in the range 2-10 ng Se, corresponding to selenium concentrations close to 1 mg/L, when aqueous solutions of selenomethionine standard as well...

  18. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

    Science.gov (United States)

    Barrett, Caitlyn W.; Reddy, Vishruth K.; Short, Sarah P.; Motley, Amy K.; Lintel, Mary K.; Bradley, Amber M.; Freeman, Tanner; Vallance, Jefferson; Ning, Wei; Parang, Bobak; Poindexter, Shenika V.; Fingleton, Barbara; Chen, Xi; Washington, Mary K.; Wilson, Keith T.; Shroyer, Noah F.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

    2015-01-01

    Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions. PMID:26053663

  19. Impaired Homocysteine Transmethylation and Protein-Methyltransferase Activity Reduce Expression of Selenoprotein P: Implications for Obesity and Metabolic Syndrome

    Science.gov (United States)

    Obesity causes Metabolic Syndrome and Type-II Diabetes, disrupting hepatic function, methionine (Met)/homocysteine (Hcy) transmethylation and methyltransferase (PRMT) activities. Selenoprotein P (SEPP1), exported from the liver, is the predominate form of plasma selenium (Se) and the physiological S...

  20. Kissing loops hide premature termination codons in pre-mRNAof selenoprotein genes and in genes containing programmedribosomal frameshifts

    DEFF Research Database (Denmark)

    Knudsen, Steen; Brunak, Søren

    1997-01-01

    A novel RNA secondary structure that places the selenocysteine codon UGA in one hairpin and a donor splice site in another, has been discovered in selenoprotein genes. The presence of the structure resolves the discrepancy that the selenocysteine triplet, UGA, should block splicing. Without a spe...

  1. Amnesia produced by altered release of neurotransmitters after intraamygdala injections of a protein synthesis inhibitor

    OpenAIRE

    Canal, Clinton E.; Chang, Qing; Gold, Paul E.

    2007-01-01

    Amnesia produced by protein synthesis inhibitors such as anisomycin provides major support for the prevalent view that the formation of long-lasting memories requires de novo protein synthesis. However, inhibition of protein synthesis might disrupt other neural functions to interfere with memory formation. Intraamygdala injections of anisomycin before inhibitory avoidance training impaired memory in rats tested 48 h later. Release of norepinephrine (NE), dopamine (DA), and serotonin, measured...

  2. Increased Selenoprotein P in Choroid Plexus and Cerebrospinal Fluid in Alzheimer’s Disease Brain

    Science.gov (United States)

    Rueli, Rachel H.L.H.; Parubrub, Arlene C.; Dewing, Andrea S.T.; Hashimoto, Ann C.; Bellinger, Miyoko T.; Weeber, Edwin J.; Uyehara-Lock, Jane H.; White, Lon R.; Berry, Marla J.; Bellinger, Frederick P.

    2015-01-01

    Subjects with Alzheimer’s disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium. PMID:25298198

  3. Direct determination of selenoproteins in polyvinylidene difluoride membranes by electrothermal atomic absorption spectrometry

    DEFF Research Database (Denmark)

    Sidenius, U; Gammelgaard, Bente

    2000-01-01

    A method for the direct determination of selenoproteins in plastic membranes after protein separation by gel electrophoresis was developed. Quantification was based on the determination of the selenium content of the proteins by electrothermal atomic absorption spectrometry (ET-AAS) after manual...... introduction of membrane pieces into the graphite furnace. The proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and subsequently transferred to a polyvinylidene difluoride (PVDF) membrane by semi-dry electroblotting. After staining the membrane, the protein bands...... were excised and chemical modifier was added on top of the excised membrane prior to atomic absorption measurement. Acceptable linearity was achieved in the range 2-10 ng Se, corresponding to selenium concentrations close to 1 mg/L, when aqueous solutions of selenomethionine standard as well...

  4. Defects in rhizobial cyclic glucan and lipopolysaccharide synthesis alter legume gene expression during nodule development

    DEFF Research Database (Denmark)

    D'Antuono, Alejandra L; Ott, Thomas; Krusell, Lene

    2008-01-01

    higher expression of phenylalanine ammonia lyase than wild-type nodules. Differences in expression pattern of genes involved in early recognition and signaling were observed in plants inoculated with the M. loti mutant strain affected in the synthesis of cyclic glucan. Udgivelsesdato: 2008-Jan......cDNA array technology was used to compare transcriptome profiles of Lotus japonicus roots inoculated with a Mesorhizobium loti wild-type and two mutant strains affected in cyclic beta(1-2) glucan synthesis (cgs) and in lipopolysaccharide synthesis (lpsbeta2). Expression of genes associated...

  5. Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism.

    Science.gov (United States)

    Steinbrenner, Holger

    2013-12-01

    An assumed link between supranutritional intake of the micronutrient selenium (Se) and type 2 diabetes mellitus is discussed controversially. Se concentrations in the habitual diet and in dietary supplements are probably not sufficient to induce overt diabetes in healthy individuals. On the other hand, high plasma Se and selenoprotein P (Sepp1) levels have been found to be associated with biomarkers of an impaired carbohydrate and lipid homeostasis in humans. Moreover, abundant expression of antioxidant selenoproteins due to dietary Se oversupply resulted in hyperinsulinemia and decreased insulin sensitivity in animal models. This review discusses findings from animal and cell culture studies in search of molecular mechanisms underlying an interference of Se and selenproteins such as the Se transport and supply protein Sepp1 and the hydrogen peroxide-reducing selenoenzyme glutathione peroxidase 1 (GPx1) with insulin-controlled metabolic pathways. A probable rationale derives from the positive and negative regulation of both glucose-induced insulin secretion and insulin-induced signaling by hydrogen peroxide. Se status and GPx1 expression have been reported to affect the activity of insulin-antagonistic phosphatases that are regulated by hydrogen peroxide-mediated reversible oxidation of catalytic cysteine residues. GPx1 and/or Sepp1 inhibited phosphorylation (activation) of key mediators in energy metabolism such as protein kinase B (Akt) and AMP-activated protein kinase (AMPK) in liver and/or skeletal muscle. Conversely, a dys-regulated carbohydrate metabolism in diabetes might affect plasma Se and Sepp1 levels, as the hepatic biosynthesis of Sepp1 is suppressed by insulin and stimulated under hyperglycemic conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Structure- and cell-specific effects of imidoselenocarbamates on selenoprotein expression and activity in liver cells in culture.

    Science.gov (United States)

    Ibáñez, Elena; Stoedter, Mette; Hofmann, Peter Josef; Plano, Daniel; Calvo, Alfonso; Nguewa, Paul A; Palop, Juan Antonio; Sanmartín, Carmen; Schomburg, Lutz

    2012-12-01

    The essential micronutrient selenium (Se) exerts its biological effects mainly through selenoproteins thereby affecting a number of physiological pathways including intracellular redox control, stress response and cancer cell proliferation. Besides affecting selenoprotein expression, some selenocompounds have been synthesized and analyzed in order to serve as chemotherapeutic substances preferentially targeting cancer cells. This promising chemotherapeutic potential has recently been verified for a particular imidoselenocarbamate in a mouse tumor model. In the present study we tested the effects of this and a number of related Se-methyl- and Se-benzyl-imidoselenocarbamates on selenoprotein expression in nontransformed and hepatic carcinoma cells in culture. Most of the Se-benzyl-imidoselenocarbamates strongly stimulated selenoprotein P (SePP) secretion while the Se-methyl-imidoselenocarbamates elicited less pronounced effects in hepatocarcinoma HepG2 cells. However, most of the Se-methyl-imidoselenocarbamates increased glutathione peroxidase (GPx) activity and decreased thioredoxin reductase (TXNRD) activity in parallel, while the majority of the Se-benzyl-imidoselenocarbamates were without a respective effect in HepG2 cells. Performing inhibitor assays in vitro, GPx activity was unaffected by the imidoselenocarbamates. In contrast, most of the Se-methyl-imidoselenocarbamates inhibited TXNRD activity in vitro in line with the results in HepG2 cells. Both classes of imidoselenocarbamates strongly induced selenoprotein S (SELS) expression without a respective increase in ER stress or unfolded protein response which are known inducers of SELS biosynthesis. Notably, many of these effects were cancer cell-specific, and not observed in nontransformed AML12 hepatocytes. Our results indicate that these novel selenocompounds affect expression and activity of crucial selenoenzymes in a compound- and cell-specific way in hepatocytes. Especially the Se

  7. Comparison of different transition metal ions for immobilized metal affinity chromatography of selenoprotein P from human plasma

    DEFF Research Database (Denmark)

    Sidenius, U; Farver, O; Jøns, O

    1999-01-01

    Cu2+, Ni2+, Zn2+, Co2+ and Cd2+ were evaluated in metal ion affinity chromatography for enrichment of selenoprotein P, and immobilized Co2+ affinity chromatography was found to be the most selective chromatographic method. The chromatography was performed by fast protein liquid chromatography...... and the fractionation was followed by analysis of the collected fractions for selenium by inductively coupled plasma mass spectrometry. By the combination of immobilized Co2+ affinity chromatography and heparin affinity chromatography a simple method was developed yielding a 14,800-fold enrichment of selenoprotein P....... The purity of the protein was determined by SDS-PAGE and by sequencing from polyvinylidene difluoride blots of SDS-PAGE gels....

  8. Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet irradiation-induced damage by modulating cell signaling pathways.

    Science.gov (United States)

    Mendelev, Natalia; Witherspoon, Sam; Li, P Andy

    2009-12-01

    Selenoprotein H (SelH) is one of the 25 so far identified selenoproteins. Selenoproteins may function as antioxidants, heavy metal antidotes, and neural survival factors. Previous studies have shown that overexpression of SelH in HT22 cells protected the cells from UVB irradiation-induced death by reducing superoxide formation. The objective of this study was to determine the effects of SelH on cell signaling pathways after UVB irradiation. We exposed both human SelH- and vector-transfected HT22 cells to UVB irradiation and collected samples at 5 and 17 h of recovery. Cell viability was assessed, as well as protein levels of caspase-3, -8, -9, apoptosis-inducing factor (AIF), P53, nuclear respiratory factor-1 (NRF-1) and heat shock protein 40 (HSP40). Mitochondrial membrane potential was determined by flow cytometry. Overexpression of SelH protected cells against UVB-induced injury by blockade of the mitochondria-initiated cell death pathway, prevention of mitochondrial membrane depolarization, and suppression of the increase of p53. Furthermore, overexpression of SelH increased levels of NRF-1, an antioxidant, and HSP40, a protein chaperone that repairs denatured protein. We conclude that SelH protects neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, by preventing mitochondrial depolarization, and by promoting cell survival pathways.

  9. Study of nuclear glasses alteration gel and synthesis of some model gels

    International Nuclear Information System (INIS)

    Ricol, S.

    1995-01-01

    This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs

  10. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    International Nuclear Information System (INIS)

    Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri

    2011-01-01

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 ± 1.24 ug/L) and hair mercury levels (0.49 ± 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5′), or both (SEPP1 3′UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: ► We explore the influence of 15 polymorphisms on urine and hair Hg levels. ► Urine and hair Hg levels in dental professionals were similar to the US population. ► GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. ► Accumulation of Hg in hair following exposure from fish was modified by genotype. ► GSTP1, GSS

  11. Glutathione enzyme and selenoprotein polymorphisms associate with mercury biomarker levels in Michigan dental professionals

    Energy Technology Data Exchange (ETDEWEB)

    Goodrich, Jaclyn M.; Wang, Yi [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Gillespie, Brenda [Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Werner, Robert [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower Parkway Suite 100, Ann Arbor, MI 48108 (United States); Franzblau, Alfred [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Basu, Niladri, E-mail: niladri@umich.edu [Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109 (United States)

    2011-12-15

    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione s-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n = 515), and total mercury content was measured. Average urine (1.06 {+-} 1.24 ug/L) and hair mercury levels (0.49 {+-} 0.63 ug/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5 Prime ), or both (SEPP1 3 Prime UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption). -- Highlights: Black-Right-Pointing-Pointer We explore the influence of 15 polymorphisms on urine and hair Hg levels. Black-Right-Pointing-Pointer Urine and hair Hg levels in dental professionals were similar to the US population. Black-Right-Pointing-Pointer GSTT1 and SEPP1 polymorphisms associated with urine Hg levels. Black

  12. Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2009-06-19

    Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.

  13. Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Díaz-Rubio Manuel

    2008-07-01

    Full Text Available Abstract Background Selenoprotein S (SelS protects the functional integrity of the endoplasmic reticulum against the deleterious effects of metabolic stress. SEPS1/SelS polymorphisms have been involved in the increased release of pro-inflammatory cytokines interleukin (IL-1β, tumor necrosis factor (TNF-α and IL-6 in macrophages. We aimed at investigating the role of the SEPS1 variants previously associated with higher plasma levels of these cytokines and of the SEPS1 haplotypes in the susceptibility to develop immune-mediated diseases characterized by an inflammatory component. Results Six polymorphisms distributed through the SEPS1 gene (rs11327127, rs28665122, rs4965814, rs12917258, rs4965373 and rs2101171 were genotyped in more than two thousand patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases and 550 healthy controls included in the case-control study. Conclusion Lack of association of SEPS1 polymorphisms or haplotypes precludes a major role of this gene increasing predisposition to these inflammatory diseases.

  14. Effects of selenium supplementation on selenoprotein gene expression and response to influenza vaccine challenge: a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Andrew J Goldson

    2011-03-01

    Full Text Available The uncertainty surrounding dietary requirements for selenium (Se is partly due to limitations in biomarkers of Se status that are related to health outcomes. In this study we determined the effect of different doses and forms of Se on gene expression of selenoprotein S (SEPS1, selenoprotein W (SEPW1 and selenoprotein R (SEPR, and responses to an immune function challenge, influenza vaccine, were measured in order to identify functional markers of Se status.A 12 week human dietary intervention study was undertaken in 119 volunteers who received placebo, 50, 100 or 200 µg/day Se-enriched yeast (Se-yeast or meals containing unenriched or Se-enriched onions (50 µg/day. Gene expression was quantified in RNA samples extracted from human peripheral blood mononuclear cells (PBMC's using quantitative RT-PCR. There was a significant increase in SEPW1 mRNA in the Se-enriched onion group (50 µg/day compared with the unenriched onion group. SEPR and SEPW1 did not change significantly over the duration of the supplementation period in the control or Se-yeast groups, except at week 10 when SEPW1 mRNA levels were significantly lower in the 200 µg/day Se-yeast group compared to the placebo group. Levels of SEPS1 mRNA increased significantly 7 days after the influenza vaccine challenge, the magnitude of the increase in SEPS1 gene expression was dose-dependent, with a significantly greater response with higher Se supplementation.This novel finding provides preliminary evidence for a role of SEPS1 in the immune response, and further supports the relationship between Se status and immune function.ClinicalTrials.gov [NCT00279812].

  15. Genistein Precipitated Hypothyroidism, Altered Leptin and C-Reactive Protein Synthesis in Pregnant Rats.

    Science.gov (United States)

    Awobajo, F O; Onokpite, B O; Ali, Y M; Babaleye, T A; Uzor, P O; Tijani, K O

    2015-12-20

    Genistein is an isoflavone constituent of soya. This study examined the mechanism by which genistein produced adverse effects in pregnant laboratory rats. Pregnant rats were divided into control (Con) and genistein (Gen) force fed (2 mg/kg) groups. At terminal gestation day (GD) ranging from 0-20, the rats were sacrificed, and blood samples and amniotic fluids were collected. Thyroid hormone, C-reactive protein (CRP) and leptin assay was carried using the blood samples. Leptin was also assayed in the placenta and amniotic fluid supernatant. Oral exposure of pregnant rats to genistein significantly altered maternal T3, (GD18; Con 1.65 ± 0.01, Gen 1.03 ± 0.04 nmol/L), T4 (GD6; Con 29.60 ± 0.00, Gen 36.04 ± 1.29 nmol/L), Leptin (Placenta GD20; Con 0.08 ± 0.01, Gen 0.31 ± 0.02 ng/ml, amniotic fluid ;GD 20; Con 0.02 ± 0.00, Gen 0.35 ± 0.05 ng/ml) in genistein group. These changes were accompanied with loss of embryonic implants and a decrease in fetal and placental weights. The CRP level was significantly decreased and increased at the onset and toward late pregnancy respectively. Oral exposure of pregnant rats to genistein precipitated hypothyroidism, altered some metabolic hormones with a reduction in fetal and placental growth and increased resorption of embryonic implants.

  16. Bacillus amyloliquefaciens alters gene expression, ROS production, and lignin synthesis in cotton seedling roots.

    Science.gov (United States)

    Irizarry, Ivelisse; White, James F

    2018-02-23

    Previous research demonstrated that applying Bacillus amyloliquefaciens to cotton seeds promotes growth, alters root architecture, and alleviates salt stress of cotton seedlings. This research was undertaken to further study the genetic responses elicited in cotton seedlings by this growth promoting bacterium. GeneChip microarrays and RT-qPCR were used to detect changes in gene expression in seedling roots inoculated with B. amyloliquefaciens. Roots were stained with 3'3-diaminobenzidine and phloroglucinol-HCl to determine whether treated seedlings had a greater accumulation of reactive oxygen species and lignin. 252 transcripts were differentially expressed in inoculated cotton seedling roots. 139 transcripts were up-regulated and 113 were down-regulated. Some up-regulated transcripts were related to nitrate assimilation, cell growth, hormones, transport, transcription factors, and antioxidants. Five genes identified to be up-regulated using microarrays were determined to be up-regulated using RT-qPCR. Inoculated cotton seedling roots had a greater accumulation of reactive oxygen species and lignin. The differential expression of genes associated with diverse functions supports that B. amyloliquefaciens elicits a complex genetic response in seedling roots. This study demonstrated that beneficial bacteria can alter gene expression of cotton that leads to growth promotion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation

    Science.gov (United States)

    Lunt, Sophia Y.; Muralidhar, Vinayak; Hosios, Aaron M.; Israelsen, William J.; Gui, Dan Y.; Newhouse, Lauren; Ogrodzinski, Martin; Hecht, Vivian; Xu, Kali; Acevedo, Paula N. Marín; Hollern, Daniel P.; Bellinger, Gary; Dayton, Talya L.; Christen, Stefan; Elia, Ilaria; Dinh, Anh T.; Stephanopoulos, Gregory; Manalis, Scott R.; Yaffe, Michael B.; Andrechek, Eran R.; Fendt, Sarah-Maria; Heiden, Matthew G. Vander

    2014-01-01

    SUMMARY Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2-deletion affects proliferation and metabolism in non-transformed, non-immortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis. PMID:25482511

  18. Altered synthesis of some secretory proteins in pancreatic lobules isolated from streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Duan, R.D.; Erlanson-Albertsson, C.

    1990-01-01

    The in vitro incorporation of [35S]cysteine into lipase, colipase, amylase, procarboxypeptidase A and B, and the serine proteases and total proteins was studied in pancreatic lobules isolated from normal and diabetic rats with or without insulin treatment. The incorporation of [35S]cysteine into total proteins was 65% greater in pancreatic lobules from diabetic animals than from normal rats. The increased incorporation was partly reversed by insulin treatment (2 U/100 g/day for 5 days) of diabetic rats. The relative rates of biosynthesis for amylase and the procarboxypeptidases in diabetic pancreatic lobules were decreased by 75 and 25%, respectively, after 1 h of incubation, while those for lipase, colipase, and the serine proteases were increased by 90, 85, and 35%, respectively. The absolute rates of synthesis for these enzymes changed in the same direction as the relative rates in diabetic lobules, except that for the procarboxypeptidases, which did not change. The changed rates of biosynthesis for the pancreatic enzymes were reversed by insulin treatment of the diabetic rats. Kinetic studies showed that the incorporation of [35S]cysteine into amylase, lipase, and colipase was linear until up to 2 h of incubation in normal pancreatic lobules, while in the diabetic lobules the incorporation into lipase and colipase was accelerated, reaching a plateau level already after 1 h of incubation. It is concluded that the biosynthesis of pancreatic secretory proteins in diabetic rats is greatly changed both in terms of quantity and kinetics

  19. Metabolic engineering of the morphology of Aspergillus oryzae by altering chitin synthesis

    DEFF Research Database (Denmark)

    Muller, C.; Mcintyre, Mhairi; Hansen, Kim

    2002-01-01

    Morphology and alpha-amylase production during submerged cultivation were examined in a wild-type strain (A1560) and in strains of Aspergillus oryzae in which chitin synthase B (chsB) and chitin synthesis myosin A (csmA) have been disrupted (ChsB/G and CM101). In a flowthrough cell, the growth...... than that in the wild type., whereas that in the ChsB/G strain was 188% higher. During batch cultivation, inseparable clumps were formed in the wild-type strain., while no or fewer large inseparable clumps existed in the cultivations of the ChsB/G and CM101 strains. The alpha-amylase productivity...... an important role for chsB in branching. However, the pattern of branching responded very slowly to the change in transcription, and increased branching did not affect alpha-amylase productivity. alpha-Amylase residing in the cell wall was stained by immunofluorescence, and the relationship between tip number...

  20. Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer

    Directory of Open Access Journals (Sweden)

    Fernández-Vega Iván

    2013-01-01

    Full Text Available Abstract Background The expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs, which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer. Methods Twenty-three infiltrating ductal adenocarcinomas (IDCs, both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest. Results No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic, while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of

  1. Increase of placental sensitivity to melatonin and the alteration to its local synthesis in hypertensive syndromes in pregnancy.

    Science.gov (United States)

    Yamamoto, Douglas de Resende; Yamamoto, Leandro de Resende; Rocha, Laura Penna; Machado, Juliana Reis; Guimarães, Camila Souza de Oliveira; Reis, Marlene Antônia Dos; Corrêa, Rosana Rosa Miranda

    2013-05-01

    To evaluate the relation between hypertensive syndromes and melatonin, and its possible protective role against lesions due to hypertension. Placentas were classified into gestational hypertension (GH), chronic hypertension (CH), pre-eclampsia (PE) and pre-eclampsia superimposed on chronic hypertension, and morphologically examined by hematoxylin-eosin and periodic acid Schiff methods. Immunohistochemistry was performed to detect tryptophan hydroxylase (TH) and melatonin receptor 1A (MR-1A). MR-1A expression was higher in all types of hypertensive syndromes in pregnancy (HSP), mainly in cases with GH, in Caesarean section delivery, preterm placentas and in the cases with alterations in the placental morphology, particularly those presenting inflammation. The expression of TH was higher in cases with CH when compared with the control. This expression was lower in primigestas, in the cases of inflammation and with PE. HSP therapies should be considered and studied, especially in the cases of HSP associated with PE, in which the placenta is more sensitive as it has more receptors, but its synthesis ability is reduced. As for GH and CH, the possible benefits should be evaluated, since the local placental ability to produce melatonin still exists.

  2. Study of nuclear glasses alteration gel and synthesis of some model gels; Etude du gel d`alteration des verres nucleaires et synthese de gels modeles

    Energy Technology Data Exchange (ETDEWEB)

    Ricol, S.

    1995-10-05

    This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs.

  3. The effect of dietary bacterial organic selenium on growth performance, antioxidant capacity, and Selenoproteins gene expression in broiler chickens.

    Science.gov (United States)

    Dalia, A M; Loh, T C; Sazili, A Q; Jahromi, M F; Samsudin, A A

    2017-08-18

    Selenium (Se) is an essential trace mineral in broilers, which has several important roles in biological processes. Organic forms of Se are more efficient than inorganic forms and can be produced biologically via Se microbial reduction. Hence, the possibility of using Se-enriched bacteria as feed supplement may provide an interesting source of organic Se, and benefit broiler antioxidant system and other biological processes. The objective of this study was to examine the impacts of inorganic Se and different bacterial organic Se sources on the performance, serum and tissues Se status, antioxidant capacity, and liver mRNA expression of selenoproteins in broilers. Results indicated that different Se sources did not significantly (P ≤ 0.05) affect broiler growth performance. However, bacterial organic Se of T5 (basal diet +0.3 mg /kg feed ADS18 Se), T4 (basal diet +0.3 mg /kg feed ADS2 Se), and T3 (basal diet +0.3 mg /kg feed ADS1 Se) exhibited significantly (P ≤ 0.05) highest Se concentration in serum, liver, and kidney respectively. Dietary inorganic Se and bacterial organic Se were observed to significantly affect broiler serum ALT, AST, LDH activities and serum creatinine level. ADS18 supplemented Se of (Stenotrophomonas maltophilia) bacterial strain showed the highest GSH-Px activity with the lowest MDA content in serum, and the highest GSH-Px and catalase activity in the kidney, while bacterial Se of ADS2 (Klebsiella pneumoniae) resulted in a higher level of GSH-Px1 and catalase in liver. Moreover, our study showed that in comparison with sodium selenite, only ADS18 bacterial Se showed a significantly higher mRNA level in GSH-Px1, GSH-Px4, DIO1, and TXNDR1, while both ADS18 and ADS2 showed high level of mRNA of DIO2 compared to sodium selenite. The supplementation of bacterial organic Se in broiler chicken, improved tissue Se deposition, antioxidant status, and selenoproteins gene expression, and can be considered as an effective alternative source of

  4. Alterations in protein synthesis in the cyanobacterium Synechococcus sp. Strain PCC 6301 in response to Calendula Micrantha extract with the Molluscicidal activity

    International Nuclear Information System (INIS)

    Hammouda, O.H.E.; Borbely, G.

    1995-01-01

    The response to the extract of the egyptian wild herb Calendula Micrantha, with the Molluscicidal activity, was examined in the unicellular no bacterium Synechococcus sp. strain PCC 6301. growth and chlorophyll of the cells were only slightly affected by low plant extract concentrations but were drastically reduced by high concentration. the rate of protein synthesis progressively decreased by increasing extract concentration. the cells preferentially induced the synthesis of a limited number of polypeptides in response to the treatment. Among the induced polypeptides were those with apparent molecular weights of 161 K (161.000), 96.7 K, 93.4 K, 69.9 K, 59 K, 49 K, 45 K, 35 K, 32.4 K, 28 K, 24 K, 21.7 K, 18 K and 16 K based on their mobilities in gel electrophoresis. these initial studies suggest that the plant extract exerted certain stress which stimulated alteration in the pattern of protein synthesis in Synechococcus sp. some of induced polypeptides are similar to that known to occur in other stresses specially heat shock stress. 3 figs

  5. Organ-Specific Alterations in Fatty Acid De Novo Synthesis and Desaturation in a Rat Model of Programmed Obesity

    Directory of Open Access Journals (Sweden)

    Desai Mina

    2011-05-01

    Full Text Available Abstract Background Small for gestational age (SGA leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR, catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity (SCD1 and rates of de novo fatty acid synthesis in young FR and Control offspring tissues at the end of the nursing period, as possible contributors to catch-up growth. Methods From gestational day 10 to term, dams fed ad libitum (Control or were 50% food-restricted to produce small FR pups. Control dams nursed all pups. At postnatal day 1 (p1 and p21, offspring body tissues were analyzed by GC/MS, and desaturation indices of palmitoleate/palmitate and oleate/stearate were calculated. SCD1 gene expression was determined by real-time PCR on adipose and liver. Offspring were enriched with deuterium that was given to dams in drinking water during lactation and de novo synthesis of offspring body tissues was determined at p21. Primary adipocyte cell cultures were established at p21 and exposed to U13C-glucose. Results FR offspring exhibited higher desaturation index in p1 and p21 adipose tissue, but decreased desaturation index in liver at p21. SCD1 gene expression at p21 was correspondingly increased in adipose and decreased in liver. FR subcutaneous fat demonstrated increased de novo synthesis at p21. Primary cell cultures exhibited increased de novo synthesis in FR. Conclusions Adipose tissue is the first site to exhibit increased de novo synthesis and desaturase activity in FR. Therefore, abnormal lipogenesis is already present prior to onset of obesity during the period of catch-up growth. These abnormalities may contribute to future obesity development.

  6. A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse

    Directory of Open Access Journals (Sweden)

    Craig Robert Wright

    2017-01-01

    Full Text Available Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD. There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S (Seps1 are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion (mdx:Seps1−/+ were generated. The mdx:Seps1−/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL muscles, mRNA expression of monocyte chemoattractant protein 1 (Mcp-1 (P=0.034, macrophage marker F4/80 (P=0.030, and transforming growth factor-β1 (Tgf-β1 (P=0.056 were increased in mdx:Seps1−/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.

  7. Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models.

    Science.gov (United States)

    Mita, Yuichiro; Nakayama, Kaho; Inari, Shogo; Nishito, Yukina; Yoshioka, Yuya; Sakai, Naoko; Sotani, Kanade; Nagamura, Takahiro; Kuzuhara, Yuki; Inagaki, Kumi; Iwasaki, Miki; Misu, Hirofumi; Ikegawa, Masaya; Takamura, Toshinari; Noguchi, Noriko; Saito, Yoshiro

    2017-11-21

    Selenoprotein P (SeP) functions as a selenium (Se)-supply protein. SeP is identified as a hepatokine, promoting insulin resistance in type 2 diabetes. Thus, the suppression of Se-supply activity of SeP might improve glucose metabolism. Here, we develop an anti-human SeP monoclonal antibody AE2 as with neutralizing activity against SeP. Administration of AE2 to mice significantly improves glucose intolerance and insulin resistance that are induced by human SeP administration. Furthermore, excess SeP administration significantly decreases pancreas insulin levels and high glucose-induced insulin secretion, which are improved by AE2 administration. Epitope mapping reveals that AE2 recognizes a region of human SeP adjacent to the first histidine-rich region (FHR). A polyclonal antibody against the mouse SeP FHR improves glucose intolerance and insulin secretion in a mouse model of diabetes. This report describes a novel molecular strategy for the development of type 2 diabetes therapeutics targeting SeP.

  8. Selenoprotein W redox-regulated Ca2+ channels correlate with selenium deficiency-induced muscles Ca2+ leak.

    Science.gov (United States)

    Yao, Haidong; Fan, Ruifeng; Zhao, Xia; Zhao, Wenchao; Liu, Wei; Yang, Jie; Sattar, Hamid; Zhao, Jinxin; Zhang, Ziwei; Xu, Shiwen

    2016-09-06

    Selenium (Se) deficiency induces Ca2+ leak and calcification in mammal skeletal muscles; however, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and selenoprotein W (SelW) gene knockdown myoblast and embryo models were used to study the mechanism. The results showed that Se deficiency-induced typical muscular injuries accompanied with Ca2+ leak and oxidative stress (P CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 (P CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca2+ channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdown induced Ca2+ leak, oxidative stress, and Ca2+ channel reduction. In addition, Ca2+ levels and the expression of the Ca2+ channels, RyR1, SERCA, CACNA1S, TRPC1, and TRPC3 were recovered to normal levels by N-acetyl-L-cysteine (NAC) treatment compared with SelW knockdown cells. Thus, with regard to the decreased Ca2+ channels, SelW knockdown closely correlated Se deficiency with Ca2+ leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca2+ leak in muscles.

  9. Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways.

    Science.gov (United States)

    Rowan-Carroll, Andrea; Halappanavar, Sabina; Williams, Andrew; Somers, Christophers M; Yauk, Carole L

    2013-05-01

    It is clear that particulate air pollution poses a serious risk to human health; however, the underlying mechanisms are not completely understood. We investigated pulmonary transcriptional responses in mice following in-situ exposure to ambient air in a heavily industrialized urban environment. Mature C57BL/CBA male mice were caged in sheds near two working steel mills and a major highway in Hamilton, Ontario, Canada in the spring/summer of 2004. Control mice were housed in the same environment, but received only high-efficiency particle filtered air (HEPA). Whole lung tissues were collected from mice exposed for 3, 10, or for 10 weeks followed by 6 weeks recovery in the laboratory (16 weeks). DNA microarrays were used to profile changes in pulmonary gene expression. Transcriptional profiling revealed changes in the expression of genes implicated in the lipid droplet synthesis (Plin I, Dgat2, Lpl, S3-12, and Agpat2), and antioxidant defense (Ucp1) pathways in mice breathing unfiltered air. We postulate that exposure to urban air, containing an abundance of particulate matter adsorbed with polycyclic aromatic hydrocarbons, triggers lipid droplet (holding depots for lipids and malformed/excess proteins tagged for degradation) synthesis in the lungs, which may act to sequester particulates. Increased lipid droplet synthesis could lead to endogenous/stressor-induced production of reactive oxygen species and activation of antioxidant mechanisms. Further investigation into the stimulation of lipid droplet synthesis in the lung in response to air pollution and the resulting health implications is warranted. Copyright © 2013 Wiley Periodicals, Inc.

  10. Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

    DEFF Research Database (Denmark)

    Vicca, S.; Bahn, M.; Estiarte, M.

    2014-01-01

    dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is 'no' - as based on the most reliable data sets available. We strongly recommend that future experiments focus more...

  11. Suppressing Sorbitol Synthesis Substantially Alters the Global Expression Profile of Stress Response Genes in Apple (Malus domestica) Leaves.

    Science.gov (United States)

    Wu, Ting; Wang, Yi; Zheng, Yi; Fei, Zhangjun; Dandekar, Abhaya M; Xu, Kenong; Han, Zhenhai; Cheng, Lailiang

    2015-09-01

    Sorbitol is a major product of photosynthesis in apple (Malus domestica) that is involved in carbohydrate metabolism and stress tolerance. However, little is known about how the global transcript levels in apple leaves respond to decreased sorbitol synthesis. In this study we used RNA sequencing (RNA-seq) profiling to characterize the transcriptome of leaves from transgenic lines of the apple cultivar 'Greensleeves' exhibiting suppressed expression of aldose-6-phosphate reductase (A6PR) to gain insights into sorbitol function and the consequences of decreased sorbitol synthesis on gene expression. We observed that, although the leaves of the low sorbitol transgenic lines accumulate higher levels of various primary metabolites, only very limited changes were found in the levels of transcripts associated with primary metabolism. We suggest that this is indicative of post-transcriptional and/or post-translational regulation of primary metabolite accumulation and central carbon metabolism. However, we identified significantly enriched gene ontology terms belonging to the 'stress related process' category in the antisense lines (P-value apple trees to abiotic and biotic stresses. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Formaldehyde alters triglyceride synthesis and very low-density lipoprotein secretion in a time-dependent manner.

    Science.gov (United States)

    Bai, Jianying; Wang, Pan; Liu, Yanfei; Zhang, Yan; Li, Yaofu; He, Zhen; Hou, Lifang; Liang, Ruifeng

    2017-12-01

    Formaldehyde is a common indoor air pollutant that is toxic to the liver. This study aimed to investigate the effects of formaldehyde on triglyceride metabolism in human hepatocellular carcinoma cells (HepG2). Cell viability was detected using a MTT (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide) assay. Following treatment with different concentrations of formaldehyde for 24 and 48h, the intra and extra-hepatocellular triglyceride (TG) content was determined using a chemical-enzymatic method; Western blotting was used to detect the levels of fatty acid synthesis and VLDL-related proteins. Our results showed that cell viability significantly decreased after formaldehyde treatment (0.5-12.5mM, 24/48h). Extracellular TG levels in the hepatocytes increased after formaldehyde treatment at 0.004mM-0.1mM for 24h. SREBP-1c, ACC, FASN, and MTP, CES3 and DGAT1 proteins increased significantly after 24h of formaldehyde treatment. Intracellular TG levels decreased for 48h treatment of formaldehyde. AMPKα increased significantly in all tested groups and p-AMPK increased significantly after 0.1mM formaldehyde treatment for 48h. Our results indicated that short-term formaldehyde exposure balances triglyceride metabolism by promoting hepatocellular TG synthesis and VLDL secretion; Long-term formaldehyde disturbs the TG metabolism balance in the hepatocytes. Copyright © 2017. Published by Elsevier B.V.

  13. Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders.

    Science.gov (United States)

    di Giuseppe, Romina; Plachta-Danielzik, Sandra; Koch, Manja; Nöthlings, Ute; Schlesinger, Sabrina; Borggrefe, Jan; Both, Marcus; Müller, Hans-Peter; Kassubek, Jan; Jacobs, Gunnar; Lieb, Wolfgang

    2018-02-14

    The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease. In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits. Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits. Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

  14. Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Dai, Jie; Liu, Hongmei; Zhou, Jun; Huang, Kaixun

    2016-02-10

    Selenium is an essential micronutrient for humans. Much of selenium's beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d-galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells.

  15. Lower Selenoprotein T Expression and Immune Response in the Immune Organs of Broilers with Exudative Diathesis Due to Selenium Deficiency.

    Science.gov (United States)

    Pan, Tingru; Liu, Tianqi; Tan, Siran; Wan, Na; Zhang, Yiming; Li, Shu

    2018-04-01

    The objective of the present study was to investigate whether dietary selenium (Se) deficiency would affect the expression of selenoprotein T (SelT) and immune response in the immune organs of broilers. Changes in expression of inflammatory cytokines and oxidative stress response caused by Se deficiency can lead to organism damage, which in turn leads to immune response. Sixty (1-day-old) broilers were divided into the control group and Se-deficiency group. Animal models with exudative diathesis were duplicated in the broilers by feeding them Se-deficient diet for 20 days. After the Se-deficient group exhibited symptoms of exudative diathesis, all the broilers were euthanized, and their immune organs were taken for analysis. The tissues including spleen, bursa of Fabricius, and thymus were treated to determine the pathological changes (including microscopic and ultramicroscopic), the messenger RNA (mRNA) expression levels of SelT and its synthetase (SecS and SPS1), cytokine mRNA expression levels, and antioxidant status. The microscopic and ultramicroscopic analyses showed that immune tissues were obviously injured in the Se-deficient group. The mRNA expression of SelT was decreased compared with that in the control group. Meanwhile, the mRNA expression levels of SecS and SPS1 were downregulated. In the Se-deficient group, the mRNA expression levels of IL-1R and IL-1β were higher than those of three control organs. Additionally, the IL-2 and INF-γ mRNA expression levels were lower than those of the control group. The activity of CAT was decreased, and the contents of H 2 O 2 and •OH were increased due to Se deficiency. Pearson method analysis showed that the expression of SelT had a positive correlation with IL-2, INF-γ, SecS, and SPS1 and a negative correlation with IL-1R and IL-1β. In summary, these data indicated that Se-deficient diet decreased the SelT expression and its regulation of oxidative stress, and it inhibited a pleiotropic mechanism of the

  16. Selenoprotein-P is down-regulated in prostate cancer, which results in lack of protection against oxidative damage.

    Science.gov (United States)

    Gonzalez-Moreno, Oscar; Boque, Noemi; Redrado, Miriam; Milagro, Fermin; Campion, Javier; Endermann, Tobias; Takahashi, Kazuhiko; Saito, Yoshiro; Catena, Raul; Schomburg, Lutz; Calvo, Alfonso

    2011-06-01

    Oxidative stress plays a role in prostate cancer (PrCa) initiation and development. Selenoprotein-P (SepP; a protein involved in antioxidant defence) mRNA levels are down-regulated in PrCa. The main goal of our study was to assess whether SepP protects prostate cells from reactive oxygen species (ROS) in prostate carcinogenesis. Modification of SepP levels and ROS conditions in C3(1)/Tag-derived cell lines representing prostate epithelial neoplasia (PIN) lesions (Pr-111, with high SepP expression); and invasive tumors (Pr-14, with very low SepP expression). Both Pr-111 and Pr-14 cells express ApoER2 (SepP receptor), which suggests that they may uptake SepP. Pr-14 cells had much higher ROS levels than Pr-111 cells and were highly sensitive to H(2)O(2)-mediated cytotoxicity. When SepP mRNA levels were knocked down with siRNAs in Pr-111 cells, a significant increase in ROS and cell growth inhibition upon H(2)O(2) exposure was found. Subsequent administration of purified SepP in the culture medium of these cells was able to rescue the original phenotype. Similarly, administration of SepP to Pr-14 cells was able to reduce ROS concentrations. Administration of flutamide decreased SepP mRNA levels whereas dihydrotestosterone or synthetic androgens induced SepP expression, indicating the importance of androgens for SepP expression. Immunohistochemical analysis using a PrCa tissue microarray further revealed that SepP protein was reduced in 60.8% prostate tumors compared to benign prostates. Levels of SepP in prostate cells determine basal ROS levels and sensitivity to H(2)O(2)-induced cytotoxicity. Deregulation of SepP during prostate carcinogenesis may increase free radicals, thus promoting tumor development and de-differentiation. Copyright © 2010 Wiley-Liss, Inc.

  17. Nitrogen fertilizer application affects lodging resistance by altering secondary cell wall synthesis in japonica rice (Oryza sativa).

    Science.gov (United States)

    Zhang, Wujun; Wu, Longmei; Ding, Yanfeng; Yao, Xiong; Wu, Xiaoran; Weng, Fei; Li, Ganghua; Liu, Zhenghui; Tang, She; Ding, Chengqiang; Wang, Shaohua

    2017-09-01

    Stem mechanical strength is an important agricultural quantitative trait that is closely related to lodging resistance in rice, which is known to be reduced by fertilizer with higher levels of nitrogen. To understand the mechanism that regulates stem mechanical strength in response to nitrogen, we analysed stem morphology, anatomy, mechanical properties, cell wall components, and expression of cell wall-related genes, in two varieties of japonica rice, namely, Wuyunjing23 (lodging-resistant variety) and W3668 (lodging-susceptible variety). The results showed that higher nitrogen fertilizer increased the lodging index in both varieties due to a reduction in breaking strength and bending stress, and these changes were larger in W3668. Cellulose content decreased slightly under higher nitrogen fertilizer, whereas lignin content reduced remarkably. Histochemical staining revealed that high nitrogen application decreased lignin deposition in the secondary cell wall of the sclerenchyma cells and vascular bundle cells compared with the low nitrogen treatments, while it did not alter the pattern of cellulose deposition in these cells in both Wuyunjing23 and W3668. In addition, the expression of the genes involved in lignin biosynthesis, OsPAL, OsCoMT, Os4CL3, OsCCR, OsCAD2, OsCAD7, OsCesA4, and OsCesA7, were also down-regulated under higher nitrogen conditions at the early stage of culm growth. These results suggest that the genes involved in lignin biosynthesis are down-regulated by higher nitrogen fertilizer, which causes lignin deficiency in the secondary cell walls and the weakening of mechanical tissue structure. Subsequently, this results in these internodes with reduced mechanical strength and poor lodging resistance.

  18. Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

    Science.gov (United States)

    Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

    2018-02-14

    Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

  19. Fatty acid elongase 5 (ELOVL5) alters the synthesis of long-chain unsaturated fatty acids in goat mammary epithelial cells.

    Science.gov (United States)

    Shi, H B; Du, Y; Zhang, C H; Sun, C; He, Y L; Wu, Y H; Liu, J X; Luo, J; Loor, J J

    2018-02-14

    Increased production of long-chain unsaturated fatty acids (LCUFA) can have a positive effect on the nutritional value of ruminant milk for human consumption. In nonruminant species, fatty acid elongase 5 (ELOVL5) is a key enzyme for endogenous synthesis of long-chain unsaturated fatty acids. However, whether ELOVL5 protein plays a role (if any) in ruminant mammary tissue remains unclear. In the present study, we assessed the mRNA abundance of ELOVL5 at 3 stages of lactation in goat mammary tissue. Results revealed that ELOVL5 had the lowest expression at peak lactation compared with the nonlactating and late-lactating periods. The ELOVL5 was overexpressed or knocked down to assess its role in goat mammary epithelial cells. Results revealed that ELOVL5 overexpression increased the expression of perilipin2 (PLIN2) and decreased diacylglycerolacyltransferase 2 (DGAT2) and fatty acid desaturase 2 (FADS2) mRNA, but had no effect on the expression of DGAT1, FADS1, and stearoyl-CoA desaturase 1 (SCD1). Overexpression of ELOVL5 decreased the concentration of C16:1n-7, whereas no significant change in C18:1n-7 and C18:1n-9 was observed. Knockdown of ELOVL5 decreased the expression of PLIN2 but had no effect on DGAT1, DGAT2, FADS1, FADS2, and SCD1 mRNA expression. Knockdown of ELOVL5 increased the concentration of C16:1n-7 and decreased that of C18:1n-7. The alterations of expression of genes related to lipid metabolism after overexpression or knockdown of ELOVL5 suggested a negative feedback regulation by the products of ELOVL5 activation. However, the content of triacylglycerol was not altered by knockdown or overexpression of ELOVL5 in goat mammary epithelial cells, which might have been due to the insufficient availability of substrate in vitro. Collectively, these are the first in vitro results highlighting an important role of ELOVL5 in the elongation of 16-carbon to 18-carbon unsaturated fatty acids in ruminant mammary cells. Copyright © 2018 American Dairy Science

  20. Prenatal Exposure of Cypermethrin Induces Similar Alterations in Xenobiotic-Metabolizing Cytochrome P450s and Rate-Limiting Enzymes of Neurotransmitter Synthesis in Brain Regions of Rat Offsprings During Postnatal Development.

    Science.gov (United States)

    Singh, Anshuman; Mudawal, Anubha; Maurya, Pratibha; Jain, Rajeev; Nair, Saumya; Shukla, Rajendra K; Yadav, Sanjay; Singh, Dhirendra; Khanna, Vinay Kumar; Chaturvedi, Rajnish Kumar; Mudiam, Mohana K R; Sethumadhavan, Rao; Siddiqi, Mohammad Imran; Parmar, Devendra

    2016-08-01

    Oral administration of low doses of cypermethrin to pregnant Wistar rats led to a dose-dependent differences in the induction of xenobiotic-metabolizing cytochrome P450s (CYPs) messenger RNA (mRNA) and protein in brain regions isolated from the offsprings postnatally at 3 weeks that persisted up to adulthood. Similar alterations were observed in the expression of rate-limiting enzymes of neurotransmitter synthesis in brain regions of rat offsprings. These persistent changes were associated with alterations in circulating levels of growth hormone (GH), cognitive functions, and accumulation of cypermethrin and its metabolites in brain regions of exposed offsprings. Though molecular docking studies failed to identify similarities between the docked conformations of cypermethrin with CYPs and neurotransmitter receptors, in silico analysis identified regulatory sequences of CYPs in the promoter region of rate-limiting enzymes of neurotransmitter synthesis. Further, rechallenge of the prenatally exposed offsprings at adulthood with cypermethrin (p.o. 10 mg/kg × 6 days) led to a greater magnitude of alterations in the expression of CYPs and rate-limiting enzymes of neurotransmitter synthesis in different brain regions. These alterations were associated with a greater magnitude of decrease in the circulating levels of GH and cognitive functions in rechallenged offsprings. Our data has led us to suggest that due to the immaturity of CYPs in fetus or during early development, even the low-level exposure of cypermethrin may be sufficient to interact with the CYPs, which in turn affect the neurotransmission processes and may help in explaining the developmental neurotoxicity of cypermethrin.

  1. The Timing of Multiple Retrieval Events Can Alter GluR1 Phosphorylation and the Requirement for Protein Synthesis in Fear Memory Reconsolidation

    Science.gov (United States)

    Jarome, Timothy J.; Kwapis, Janine L.; Werner, Craig T.; Parsons, Ryan G.; Gafford, Georgette M.; Helmstetter, Fred J.

    2012-01-01

    Numerous studies have indicated that maintaining a fear memory after retrieval requires de novo protein synthesis. However, no study to date has examined how the temporal dynamics of repeated retrieval events affect this protein synthesis requirement. The present study varied the timing of a second retrieval of an established auditory fear memory…

  2. Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells

    Science.gov (United States)

    Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

    2016-01-01

    Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells. PMID:26943035

  3. Alterations induced by x-rays and ultraviolet light on the synthesis and maintenance of macromolecular components within cells. Progress report, March 1, 1975--February 1, 1976

    International Nuclear Information System (INIS)

    Billen, D.

    1976-01-01

    Progress is reported on the following research projects: role of DNA polymerases and DNA ligase in repair synthesis in Escherichia coli and Bacillus subtilis following exposure to x radiation; effects of Tween-80 on permeability of hamster ovary cells to nucleotides; effects of uv radiation on DNA metabolism in B. subtilis; and studies on the nature of repair-deficient mutants of B. subtilis

  4. Salsalate and Adiponectin Improve Palmitate-Induced Insulin Resistance via Inhibition of Selenoprotein P through the AMPK-FOXO1α Pathway.

    Directory of Open Access Journals (Sweden)

    Tae Woo Jung

    Full Text Available Selenoprotein P (SeP was recently identified as a hepatokine that induces insulin resistance (IR in rodents and humans. Recent clinical trials have shown that salsalate, a prodrug of salicylate, significantly lowers blood glucose levels and increases adiponectin concentrations. We examined the effects of salsalate and full length-adiponectin (fAd on the expression of SeP under hyperlipidemic conditions and explored their regulatory mechanism on SeP. In palmitate-treated HepG2 cells as well as high fat diet (HFD-fed male Spraque Dawley (SD rats and male db/db mice, SeP expression and its regulatory pathway, including AMPK-FOXO1α, were evaluated after administration of salsalate and salicylate. Palmitate treatment significantly increased SeP expression and aggravated IR, while knock-down of SeP by siRNA restored these changes in HepG2 cells. Palmitate-induced SeP expression was inhibited by both salsalate and salicylate, which was mediated by AMPK activation, and was blocked by AMPK siRNA or an inhibitor of AMPK. Chromatin immunoprecipitation (ChIP and electrophoretic mobility shift (EMSA assay showed that salsalate suppressed SeP expression by AMPK-mediated phosphorylation of FOXO1α. Moreover, fAd also reduced palmitate-induced SeP expression through the activation of AMPK, which results in improved IR. Both salsalate and salicylate treatment significantly improved glucose intolerance and insulin sensitivity, accompanied by reduced SeP mRNA and protein expression in HFD-fed rats and db/db mice, respectively. Taken together, we found that salsalate and adiponectin ameliorated palmitate-induced IR in hepatocytes via SeP inhibition through the AMPK-FOXO1α pathway. The regulation of SeP might be a novel mechanism mediating the anti-diabetic effects of salsalate and adiponectin.

  5. Up-regulation of selenoprotein P and HIP/PAP mRNAs in hepatocytes by intermittent hypoxia via down-regulation of miR-203

    Directory of Open Access Journals (Sweden)

    Tomoko Uchiyama

    2017-09-01

    Full Text Available Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH] and is a risk factor for insulin resistance/type 2 diabetes. However, the mechanisms linking IH stress and insulin resistance remain elusive. We exposed human hepatocytes (JHH5, JHH7, and HepG2 to experimental IH or normoxia for 24 h, measured mRNA levels by real-time reverse transcription polymerase chain reaction (RT-PCR, and found that IH significantly increased the mRNA levels of selenoprotein P (SELENOP — a hepatokine — and hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP — one of REG (Regenerating gene family. We next investigated promoter activities of both genes and discovered that they were not increased by IH. On the other hand, a target mRNA search of micro RNA (miRNA revealed that both mRNAs have a potential target sequence for miR-203. The miR-203 level of IH-treated cells was significantly lower than that of normoxia-treated cells. Thus, we introduced miR-203 inhibitor and a non-specific control RNA (miR-203 inhibitor NC into HepG2 cells and measured the mRNA levels of SELENOP and HIP/PAP. The IH-induced expression of SELENOP and HIP/PAP was abolished by the introduction of miR-203 inhibitor but not by miR-203 inhibitor NC. These results demonstrate that IH stress up-regulates the levels of SELENOP in human hepatocytes to accelerate insulin resistance and up-regulates the levels of HIP/PAP mRNAs to proliferate such hepatocytes, via the miR-203 mediated mechanism.

  6. Di(2-ethylhexyl)phthalate Alters the Synthesis and β-Oxidation of Fatty Acids and Hinders ATP Supply in Mouse Testes via UPLC-Q-Exactive Orbitrap MS-Based Metabonomics Study.

    Science.gov (United States)

    Shen, Guolin; Zhou, Lili; Liu, Wei; Cui, Yuan; Xie, Wenping; Chen, Huiming; Yu, Wenlian; Li, Wentao; Li, Haishan

    2017-06-21

    Di(2-ethylhexyl) phthalate (DEHP) is considered to be an environmental endocrine disruptor at high levels of general exposure. Studies show that DEHP may cause testicular toxicity on human being. In this study, metabonomics techniques were used to identify differential endogenous metabolites, draw the network metabolic pathways, and conduct network analysis, to determine the underlying mechanisms of testicular toxicity induced by DEHP. The results showed that DEHP inhibited synthesis and accelerated β-oxidation of fatty acids and impaired the tricarboxylic acid cycle (TCA cycle) and gluconeogenesis, resulting in lactic acid accumulation and an insufficient ATP supply in the microenvironment of the testis. These alterations led to testicular atrophy and, thus, may be the underlying causes of testicular toxicity. DEHP also inhibited peroxisome proliferator activated receptors in the testis, which may be another potential reason for the testicular atrophy. These findings provided new insights to better understand the mechanisms of testicular toxicity induced by DEHP exposure.

  7. Synthesis of [13C4]-labeled ∆9-Tetrahydrocannabinol and 11-nor-9-Carboxy-∆9-tetrahydrocannabinol as Internal Standards for Reducing Ion Suppressing/Alteration Effects in LC/MS-MS Quantification

    Directory of Open Access Journals (Sweden)

    Morten Karlsen

    2014-09-01

    Full Text Available (−-∆9-Tetrahydrocannabinol is the principal psychoactive component of the cannabis plant and also the active ingredient in some prescribed drugs. To detect and control misuse and monitor administration in clinical settings, reference samples of the native drugs and their metabolites are needed. The accuracy of liquid chromatography/mass spectrometric quantification of drugs in biological samples depends among others on ion suppressing/alteration effects. Especially, 13C-labeled drug analogues are useful for minimzing such interferences. Thus, to provide internal standards for more accurate quantification and for identification purpose, synthesis of [13C4]-∆9-tetrahydro-cannabinol and [13C4]-11-nor-9-carboxy-∆9-tetrahydrocannabinol was developed via [13C4]-olivetol. Starting from [13C4]-olivetol the synthesis of [13C4]-11-nor-9-carboxy-∆9-tetrahydrocannabinol was shortened from three to two steps by employing nitromethane as a co-solvent in condensation with (+-apoverbenone.

  8. Momordica charantia ameliorates insulin resistance and dyslipidemia with altered hepatic glucose production and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice.

    Science.gov (United States)

    Shih, Chun-Ching; Shlau, Min-Tzong; Lin, Cheng-Hsiu; Wu, Jin-Bin

    2014-03-01

    Momordica charantia Linn. (Cucurbitaceae) fruit is commonly known as bitter melon. C57BL/6J mice were firstly divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% high-fat (HF) diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and still on HF diet and was given orally M. charantia extract (MCE) or rosiglitazone (Rosi) or not for 4 weeks. M. charantia decreased the weights of visceral fat and caused glucose lowering. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. MCE significantly increases the hepatic protein contents of AMPK phosphorylation by 126.2-297.3% and reduces expression of phosphenolpyruvate carboxykinase (PEPCK) and glucose production. Most importantly, MCE decreased expression of hepatic 11beta hydroxysteroid dehydroxygenase (11beta-HSD1) gene, which contributed in attenuating diabetic state. Furthermore, MCE lowered serum triglycerides (TGs) by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein 1c and fatty acid synthase mRNA leading to reduction in TGs synthesis. This study demonstrates M. charantia ameliorates diabetic and hyperlipidemic state in HF-fed mice occurred by regulation of hepatic PEPCK, 11beta-HSD1 and AMPK phosphorylation. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Directory of Open Access Journals (Sweden)

    Mafu Akier

    2002-01-01

    Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

  10. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Science.gov (United States)

    St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH

    2002-01-01

    Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344

  11. Transcriptomic analysis of tomato carpel development reveals alterations in ethylene and gibberellin synthesis during pat3/pat4 parthenocarpic fruit set

    Directory of Open Access Journals (Sweden)

    Pascual Laura

    2009-05-01

    Full Text Available Abstract Background Tomato fruit set is a key process that has a great economic impact on crop production. We employed the Affymetrix GeneChip Tomato Genome Array to compare the transcriptome of a non-parthenocarpic line, UC82, with that of the parthenocarpic line RP75/59 (pat3/pat4 mutant. We analyzed the transcriptome under normal conditions as well as with forced parthenocarpic development in RP75/59, emasculating the flowers 2 days before anthesis. This analysis helps to understand the fruit set in tomato. Results Differentially expressed genes were extracted with maSigPro, which is designed for the analysis of single and multiseries time course microarray experiments. 2842 genes showed changes throughout normal carpel development and fruit set. Most of them showed a change of expression at or after anthesis. The main differences between lines were concentrated at the anthesis stage. We found 758 genes differentially expressed in parthenocarpic fruit set. Among these genes we detected cell cycle-related genes that were still activated at anthesis in the parthenocarpic line, which shows the lack of arrest in the parthenocarpic line at anthesis. Key genes for the synthesis of gibberellins and ethylene, which were up-regulated in the parthenocarpic line were also detected. Conclusion Comparisons between array experiments determined that anthesis was the most different stage and the key point at which most of the genes were modulated. In the parthenocarpic line, anthesis seemed to be a short transitional stage to fruit set. In this line, the high GAs contends leads to the development of a parthenocarpic fruit, and ethylene may mimic pollination signals, inducing auxin synthesis in the ovary and the development of a jelly fruit.

  12. Transcriptomic analysis of tomato carpel development reveals alterations in ethylene and gibberellin synthesis during pat3/pat4 parthenocarpic fruit set.

    Science.gov (United States)

    Pascual, Laura; Blanca, Jose M; Cañizares, Joaquin; Nuez, Fernado

    2009-05-29

    Tomato fruit set is a key process that has a great economic impact on crop production. We employed the Affymetrix GeneChip Tomato Genome Array to compare the transcriptome of a non-parthenocarpic line, UC82, with that of the parthenocarpic line RP75/59 (pat3/pat4 mutant). We analyzed the transcriptome under normal conditions as well as with forced parthenocarpic development in RP75/59, emasculating the flowers 2 days before anthesis. This analysis helps to understand the fruit set in tomato. Differentially expressed genes were extracted with maSigPro, which is designed for the analysis of single and multiseries time course microarray experiments. 2842 genes showed changes throughout normal carpel development and fruit set. Most of them showed a change of expression at or after anthesis. The main differences between lines were concentrated at the anthesis stage. We found 758 genes differentially expressed in parthenocarpic fruit set. Among these genes we detected cell cycle-related genes that were still activated at anthesis in the parthenocarpic line, which shows the lack of arrest in the parthenocarpic line at anthesis. Key genes for the synthesis of gibberellins and ethylene, which were up-regulated in the parthenocarpic line were also detected. Comparisons between array experiments determined that anthesis was the most different stage and the key point at which most of the genes were modulated. In the parthenocarpic line, anthesis seemed to be a short transitional stage to fruit set. In this line, the high GAs contends leads to the development of a parthenocarpic fruit, and ethylene may mimic pollination signals, inducing auxin synthesis in the ovary and the development of a jelly fruit.

  13. Association study of polymorphisms in selenoprotein genes and Kashin-Beck disease and serum selenium/iodine concentration in a Tibetan population.

    Directory of Open Access Journals (Sweden)

    Lulin Huang

    Full Text Available BACKGROUND: Kashin-Beck disease is a kind of degenerative osteoarthropathy. Genetic factors may play an important role in the pathogenesis of KBD. OBJECTIVE: To investigate the association of the selenoprotein genes GPX1 (rs1050450, rs1800668, and rs3811699, TrxR2 (rs5748469, and DIO2 (rs225014 with Kashin-Beck disease (KBD in a Tibetan population and to investigate the association of these SNPs with the serum iodine/selenium concentration in the Tibetan population. DESIGN: Five SNPs including rs1050450, rs1800668, and rs3811699 in the GPX1 gene, rs5748469 in the TrxR2 gene, and rs225014 in the DIO2 gene were analyzed in Tibetan KBD patients and controls using the SNaPshot method. P trend values of the SNPs were calculated using an additive model. RESULTS: None of the five SNPs in the three genes showed a significant association with KBD. Haplotypes TCC, TTC and TTT of rs1050450, rs1800668 and rs3811699 in GPX1 showed a significant association with KBD and controls with P value of 0.0421, 5.0E-4 and 0.0066, respectively. The GPX1 gene (rs1050450 showed a potential significant association with the iodine concentration in the Tibetan study population (P = 0.02726. However, no such association was detected with the selenium concentration (P = 0.2849. CONCLUSIONS: In this study, we showed that single SNPs in the genes GPX1 (rs1050450, rs1800668 and rs3811699, TrxR2 (rs5748469, and DIO2 (rs225014 may not be significantly associated with KBD in a Tibetan population. However, haplotype analysis of SNPs rs1050450, rs1800668 and rs3811699 in GPX1 gene showed a significant association with KBD. The results suggested that GPX1 gene play a protective role in the susceptivity of KBD in Tibetans. Furthermore, the GPX1 gene (rs1050450 may be significantly associated with the serum iodine concentration in Tibetans.

  14. Increased signaling by the autism-related Engrailed-2 protein enhances dendritic branching and spine density, alters synaptic structural matching, and exaggerates protein synthesis.

    Directory of Open Access Journals (Sweden)

    Asma Soltani

    Full Text Available Engrailed 1 (En1 and 2 (En2 code for closely related homeoproteins acting as transcription factors and as signaling molecules that contribute to midbrain and hindbrain patterning, to development and maintenance of monoaminergic pathways, and to retinotectal wiring. En2 has been suggested to be an autism susceptibility gene and individuals with autism display an overexpression of this homeogene but the mechanisms remain unclear. We addressed in the present study the effect of exogenously added En2 on the morphology of hippocampal cells that normally express only low levels of Engrailed proteins. By means of RT-qPCR, we confirmed that En1 and En2 were expressed at low levels in hippocampus and hippocampal neurons, and observed a pronounced decrease in En2 expression at birth and during the first postnatal week, a period characterized by intense synaptogenesis. To address a putative effect of Engrailed in dendritogenesis or synaptogenesis, we added recombinant En1 or En2 proteins to hippocampal cell cultures. Both En1 and En2 treatment increased the complexity of the dendritic tree of glutamatergic neurons, but only En2 increased that of GABAergic cells. En1 increased the density of dendritic spines both in vitro and in vivo. En2 had similar but less pronounced effect on spine density. The number of mature synapses remained unchanged upon En1 treatment but was reduced by En2 treatment, as well as the area of post-synaptic densities. Finally, both En1 and En2 elevated mTORC1 activity and protein synthesis in hippocampal cells, suggesting that some effects of Engrailed proteins may require mRNA translation. Our results indicate that Engrailed proteins can play, even at low concentrations, an active role in the morphogenesis of hippocampal cells. Further, they emphasize the over-regulation of GABA cell morphology and the vulnerability of excitatory synapses in a pathological context of En2 overexpression.

  15. Increased signaling by the autism-related Engrailed-2 protein enhances dendritic branching and spine density, alters synaptic structural matching, and exaggerates protein synthesis.

    Science.gov (United States)

    Soltani, Asma; Lebrun, Solène; Carpentier, Gilles; Zunino, Giulia; Chantepie, Sandrine; Maïza, Auriane; Bozzi, Yuri; Desnos, Claire; Darchen, François; Stettler, Olivier

    2017-01-01

    Engrailed 1 (En1) and 2 (En2) code for closely related homeoproteins acting as transcription factors and as signaling molecules that contribute to midbrain and hindbrain patterning, to development and maintenance of monoaminergic pathways, and to retinotectal wiring. En2 has been suggested to be an autism susceptibility gene and individuals with autism display an overexpression of this homeogene but the mechanisms remain unclear. We addressed in the present study the effect of exogenously added En2 on the morphology of hippocampal cells that normally express only low levels of Engrailed proteins. By means of RT-qPCR, we confirmed that En1 and En2 were expressed at low levels in hippocampus and hippocampal neurons, and observed a pronounced decrease in En2 expression at birth and during the first postnatal week, a period characterized by intense synaptogenesis. To address a putative effect of Engrailed in dendritogenesis or synaptogenesis, we added recombinant En1 or En2 proteins to hippocampal cell cultures. Both En1 and En2 treatment increased the complexity of the dendritic tree of glutamatergic neurons, but only En2 increased that of GABAergic cells. En1 increased the density of dendritic spines both in vitro and in vivo. En2 had similar but less pronounced effect on spine density. The number of mature synapses remained unchanged upon En1 treatment but was reduced by En2 treatment, as well as the area of post-synaptic densities. Finally, both En1 and En2 elevated mTORC1 activity and protein synthesis in hippocampal cells, suggesting that some effects of Engrailed proteins may require mRNA translation. Our results indicate that Engrailed proteins can play, even at low concentrations, an active role in the morphogenesis of hippocampal cells. Further, they emphasize the over-regulation of GABA cell morphology and the vulnerability of excitatory synapses in a pathological context of En2 overexpression.

  16. A novel FC116/BC10 mutation distinctively causes alteration in the expression of the genes for cell wall polymer synthesis in rice

    Directory of Open Access Journals (Sweden)

    Mingliang Zhang

    2016-09-01

    Full Text Available We report isolation and characterization of a fragile culm mutant fc116 that displays reduced mechanical strength caused by decreased cellulose content and altered cell wall structure in rice. Map-based cloning revealed that fc116 was a base substitution mutant (G to A in a putative beta-1,6-N-acetylglucosaminyltransferase (C2GnT gene (LOC_Os05g07790, allelic to BC10. This mutation resulted in one amino acid missing within a newly-identified protein motif R, RXG, RA. The FC116/BC10 gene was lowly but ubiquitously expressed in the all tissues examined across the whole life cycle of rice, and slightly down-regulated during secondary growth. This mutant also exhibited a significant increase in the content of hemicelluloses and lignins, as well as the content of pentoses (xylose and arabinose. But the content of hexoses (glucose, mannose and galactose was decreased in both cellulosic and non-cellulosic (pectins and hemicelluloses fractions of the mutant. Transcriptomic analysis indicated that the typical genes in the fc116 mutant were up-regulated corresponding to xylan biosynthesis, as well as lignin biosynthesis including p-hydroxyphenyl (H, syringyl (S and guaiacyl (G. Our results indicate that FC116 has universal function in regulation of the cell wall polymers in rice.

  17. Rational design and synthesis of altered peptide ligands based on human myelin oligodendrocyte glycoprotein 35-55 epitope: inhibition of chronic experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Tselios, Theodore; Aggelidakis, Mihalis; Tapeinou, Anthi; Tseveleki, Vivian; Kanistras, Ioannis; Gatos, Dimitrios; Matsoukas, John

    2014-11-04

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35-55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR) contact residues of the human MOG35-55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35-55 peptide at the time of immunization.

  18. Green synthesis of anticancerous honeycomb PtNPs clusters: Their alteration effect on BSA and HsDNA using fluorescence probe.

    Science.gov (United States)

    Pansare, Amol V; Kulal, Dnyaneshwar K; Shedge, Amol A; Patil, Vishwanath R

    2016-09-01

    The screening and characterization of cancer cells has been challenging due to sample insufficiency and extravagant. In this article, we highlighted easy green synthesis of Platinum nanoparticles (PtNPs) in the honeycomb like clusters, and their optical properties (by HRTEM, XRD, DLS, Zeta potential, EDAX, and UV-Visible techniques). PtNPs were responsive of binding mechanisms with the bovine serum albumin (BSA), herring sperm deoxyribonucleic acid (HsDNA) and cytotoxicity of human carcinomas cell. We are able to elucidate the responses of various concentrations of PtNPs for the control of MDA-MB-468 cell and binding conformation of BSA and HsDNA by using multi-spectroscopic techniques under the physiological conditions. The extent of quenching was in agreement of PtNPs-BSA binding reaction was mainly a static. The Ksv, K, the number of binding sites at different temperatures and the thermodynamic parameters between BSA and PtNPs were calculated. The positive ΔS(0) and negative ΔH(0), ΔG(0) values indicated that the binding pattern was determined by spontaneous hydrogen bond electrostatic interaction of BSA with esterage like activity. The binding properties of the PtNPs with HsDNA have been investigated by thermal denaturation, competitive DNA-binding studies with ethidium bromide (EB), Hochest-33258 and relative viscosity. The negative ΔH(0), ΔS(0) and ΔG(0) values indicated that the hydrophilic interaction were main force in spontaneity in binding mechanism of PtNPs to HsDNA. GI50 value of PtNPs demonstrated that these nanoparticles showed cytotoxicity against MDA-MB-468 human breast cancer cell line. Our results also clarified that PtNPs bind to BSA and can be effectively transported in the body and eliminated. PtNPs showed minor groove binding with HsDNA, which could be a useful guideline for further versatile approach to develop biomedical coatings with different functions of drug design. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Synthesis, in vitro and in vivo small-animal SPECT evaluation of novel technetium labeled bile acid analogues to study (altered) hepatic transporter function

    International Nuclear Information System (INIS)

    Neyt, Sara; Vliegen, Maarten; Verreet, Bjorn; De Lombaerde, Stef; Braeckman, Kim; Vanhove, Christian; Huisman, Maarten Thomas; Dumolyn, Caroline; Kersemans, Ken; Hulpia, Fabian; Van Calenbergh, Serge; Mannens, Geert; De Vos, Filip

    2016-01-01

    Introduction: Hepatobiliary transport mechanisms are crucial for the excretion of substrate toxic compounds. Drugs can inhibit these transporters, which can lead to drug–drug interactions causing toxicity. Therefore, it is important to assess this early during the development of new drug candidates. The aim of the current study is the (radio)synthesis, in vitro and in vivo evaluation of a technetium labeled chenodeoxycholic and cholic acid analogue: [ 99m Tc]-DTPA-CDCA and [ 99m ]Tc-DTPA-CA, respectively, as biomarker for disturbed transporter functionality. Methods: [99mTc]-DTPA-CDCA([ 99m Tc]-3a) and [99mTc]-DTPA-CA ([ 99m Tc]-3b) were synthesized and evaluated in vitro and in vivo. Uptake of both tracers was investigated in NTCP, OCT1, OATP1B1, OATP1B3 transfected cell lines. K m and V max values were determined and compared to [ 99m Tc]-mebrofenin ([ 99m Tc]-MEB). Efflux was investigated by means of CTRL, MRP2 and BSEP transfected inside-out vesicles. Metabolite analysis was performed using pooled human liver S9. Wild type (n = 3) and rifampicin treated (n = 3) mice were intravenously injected with 37 MBq of tracer. After dynamic small-animal SPECT and short CT acquisitions, time–activity curves of heart, liver, gallbladder and intestines were obtained. Results: We demonstrated that OATP1B1 and OATP1B3 are the involved uptake transporters of both compounds. Both tracers show a higher affinity compared to [ 99m Tc]-MEB, but are in a similar range as endogenous bile acids for OATP1B1 and OATP1B3. [ 99m Tc]-3a shows higher affinities compared to [ 99m Tc]-3b. V max values were lower compared to [ 99m Tc]-MEB, but in the same range as endogenous bile acids. MRP2 was identified as efflux transporter. Less than 7% of both radiotracers was metabolized in the liver. In vitro results were confirmed by in vivo results. Uptake in the liver and efflux to gallbladder + intestines and urinary bladder of both tracers was observed. Transport was inhibited by rifampicin

  20. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  1. Selenium and chronic diseases: a nutritional genomics perspective.

    Science.gov (United States)

    Méplan, Catherine

    2015-05-15

    Mechanistic data have revealed a key role for selenium (Se) and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP) altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk.

  2. Selenium and Chronic Diseases: A Nutritional Genomics Perspective

    Directory of Open Access Journals (Sweden)

    Catherine Méplan

    2015-05-01

    Full Text Available Mechanistic data have revealed a key role for selenium (Se and selenoproteins in biological pathways known to be altered in multifactorial diseases, such as cellular maintenance, response to oxidative stress and correct protein folding. Although epidemiological studies indicate that low Se intake is linked to increased risk for various chronic diseases, supplementation trials have given confusing outcomes, suggesting that additional genetic factors could affect the relationship between Se and health. Genetic data support this hypothesis, as risk for several chronic diseases, in particular cancer, was linked to a number of single nucleotide polymorphisms (SNP altering Se metabolism, selenoprotein synthesis or activity. Interactions between SNPs in selenoprotein genes, SNPs in related molecular pathways and biomarkers of Se status were found to further modulate the genetic risk carried by the SNPs. Taken together, nutritional genomics approaches uncovered the potential implication of some selenoproteins as well as the influence of complex interactions between genetic variants and Se status in the aetiology of several chronic diseases. This review discusses the results from these genetic associations in the context of selenoprotein functions and epidemiological investigations and emphasises the need to assess in future studies the combined contribution of Se status, environmental stress, and multiple or individual SNPs to disease risk.

  3. Genistein Precipitated Hypothyroidism, Altered Leptin and C ...

    African Journals Online (AJOL)

    Genistein Precipitated Hypothyroidism, Altered Leptin and C-Reactive Protein Synthesis in Pregnant Rats. ... Thyroid hormone, C-reactive protein (CRP) and leptin assay was carried using the blood samples. Leptin was also assayed in the placenta and amniotic fluid supernatant. Oral exposure of pregnant rats to genistein ...

  4. Organic synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, S.E.

    1991-01-01

    This paper reports on reactions of organoboranes. Organoboron routes to unsaturated hydrocarbons. Boronic ester homologation. Properties of organosilicon compounds. Alkene synthesis (Peterson olefination). Allylsilanes and acylsilanes.

  5. Fire Synthesis

    Indian Academy of Sciences (India)

    1000ºC or special infrastructure which require careful maintenance. In such a situation fire synthesis is a simpler method that can be adopted for the bulk production of high purity alumina and related oxides. Fire Synthesis. Preparation of Alumina ...

  6. Effects of combined treatment of α-tocopherol, L-ascorbic acid, selenium and zinc on bleomycin, etoposide and cisplatin-induced alterations in testosterone synthesis pathway in rats.

    Science.gov (United States)

    Kilarkaje, Narayana

    2014-12-01

    To investigate the effects of therapeutically relevant dose levels of bleomycin, etoposide and cisplatin (BEP) on testicular steroidogenic enzymes, and possible protective effects of an antioxidant cocktail (AC). Adult Sprague-Dawley rats received BEP with or without the AC (α-tocopherol, L-ascorbic acid, selenium and zinc) for either (a) 4 days (short term; 1.5, 15 and 3 mg/kg), or (b) three cycles of 21 days each (0.75, 7.5 and 1.5 mg/kg), or (c) the three cycles with a 63-day recovery period. The expression of steroidogenic enzymes were measured in the testes by Western blotting and immunofluorescent labeling. The short-term BEP exposure resulted in a decrease in scavenger receptor class-B1 and an increase in luteinizing hormone receptor (LHR). The AC with or without BEP has increased the levels of LHR, 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD, but without significant changes in testosterone levels. The three cycles of BEP up-regulated the expression of steroidogenic acute regulatory protein (StAR) and down-regulated that of cholesterol side chain cleavage enzyme (P450scc), cytochrome p450 17A1 (Cyp17A1, recovered by the AC) and 17β-HSD, associated with significant reduction in testosterone levels. The three cycles with the recovery time led to decreases in LHR, StAR, P450scc and Cyp17A1 and increases in 3β-HSD and 17β-HSD. The AC did not enhance the recovery of the enzyme levels. The three cycles of BEP treatment inhibit the testosterone synthesis pathway even after the recovery time. The AC recovers the effects of BEP chemotherapy on a few steroidogenic enzymes.

  7. Organic synthesis

    International Nuclear Information System (INIS)

    Lallemand, J.Y.; Fetizon, M.

    1988-01-01

    The 1988 progress report of the Organic Synthesis Chemistry laboratory (Polytechnic School, France), is presented. The laboratory activities are centered on the chemistry of natural products, which have a biological activity and on the development of new reactions, useful in the organic synthesis. The research works involve the following domains: the natural products chemistry which are applied in pharmacology, the plants and insects chemistry, the organic synthesis, the radical chemistry new reactions and the bio-organic physicochemistry. The published papers, the congress communications and the thesis are listed [fr

  8. Hypoxia. 3. Hypoxia and neurotransmitter synthesis

    OpenAIRE

    Kumar, Ganesh K.

    2011-01-01

    Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/modulators is regulated by O2-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O2 homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hyp...

  9. Radiation protection philosophy alters

    International Nuclear Information System (INIS)

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  10. Predictive Mathematical Model for Polyhydroxybutyrate Synthesis in Escherichia coli

    OpenAIRE

    Dixon, Angela

    2011-01-01

    Polyhydroxybutyrate has been studied as a potential biodegradable replacement for petrochemical plastics. Polyhydroxybutyrate synthesis is not native to Escherichia coli, but the genes have successfully been inserted through plasmids. However, polyhydroxybutyrate production needs to be more cost-effective before it can be commercially produced. A mathematical model for polyhydroxybutyrate synthesis was developed to identify genes that could be altered to increase polyhydroxybutyrate productio...

  11. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  12. Fire Synthesis

    Indian Academy of Sciences (India)

    her PhD degree from. Bangalore University. She is currently working as a Research Associate at the Department of. Inorganic and Physical. Chemistry, Indian. Institute of Science,. Bangalore, on the synthesis of .... This method uses the experiences of propellant chemistry in making the redox mixture. The . stoichiometry or ...

  13. Fire Synthesis

    Indian Academy of Sciences (India)

    special infrastructure which require careful maintenance. In such situation fire synthesis is a simpler method that can be adopted for the bulk production of high purity .... reaction between Ti and B to form titanium boride. The reaction between titanium (fuel- electron donor) and boron (oxidiser-electron acceptor) once initiated ...

  14. Fire Synthesis

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 12. Fire Synthesis - Preparation of Alumina Products. Tanu Mimani. Volume 16 Issue 12 December 2011 pp 1324-1332. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/016/12/1324-1332 ...

  15. Fire Synthesis

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 2. Fire Synthesis - Preparation of Alumina Products. Tanu Mimani. General Article Volume 5 Issue 2 February 2000 pp 50-57. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/005/02/0050-0057 ...

  16. Altered protein mannosylation in developing cerebral cortex by streptomycin.

    Science.gov (United States)

    Alperin, M D; Calandria, J M; Carminatti, H; Idoyaga-Vargas, V P

    2000-11-09

    Our research objective was to characterize the biochemical effect of streptomycin during postnatal rat cerebral cortex development using a sensitive method that preserves the in situ topological relationship. We found a decrease in the mannosylation of asparagine-linked oligosaccharides without affecting polypeptide synthesis, DNA synthesis or glucose and mannose disappearance from the medium in mini-tissue units derived from P5. In addition, the rate of Dolp-GlcNAc2 Man9 Glc3 synthesis and the oligosaccharide protein transferase activity did not change in the presence of the aminoglycoside. These findings strongly suggested that the alteration of protein mannosylation occurred downstream of G3 transfer to nascent polypeptides. Further, the mini-tissue units may be useful for the assessment of neurological toxicity of antibacterial agents.

  17. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  18. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    Science.gov (United States)

    2016-09-01

    trophic factor for the fetal brain before it acts as a neurotransmitter . 5-HT signaling modulates fetal brain wiring mechanisms and its disruption at...metabolism in the placenta, and consequently placental 5-HT synthesis , may directly affect fetal brain development and constitute a new molecular...Aim I: To determine whether maternal inflammation alters placental synthesis and fetal exposure to 5-HT and kynurenine-pathway compounds. This

  19. SELENIUM SUBSTITUTION – EFFECT ON THYROID FUNCTION

    Directory of Open Access Journals (Sweden)

    Milica Pešić

    2015-03-01

    Full Text Available The understanding of the essential role of selenium (Se in thyroid hormone synthesis, metabolism and action, as well as normal thyroid function, increased during the past decades. The thyroid gland is among the human tissues with the highest Se content per mas unit, similar to other endocrine organs and brain. Biological actions of Se are mediated, in most cases, through the expression of at least 30 selenoproteins coded by 25 selenoprotein genes in the human. Via the selenoproteins, selenium can influence the cell function through antioxidant activites, modifying redox status and thyroid hormone synthesis and metabolism. Selenoproteins iodothyronine deiodinases are present in most tissues and have a role to increase the production of bioactive tri-iodothyronine. Futhermore, Se has been shown to be important in the regulation of immune function. Se deficiency is accompained by the loss of immune competence. The links between Se deficiency, altered immune function and inflamation have prompted studies in humans to examine if Se suplementation can modify auto-antibodies production in patients with chronic autoimmune thyroiditis. Until now, several randomised prospective clinical trials have been performed in patients with established chronic autoimmune thyrioditis. The clinical endpoint of each study was the decrease in TPO antibodies concentration after 3-12 months of treatment. Ussualy, the dosage of daily Se supplementation was 200µg. Selenium suplemetation had no significant effect on the concentration of TSH or thyroid hormone concentrations. These studies indicate that Se treatment result in reduced inflammatory activity, but it does not cure chronc autoimmune process.

  20. Altered Perspectives: Immersive Environments

    Science.gov (United States)

    Shipman, J. S.; Webley, P. W.

    2016-12-01

    Immersive environments provide an exciting experiential technology to visualize the natural world. Given the increasing accessibility of 360o cameras and virtual reality headsets we are now able to visualize artistic principles and scientific concepts in a fully immersive environment. The technology has become popular for photographers as well as designers, industry, educational groups, and museums. Here we show a sci-art perspective on the use of optics and light in the capture and manipulation of 360o images and video of geologic phenomena and cultural heritage sites in Alaska, England, and France. Additionally, we will generate intentionally altered perspectives to lend a surrealistic quality to the landscapes. Locations include the Catacombs of Paris, the Palace of Versailles, and the Northern Lights over Fairbanks, Alaska. Some 360o view cameras now use small portable dual lens technology extending beyond the 180o fish eye lens previously used, providing better coverage and image quality. Virtual reality headsets range in level of sophistication and cost, with the most affordable versions using smart phones and Google Cardboard viewers. The equipment used in this presentation includes a Ricoh Theta S spherical imaging camera. Here we will demonstrate the use of 360o imaging with attendees being able to be part of the immersive environment and experience our locations as if they were visiting themselves.

  1. Music alters visual perception.

    Science.gov (United States)

    Jolij, Jacob; Meurs, Maaike

    2011-04-21

    Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory) and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  2. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  3. Field Usage of Alternative Deicers for Snow and Ice Control : Transportation Research Synthesis.

    Science.gov (United States)

    2017-09-01

    This Transportation Research Synthesis (TRS) summarizes non-chloride based deicers available on the market at this time, including acetate, formate, glycol, and succinate based deicing products. This report explores their feasibility for use as alter...

  4. Radiation-induced inhibition of RNA synthesis in Tetrahymena pyriformis

    International Nuclear Information System (INIS)

    Ernst, S.G.; Rustad, R.C.; Oleinick, N.L.

    1975-01-01

    Radiation-induced disturbances in RNA synthesis were investigated in exponentially growing Tetrahymena. Sub-lethal doses of γ-radiation lead to a transient, dose-dependent decrease in the rate of total RNA synthesis measured by 3 H-uridine incorporation, without an alteration of 3 H-uridine uptake by the cells. The rate of 3 H-uridine incorporation decreased exponentially with dose. In contrast, the duration of inhibition of RNA synthesis was linearly dependent on dose. Target-theory calculations suggest that the sensitive molecule has a molecular weight of about 2x10 7 Daltons. (author)

  5. Sexual Dimorphism in the Selenocysteine Lyase Knockout Mouse

    Directory of Open Access Journals (Sweden)

    Ashley N. Ogawa-Wong

    2018-01-01

    Full Text Available Selenium (Se is an essential micronutrient known for its antioxidant properties and health benefits, attributed to its presence in selenoproteins as the amino acid, selenocysteine. Selenocysteine lyase (Scly catalyzes hydrolysis of selenocysteine to selenide and alanine, facilitating re-utilization of Se for de novo selenoprotein synthesis. Previously, it was reported that male Scly−/− mice develop increased body weight and body fat composition, and altered lipid and carbohydrate metabolism, compared to wild type mice. Strikingly, females appeared to present with a less severe phenotype, suggesting the relationship between Scly and energy metabolism may be regulated in a sex-specific manner. Here, we report that while body weight and body fat gain occur in both male and female Scly−/− mice, strikingly, males are susceptible to developing glucose intolerance, whereas female Scly−/− mice are protected. Because Se is critical for male reproduction, we hypothesized that castration would attenuate the metabolic dysfunction observed in male Scly−/− mice by eliminating sequestration of Se in testes. We report that fasting serum insulin levels were significantly reduced in castrated males compared to controls, but islet area was unchanged between groups. Finally, both male and female Scly−/− mice exhibit reduced hypothalamic expression of selenoproteins S, M, and glutathione peroxidase 1.

  6. Total synthesis of ciguatoxin.

    Science.gov (United States)

    Hamajima, Akinari; Isobe, Minoru

    2009-01-01

    Something fishy: Ciguatoxin (see structure) is one of the principal toxins involved in ciguatera poisoning and the target of a total synthesis involving the coupling of three segments. The key transformations in this synthesis feature acetylene-dicobalthexacarbonyl complexation.

  7. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)

    1994-12-01

    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  8. Microbiome, inflammation, epigenetic alterations, and mental diseases.

    Science.gov (United States)

    Alam, Reza; Abdolmaleky, Hamid M; Zhou, Jin-Rong

    2017-09-01

    Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders. © 2017 Wiley Periodicals, Inc.

  9. Altered erythropoiesis and iron metabolism in carriers of thalassemia

    Science.gov (United States)

    Guimarães, Jacqueline S.; Cominal, Juçara G.; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z.; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

    2014-01-01

    The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis and dysfunctional iron metabolism have not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changings in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferrin and (hepcidin/ferritin)/sTfR are respectively increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis. PMID:25307880

  10. On the pathologically altered pulmonary pattern

    International Nuclear Information System (INIS)

    Ginzburg, M.A.; Kinoshenko, Yu.T.

    1982-01-01

    The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

  11. Systemic dystrophic alterations of skeleton

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

    1984-01-01

    A roentgenologic picture of dystrophic alterations of bones following hard, acute and chronic infections diseases, distinct disorders of vitanium balance, diseases of endocrine system, disorder of metabolism and diet, long-term exogenous intoxications including medicinal is given. Distinct dystrophic disorders are characterized both by quantitative and qualitative deviations in physiological change of bones

  12. Art as Alterity in Education

    Science.gov (United States)

    Zhao, Guoping

    2014-01-01

    In education, art has often been perceived as entertainment and decoration and is the first subject to go when there are budget cuts or test-score pressures. Drawing on Emmanuel Lévinas's idea of the primacy of radical alterity that breaks the totality of our being, enables self-transformation and ethics, and ensures community as a totality…

  13. Peary, Verifiability, and Altered Data

    Science.gov (United States)

    Rawlins, Dennis

    1991-01-01

    Robert Peary's alleged 1909 sledge-achievement of the North Pole is critically examined for credibility and consistency, with respect to terrestrial magnetism, solar-altitude, drift, and written & eyewitness testimony. Several alterations of the record are detected, and the dubiousness of navigation without determining longitude is emphasized.

  14. Synthesis of Mechanisms

    DEFF Research Database (Denmark)

    Hansen, John Michael

    1999-01-01

    These notes describe an automated procedure for analysis and synthesis of mechanisms. The analysis method is based on the body coordinate formulation, and the synthesis is based on applying optimization methods, used to minimize the difference between an actual and a desired behaviour......These notes describe an automated procedure for analysis and synthesis of mechanisms. The analysis method is based on the body coordinate formulation, and the synthesis is based on applying optimization methods, used to minimize the difference between an actual and a desired behaviour...

  15. Alteration and alterability of the anorthosite from Angola

    OpenAIRE

    Simão, J.; Silva, Z. C. G.

    2010-01-01

    Siliceous rocks are widely used as dimension stone but the last decades have registered an increase rate of their alteration when exposed to polluted environments. Anorthosites were treated by acidified solutions of HCl, HN03 and H2S04 simulating acid rain and the response was recorded through different experiments such as on the surface of the polished rock and on the surface of uncovered thin sections. The main components, plagioclase and olivine, both responded in similar ways to each acid...

  16. Hypoxia. 3. Hypoxia and neurotransmitter synthesis.

    Science.gov (United States)

    Kumar, Ganesh K

    2011-04-01

    Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/modulators is regulated by O(2)-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O(2) homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hypoxia (CH) and intermittent hypoxia (IH). CH is often seen during high altitude sojourns, whereas IH is experienced in sleep-disordered breathing with recurrent apneas (i.e., brief, repetitive cessations of breathing). This article presents what is currently known on the effects of both forms of hypoxia on neurotransmitter levels and neurotransmitter synthesizing enzymes in the central and peripheral nervous systems.

  17. Chemosensory alterations and cancer therapies

    International Nuclear Information System (INIS)

    Bartoshuk, L.M.

    1990-01-01

    Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems

  18. Interventions in the Alteration on Lingual Frenum: Systematic Review

    Science.gov (United States)

    Miranda, Priscilla Poliseni; Cardoso, Carolina Louise; Gomes, Erissandra

    2015-01-01

    Introduction  Altered lingual frenum modifies the normal tongue mobility, which may influence the stomatognathic functions, resulting in anatomical, physiological and social damage to the subject. It is necessary that health professionals are aware of the process of evaluation, diagnostics and treatment used today, guiding their intervention. Objective  To perform a systematic review of what are the treatment methods used in cases of lingual frenum alteration. Data Synthesis  The literature searches were conducted in MEDLINE, LILACS, SciELO, Cochrane and IBECS, delimited by language (Portuguese, English, Spanish), date of publication (January 2000 to January 2014) and studies performed in humans. The selection order used to verify the eligibility of the studies were related to: full text availability; review the abstract; text analysis; final selection. Of the total 443 publications, 26 remained for analysis. The surgical approach was used in all studies, regardless of the study population (infants, children and adults), with a range of tools and techniques employed; speech therapy was recommended in the post surgical in 4 studies. Only 4 studies, all with infants, showed scientific evidence. Conclusion  Surgical intervention is effective for the remission of the limitations caused by the alteration on lingual frenum, but there is a deficit of studies with higher methodological quality. The benefits of speech therapy in the post surgical period are described from improvement in the language of mobility aspects and speech articulation. PMID:27413412

  19. Total Synthesis of Avrainvilleol.

    Science.gov (United States)

    Wegener, Aaron; Miller, Kenneth A

    2017-11-03

    The first total synthesis of the marine natural product avrainvilleol is reported. The total synthesis features the first application of the transition-metal-free coupling of a tosyl hydrazone and a boronic acid to the preparation of a complex natural product, and the first example of this coupling with a hindered diortho substituted hydrazone substrate.

  20. Difluoromethylenephosphonates: synthesis and transformations

    International Nuclear Information System (INIS)

    Chunikhin, Konstantin S; Kadyrov, A A; Pasternak, P V; Chkanikov, Nikolai D

    2010-01-01

    The data on the synthesis of organic compounds containing the difluoromethylenephosphonate group are analyzed and generalized. The attention is focused on the introduction of this group into various organic molecules and subsequent transformations of the compounds thus formed. Individual sections are devoted to the synthesis of heterocyclic compounds and analogues of natural substances containing difluoromethylenephosphonate groups.

  1. Synthesis of Isoiminosugars

    DEFF Research Database (Denmark)

    Hyldtoft, Lene; Godskesen, Michael Anders; Lundt, Inge

    1998-01-01

    A short synthesis of isoiminosugars have been developed. Bromolactones are diastereoselectively alkylated at C-2 followed by ring closure to the corresponding lactams. Reduction of these then gives isoiminosugars......A short synthesis of isoiminosugars have been developed. Bromolactones are diastereoselectively alkylated at C-2 followed by ring closure to the corresponding lactams. Reduction of these then gives isoiminosugars...

  2. Synthesis of oligonucleotide phosphorodithioates

    DEFF Research Database (Denmark)

    Beaton, G.; Brill, W. K D; Grandas, A.

    1991-01-01

    The synthesis of DNA containing sulfur at the two nonbonding internucleotide valencies is reported. Several different routes using either tervalent or pentavalent mononucleotide synthons are described.......The synthesis of DNA containing sulfur at the two nonbonding internucleotide valencies is reported. Several different routes using either tervalent or pentavalent mononucleotide synthons are described....

  3. Technology, relationships, and problems: a research synthesis.

    Science.gov (United States)

    Hertlein, Katherine M; Webster, Megan

    2008-10-01

    The advances in technology alter the ways we interact with each other. For some, the use of technology can facilitate a relationship; for others, technology can complicate aspects of a relationship. The purpose of this research synthesis is to summarize current research exploring the ways in which technology impacts relationships negatively. Eight studies were reviewed across the following areas: preoperational definitions, sample, methodology, control of extraneous variables, causal influence, generalizability, validity of statistical findings, and conclusions. Implications for authors, researchers, and therapists working with couples and families struggling with technology issues are discussed.

  4. Polyoxometalate-assited metal nanomaterials synthesis

    International Nuclear Information System (INIS)

    Seong, Ji Hyun; Kim, Dong Heun; Han, Sang Woo; Lee, Sang Bok

    2015-01-01

    In this review, we present the polyoxometalate (POM)-mediated synthesis of nanomaterials and their performance as catalysts. Various nanomaterials have been successfully synthesized in a facile process using POMs as a reducing and stabilizing agent. The reduction of metal ions was effected by the reduced POMs, which converted their oxidation state without structural change. The presence of POMs on the nanomaterials was confirmed through a variety of analytical methods. The alteration of the size and morphology of nanomaterials was observed to be controlled by the molar ratio of metal salt to the POMs. The synthesized nanomaterials showed good catalytic activity, which could be used as multifunctional catalysts

  5. VHDL for logic synthesis

    CERN Document Server

    Rushton, Andrew

    2011-01-01

    Many engineers encountering VHDL (very high speed integrated circuits hardware description language) for the first time can feel overwhelmed by it. This book bridges the gap between the VHDL language and the hardware that results from logic synthesis with clear organisation, progressing from the basics of combinational logic, types, and operators; through special structures such as tristate buses, register banks and memories, to advanced themes such as developing your own packages, writing test benches and using the full range of synthesis types. This third edition has been substantially rewritten to include the new VHDL-2008 features that enable synthesis of fixed-point and floating-point hardware. Extensively updated throughout to reflect modern logic synthesis usage, it also contains a complete case study to demonstrate the updated features. Features to this edition include: * a common VHDL subset which will work across a range of different synthesis systems, targeting a very wide range of technologies...

  6. Assessing glycolytic flux alterations resulting from genetic perturbations in E. coli using a biosensor

    DEFF Research Database (Denmark)

    Lehning, Christina Eva; Siedler, Solvej; Ellabaan, Mostafa M Hashim

    2017-01-01

    We describe the development of an optimized glycolytic flux biosensor and its application in detecting altered flux in a production strain and in a mutant library. The glycolytic flux biosensor is based on the Cra-regulated ppsA promoter of E. coli controlling fluorescent protein synthesis. We...... validated the glycolytic flux dependency of the biosensor in a range of different carbon sources in six different E. coli strains and during mevalonate production. Furthermore, we studied the flux-altering effects of genome-wide single gene knock-outs in E. coli in a multiplex FlowSeq experiment. From...

  7. Altered mitochondrial function after acute alteration of the endogenous insulin/glucagon ratio

    International Nuclear Information System (INIS)

    Rohweder-Dunn, G.; Aprille, J.R.

    1986-01-01

    Mannoheptulose (MH) affects pancreatic Islet cells to cause a drop in serum insulin and a rise in glucagon. This effect peaks 1 hr after injection and results in a 3-fold increase in serum glucose. Here they examined whether metabolic functions of liver mitochondria (mito) are altered by this change in hormone status. Rats fed ad lib on 12 hr light/dark cycles were given MH (2g/kg) or vehicle i.p. during the first 2 hrs of the light cycle. Liver mito were isolated 1 hr later. Acid-extracts were assayed for ATP+ADP+AMP (nmol/mg prot). Citrulline synthesis and pyruvate carboxylation rates (nmol/min/mg prot) were assayed by following H[ 14 C]O 3 - fixation in appropriate media. State 3 and 2,4-DNP-uncoupled respiratory rates (1/2 nmol O 2 /min/mg prot) were assayed polarographically with succinate. The effects of MH on mito are comparable to reported effects of glucagon injection. MH evokes acute reciprocal changes in insulin and glucagon that are highly reproducible. Thus, MH offers an interesting model for studying the effect of endogenous hormones on mito functions

  8. Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture

    Energy Technology Data Exchange (ETDEWEB)

    Roeder, R.A.; Thorpe, S.D.; Byers, F.M.; Schelling, G.T.; Gunn, J.M.

    Muscle cell culture (L/sub 6/) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effect of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 ..mu..M compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of (/sup 3/H) leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using (/sup 3/H) leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes by dexamethasone, but increased in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 ..mu..M level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle.

  9. Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture

    International Nuclear Information System (INIS)

    Roeder, R.A.; Thorpe, S.D.; Byers, F.M.; Schelling, G.T.; Gunn, J.M.

    1986-01-01

    Muscle cell culture (L 6 ) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effect of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 μM compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of [ 3 H] leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using [ 3 H] leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes by dexamethasone, but increased in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 μM level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle

  10. ALTER-GLOBALISM AND DEVELOPMENT IN MIGRATION CONDITIONS. THE CASE OF AN EAST EUROPEAN COUNTRY

    OpenAIRE

    Alina HALLER

    2017-01-01

    Globalisation is a process that brings advantages and disadvantages to all states, regardless of their stage of development. The relative deprivation, especially the financial one, of the developing countries is a reason of frustration, which motivates the emigration decision; hence our orientation to alter-globalism. In this paper, I intend to highlight by means of analysis, synthesis, deduction, induction, and statistic data, the causes and types of migration in Romania’s case, one of the m...

  11. Altering prolactin concentrations in sows.

    Science.gov (United States)

    Farmer, C

    2016-07-01

    Prolactin has a multiplicity of actions, but it is of particular importance in gestating and lactating animals. In sows, it is involved in the control of mammary development and also holds essential roles in the lactogenic and galactopoietic processes. Furthermore, low circulating concentrations of prolactin are associated with the agalactia syndrome. The crucial role of prolactin makes it important to understand the various factors that can alter its secretion. Regulation of prolactin secretion is largely under the negative control of dopamine, and dopamine agonists consistently decrease prolactin concentrations in sows. On the other hand, injections of dopamine antagonists can enhance circulating prolactin concentrations. Besides pharmacologic agents, many other factors can also alter prolactin concentrations in sows. The use of Chinese-derived breeds, for instance, leads to increased prolactin concentrations in lactating sows compared with standard European white breeds. Numerous husbandry and feeding practices also have a potential impact on prolactin concentrations in sows. Factors, such as provision of nest-building material prepartum, housing at farrowing, high ambient temperature, stress, transient weaning, exogenous thyrotropin-releasing factor, exogenous growth hormone-releasing factor, nursing frequency, prolonged photoperiod, fasting, increased protein and/or energy intake, altered energy sources, feeding high-fiber diets, sorghum ergot or plant extracts, were all studied with respect to their prolactinemic properties. Although some of these practices do indeed affect circulating prolactin concentrations, none leads to changes as drastic as those brought about by dopamine agonists or antagonists. It appears that the numerous factors regulating prolactin concentrations in sows are still not fully elucidated, and that studies to develop novel applicable ways of increasing prolactin concentrations in sows are warranted. Crown Copyright © 2015. Published

  12. Acid Sulfate Alteration on Mars

    Science.gov (United States)

    Ming, D. W.; Morris, R. V.

    2016-01-01

    A variety of mineralogical and geochemical indicators for aqueous alteration on Mars have been identified by a combination of surface and orbital robotic missions, telescopic observations, characterization of Martian meteorites, and laboratory and terrestrial analog studies. Acid sulfate alteration has been identified at all three landing sites visited by NASA rover missions (Spirit, Opportunity, and Curiosity). Spirit landed in Gusev crater in 2004 and discovered Fe-sulfates and materials that have been extensively leached by acid sulfate solutions. Opportunity landing on the plains of Meridiani Planum also in 2004 where the rover encountered large abundances of jarosite and hematite in sedimentary rocks. Curiosity landed in Gale crater in 2012 and has characterized fluvial, deltaic, and lacustrine sediments. Jarosite and hematite were discovered in some of the lacustrine sediments. The high elemental abundance of sulfur in surface materials is obvious evidence that sulfate has played a major role in aqueous processes at all landing sites on Mars. The sulfate-rich outcrop at Meridiani Planum has an SO3 content of up to 25 wt.%. The interiors of rocks and outcrops on the Columbia Hills within Gusev crater have up to 8 wt.% SO3. Soils at both sites generally have between 5 to 14 wt.% SO3, and several soils in Gusev crater contain around 30 wt.% SO3. After normalization of major element compositions to a SO3-free basis, the bulk compositions of these materials are basaltic, with a few exceptions in Gusev crater and in lacustrine mudstones in Gale crater. These observations suggest that materials encountered by the rovers were derived from basaltic precursors by acid sulfate alteration under nearly isochemical conditions (i.e., minimal leaching). There are several cases, however, where acid sulfate alteration minerals (jarosite and hematite) formed in open hydrologic systems, e.g., in Gale crater lacustrine mudstones. Several hypotheses have been suggested for the

  13. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  14. Asymmetric synthesis v.4

    CERN Document Server

    Morrison, James

    1984-01-01

    Asymmetric Synthesis, Volume 4: The Chiral Carbon Pool and Chiral Sulfur, Nitrogen, Phosphorus, and Silicon Centers describes the practical methods of obtaining chiral fragments. Divided into five chapters, this book specifically examines initial chiral transmission and extension. The opening chapter describes the so-called chiral carbon pool, the readily available chiral carbon fragments used as building blocks in synthesis. This chapter also provides a list of 375 chiral building blocks, along with their commercial sources, approximate prices, and methods of synthesis. Schemes involving

  15. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    Science.gov (United States)

    ... Methamphetamine Alters Brain Structures, Impairs Mental Flexibility Email Facebook Twitter March 20, 2014 A new study adds to the copious existing evidence that chronic exposure to addictive drugs alters the brain in ways that make ...

  16. Thermal alteration of aquatic ecosystems

    International Nuclear Information System (INIS)

    Gibbons, J.W.; Sharitz, R.R.

    1974-01-01

    The studies summarized emphasize that heated effluents may function to enrich or to stress an ecosystem, depending upon the biological feature examined. However, the potential for negative impact on aquatic environments must not be underestimated. The ultimate consequences of the sometimes drastic alteration of behavior patterns and life-history phenomena in the surviving inhabitants of thermal areas have yet to be assessed. The relatively short time span of thermal field studies has not allowed thorough understanding of the biological chain reactions that may take place as physiological and genetic adjustments are made. Ensuing changes in species interactions, practically uninvestigated at this time, may create heretofore unsuspected ecosystem changes. Man's challenge for the future is to gain a more thorough comprehension of thermal ecology and to determine how waste heat may be used as an energy subsidy rather than a stress to aquatic systems. These and subsequent studies may assist in understanding how natural ecosystems respond to temperature elevation and will lead to the development of concepts and principles pertaining to thermally altered environmental systems. (U.S.)

  17. Circadian disorganization alters intestinal microbiota.

    Science.gov (United States)

    Voigt, Robin M; Forsyth, Christopher B; Green, Stefan J; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H; Turek, Fred W; Keshavarzian, Ali

    2014-01-01

    Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

  18. SYNTHESIS, CHARACTERIZATION AND ANTIBACTERIAL ...

    African Journals Online (AJOL)

    Preferred Customer

    E-mail: a-ahmadi@kiau.ac.ir; ahmadikiau@yahoo.com. SYNTHESIS, CHARACTERIZATION AND ANTIBACTERIAL EVALUATION OF. SOME NOVEL DERIVATIVES OF 2-BROMOMETHYL-BENZIMIDAZOLE. Abbas Ahmadi*. Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University,.

  19. 2002 Annual report: synthesis

    International Nuclear Information System (INIS)

    2003-01-01

    This synthesis of the Annual Report 2002 presents information of the main activities on the scope of the radiation protection and nuclear safety of the Nuclear Regulatory Authority (ARN) of the Argentina during 2002

  20. 2001 Annual report: synthesis

    International Nuclear Information System (INIS)

    2001-01-01

    This synthesis of the Annual Report 2001 presents information of the main activities on the scope of the radiation protection and nuclear safety of the Nuclear Regulatory Authority (ARN) of the Argentina during 2001

  1. 2000 Annual report: synthesis

    International Nuclear Information System (INIS)

    2001-01-01

    This synthesis of the Annual Report 2000 present information of the main activities on the scope of the radiation protection and nuclear safety of the Nuclear Regulatory Authority (NRA) of the Argentina during 2000

  2. Synthesis of Acetylhomoagmatine

    Directory of Open Access Journals (Sweden)

    Carmenza Duque

    2006-08-01

    Full Text Available Abstract: The first total synthesis of acetylhomoagmatine, a natural product isolated form the methanolic extracts from the sponge Cliona celata, is performed in four steps in a very high yield.

  3. DNA alterations photosensitized by tetracycline and some of its derivatives

    International Nuclear Information System (INIS)

    Piette, J.; Decuyper, J.; Van de Vorst, A.

    1986-01-01

    Bacteriophage M13 mp10 DNA were irradiated with near-UV light in the presence of tetracycline derivatives and primed with synthetic oligonucleotide to be used for DNA synthesis using Escherichia coli DNA polymerase. Chain terminations were observed by denaturing polyacrylamide gel electrophoresis and mapped precisely. All the synthesis stops occurred before or at the level of guanine residues, showing that the photoreaction mediated by tetracycline derivatives led to a preferential alteration of guanine residues. These lesions were demonstrated to be induced in DNA through a pathway involving singlet oxygen. Tetracycline derivatives also photoinduced the breakage of the DNA sugar-phosphate backbone monitored by the conversion of supercoiled phi X174 DNA to a relaxed form. This lesion was shown to be initiated by hydroxyl radicals. The production of this free radical has been confirmed by electron paramagnetic resonance (EPR) spin trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide as spin trap. In addition to the EPR signal due to OH radicals trapping another unassigned signal has been detected

  4. Type V Collagen is Persistently Altered after Inguinal Hernia Repair

    DEFF Research Database (Denmark)

    Lorentzen, L; Henriksen, N A; Juhl, P

    2018-01-01

    elective cholecystectomy served as controls (n = 10). Whole venous blood was collected 35-55 months after operation. Biomarkers for type V collagen synthesis (Pro-C5) and degradation (C5M) and those for type IV collagen synthesis (P4NP) and degradation (C4M2) were measured by a solid-phase competitive...... assay. RESULTS: The turnover of type V collagen (Pro-C5/C5M) was slightly higher postoperatively when compared to preoperatively in the inguinal hernia group (P = 0.034). In addition, the results revealed a postoperatively lower type V collagen turnover level in the inguinal hernia group compared...... and incisional hernia. The aim of this study was to determine if the altered collagen metabolism was persistent after hernia repair. MATERIAL AND METHODS: Patients who had undergone repairs for inguinal hernia (n = 11) or for incisional hernia (n = 17) were included in this study. Patients who had undergone...

  5. Instrument Modeling and Synthesis

    Science.gov (United States)

    Horner, Andrew B.; Beauchamp, James W.

    During the 1970s and 1980s, before synthesizers based on direct sampling of musical sounds became popular, replicating musical instruments using frequency modulation (FM) or wavetable synthesis was one of the “holy grails” of music synthesis. Synthesizers such as the Yamaha DX7 allowed users great flexibility in mixing and matching sounds, but were notoriously difficult to coerce into producing sounds like those of a given instrument. Instrument design wizards practiced the mysteries of FM instrument design.

  6. Epigenetic alterations underlying autoimmune diseases.

    Science.gov (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  7. Window to 'Clovis's' Altered Past

    Science.gov (United States)

    2004-01-01

    This image taken by the Mars Exploration Rover Spirit shows a rock outcrop dubbed 'Clovis.' The rock was discovered to be softer than other rocks studied so far at Gusev Crater after the rover easily ground a hole (center) into it with its rock abrasion tool. An analysis of the interior of the hole with the rover's alpha particle X-ray spectrometer found higher concentrations of sulfur, bromine and chlorine compared to basaltic, or volcanic, rocks at Gusev. This might indicate that Clovis was chemically altered, and that fluids once flowed through the rock depositing these elements. Spirit's solar panels can be seen in the foreground. This image was taken by the rover's navigation camera on sol 205 (July 31, 2004).

  8. Self-alteration in HRI

    DEFF Research Database (Denmark)

    Yamazaki, Ryuji; Nørskov, Marco

    Humanlike androids are being developed with the ambition to be immersed into our daily life and meet us on an equal level in social interaction. The possibilities and limitations of these types of robots can potentially change societies and Human-Robot Interaction might affect the very way in which...... and Denmark, we examine how Telenoid, a new type of teleoperated android robot designed as a minimalistic human, affect people in the real world. We introduce Telenoid to real-world as the fields of elderly care and child education by focusing on the social aspects of the android robot that might facilitate...... the ways in which our subjectivity can be innerly transformed, decentred, in other words, self-altered. In our trials so far, we have been investigating the potential of teleoperated androids, which are embodied telecommunication media with humanlike appearances. By conducting pilot studies in Japan...

  9. Serotonin synthesis studied with positron emission tomography, (PET)

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Lundquist, Pinelopi

    Positron emission tomography (PET) has the potential to study the biosynthesis and release of serotonin (5HT) at brain serotonergic neurons. PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes. This section focuses on probes to measure...... seroonin synthesis rate. Knowledge of altered 5HT synthesis and release in disease states may furnish basis for effective pharmacotherapy that may improve the care of psychiatric and neurological disease. Validation of PET measurements of the two PET tracers using perturbation showed that 5-hydroxy...... different from those of 5HTP, suggesting that the two PET probes provide estimates related to the enzyme activity of different steps in the 5HT synthesis pathway. Applications of the two tracers HTP and AMT are reviewed. Up to now, 5HTP has mainly been used for the detection, staging and treatment...

  10. Synthesis and Characterization of Surface Functionalized Nanobiocomposite by Nano Hydroxyapatite

    OpenAIRE

    M. Meskinfam; M. S. Sadjadi; H. Jazdarreh

    2012-01-01

    In this study, synthesis of biomemitic patterned nano hydroxyapatite-starch biocomposites using different concentration of starch to evaluate effect of polymer alteration on biocomposites structural properties has been reported. Formation of hydroxyapatite nano particles was confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Size and morphology of the samples were characterized using scanning and transmission electron microscopy (SEM...

  11. Optical tweezers reveal how proteins alter replication

    Science.gov (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  12. Effect of Streptomycin Deprivation on Enzyme Synthesis in Streptomycin-Dependent Escherichia coli

    Science.gov (United States)

    Goodman, R. E.; Spotts, Charles R.

    1967-01-01

    During growth of streptomycin-dependent strains of Escherichia coli in the absence of streptomycin (deprived growth), both constitutive and inducible synthesis of β-galactosidase were preferentially inhibited. A similar preferential inhibition of constitutive and derepressed synthesis of alkaline phosphatase was observed. Catabolite repression accounted for part, but not all, of the inhibition of the inducible β-galactosidase synthesis. Serological experiments indicated that that part of the inhibition specificially associated with streptomycin deprivation was not a result of the production of altered β-galactosidase. It is suggested that during deprived growth the ribosomes of streptomycin-dependent bacteria become impaired in their ability to translate certain messages. PMID:4860910

  13. Detonation-synthesis nanodiamonds: synthesis, structure, properties and applications

    International Nuclear Information System (INIS)

    Dolmatov, Valerii Yu

    2007-01-01

    The review outlines the theoretical foundations and industrial implementations of modern detonation synthesis of nanodiamonds and chemical purification of the nanodiamonds thus obtained. The structure, key properties and promising fields of application of detonation-synthesis nanodiamonds are considered.

  14. Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2017-12-01

    Full Text Available The pathogenesis of schizophrenia (SCH is associated with the dysfunction of monoamine neurotransmitters, the synthesis and release of which are mainly regulated by a key structure, the habenular (Hb nucleus. However, little is known regarding whether SCH is associated with structural or functional alterations in the Hb. In this study, we combined structural and resting-state functional magnetic resonance imaging to investigate the changes in volume and functional connectivity of the Hb in 15 patients with SCH vs. 16 age- and gender-matched healthy controls (HCs. Morphologically, the absolute volume of the bilateral Hb was significantly lower in the SCH patients than in the HCs. Functionally, the bilateral Hb showed significantly enhanced functional connectivity with the left medial prefrontal cortex (mPFC in the SCH patients. Additionally, the SCH patients exhibited increased functional connectivity of the left Hb with the left lingual gyrus and right inferior frontal gyrus (IFG. A further exploratory analysis revealed that the SCH patients showed increased functional connectivity between the right Hb and several subcortical regions related to dopaminergic pathways, including the left ventral striatum, caudate and putamen. Finally, the increased functional connectivity of the right Hb with the mPFC was positively correlated with the Brief Psychiatric Rating Scale (BPRS scores in the patients. Together, these results suggest that the altered volume and functional connectivity of the Hb may be involved in the pathogenesis of SCH and thus that the Hb may serve as a potential target in developing new therapeutic strategies in SCH.

  15. Synthesis of phenanthrenes

    International Nuclear Information System (INIS)

    Clarke, C.

    1983-01-01

    A new and improved synthesis of 7-methoxy-12-methyl-2-oxo-2,3,4,9,10,12-hexahydrophenanthrene has been described. The compound is an important intermediate for the synthesis of many di- and tri-terpenes, and was required in this work for the synthesis of 17-acetyl-5α-etiojerva-12,14,16-trien-3β-ol. This compound is a known starting material for the synthesis of the veratrum alkaloids jervine, veratramine and verarine. Two synthetic routes to the synthesis of 7-methoxy-12-methyl-2-oxo-2,3,4,9,10,12-hexahydrophenanthrene were investigated. The first route required preparation of the intermediate 1-(5-methyl-2-furyl)-3-(3'-methoxyphenyl)propane which, by simple manipulation involving mainly the furan ring, gave the desired compound in 33% yield. All of the reactions involved are suitable for both large and small scale preparations. The synthesis of 17-acetyl-5α-etiojerva-12,14,16-trien-3B-ol can be achieved by the hyde and 3-methoxyacetophenone, followed by hydrogeneration and Wolff-Kishner reduction. A less successful synthesis of the above compound was achieved by condensing the Grignard derivative of 2-(3'-methoxyphenyl)ethyl bromide with 5-methylfurfuraldehyde to form a furyl alcohol, which was oxidized and reduced to give 1-(5-methyl-2-furyl)-3-(3'-methoxyphenyl)propane in only 7% overall yield, but the starting materials are inexpensive and readily available. The compound was also prepared in 40% yield by condensing 2-lithio-5-methylfuran with 3-(3'methoxyphenyl)propyl bromide. An appendix describes the reaction of 3-ethoxy-cyclohex-2-en-1-one with ethylmagnesium bromide, followed by aromatization. A second appendix describes the reductive alkylation of 8-methoxy-12-methyl-2-oxo-2,3,4,9,10,12-hexahydrophenanthrene

  16. Alteration of granite stone used in building construction

    Directory of Open Access Journals (Sweden)

    Esbert Alemany, R. M.ª

    2007-12-01

    Full Text Available The article contains a synthesis of the different factors involved in the alteration of granite ashlars or cladding used in building construction. Emphasis is placed on the – primarily fissure-like – anisotropies often present in granite, which are usually related to the structural conditions of the quarry where it is mined. Such anisotropies condition the development of certain types of alterations that appear over time, particularly in ashlars. Stone petrography, particularly as regards the chemical composition of the minerals comprising granite, also govern its alteration. Moreover, the commercial term granite often includes other more alkaline rocks generically known as granitoids, whose alterability is higher than in granite per se. The values of some of the physical properties of these rocks, which must be quantified to evaluate their durability, are shown to differ in keeping with their anisotropy. Finally, the forms, causes and mechanisms involved in granite decay are reviewed in the context of its use in building construction.En el artículo se sintetizan los diversos aspectos que inciden en la alteración de las rocas graníticas, cuando estas se utilizan en los edificios, ya sea en forma de sillares o de losetas de revestimiento. Se hace especial hincapié en las anisotropías, fundamentalmente de carácter fisural que suelen presentar los granitos. Estas suelen estar relacionadas con las condiciones estructurales del yacimiento del cual proceden. Dichas anisotropías condicionan el desarrollo de determinadas formas de alteración que con el paso del tiempo se aprecian, sobre todo en los sillares. También se recuerda que la petrografía, y en especial la composición química de los minerales que componen las rocas graníticas, condicionan su alteración, y que dentro del término comercial granito se suelen incluir otras rocas más alcalinas denominadas genéricamente granitoides y más alterables que el granito sensu

  17. Epigenetic Alterations in Parathyroid Cancers

    Directory of Open Access Journals (Sweden)

    Chiara Verdelli

    2017-02-01

    Full Text Available Parathyroid cancers (PCas are rare malignancies representing approximately 0.005% of all cancers. PCas are a rare cause of primary hyperparathyroidism, which is the third most common endocrine disease, mainly related to parathyroid benign tumors. About 90% of PCas are hormonally active hypersecreting parathormone (PTH; consequently patients present with complications of severe hypercalcemia. Pre-operative diagnosis is often difficult due to clinical features shared with benign parathyroid lesions. Surgery provides the current best chance of cure, though persistent or recurrent disease occurs in about 50% of patients with PCas. Somatic inactivating mutations of CDC73/HRPT2 gene, encoding parafibromin, are the most frequent genetic anomalies occurring in PCas. Recently, the aberrant DNA methylation signature and microRNA expression profile have been identified in PCas, providing evidence that parathyroid malignancies are distinct entities from parathyroid benign lesions, showing an epigenetic signature resembling some embryonic aspects. The present paper reviews data about epigenetic alterations in PCas, up to now limited to DNA methylation, chromatin regulators and microRNA profile.

  18. ALTERATIONS INDUCED BY LOW LEVELS OF DEOXYNIVALENOL IN WEANED PIGLETS

    Directory of Open Access Journals (Sweden)

    DANIELA ELIZA MARIN

    2007-05-01

    Full Text Available Deoxynivalenol (DON is a mycotoxin produced by different species of Fusarium genus that may contaminate feed and food. In the present study we investigated the effect of low levels of DON on the modulation of performance, hemodynamic parameters, cellular and humoral immune response in weaned pigs. Histological alterations in different organ tissues were also analyzed. Our results showed that a short in vivo exposure (14 days of weanling piglets to 0; 0.5; 1.5 mg/day of DON significantly induced a dose dependent increase of cellular immune response (lymphocytes proliferation and leucocytes numbers. The 0.5 and 1.5 mg/day of DON modulated also the humoral immune response by increasing the immunoglobulin A synthesis with 7.32 % and 37.98 % and by decreasing that of immunoglubulin G with 11.15 % and 36.87 %, respectively when compared with the control. DON produced also alterations in the hemodynamic parameters of intoxicated piglets; the activity of lactate dehydrogenase significantly increased while the activity of L-glutamate, alkaline phosphatase, urea and creatinine significantly decreased. Both doses of the toxin induced microscopic alterations of the internal organ structure. By contrast, ingestion of the contaminated material had no effect on the performance (weight gain, feed consumption, and feed efficiency, organ weights, and total serum concentration of cholesterol, calcium, sodium and potassium. Taken together these results suggest that even when present at low level DON can affect blood parameters, humoral and cellular immune response in weaned piglets with a significant importance for the swine health.

  19. Behavioral synthesis of asynchronous circuits

    DEFF Research Database (Denmark)

    Nielsen, Sune Fallgaard

    2005-01-01

    This thesis presents a method for behavioral synthesis of asynchronous circuits, which aims at providing a synthesis flow which uses and tranfers methods from synchronous circuits to asynchronous circuits. We move the synchronous behavioral synthesis abstraction into the asynchronous handshake...... is idle. This reduces unnecessary switching activity in the individual functional units and therefore the energy consumption of the entire circuit. A collection of behavioral synthesis algorithms have been developed allowing the designer to perform time and power constrained design space exploration...

  20. Synthesis of organosilicon compounds

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, G. [Iowa State Univ., Ames, IA (United States)

    1996-01-01

    Silicon-containing polymers have been a focus of synthesis and study in Dr. Barton`s group because of their chemistry and properties which are not offered by other systems or materials. For example, the polymer -[-SiMe2C≡C-]n-can be easily processed to films or fibers from melt or solution, and thermally converted to a SiC-containing ceramic in high yield at high temperature. In recent years, carbosilane dendritic polymers have been of great interests in many research groups. However, no synthesis of carbosilane dendrimers with functionalties both inside and outside the dendrimer has been reported. Functionality is very important in the synthesis of preceramic polymers. This thesis will be devoted to exploring several new organosilicon polymer systems.

  1. Interactions ARN-protéines dans le mécanisme de biosynthèse des sélénoprotéines

    OpenAIRE

    Takeuchi , Akiko

    2009-01-01

    The 21st amino acid selenocysteine is encoded by a UGA codon that usually signifies translational termination. Selenoprotein synthesis therefore requires specialized factors. Among these is SBP2 that binds the SECIS, a stem-loop structure in the 3'UTR of selenoprotein mRNAs. In structural analyses of SBP2, we isolated and functionally characterized Drosophila melanogaster SBP2. By comparing it with human SBP2, we identified an additional RNA binding domain that is essential for SECIS and 60S ...

  2. Altered mental status from acyclovir.

    Science.gov (United States)

    Martinez-Diaz, Gabriel J; Hsia, Renee

    2011-07-01

    Acyclovir is widely used in the treatment of herpes virus infections, particularly herpes simplex virus and varicella-zoster virus. Acyclovir, when given promptly upon the start of a herpes zoster eruption, speeds healing and diminishes acute pain. Because acyclovir is a commonly used medication, it is crucial for health providers to be aware of appropriate dosing as well as possible side effects. We present this case to increase awareness of the potential for inappropriate dosing of acyclovir and the presentations of patients with toxic effects. We report the case of a 65-year-old man with a past medical history significant for chronic kidney disease who presented to the Emergency Department with progressive confusion and ataxia over 2 days. Thorough questioning in the patient's native language revealed that he had recently started a medication for a "rash." Neither he nor his family knew the name of the new medication; further investigation revealed it to be acyclovir. Although other diagnoses were considered in the differential diagnosis for this patient with altered mental status, he was treated for presumed acyclovir toxicity and given prompt dialysis, upon which his symptoms resolved. It is important for physicians to remember that even common medications such as acyclovir can have serious side effects and complications. In this case, renal dosing was not used in a patient on hemodialysis. Acyclovir must be renally dosed and carefully monitored through drug level measurement in patients with limited kidney function to prevent serious side effects, such as the neurological sequelae demonstrated in this case report. Emergency physicians should be aware of the potential for inappropriate dosing of this medication and the presentations of patients with toxic effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Total Synthesis of Strychnine.

    Science.gov (United States)

    Lee, Geun Seok; Namkoong, Gil; Park, Jisook; Chen, David Y-K

    2017-11-16

    The total synthesis of the flagship Strychnos indole alkaloid, strychnine, has been accomplished. The developed synthetic sequence features a novel vinylogous 1,4-addition, a challenging iodinium salt mediated silyl enol ether arylation, a palladium-catalyzed Heck reaction, and a streamlined late-stage conversion to strychnine. Furthermore, an application of asymmetric counterion-directed catalysis (ACDC) in the context of target-oriented organic synthesis has been rendered access to an optically active material. The synthetic sequence described herein represents the most concise entry to optically active strychnine to date. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Supercritical Synthesis of Biodiesel

    Directory of Open Access Journals (Sweden)

    Michel Vaultier

    2012-07-01

    Full Text Available The synthesis of biodiesel fuel from lipids (vegetable oils and animal fats has gained in importance as a possible source of renewable non-fossil energy in an attempt to reduce our dependence on petroleum-based fuels. The catalytic processes commonly used for the production of biodiesel fuel present a series of limitations and drawbacks, among them the high energy consumption required for complex purification operations and undesirable side reactions. Supercritical fluid (SCF technologies offer an interesting alternative to conventional processes for preparing biodiesel. This review highlights the advances, advantages, drawbacks and new tendencies involved in the use of supercritical fluids (SCFs for biodiesel synthesis.

  5. Direct dimethyl ether synthesis from synthesis gas: The influence of methanol dehydration on methanol synthesis reaction

    OpenAIRE

    Dadgar, Farbod; Myrstad, Rune; Pfeifer, Peter; Holmen, Anders; Venvik, Hilde Johnsen

    2016-01-01

    Direct dimethyl ether (DME) synthesis from synthesis gas is studied with regard to potential effects of methanol dehydration on methanol formation and copper-based catalyst performance. For this, the influence of the operating conditions (space velocity, temperature, pressure, time-on-stream and syngas composition) on activity, selectivity and stability of the catalyst was studied and compared for methanol synthesis and direct DME synthesis. The advantage of the direct over the two-step DME s...

  6. Do invasive plant species alter soil health?

    Science.gov (United States)

    Invasive species may alter soil characteristics or interact with the soil microbial community to yield a competitive advantage. Our objectives were to determine: if invasive plant species alter soil properties important to soil health; and the long-term effects of invasive plant species on soil pro...

  7. An Analysis of the Alteration Specialist Occupation.

    Science.gov (United States)

    Buerkel, Elaine; Rehling, Joseph H.

    The general purpose of the occupational analysis is to provide workable, basic information dealing with the many and varied duties performed in the textile service occupation. The industry needs properly trained alteration specialists, bushelmen and dressmakers, in the repairing, remodeling, altering or renovating of garments. Their personal…

  8. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Computer Aided Synthesis of a Four-Bar Mechanism For Soil Tilling ...

    African Journals Online (AJOL)

    points, circle points, lengths, and the coupler point of interest of the chosen mechanism were altered and the resulting coupler curve plotted. The process was repeated until a suitable coupler curve and acceptable dimensions and fixed points locations were obtained. Keywords: Computer synthesis, four-bar mechanism, ...

  10. Ecohydrologic impacts of rangeland fire on runoff and erosion: A literature synthesis

    Science.gov (United States)

    Frederick B. Pierson; C. Jason Williams

    2016-01-01

    Fire can dramatically influence rangeland hydrology and erosion by altering ecohydrologic relationships. This synthesis presents an ecohydrologic perspective on the effects of fire on rangeland runoff and erosion through a review of scientific literature spanning many decades. The objectives are: (1) to introduce rangeland hydrology and erosion concepts necessary for...

  11. An Approach to Interface Synthesis

    DEFF Research Database (Denmark)

    Madsen, Jan; Hald, Bjarne

    1995-01-01

    Presents a novel interface synthesis approach based on a one-sided interface description. Whereas most other approaches consider interface synthesis as optimizing a channel to existing client/server modules, we consider the interface synthesis as part of the client/server module synthesis (which...... may contain the re-use of existing modules). The interface synthesis approach describes the basic transformations needed to transform the server interface description into an interface description on the client side of the communication medium. The synthesis approach is illustrated through a point......-to-point communication, but is applicable to synthesis of a multiple client/server environment. The interface description is based on a formalization of communication events....

  12. Enzymatic synthesis of vanillin

    NARCIS (Netherlands)

    van den Heuvel, RHH; Fraaije, MW; Laane, C; van Berkel, WJH; Heuvel, Robert H.H. van den; Berkel, Willem J.H. van

    Due to increasing interest in natural vanillin, two enzymatic routes for the synthesis of vanillin were developed. The flavoprotein vanillyl alcohol oxidase (VAO) acts on a wide range of phenolic compounds and converts both creosol and vanillylamine to vanillin with high yield. The VAO-mediated

  13. Enzymatic synthesis of vanillin

    NARCIS (Netherlands)

    Heuvel, van den R.H.H.; Fraaije, M.W.; Laane, C.; Berkel, van W.J.H.

    2001-01-01

    Due to increasing interest in natural vanillin, two enzymatic routes for the synthesis of vanillin were developed. The flavoprotein vanillyl alcohol oxidase (VAO) acts on a wide range of phenolic compounds and converts both creosol and vanillylamine to vanillin with high yield. The VAO-mediated

  14. Design synthesis exercise 2012

    NARCIS (Netherlands)

    Melkert, J.A.

    2013-01-01

    The design synthesis exercise forms the closing piece of the third year of the Bachelor degree curriculum of the Faculty of Aerospace Engineering at TU Delft. In this exercise the students learn to apply their acquired knowledge from all aerospace disciplines in one complete design. The object of

  15. Asymmetric synthesis of acetomycin

    NARCIS (Netherlands)

    Kinderman, S.S.; Feringa, B.L.

    1998-01-01

    The synthesis of (-)-acetomycin, a highly functionalized γ-lactone with antitumor activity, was achieved in five steps with nearly complete enantioselectivity. The key step was realized by a large scale lipase R catalyzed esterification of 5-hydroxy-4-methyl-2(5H)-furanone providing

  16. Synthesis de 1-dotriacotanol

    International Nuclear Information System (INIS)

    Hernandez, L.; Gonzalez, J.C.

    1996-01-01

    In order to prepare isotopic labeled long chain aliphatic primary alcohol's, the synthesis overall yielding and chemical purity of 1-dotriacotanol were 41% and 98%, respectively. This procedure is very useful for carbon-14 and tritium labeling at Beta position of saturated fatty alcohol's

  17. Synthesis of Camalexin

    Directory of Open Access Journals (Sweden)

    V. Kovacik

    2001-08-01

    Full Text Available In this paper we describe a new method for the synthesis of camalexin (1 based on the reaction of 1-(tert-butoxycarbonylindole-3-carboxaldehyde with methyl Lcysteinate hydrochloride, followed by oxidation and decarboxylation. Compounds 1, and intermediates 5-7 were identified by elemental analysis, 1H NMR, 13C NMR and mass spectroscopy.

  18. Synthesis of Camalexin

    OpenAIRE

    Dzurilla, M.; Kutschy, P.; Zaletova, J.; Ruzinsky, M.; Kovacik, V.

    2001-01-01

    In this paper we describe a new method for the synthesis of camalexin (1) based on the reaction of 1-(tert-butoxycarbonyl)indole-3-carboxaldehyde with methyl Lcysteinate hydrochloride, followed by oxidation and decarboxylation. Compounds 1, and intermediates 5-7 were identified by elemental analysis, 1H NMR, 13C NMR and mass spectroscopy.

  19. Synthesis of acrylic prepolymer

    International Nuclear Information System (INIS)

    Hussin bin Mohd Nor; Dahlan bin Haji Mohd; Mohamad Hilmi bin Mahmood.

    1988-04-01

    An acrylic prepolymer was synthesized from glycidyl methacrylate (GMA), butyl methacrylate (BMA), methyl methacrylate (MMA) and acrylic acid (AA). Butyl acetate (BAc), benzoyl peroxide (BzO), 4-methoxyphenol (MPh) and triethylamine (TEA) were used as solvent, initiator, inhibitor and catalyst respectively. Observations of the synthesis leading to the formation of acrylic prepolymer are described. (author)

  20. Synthesis, characterization and properties

    Indian Academy of Sciences (India)

    Unknown

    C−H⋅⋅⋅O bonds leading to an intricate hydrogen bonding network. Keywords. Synthesis .... in the refinement riding on their respective parent atoms. ..... nent peaks at 326 and 255 nm which can be assigned to transitions of the intramolecularly hydrogen-bon- ded salicylidenimino chromophore. Cotton effects of negative ...

  1. Synthesis of new radiotracers

    International Nuclear Information System (INIS)

    Chahed, Ahlem

    2008-01-01

    The brain's sensibility besides to the rigorous selectivity of changes taking place on brain's barriers leads us to synthesis specifics radiotracers based on diamine ethylene and marked with technetium radioisotope to form a radiotracer able to pass these barriers and diagnose illnesses in an early stage. These radiotracers are tested by a biodistribution on a small animal to be ratified. (Author)

  2. Synthesis of arabinoxylan fragments

    DEFF Research Database (Denmark)

    Underlin, Emilie Nørmølle; Böhm, Maximilian F.; Madsen, Robert

    , or production of commercial chemicals which are mainly obtained from fossil fuels today.The arbinoxylan fragments have a backbone of β-1,4-linked xylans with α-L-arabinose units attached at specific positions. The synthesis ultilises an efficient synthetic route, where all the xylan units can be derived from D...

  3. Total synthesis of aquatolide

    NARCIS (Netherlands)

    Saya, J.M.; Vos, K.; Klein Nijenhuis, R.A.; van Maarseveen, J.H.; Ingemann, S.; Hiemstra, H.

    2015-01-01

    A total synthesis of the sesquiterpene lactone aquatolide has been accomplished. The central step is an intramolecular [2 + 2]-photocycloaddition of an allene onto an alpha,beta-unsaturated delta-lactone. Other key steps are an intramolecular Horner-Wadsworth-Emmons reaction to close the lactone and

  4. The synthesis of gemcitabine.

    Science.gov (United States)

    Brown, Kylie; Dixey, Michael; Weymouth-Wilson, Alex; Linclau, Bruno

    2014-03-31

    Gemcitabine is a fluorinated nucleoside currently administered against a number of cancers. It consists of a cytosine base and a 2-deoxy-2,2-difluororibose sugar. The synthetic challenges associated with the introduction of the fluorine atoms, as well as with nucleobase introduction of 2,2-difluorinated sugars, combined with the requirement to have an efficient process suitable for large scale synthesis, have spurred significant activity towards the synthesis of gemcitabine exploring a wide variety of synthetic approaches. In addition, many methods have been developed for selective crystallisation of diastereomeric (including anomeric) mixtures. In that regard, the 2-deoxy-2,2-difluororibose sugar is one of the most investigated fluorinated carbohydrates in terms of its synthesis. The versatility of synthetic methods employed is illustrative of the current state of the art of fluorination methodology for the synthesis of CF2-containing carbohydrates, and involves the use of fluorinated building blocks, as well as nucleophilic and electrophilic fluorination of sugar precursors. Copyright © 2014. Published by Elsevier Ltd.

  5. Synthesis of the catalyst

    Indian Academy of Sciences (India)

    Admin

    62 11; Palhagen S, Canger R, Henriksen O, Van Parys J A, Riviere M E and Karolchyk M A 2001 Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy; Epilepsy Res. 43, 115; Bakunov S A, Bakunova S M, Wenzler T, Ghebru M, Werbovetz K A, Brun R and Tidwell R R 2010 Synthesis ...

  6. Industrial scale gene synthesis.

    Science.gov (United States)

    Notka, Frank; Liss, Michael; Wagner, Ralf

    2011-01-01

    The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. A Propensity for n-omega-Amino Acids in Thermally-Altered Antarctic Meteorites

    Science.gov (United States)

    Burton, Aaron S.; Elsila, Jamie E.; Callahan, Michael P.; Martin, Mildred G.; Glavin, Daniel P.; Johnson, Natasha M.; Dworkin, Jason P.

    2012-01-01

    Carbonaceous meteorites are known to contain a wealth of indigenous organic molecules, including amino acids, which suggests that these meteorites could have been an important source of prebiotic organic material during the origins of life on Earth and possibly elsewhere. We report the detection of extraterrestrial amino acids in thermally-altered type 3 CV and CO carbonaceous chondrites and ureilites recovered from Antarctica. The amino acid concentrations of the thirteen Antarctic meteorites were generally less abundant than in more amino acid-rich CI, CM, and CR carbonaceous chondrites that experienced much lower temperature aqueous alteration on their parent bodies. In contrast to low-temperature aqueously-altered meteorites that show complete structural diversity in amino acids formed predominantly by Strecker-cyanohydrin synthesis, the thermally-altered meteorites studied here are dominated by small, straight-chain, amine terminal (n-omega-amino) amino acids that are not consistent with Strecker formation. The carbon isotopic ratios of two extraterrestrial n-omega-amino acids measured in one of the CV chondrites are consistent with C-13-depletions observed previously in hydrocarbons produced by Fischer-Tropsch type reactions. The predominance of n-omega-amino acid isomers in thermally-altered meteorites hints at cosmochemical mechanisms for the preferential formation and preservation of a small subset of the possible amino acids.

  8. Asymmetric Synthesis of Fluoroamines from Chiral Aziridines

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyeonjeong; Yoon, Dooha; Ha, Hyunjoon [Hankuk Univ. of Foreign Studies, Yongin (Korea, Republic of); Son, Se In; Lee, Won Koo [Sogang Univ., Seoul (Korea, Republic of)

    2014-03-15

    We described an efficient preparation of fluoroamines by the ring-opening reactions of chiral aziridines with Et{sub 3}N·3HF. At most cases both regioisomers were obtained from the ring openings at C2 and C3 positions depending on the substituents at C2 of the starting substrates.The fluorinated organic molecules have attracted great attentions from synthetic and medicinal chemists with wide use of various agrochemicals and pharmaceuticals. Their uniqueness is originated from its electronic characteristics and the small size without altering the molecular conformations of non-fluorinated compounds. The fluorine is the second most widely used atom in the commercial drugs following the amine. Thereby, the elaboration of fluoro-amines bearing two most widely used atoms in drugs is one of the most challenging problems in drug synthesis and its development.

  9. Total Chemical Synthesis of Modified Histones.

    Science.gov (United States)

    Qi, Yun-Kun; Ai, Hua-Song; Li, Yi-Ming; Yan, Baihui

    2018-01-01

    In the post-genome era, epigenetics has received increasing attentions in recent years. The post-translational modifications (PTMs) of four core histones play central roles in epigenetic regulation of eukaryotic genome by either directly altering the biophysical properties of nucleosomes or by recruiting other effector proteins. In order to study the biological functions and structural mechanisms of these histone PTMs, an obligatory step is to prepare a sufficient amount of homogeneously modified histones. This task cannot be fully accomplished either by recombinant technology or enzymatic modification. In this context, synthetic chemists have developed novel protein synthetic tools and state-of-the-art chemical ligation strategies for the preparation of homologous modified histones. In this review, we summarize the recent advances in the preparation of modified histones, focusing on the total chemical synthesis strategies. The importance and potential of synthetic chemistry for the study of histone code will be also discussed.

  10. Convenient synthesis and application of versatile nucleic acid lipid membrane anchors in the assembly and fusion of liposomes

    DEFF Research Database (Denmark)

    Ries, Oliver; Löffler, Philipp M. G.; Vogel, Stefan

    2015-01-01

    or the construction of DNA origami structures. We herein present the synthesis and applications of versatile lipid membrane anchor building blocks suitable for solid phase oligonucleotide synthesis. These are readily synthesized in bulk in five to seven steps from commercially available precursors and can...... be incorporated at any position within an oligonucleotide without significantly altering duplex stability and structure as proven by thermal denaturation experiments and circular dichroism. Furthermore, applicability could be demonstrated by assembly and fusion of liposomes mediated by lipid...

  11. Synthesis and characterization of nanosize sodium titanates

    Energy Technology Data Exchange (ETDEWEB)

    Elvington, M. C.; Tosten, M.; Taylor-Pashow, K. M. L.; Hobbs, D. T., E-mail: david.hobbs@srnl.doe.gov [Savannah River National Laboratory (United States)

    2012-11-15

    This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST). The synthesis method was derived from a sol-gel process used to produce micron-sized monosodium titanate (MST). Key modifications to this process include altering reagent concentrations, omitting a particle seed step, and introducing a non-ionic surfactant to facilitate control of particle formation and growth. The nMST material exhibits spherical-shaped particle morphology with a monodisperse distribution of particle diameters in the range from 100 to 150 nm. The BET surface area and isoelectric point of the nMST measured 285 m{sup 2} g{sup -1} and 3.34 pH units, respectively, which is more than an order of magnitude higher in surface area and a pH unit lower than that measured for the microsize MST. The nMST material serves as an effective ion exchanger under both weakly acidic and strongly alkaline conditions and was converted to a peroxotitanate form by reaction with hydrogen peroxide.

  12. Systematic Review and Meta-Analysis on Incidence of Altered Sensation of Mandibular Implant Surgery

    Science.gov (United States)

    Lin, Chia-Shu; Wu, Shih-Yun; Huang, Hsin-Yi; Lai, Yu-Lin

    2016-01-01

    Altered sensation (including paresthesia, dysesthesia and hypoesthesia) after mandibular implant surgery may indicate transient or permanent injury of the inferior alveolar nerve and the mental branch, and considerably lower patients’ satisfaction about the therapy. Previous studies have shown a great degree of variability on the incidence of altered sensation. We here reported the incidence of altered sensation after mandibular implant surgery based on a meta-analysis of 26 articles published between 1990.1.1 and 2016.1.1. Study quality and risk of bias was assessed and the studies with a lower score were excluded in the meta-analysis. Data synthesis was performed using the logistic-normal random-effect model. The meta-analyses revealed that the short-term (10 days after implant placement) and long-term (1 year after implant placement) incidence was 13% (95% CI, 6%-25%) and 3% (95% CI, 1%-7%), respectively. (2) For the patients who initially reported altered sensation, 80% (95% CI, 52%-94%) of them would return to normal sensation within 6 months after surgery, and 91% (95% CI, 78%-96%) of them would return to normal sensation one year after surgery. We concluded that dentist-patient communication about the risk of altered sensation is critical to treatment planning, since the short-term incidence of altered sensation is substantial (13%). When a patient reports altered sensation, regular assessment for 6 months would help tracing the changes of symptoms. In terms of long-term follow-up (1 year after surgery), the incidence is much lower (3%) and most patients (91%) would return to normal sensation. PMID:27100832

  13. Alterations of intestinal glycoprotein hydrolases in congenital diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Najjar, S.M.

    1989-01-01

    The diabetic BioBreed (BB{sub d}) rat was used for the study of the molecular structure of intestinal brush border sucrase-{alpha}-dextrinase (SD) and aminooligopeptidase (AOP) in diabetes mellitus. The specific catalytic activity of S-D and AOP in the BB{sub d} rat is normal. However, solid-phase radioimmunoassay revealed loss of some antigenic determinants in the BB{sub d} rat. S-D and AOP migrated abnormally on 6% SDS-gel electrophoresis in the BB{sub d} rat. S was larger (+5 kDa), D was either smaller (-5 kDa) or unaltered, and AOP was smaller (-5 kDa) in the BB{sub d} than in the normal Wistar. The structural abnormalities were independent of hyperglycemia or ketoacidosis and restored to normal by daily insulin treatment (NPH, 3-4 units/rat) for two to three weeks. Newly-synthesized brush border hydrolases were examined after 6 hours of intraperitoneal injection of ({sup 35}S) methionine (2 mCi) and found to be altered, suggesting that structural abnormality appeared acutely during intracellular synthesis rather than being due to slow extracellular modifications such as non-enzymatic glycosylation. Deglycosylation of brush border proteins by trifluoromethanesulfonic acid resulted in an apoprotein with normal electrophoretic migration in BB{sub d}, indicating that the alteration was due to the carbohydrates component of the glycoprotein. Pulse-chase studies with ({sup 35}S) methionine were consistent with normal protein an co-translational and initial N-linked carbohydrate assembly in association with the endoplasmic reticulum in BB{sub d}. However, the post-translational maturation of N-linked and addition of 0-linked carbohydrate chains in Golgi were prolonged, and produced a larger single-chain precursor of S-D in BB{sub d} than normal.

  14. Alterations of intestinal glycoprotein hydrolases in congenital diabetes

    International Nuclear Information System (INIS)

    Najjar, S.M.

    1989-01-01

    The diabetic BioBreed (BB d ) rat was used for the study of the molecular structure of intestinal brush border sucrase-α-dextrinase (SD) and aminooligopeptidase (AOP) in diabetes mellitus. The specific catalytic activity of S-D and AOP in the BB d rat is normal. However, solid-phase radioimmunoassay revealed loss of some antigenic determinants in the BB d rat. S-D and AOP migrated abnormally on 6% SDS-gel electrophoresis in the BB d rat. S was larger (+5 kDa), D was either smaller (-5 kDa) or unaltered, and AOP was smaller (-5 kDa) in the BB d than in the normal Wistar. The structural abnormalities were independent of hyperglycemia or ketoacidosis and restored to normal by daily insulin treatment (NPH, 3-4 units/rat) for two to three weeks. Newly-synthesized brush border hydrolases were examined after 6 hours of intraperitoneal injection of [ 35 S] methionine (2 mCi) and found to be altered, suggesting that structural abnormality appeared acutely during intracellular synthesis rather than being due to slow extracellular modifications such as non-enzymatic glycosylation. Deglycosylation of brush border proteins by trifluoromethanesulfonic acid resulted in an apoprotein with normal electrophoretic migration in BB d , indicating that the alteration was due to the carbohydrates component of the glycoprotein. Pulse-chase studies with [ 35 S] methionine were consistent with normal protein an co-translational and initial N-linked carbohydrate assembly in association with the endoplasmic reticulum in BB d . However, the post-translational maturation of N-linked and addition of 0-linked carbohydrate chains in Golgi were prolonged, and produced a larger single-chain precursor of S-D in BB d than normal

  15. Locomotion in Lymphocytes is Altered by Differential PKC Isoform Expression

    Science.gov (United States)

    Sundaresan, A.; Risin, D.; Pellis, N. R.

    1999-01-01

    Lymphocyte locomotion is critical for proper elicitation of the immune response. Locomotion of immune cells via the interstitium is essential for optimal immune function during wound healing, inflammation and infection. There are conditions which alter lymphocyte locomotion and one of them is spaceflight. Lymphocyte locomotion is severely inhibited in true spaceflight (true microgravity) and in rotating wall vessel culture (modeled microgravity). When lymphocytes are activated prior to culture in modeled microgravity, locomotion is not inhibited and the levels are comparable to those of static cultured lymphocytes. When a phorbol ester (PMA) is used in modeled microgravity, lymphocyte locomotion is restored by 87%. This occurs regardless if PMA is added after culture in the rotating wall vessel or during culture. Inhibition of DNA synthesis also does not alter restoration of lymphocyte locomotion by PMA. PMA is a direct activator of (protein kinase C) PKC . When a calcium ionophore, ionomycin is used it does not possess any restorative properties towards locomotion either alone or collectively with PMA. Since PMA brings about restoration without help from calcium ionophores (ionomycin), it is infer-red that calcium independent PKC isoforms are involved. Changes were perceived in the protein levels of PKC 6 where levels of the protein were downregulated at 24,72 and 96 hours in untreated rotated cultures (modeled microgravity) compared to untreated static (1g) cultures. At 48 hours there is an increase in the levels of PKC & in the same experimental set up. Studies on transcriptional and translational patterns of calcium independent isoforms of PKC such as 8 and E are presented in this study.

  16. Voice synthesis application

    Science.gov (United States)

    Lightstone, P. C.; Davidson, W. M.

    1982-04-01

    The military detection assessment laboratory houses an experimental field system which assesses different alarm indicators such as fence disturbance sensors, MILES cables, and microwave Racons. A speech synthesis board which could be interfaced, by means of a computer, to an alarm logger making verbal acknowledgement of alarms possible was purchased. Different products and different types of voice synthesis were analyzed before a linear predictive code device produced by Telesensory Speech Systems of Palo Alto, California was chosen. This device is called the Speech 1000 Board and has a dedicated 8085 processor. A multiplexer card was designed and the Sp 1000 interfaced through the card into a TMS 990/100M Texas Instrument microcomputer. It was also necessary to design the software with the capability of recognizing and flagging an alarm on any 1 of 32 possible lines. The experimental field system was then packaged with a dc power supply, LED indicators, speakers, and switches, and deployed in the field performing reliably.

  17. Synthesis of quantum dots

    Science.gov (United States)

    McDaniel, Hunter

    2017-10-17

    Common approaches to synthesizing alloyed quantum dots employ high-cost, air-sensitive phosphine complexes as the selenium precursor. Disclosed quantum dot synthesis embodiments avoid these hazardous and air-sensitive selenium precursors. Certain embodiments utilize a combination comprising a thiol and an amine that together reduce and complex the elemental selenium to form a highly reactive selenium precursor at room temperature. The same combination of thiol and amine acts as the reaction solvent, stabilizing ligand, and sulfur source in the synthesis of quantum dot cores. A non-injection approach may also be used. The optical properties of the quantum dots synthesized by this new approach can be finely tuned for a variety of applications by controlling size and/or composition of size and composition. Further, using the same approach, a shell can be grown around a quantum dot core that improves stability, luminescence efficiency, and may reduce toxicity.

  18. Prebiotic synthesis of histidine

    Science.gov (United States)

    Shen, C.; Yang, L.; Miller, S. L.; Oro, J.

    1990-01-01

    The prebiotic formation of histidine (His) has been accomplished experimentally by the reaction of erythrose with formamidine followed by a Strecker synthesis. In the first step of this reaction sequence, the formation of imidazole-4-acetaldehyde took place by the condensation of erythrose and formamidine, two compounds that are known to be formed under prebiotic conditions. In a second step, the imidazole-4-acetaldehyde was converted to His, without isolation of the reaction products by adding HCN and ammonia to the reaction mixture. LC, HPLC, thermospray liquid chromatography-mass spectrometry, and tandem mass spectrometry were used to identify the product, which was obtained in a yield of 3.5% based on the ratio of His/erythrose. This is a new chemical synthesis of one of the basic amino acids which had not been synthesized prebiotically until now.

  19. Distributed PROMPT-LTL Synthesis

    Directory of Open Access Journals (Sweden)

    Swen Jacobs

    2016-09-01

    Full Text Available We consider the synthesis of distributed implementations for specifications in Prompt Linear Temporal Logic (PROMPT-LTL, which extends LTL by temporal operators equipped with parameters that bound their scope. For single process synthesis it is well-established that such parametric extensions do not increase worst-case complexities. For synchronous systems, we show that, despite being more powerful, the distributed realizability problem for PROMPT-LTL is not harder than its LTL counterpart. For asynchronous systems we have to consider an assume-guarantee synthesis problem, as we have to express scheduling assumptions. As asynchronous distributed synthesis is already undecidable for LTL, we give a semi-decision procedure for the PROMPT-LTL assume-guarantee synthesis problem based on bounded synthesis.

  20. Microwave multicomponent synthesis.

    Science.gov (United States)

    Hügel, Helmut M

    2009-12-01

    In the manner that very important research is often performed by multidisciplinary research teams, the applications of multicomponent reactions involving the combination of multiple starting materials with different functional groups leading to the higher efficiency and environmentally friendly construction of multifunctional/complex target molecules is growing in importance. This review will explore the advances and advantages in microwave multicomponent synthesis (MMS) that have been achieved over the last five years.

  1. Microwave Multicomponent Synthesis

    Directory of Open Access Journals (Sweden)

    Helmut M. Hügel

    2009-12-01

    Full Text Available In the manner that very important research is often performed by multidisciplinary research teams, the applications of multicomponent reactions involving the combination of multiple starting materials with different functional groups leading to the higher efficiency and environmentally friendly construction of multifunctional/complex target molecules is growing in importance. This review will explore the advances and advantages in microwave multicomponent synthesis (MMS that have been achieved over the last five years.

  2. Microwave Multicomponent Synthesis

    OpenAIRE

    Helmut M. Hügel

    2009-01-01

    In the manner that very important research is often performed by multidisciplinary research teams, the applications of multicomponent reactions involving the combination of multiple starting materials with different functional groups leading to the higher efficiency and environmentally friendly construction of multifunctional/complex target molecules is growing in importance. This review will explore the advances and advantages in microwave multicomponent synthesis (MMS) that have been achiev...

  3. Synthesis of functionalised sulfonamides

    OpenAIRE

    Mok, B. L.

    2008-01-01

    Sulfonamides are important therapeutic agents and have a diverse array of biological functions in biology and medicine. Their means of synthesis has often involved the use of unstable sulfonyl chloride species; however, recent research has established pentafluorophenyl (PFP) sulfonate esters as a useful stable alternative to such species. This thesis describes the use of PFP vinyl sulfonate in a [3+2] cycloaddition with a variety of N-methyl-nitrones, providing access to the corresponding...

  4. Phase contrast image synthesis

    DEFF Research Database (Denmark)

    Glückstad, J.

    1996-01-01

    A new method is presented for synthesizing arbitrary intensity patterns based on phase contrast imaging. The concept is grounded on an extension of the Zernike phase contrast method into the domain of full range [0; 2 pi] phase modulation. By controlling the average value of the input phase funct...... function and by choosing appropriate phase retardation at the phase contrast filter, a pure phase to intensity imaging is accomplished. The method presented is also directly applicable in dark field image synthesis....

  5. Integrated methanol synthesis

    International Nuclear Information System (INIS)

    Jaeger, W.

    1982-01-01

    This invention concerns a plant for methanol manufacture from gasified coal, particularly using nuclear power. In order to reduce the cost of the hydrogen circuits, the methanol synthesis is integrated in the coal gasification plant. The coal used is gasified with hydration by means of hydrogen and the crude gas emerging, after cooling and separating the carbon dioxide and hydrogen sulphide, is mixed with the synthetic gas leaving the methane cracking furnace. This mixture is taken to the methanol synthesis and more than 90% is converted into methanol in one pass. The gas mixture remaning after condensation and separation of methanol is decomposed into three fractions in low temperature gas decomposition with a high proportion of unconverted carbon monoxide. The flow of methane is taken to the cracking furnace with steam, the flow of hydrogen is taken to the hydrating coal gasifier, and the flow of carbon monoxide is taken to the methanol synthesis. The heat required for cracking the methane can either be provided by a nuclear reactor or by the coke left after hydrating gasification. (orig./RB) [de

  6. Gold Nanoparticle Microwave Synthesis

    International Nuclear Information System (INIS)

    Krantz, Kelsie E.; Christian, Jonathan H.; Coopersmith, Kaitlin; Washington II, Aaron L.; Murph, Simona H.

    2016-01-01

    At the nanometer scale, numerous compounds display different properties than those found in bulk material that can prove useful in areas such as medicinal chemistry. Gold nanoparticles, for example, display promise in newly developed hyperthermia therapies for cancer treatment. Currently, gold nanoparticle synthesis is performed via the hot injection technique which has large variability in final particle size and a longer reaction time. One underdeveloped area by which these particles could be produced is through microwave synthesis. To initiate heating, microwaves agitate polar molecules creating a vibration that gives off the heat energy needed. Previous studies have used microwaves for gold nanoparticle synthesis; however, polar solvents were used that partially absorbed incident microwaves, leading to partial thermal heating of the sample rather than taking full advantage of the microwave to solely heat the gold nanoparticle precursors in a non-polar solution. Through this project, microwaves were utilized as the sole heat source, and non-polar solvents were used to explore the effects of microwave heating only as pertains to the precursor material. Our findings show that the use of non-polar solvents allows for more rapid heating as compared to polar solvents, and a reduction in reaction time from 10 minutes to 1 minute; this maximizes the efficiency of the reaction, and allows for reproducibility in the size/shape of the fabricated nanoparticles.

  7. Gold Nanoparticle Microwave Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Krantz, Kelsie E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Christian, Jonathan H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Coopersmith, Kaitlin [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Washington, II, Aaron L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Murph, Simona H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-07-27

    At the nanometer scale, numerous compounds display different properties than those found in bulk material that can prove useful in areas such as medicinal chemistry. Gold nanoparticles, for example, display promise in newly developed hyperthermia therapies for cancer treatment. Currently, gold nanoparticle synthesis is performed via the hot injection technique which has large variability in final particle size and a longer reaction time. One underdeveloped area by which these particles could be produced is through microwave synthesis. To initiate heating, microwaves agitate polar molecules creating a vibration that gives off the heat energy needed. Previous studies have used microwaves for gold nanoparticle synthesis; however, polar solvents were used that partially absorbed incident microwaves, leading to partial thermal heating of the sample rather than taking full advantage of the microwave to solely heat the gold nanoparticle precursors in a non-polar solution. Through this project, microwaves were utilized as the sole heat source, and non-polar solvents were used to explore the effects of microwave heating only as pertains to the precursor material. Our findings show that the use of non-polar solvents allows for more rapid heating as compared to polar solvents, and a reduction in reaction time from 10 minutes to 1 minute; this maximizes the efficiency of the reaction, and allows for reproducibility in the size/shape of the fabricated nanoparticles.

  8. Approach to syncope and altered mental status.

    Science.gov (United States)

    MacNeill, Emily C; Vashist, Sudhir

    2013-10-01

    Children who present with an episode of altered mental status, whether transient or persistent, present a diagnostic challenge for practitioners. This article describes some of the more common causes of altered mental status and delineates a rational approach to these patients. This will help practitioners recognize the life-threatening causes of these frightening presentations as well as help avoid unnecessary testing for the more benign causes. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Effects of anaerobiosis on in vivo protein synthesis in the roots of a marine angiosperm zostera marina

    International Nuclear Information System (INIS)

    Smith, R.D.; Alberte, R.S.

    1989-01-01

    The roots of the temperate seagrass Zostera marina undergo daily periods of anaerobiosis at night. These diurnal periods of anoxia alter many metabolic processes in the roots including carbon and nitrogen metabolism, amino acid synthesis, and synthesis and levels of ATP, ADP and AMP. To further characterize the effects of anaerobiosis, we determined in vivo rates of protein synthesis by measuring the relative incorporation of 35 S-MET in TCA precipitated protein samples. Results from these studies show that in vivo protein synthesis decreases continuously during 12 h of anaerobiosis and correlates with changes in ATP levels under similar conditions. Furthermore, polypeptide patterns obtained by SDS-PAGE and 2D-SDSPAGE indicate that anaerobiosis leads to differential protein synthesis in the roots

  10. Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man

    International Nuclear Information System (INIS)

    Pooler, P.A.; Duane, W.C.

    1988-01-01

    In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from [26-14C]cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man

  11. Sleep Deprivation Alters Choice Strategy Without Altering Uncertainty or Loss Aversion Preferences

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman

    2015-10-01

    Full Text Available Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  12. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences.

    Science.gov (United States)

    Mullette-Gillman, O'Dhaniel A; Kurnianingsih, Yoanna A; Liu, Jean C J

    2015-01-01

    Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  13. Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

    Directory of Open Access Journals (Sweden)

    Katharine A. Horzmann

    2016-08-01

    Full Text Available Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed.

  14. Phospholipid synthesis participates in the regulation of diacylglycerol required for membrane trafficking at the Golgi complex.

    Science.gov (United States)

    Sarri, Elisabet; Sicart, Adrià; Lázaro-Diéguez, Francisco; Egea, Gustavo

    2011-08-12

    The lipid metabolite diacylglycerol (DAG) is required for transport carrier biogenesis at the Golgi, although how cells regulate its levels is not well understood. Phospholipid synthesis involves highly regulated pathways that consume DAG and can contribute to its regulation. Here we altered phosphatidylcholine (PC) and phosphatidylinositol synthesis for a short period of time in CHO cells to evaluate the changes in DAG and its effects in membrane trafficking at the Golgi. We found that cellular DAG rapidly increased when PC synthesis was inhibited at the non-permissive temperature for the rate-limiting step of PC synthesis in CHO-MT58 cells. DAG also increased when choline and inositol were not supplied. The major phospholipid classes and triacylglycerol remained unaltered for both experimental approaches. The analysis of Golgi ultrastructure and membrane trafficking showed that 1) the accumulation of the budding vesicular profiles induced by propanolol was prevented by inhibition of PC synthesis, 2) the density of KDEL receptor-containing punctated structures at the endoplasmic reticulum-Golgi interface correlated with the amount of DAG, and 3) the post-Golgi transport of the yellow fluorescent temperature-sensitive G protein of stomatitis virus and the secretion of a secretory form of HRP were both reduced when DAG was lowered. We confirmed that DAG-consuming reactions of lipid synthesis were present in Golgi-enriched fractions. We conclude that phospholipid synthesis pathways play a significant role to regulate the DAG required in Golgi-dependent membrane trafficking.

  15. Injury-induced inhibition of small intestinal protein and nucleic acid synthesis

    International Nuclear Information System (INIS)

    Carter, E.A.; Hatz, R.A.; Yarmush, M.L.; Tompkins, R.G.

    1990-01-01

    Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury

  16. Vitamin A Deficiency and Alterations in the Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Teresa Barber

    2014-11-01

    Full Text Available Vitamin A or retinol which is the natural precursor of several biologically active metabolites can be considered the most multifunctional vitamin in mammals. Its deficiency is currently, along with protein malnutrition, the most serious and common nutritional disorder worldwide. It is necessary for normal embryonic development and postnatal tissue homeostasis, and exerts important effects on cell proliferation, differentiation and apoptosis. These actions are produced mainly by regulating the expression of a variety of proteins through transcriptional and non-transcriptional mechanisms. Extracellular matrix proteins are among those whose synthesis is known to be modulated by vitamin A. Retinoic acid, the main biologically active form of vitamin A, influences the expression of collagens, laminins, entactin, fibronectin, elastin and proteoglycans, which are the major components of the extracellular matrix. Consequently, the structure and macromolecular composition of this extracellular compartment is profoundly altered as a result of vitamin A deficiency. As cell behavior, differentiation and apoptosis, and tissue mechanics are influenced by the extracellular matrix, its modifications potentially compromise organ function and may lead to disease. This review focuses on the effects of lack of vitamin A in the extracellular matrix of several organs and discusses possible molecular mechanisms and pathologic implications.

  17. Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

    Science.gov (United States)

    He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

    2012-07-01

    Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

  18. Traumatic brain injury alters methionine metabolism: implications for pathophysiology

    Directory of Open Access Journals (Sweden)

    Pramod K Dash

    2016-04-01

    Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

  19. Synthesis, Chapter 19

    Science.gov (United States)

    L.H. Pardo; L.H. Geiser; M.E. Fenn; C.T. Driscoll; C.L. Goodale; E.B. Allen; J.S. Baron; R. Bobbink; W.D. Bowman; C.M. Clark; B. Emmett; F.S. Gilliam; T. Greaver; S.J. Hall; E.A. Lilleskov; L. Liu; J.A. Lynch; K. Nadelhoffer; S.S. Perakis; M.J. Robin-Abbott; J.L. Stoddard; K.C. Weathers

    2011-01-01

    Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition (Galloway et al. 2003). Because of past, and, in some regions, continuing increases in emissions (Lehmann et al. 2005, Nilles and Conley 2001), this N deposition has reached a level that has caused or is likely to cause alterations and damage in many ecosystems...

  20. Application of chalcones in heterocycles synthesis: Synthesis of 2 ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 125; Issue 3. Application of chalcones in heterocycles synthesis: Synthesis of 2-(isoxazolo, pyrazolo and pyrimido) substituted analogues of 1,4-benzodiazepin-5-carboxamides linked through an oxyphenyl bridge. N Kaur D Kishore. Volume 125 Issue 3 May 2013 pp ...

  1. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8, incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches

  2. Modeling GABA alterations in schizophrenia: a link between impaired inhibition and altered gamma and beta range auditory entrainment.

    Science.gov (United States)

    Vierling-Claassen, Dorea; Siekmeier, Peter; Stufflebeam, Steven; Kopell, Nancy

    2008-05-01

    The disorganized symptoms of schizophrenia, including severely disordered thought patterns, may be indicative of a problem with the construction and maintenance of cell assemblies during sensory processing and attention. The gamma and beta frequency bands (15-70 Hz) are believed relevant to such processing. This paper addresses the results of an experimental examination of the cortical response of 12 schizophrenia patients and 12 control subjects when presented with auditory click-train stimuli in the gamma/beta frequency band during measurement using magnetoencephalography (MEG), as well as earlier work by Kwon et al. These data indicate that control subjects show an increased 40-Hz response to both 20- and 40-Hz stimulation as compared with patients, whereas schizophrenic subjects show a preference for 20-Hz response to the same driving frequencies. In this work, two computational models of the auditory cortex are constructed based on postmortem studies that indicate cortical interneurons in schizophrenic subjects have decreased GAT-1 (a GABA transporter) and GAD(67) (1 of 2 enzymes responsible for GABA synthesis). The models transition from control to schizophrenic frequency response when an extended inhibitory decay time is introduced; this change captures a possible effect of these GABA alterations. Modeling gamma/beta range auditory entrainment in schizophrenia provides insight into how biophysical mechanisms can impact cognitive function. In addition, the study of dynamics that underlie auditory entrainment in schizophrenia may contribute to the understanding of how gamma and beta rhythms impact cognition in general.

  3. Synthesis of Bimetal Fe and Cu Altered TUD-1: A Mesoporous Catalyst for Phenol Hydroxylation Reaction.

    Science.gov (United States)

    Pachamuthu, Muthusamy Poomalai; Subhapriya, Pushparaju

    2018-04-01

    Fe and Cu ions incorporated (Si/Cu = 50, Si/Fe = 50 and Si/Cu + Fe = 50) amorphous, wormhole structured mesoporous catalysts (CuTUD-1, FeTUD-1 and FeCuTUD-1) (TUD-1-Technische Universiteit Delft) have been synthesized hydrothermally using low cost, non-surfactant template triethanolamine (TEA). Physicochemical properties of the catalysts were made using X-ray diffraction (XRD), Nitrogen sorption, FT-IR, DRS UV Visible, FT Raman, SEM, TEM and TG-DTG techniques. The results showed that the materials possess mesoporous, foam type morphology, surface area 485-634 m2/g, pore size 4.8-6.8 nm, pore volume 0.67-0.83 cm3/g and metal ions (Cu2+ and Fe3+) coordinative environment. The highly dispersed Cu2+ and Fe3+ active sites are observed in FeCuTUD-1 catalyst. Also, the synthesized catalysts are tested in the oxidation of phenol with hydrogen peroxide (H2O2) oxidant. Further, reaction parameters such as time, temperature, and catalyst were also investigated.

  4. Lack of Globulin Synthesis during Seed Development Alters Accumulation of Seed Storage Proteins in Rice.

    Science.gov (United States)

    Lee, Hye-Jung; Jo, Yeong-Min; Lee, Jong-Yeol; Lim, Sun-Hyung; Kim, Young-Mi

    2015-06-30

    The major seed storage proteins (SSPs) in rice seeds have been classified into three types, glutelins, prolamins, and globulin, and the proportion of each SSP varies. It has been shown in rice mutants that when either glutelins or prolamins are defective, the expression of another type of SSP is promoted to counterbalance the deficit. However, we observed reduced abundances of glutelins and prolamins in dry seeds of a globulin-deficient rice mutant (Glb-RNAi), which was generated with RNA interference (RNAi)-induced suppression of globulin expression. The expression of the prolamin and glutelin subfamily genes was reduced in the immature seeds of Glb-RNAi lines compared with those in wild type. A proteomic analysis of Glb-RNAi seeds showed that the reductions in glutelin and prolamin were conserved at the protein level. The decreased pattern in glutelin was also significant in the presence of a reductant, suggesting that the polymerization of the glutelin proteins via intramolecular disulfide bonds could be interrupted in Glb-RNAi seeds. We also observed aberrant and loosely packed structures in the storage organelles of Glb-RNAi seeds, which may be attributable to the reductions in SSPs. In this study, we evaluated the role of rice globulin in seed development, showing that a deficiency in globulin could comprehensively reduce the expression of other SSPs.

  5. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.; Reily, M.D.; Lu, Z.; Lehman-McKeeman, L.D.; Cherrington, N.J.

    2013-01-01

    Roč. 268, č. 2 (2013), s. 132-140 ISSN 0041-008X Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : Bile Acids * Liver * Metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.630, year: 2013

  6. Lack of Globulin Synthesis during Seed Development Alters Accumulation of Seed Storage Proteins in Rice

    Directory of Open Access Journals (Sweden)

    Hye-Jung Lee

    2015-06-01

    Full Text Available The major seed storage proteins (SSPs in rice seeds have been classified into three types, glutelins, prolamins, and globulin, and the proportion of each SSP varies. It has been shown in rice mutants that when either glutelins or prolamins are defective, the expression of another type of SSP is promoted to counterbalance the deficit. However, we observed reduced abundances of glutelins and prolamins in dry seeds of a globulin-deficient rice mutant (Glb-RNAi, which was generated with RNA interference (RNAi-induced suppression of globulin expression. The expression of the prolamin and glutelin subfamily genes was reduced in the immature seeds of Glb-RNAi lines compared with those in wild type. A proteomic analysis of Glb-RNAi seeds showed that the reductions in glutelin and prolamin were conserved at the protein level. The decreased pattern in glutelin was also significant in the presence of a reductant, suggesting that the polymerization of the glutelin proteins via intramolecular disulfide bonds could be interrupted in Glb-RNAi seeds. We also observed aberrant and loosely packed structures in the storage organelles of Glb-RNAi seeds, which may be attributable to the reductions in SSPs. In this study, we evaluated the role of rice globulin in seed development, showing that a deficiency in globulin could comprehensively reduce the expression of other SSPs.

  7. Alterations in the transcriptome and antibiotic susceptibility of Staphylococcus aureus grown in the presence of diclofenac

    Science.gov (United States)

    2011-01-01

    Background Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) S. aureus strains. Methods Transcriptional alterations in response to growth with diclofenac were measured using S. aureus gene expression microarrays and quantitative real-time PCR. Antimicrobial susceptibility was determined by agar diffusion MICs and gradient plate analysis. Ciprofloxacin accumulation was measured by fluorescence spectrophotometry. Results Growth of S. aureus strain COL with 80 μg/ml (0.2 × MIC) of diclofenac resulted in the significant alteration by ≥2-fold of 458 genes. These represented genes encoding proteins for transport and binding, protein and DNA synthesis, and the cell envelope. Notable alterations included the strong down-regulation of antimicrobial efflux pumps including mepRAB and a putative emrAB/qacA-family pump. Diclofenac up-regulated sigB (σB), encoding an alternative sigma factor which has been shown to be important for antimicrobial resistance. Staphylococcus aureus microarray metadatabase (SAMMD) analysis further revealed that 46% of genes differentially-expressed with diclofenac are also σB-regulated. Diclofenac altered S. aureus susceptibility to multiple antibiotics in a strain-dependent manner. Susceptibility increased for ciprofloxacin, ofloxacin and norfloxacin, decreased for oxacillin and vancomycin, and did not change for tetracycline or chloramphenicol. Mutation to DcRS did not affect susceptibility to the above antibiotics. Reduced ciprofloxacin MICs with diclofenac in strain BB255, were not associated with increased drug accumulation. Conclusions The results of

  8. Gene Synthesis with HG Khorana

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 12. Gene Synthesis with H G Khorana. Marvin H Caruthers. General Article Volume 17 Issue 12 December 2012 pp ... Keywords. Chemical synthesis of genes for yeast alanine tRNA and E. coli supressor tRNA; Khorana's philosophy on science.

  9. Organic synthesis with stable isotopes

    International Nuclear Information System (INIS)

    Blazer, R.M.; Daub, G.H.; Kerr, V.N.; Williams, D.L.; Whaley, T.W.

    1982-01-01

    Described is a scheme for the synthesis of L-arginine-1- 13 C utilizing methods developed for the synthesis of L-ornithine-1- 13 C from L-ornithine-2- 13 C and then converting ornithine into arginine with the enzyme acylase

  10. Chemical synthesis on SU-8

    DEFF Research Database (Denmark)

    Qvortrup, Katrine; Taveras, Kennedy; Thastrup, Ole

    2011-01-01

    In this paper we describe a highly effective surface modification of SU-8 microparticles, the attachment of appropriate linkers for solid-supported synthesis, and the successful chemical modification of these particles via controlled multi-step organic synthesis leading to molecules attached...

  11. Organic Synthesis using Clay Catalysts

    Indian Academy of Sciences (India)

    His work includes organic synthesis and reaction mechanisms mainly in the area of organosilicon chemistry. Presently he is also working on organic synthesis under solvent- free conditions and using clay-catalyses. Keywords. Montmorillonite, ion-exchange, clay-nanomaterials, dehydration pyrolysis, rearrangement, steric.

  12. First total synthesis of Boehmenan

    Indian Academy of Sciences (India)

    The first total synthesis of dilignan Boehmenan has been achieved. A biomimetic oxidative coupling of the ferulic acid methyl ester in the presence of silver oxide is the crucial step in the synthesis sequence, generating the dihydrobenzofuran skeleton. Hydroxyl group was protected with DHP and reducted with LiAlH4 to ...

  13. SHORT COMMUNICATION SYNTHESIS AND ANTIBACTERIAL ...

    African Journals Online (AJOL)

    Admin

    a. sodium nitrite, b. ethylacetoacetate, c. phenyl hydrazine, d. hydrazine hydrate, e. hydroxyl- amine hydrochloride, f. Salycylaldehye, g. chloroacetyl chloride, h. thioglycollic acid. Scheme 1. Synthesis of heterocyclic derivatives of sulfanilamide. Synthesis of compound 1 and 2a-e were done as per the reported method [7-8] ...

  14. Total synthesis of proposed auranthine.

    Science.gov (United States)

    Kshirsagar, Umesh A; Puranik, Vedavati G; Argade, Narshinha P

    2010-04-16

    Starting from CBz-protected glutamic anhydride and Boc-protected o-aminobenzyl amine, the first total synthesis of proposed structure of auranthine has been reported. An intramolecular aza-Wittig reaction involving a lactam carbonyl group that delivered the diazepine core unit was the key step in the synthesis.

  15. First total synthesis of Boehmenan

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 126; Issue 3 ... The first total synthesis of dilignan Boehmenan has been achieved. A biomimetic oxidative coupling of the ferulic acid methyl ester in the presence of silver oxide is the crucial step in the synthesis sequence, generating the dihydrobenzofuran skeleton.

  16. Stereoselective total synthesis of sphingolipids

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 128; Issue 11. Stereoselective total synthesis of sphingolipids. PARAMESH JANGILI PERLA ... Keywords. 1,2-Diacetyl D-erythro-sphinganine; 1,2-diacetyl L-threo-sphinganine; D-erythro-sphinganine triacetate; sphingolipids; total synthesis; Garner aldehyde.

  17. Chemical Synthesis of Antimicrobial Peptides.

    Science.gov (United States)

    Münzker, Lena; Oddo, Alberto; Hansen, Paul R

    2017-01-01

    Solid-phase peptide synthesis (SPPS) is the method of choice for chemical synthesis of peptides. In this nonspecialist review, we describe commonly used resins, linkers, protecting groups, and coupling reagents in 9-fluorenylmethyloxycarbonyl (Fmoc) SPPS. Finally, a detailed protocol for manual Fmoc SPPS is presented.

  18. Methyltrioctylammonium chloride catalysed sonochemical synthesis ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 125; Issue 5. Methyltrioctylammonium chloride catalysed sonochemical synthesis of acridine diones ... The greener, clean and efficient protocol for the synthesis of acridine diones derivatives has been achieved by reacting aromatic aldehyde, dimedone and amines ...

  19. Lactobacillusassisted synthesis of titanium nanoparticles

    Directory of Open Access Journals (Sweden)

    Jha Anal

    2007-01-01

    Full Text Available AbstractAn eco-friendlylactobacillussp. (microbe assisted synthesis of titanium nanoparticles is reported. The synthesis is performed at room temperature. X-ray and transmission electron microscopy analyses are performed to ascertain the formation of Ti nanoparticles. Individual nanoparticles as well as a number of aggregates almost spherical in shape having a size of 40–60 nm are found.

  20. Microemulsion Synthesis of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Gotić, M.

    2013-11-01

    Full Text Available Nanoparticles and nanomaterials have wide applications in electronics, physics, material design, being also utilized as sensors, catalysts, and more and more in biomedicine. Microemulsions are an exceptionally suitable medium for the synthesis of nanoparticles due to their thermodynamical stability, great solubility of both polar and nonpolar components, as well as their ability to control the size, dispersity and shape of the particles. This review presents microemulsion techniques for the synthesis of inorganic nanoparticles. It takes place in water-in-oil microemulsions by mixing one microemulsion with a cationic precursor, and the other with a precipitating or reducing agent, or by direct addition of reducing agents or gas (O2, NH3 ili CO2 into microemul sion (Fig. 1. Metal nanoparticles are used as catalysts, sensors, ferrofluids etc. They are produced by reducing the metal cation with a suitable reducing agent. In a similar way, one can prepare nanoparticles of alloys from the metal salts, provided that the metals are mutually soluble. The microemulsion technique is also suitable for depositing nanoparticles onto various surfaces. Highly active catalysts made from nanoparticles of Pt, Pd, Rh and other noble metals may be obtained in this way. Metal oxides and hydroxides may be prepared by hydrolysis or precipitation in the water core of microemulsion. Precipitation can be initiated by adding the base or precipitating agent into the microemulsion with water solution of metal ions. Similarly, nanoparticles may be prepared of sulphides, halogenides, cyanides, carbonates, sulphates and other insoluble metal salts. To prevent oxidation of nanoparticles, especially Fe, the particles are coated with inert metals, oxides, various polymers etc. Coating may provide additional functionality; e.g. coating with gold allows subsequent functionalization with organic compounds containing sulphur, due to the strong Au–S bond. Polymer coatings decrease

  1. Total Synthesis of Hyperforin.

    Science.gov (United States)

    Ting, Chi P; Maimone, Thomas J

    2015-08-26

    A 10-step total synthesis of the polycyclic polyprenylated acylphloroglucinol (PPAP) natural product hyperforin from 2-methylcyclopent-2-en-1-one is reported. This route was enabled by a diketene annulation reaction and an oxidative ring expansion strategy designed to complement the presumed biosynthesis of this complex meroterpene. The described work enables the preparation of a highly substituted bicyclo[3.3.1]nonane-1,3,5-trione motif in only six steps and thus serves as a platform for the construction of easily synthesized, highly diverse PPAPs modifiable at every position.

  2. Dibutylphosphoric acid synthesis

    International Nuclear Information System (INIS)

    Elias, H.; Boumaout, R.; Kellou, N.; Amedjkouh, A.; Hamidi, A.

    1995-09-01

    This work consists on the synthesis of dibutylphosphoric acis (DBP) by reaction of butanol with phosphorus pentoxid and on its separation by liquid-liquid extraction. It also deals with the characterization of DBP by some physicochemical analysis methods such as : chromatography, pH-metry and infrared and ultraviolet spectrophotometries. this study showed essentialy, that DBP can be formed in an appreciable amount (55%) when the reaction is realised with butanol/pentoxid molar ratio upper than 3 at temperature of 95 C

  3. Catalytic Oligopeptide Synthesis.

    Science.gov (United States)

    Liu, Zijian; Noda, Hidetoshi; Shibasaki, Masakatsu; Kumagai, Naoya

    2018-02-02

    Waste-free catalytic assembly of α-amino acids is fueled by a multiboron catalyst that features a characteristic B 3 NO 2 heterocycle, providing a versatile catalytic protocol wherein functionalized natural α-amino acid units are accommodated and commonly used protecting groups are tolerated. The facile dehydrative conditions eliminate the use of engineered peptide coupling reagents, exemplifying a greener catalytic alternative for peptide coupling. The catalysis is sufficiently robust to enable pentapeptide synthesis, constructing all four amide bond linkages in a catalytic fashion.

  4. Learning via Query Synthesis

    KAUST Repository

    Alabdulmohsin, Ibrahim Mansour

    2017-05-07

    Active learning is a subfield of machine learning that has been successfully used in many applications. One of the main branches of active learning is query synthe- sis, where the learning agent constructs artificial queries from scratch in order to reveal sensitive information about the underlying decision boundary. It has found applications in areas, such as adversarial reverse engineering, automated science, and computational chemistry. Nevertheless, the existing literature on membership query synthesis has, generally, focused on finite concept classes or toy problems, with a limited extension to real-world applications. In this thesis, I develop two spectral algorithms for learning halfspaces via query synthesis. The first algorithm is a maximum-determinant convex optimization method while the second algorithm is a Markovian method that relies on Khachiyan’s classical update formulas for solving linear programs. The general theme of these methods is to construct an ellipsoidal approximation of the version space and to synthesize queries, afterward, via spectral decomposition. Moreover, I also describe how these algorithms can be extended to other settings as well, such as pool-based active learning. Having demonstrated that halfspaces can be learned quite efficiently via query synthesis, the second part of this thesis proposes strategies for mitigating the risk of reverse engineering in adversarial environments. One approach that can be used to render query synthesis algorithms ineffective is to implement a randomized response. In this thesis, I propose a semidefinite program (SDP) for learning a distribution of classifiers, subject to the constraint that any individual classifier picked at random from this distributions provides reliable predictions with a high probability. This algorithm is, then, justified both theoretically and empirically. A second approach is to use a non-parametric classification method, such as similarity-based classification. In this

  5. Synthesis of deuterated clenbuterol

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, Ole [Risoe National Lab., Roskilde (Denmark). Solid State Physics Dept.; Egsgaard, Helge; Larsen, Elfinn [Risoe National Lab., Roskilde (Denmark). Science and Technology Dept.

    1996-11-01

    The synthesis of D{sub 9}-clenbuterol (I) and D{sub 3}-clenbuterol (II) is described. D{sub 9}-clenbuterol (I) was prepared from 4-amino-{alpha}-bromo-3, 5-dichloroacetophenone by reaction with D{sub 9}-tert-butylamine followed by reduction of the keto group with NaBH{sub 4}. D{sub 3}-clenbuterol (II) was prepared from 4-amino-{alpha}-tert-butylamino-3, 5-dichloroacetophenone by an exchange reaction of the {alpha}-hydrogens with deuterium followed by reduction of the keto group with NaBD{sub 4}. The eventual products were characterized by mass spectrometry and NMR. (author).

  6. Synthesis in land change science

    DEFF Research Database (Denmark)

    Magliocca, Nicholas R.; Rudel, Thomas K.; Verburg, Peter H.

    2015-01-01

    of these changes, land change science (LCS) draws on a wide array synthetic and meta-study techniques to generate global and regional knowledge from local case studies of land change. Here, we review the characteristics and applications of synthesis methods in LCS and assess the current state of synthetic research...... based on a meta-analysis of synthesis studies from 1995 to 2012. Publication of synthesis research is accelerating, with a clear trend toward increasingly sophisticated and quantitative methods, including meta-analysis. Detailed trends in synthesis objectives, methods, and land change phenomena......, synthesis methods based on local case studies will remain essential for generating systematic global and regional understanding of local land change for the foreseeable future, and multiple opportunities exist to accelerate and enhance the reliability of synthetic LCS research in the future. Demand...

  7. Public health implications of altered puberty timing

    DEFF Research Database (Denmark)

    Golub, M.S.; Collman, G.W.; Foster, P.M.

    2008-01-01

    Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early...... sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated....... Altered timing of puberty also has implications for behavioral disorders. For example, an early maturation is associated with a greater incidence of conduct and behavior disorders during adolescence. Finally, altered puberty timing is considered an adverse effect in reproductive toxicity risk assessment...

  8. Public health implications of altered puberty timing

    DEFF Research Database (Denmark)

    Golub, M.S.; Collman, G.W.; Foster, P.M.

    2008-01-01

    sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated....... Altered timing of puberty also has implications for behavioral disorders. For example, an early maturation is associated with a greater incidence of conduct and behavior disorders during adolescence. Finally, altered puberty timing is considered an adverse effect in reproductive toxicity risk assessment......Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early...

  9. Mortar alteration: experimental study and ancient analogues

    International Nuclear Information System (INIS)

    Rassineux, Francois

    1987-01-01

    As the durability of cemented matrices is a matter of great importance in numerous domains, notably for the long term reliability of surface storages of radioactive wastes, the objective of this research thesis is to define mechanisms of evolution of cemented matrices when in contact with diluted aqueous solutions. The author notably studied the influence of the lixiviation mode on the evolution of two mortars having different compositions (pH, CO 2 pressure, system containment, and cement mineralogical nature appear to be the main governing parameters), the alteration (dissolution is the prevailing process in the interaction between cemented matrices and a diluted solution such as rain water), and ancient binders (archaeological binders containing mineral phases such as hydrated calcium silicates or hydro-grossulars). The obtained results lead to the definition of alteration mechanisms in modern cements, and highlight factors governing the durability of these materials when submitted to meteoric alteration [fr

  10. Alterations in physiology and anatomy during pregnancy.

    Science.gov (United States)

    Tan, Eng Kien; Tan, Eng Loy

    2013-12-01

    Pregnant women undergo profound anatomical and physiological changes so that they can cope with the increased physical and metabolic demands of their pregnancies. The cardiovascular, respiratory, haematological, renal, gastrointestinal and endocrine systems all undergo important physiological alterations and adaptations needed to allow development of the fetus and to allow the mother and fetus to survive the demands of childbirth. Such alterations in anatomy and physiology may cause difficulties in interpreting signs, symptoms, and biochemical investigations, making the clinical assessment of a pregnant woman inevitably confusing but challenging. Understanding these changes is important for every practicing obstetrician, as the pathological deviations from the normal physiological alterations may not be clear-cut until an adverse outcome has resulted. Only with a sound knowledge of the physiology and anatomy changes can the care of an obstetric parturient be safely optimized for a better maternal and fetal outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Streamflow alteration at selected sites in Kansas

    Science.gov (United States)

    Juracek, Kyle E.; Eng, Ken

    2017-06-26

    An understanding of streamflow alteration in response to various disturbances is necessary for the effective management of stream habitat for a variety of species in Kansas. Streamflow alteration can have negative ecological effects. Using a modeling approach, streamflow alteration was assessed for 129 selected U.S. Geological Survey streamgages in the State for which requisite streamflow and basin-characteristic information was available. The assessment involved a comparison of the observed condition from 1980 to 2015 with the predicted expected (least-disturbed) condition for 29 streamflow metrics. The metrics represent various characteristics of streamflow including average flow (annual, monthly) and low and high flow (frequency, duration, magnitude).Streamflow alteration in Kansas was indicated locally, regionally, and statewide. Given the absence of a pronounced trend in annual precipitation in Kansas, a precipitation-related explanation for streamflow alteration was not supported. Thus, the likely explanation for streamflow alteration was human activity. Locally, a flashier flow regime (typified by shorter lag times and more frequent and higher peak discharges) was indicated for three streamgages with urbanized basins that had higher percentages of impervious surfaces than other basins in the State. The combination of localized reservoir effects and regional groundwater pumping from the High Plains aquifer likely was responsible, in part, for diminished conditions indicated for multiple streamflow metrics in western and central Kansas. Statewide, the implementation of agricultural land-management practices to reduce runoff may have been responsible, in part, for a diminished duration and magnitude of high flows. In central and eastern Kansas, implemented agricultural land-management practices may have been partly responsible for an inflated magnitude of low flows at several sites.

  12. In utero exposure to chloroquine alters sexual development in the male fetal rat

    International Nuclear Information System (INIS)

    Clewell, Rebecca A.; Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

    2009-01-01

    Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

  13. Experimental alterations on ceramic interest basalts

    International Nuclear Information System (INIS)

    Sanfeliu-Montolio, T.; Ballbe-Lonch, E.; Querlat-Mitjans, I.; Juan-Abril, A.; Fuente-Cellell, C. de la

    1991-01-01

    This study presents the results and conclusion extracted of the chemical and mineralogical analysis made on 12 samples of recent and subrecent (IV series) Canary Island's basalt, that have been subject to different attack processes in order to cause in them controlled mineralogical alterations. The methods used were: optical analysis, x-ray fluorescence analysis and x-ray diffraction. The object of this work is to determine the alterability of these basaltic rocks that have ceramic interest since it's possible its use in same ceramic manufactures and also as petrurgic raw material. (author)

  14. Questions Regarding Alterity in Social Collaborative Networks

    Directory of Open Access Journals (Sweden)

    Florinela Floria

    2010-01-01

    Full Text Available The idea of alterity has become important in the last decades, when talking about the Information Age, which provides acknowledgement to the software development specialists about the importance of understanding the other’s behavior, needs, objectives and beliefs.
    Our main purpose is to bring to attention the question of social representation related to the images of individuals as different entities that are integrated in virtual teams, virtual projects and e-activities. Regarding the consciousness about the other’s alterity, we assert that it opens a dialogical perspective about the Information Society, where it is essential to share and communicate knowledge to the others.

  15. Direct investigations of the immobilization of radionuclides in the alteration phases of spent nuclear fuel. 1998 annual progress report

    International Nuclear Information System (INIS)

    Burns, P.C.; Finch, R.J.

    1998-01-01

    'In an oxidizing environment, such as in the proposed repository at Yucca Mountain, rapid alteration rates are expected for spent nuclear fuel. Lab.-scale simulations have repeatedly shown that the dominant alteration products under repository conditions will be uranyl phases. There is an inadequate database that relates to the effects of the alteration products on the release of radionuclides, but this information is essential to provide a radionuclide release estimate. It is likely that many of the radionuclides contained in the fuel will be incorporated into the alteration products that form, potentially with a profound impact on the future mobility of radionuclides in the repository. The authors objective is to characterize the incorporation of radionuclides into alteration products by synthesis of uranyl phases doped with radionuclides, appropriate surrogate elements, or non-radioactive isotopes, followed by detailed phase characterization by diffraction and spectroscopic techniques. The research will permit a more realistic estimate of the release rates of the radionuclides from the near-field environment. This report summarizes work after 8 months of a 3-year project. The objective of investigating radionuclide incorporation in uranyl phases has required the development of synthesis techniques for various uranyl phases that are expected to form under repository conditions. The authors have synthesized and determined the structures of several uranyl phases that are new to science and that may be important alteration products under repository conditions. They have also undertaken the determination and refinement of the crystal structures of various uranyl phases that are likely to form under repository conditions. Other experiments include the investigation of the ion-exchange properties of uranyl phases under repository conditions.'

  16. Reevaluating synthesis by biology.

    Science.gov (United States)

    Yadav, Vikramaditya G; Stephanopoulos, Gregory

    2010-06-01

    The two cornerstones of synthetic biology are the introduction of the new technology of chemical DNA synthesis and its subsequent emphasis on the use of standardized biological parts in the construction of genetic systems aimed at eliciting of desired cellular behavior. A number of high-impact applications have been proposed for this technology, notable among them being the biological synthesis of valuable compounds for chemical or pharmaceutical use. To this end, synthetic biologists propose assembling metabolic pathways in toto by combining genes isolated from a variety of sources. While pathway construction is similar to approaches established long ago by Metabolic Engineering, the two methods deviate significantly when it comes to pathway optimization. Synthetic biologists opt for gene-combinatorial methods whereby large numbers of pathways, comprising several combinations of genes from different sources, and their mutants, are evaluated in search for an optimal pathway configuration. Metabolic engineering, on the contrary, aims to optimize pathways by tuning the activity of the intermediate reaction steps. Both, rational methods based on kinetics and regulation, as well as combinatorial methods, typically in this order, are used to this end. We argue that a systematic approach consisting of fine-tuning the properties of individual pathway components, prominently enzymes, is a superior strategy to searches spanning large genetic spaces in engineering optimal microbes for the production of chemical and pharmaceutical products. Copyright 2010 Elsevier Ltd. All rights reserved.

  17. Synthesis of Lysophospholipids

    Directory of Open Access Journals (Sweden)

    Paola D’Arrigo

    2010-03-01

    Full Text Available New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs are very important in solving problems of membrane–chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs using regiospecific enzymes such as phospholipases A1 (PLA1, A2 (PLA2 phospholipase D (PLD and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo-enzymatic procedures leading to 1- and 2-LPLs will be described.

  18. Oxygenates vs. synthesis gas

    Energy Technology Data Exchange (ETDEWEB)

    Kamil Klier; Richard G. Herman; Alessandra Beretta; Maria A. Burcham; Qun Sun; Yeping Cai; Biswanath Roy

    1999-04-01

    Methanol synthesis from H{sub 2}/CO has been carried out at 7.6 MPa over zirconia-supported copper catalysts. Catalysts with nominal compositions of 10/90 mol% and 30/70 mol% Cu/ZrO{sub 2} were used in this study. Additionally, a 3 mol% cesium-doped 10/90 catalyst was prepared to study the effect of doping with heavy alkali, and this promoter greatly increased the methanol productivity. The effects of CO{sub 2} addition, water injection, reaction temperature, and H{sub 2}/C0 ratio have been investigated. Both CO{sub 2} addition to the synthesis gas and cesium doping of the catalyst promoted methanol synthesis, while inhibiting the synthesis of dimethyl ether. Injection of water, however, was found to slightly suppress methanol and dimethyl ether formation while being converted to CO{sub 2} via the water gas shift reaction over these catalysts. There was no clear correlation between copper surface area and catalyst activity. Surface analysis of the tested samples revealed that copper tended to migrate and enrich the catalyst surface. The concept of employing a double-bed reactor with a pronounced temperature gradient to enhance higher alcohol synthesis was explored, and it was found that utilization of a Cs-promoted Cu/ZnO/Cr{sub 2}O{sub 3} catalyst as a first lower temperature bed and a Cs-promoted ZnO/Cr{sub 2}O{sub 3} catalyst as a second high-temperature bed significantly promoted the productivity of 2-methyl-1-propanol (isobutanol) from H{sub 2}/CO synthesis gas mixtures. While the conversion of CO to C{sub 2+} oxygenates over the double-bed configuration was comparable to that observed over the single Cu-based catalyst, major changes in the product distribution occurred by the coupling to the zinc chromite catalyst; that is, the productivity of the C{sub 1}-C{sub 3} alcohols decreased dramatically, and 2-methyl branched alcohols were selectively formed. The desirable methanol/2-methyl oxygenate molar ratios close to 1 were obtained in the present double

  19. Response of rat brain protein synthesis to ethanol and sodium barbital

    International Nuclear Information System (INIS)

    Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

    1987-01-01

    Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14 C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the 14 C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14 C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units

  20. Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

    1987-07-01

    Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of /sup 14/C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.

  1. Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

    International Nuclear Information System (INIS)

    Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

    1987-01-01

    Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14 C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis

  2. Sulphur depletion altered somatic embryogenesis in Theobroma ...

    African Journals Online (AJOL)

    Somatic embryogenesis is a useful tool for Theobroma cacao improvement and propagation. Depending on culture medium composition, different morphogenetic structures (including somatic embryo) occur in response to alteration of genes expression patterns and biochemical changes. The effect of SO42- ion deficiency ...

  3. Plutonium alteration phases from lanthanide borosilicate glass

    International Nuclear Information System (INIS)

    Fortner, J.A.; Mertz, C.J.; Chamberlain, D.C.; Bates, J.K.

    1997-01-01

    A prototype lanthanide borosilicate (LaBS) glass containing 10 mass % plutonium was reacted with water vapor at 200 C for periods of 14 to 56 days. These tests, while not designed to replicate specific conditions that may be found in a potential geologic repository (e.g., Yucca Mountain), have been shown to accelerate alteration phase formation. The surfaces of the glass samples, along with alteration phases, were examined with a transmission electron microscope (TEM). Tests of 14 days produced macroscopic (∼ 20 microm) crystallites of a plutonium-lanthanide silicate. An extensive alteration layer was found on the glass surface containing amorphous aluminosilicate layered with bands of a cryptocrystalline plutonium silicate. After 56 days of testing, additional alteration phases were formed, including a strontium lanthanide oxide phase. One of the options for disposal of surplus plutonium, particularly for impure residues that may be unfit for production of MOX fuel, is vitrification followed by geologic disposal. Since geologic disposal requires a passive system to isolate the radiotoxic elements from the biosphere, it is important to understand the possible corrosion mechanisms of the waste form

  4. rights reserved Geophysical Identification of Hydrothermally Altered ...

    African Journals Online (AJOL)

    ADOWIE PERE

    the pole to the magnetic data aided in mapping of various hydrothermally altered structures that may favour gold mineralisation. The interpretation of the aero data set has enhanced a lot of ... water serves as a concentrating, transporting and depositing agent through faults (structures) to the earth's surface. Hydrothermal ...

  5. Alterations in the human brain in menopause

    NARCIS (Netherlands)

    Ishunina, T.A.; Swaab, D.F.

    2007-01-01

    In a series of studies we showed that menopause in women causes alterations not only in the neuronal expression of estrogen receptors (ER) alpha and beta, but also in local estrogen production in several brain areas and in the rate of neuronal metabolism. Although such changes are clearly brain

  6. Can Molecular Hippocampal Alterations Explain Behavioral ...

    Science.gov (United States)

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=15/treatment) were subjected to several non-chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non-stressed dams on GD12 but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition. Male and female stressed offspring showed reduced reversal learning on the Morris water maze and stressed females did not show a significant preference for the novel object (57 ± 8%) while control females did (71 ± 3%). This indicates altered cognition in prenatally stressed offspring. On PND 91-92, offspring were necropsied and hippocampal tissue was collected. Genotypic outcomes of prenatal stress w

  7. Altered States: Globalization, Sovereignty, and Governance | IDRC ...

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

    In Altered States, Gordon Smith and Moisés Naím provide practical recommendations for improved governance and for strengthening and reforming the United Nations. They explore the dynamics of globalization and discuss what makes today's globalization distinct. They test the prevailing wisdom about sovereignty and ...

  8. Psychobiology of Altered States of Consciousness

    Science.gov (United States)

    Vaitl, Dieter; Birbaumer, Niels; Gruzelier, John; Jamieson, Graham A.; Kotchoubey, Boris; Kubler, Andrea; Lehmann, Dietrich; Miltner, Wolfgang H. R.; Ott, Ulrich; Sammer, Gebhard; Strauch, Inge; Strehl, Ute; Wackermann, Jiri; Weiss, Thomas

    2005-01-01

    The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the…

  9. Chronic Allium sativum administration alters spontaneous ...

    African Journals Online (AJOL)

    This study was conducted to investigate the effects of Allium sativum extract on the medial prefrontal cortex and neurobehaviour of adult Wistar rats. ... altered spontaneous alternation, while cellular pathologic changes were observed in the medial prefrontal cortex of these test groups in a dose dependent sequence.

  10. Altered membrane permeability in multidrug resistant Escherichia ...

    African Journals Online (AJOL)

    The study was conducted with the objective of examining the outer membrane proteins and their involvement during the transport of β - lactams in multidrug resistant Escherichia coli isolated from extra-intestinal infections. Also, the response of gram negative bacterial biomembrane alteration was studied using extended ...

  11. Connective tissue alteration in abdominal wall hernia

    DEFF Research Database (Denmark)

    Henriksen, N A; Yadete, D H; Sørensen, Lars Tue

    2011-01-01

    The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations...... in abdominal wall hernia formation....

  12. Restraint Stress Impairs Glucose Homeostasis Through Altered ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the ...

  13. Geophysical Identification of Hydrothermally Altered Structures That ...

    African Journals Online (AJOL)

    This research study uses geophysical method (aeromagnetic) to identify hydrothermally altered structures which favour the inflow of hydrothermal fluid that usually brings about gold mineralisation in Egbe-Isanlu Schist Belt Area, North Central Nigeria. The application of data enhancement filtering algorithm such as ...

  14. Global alteration of climate - hopes and fears

    International Nuclear Information System (INIS)

    Viktorov, V.V.

    1992-01-01

    Problems concerning gaseous emission affecting the global climate alteration connected with hotbed effect are considered. Economical and social-political ways of solution of the problem of minimization of gaseous wastes are described. Role of nuclear power plants and alternative power plants in the hotbed effect are analyzed. International cooperation in environmental protection policy is discussed

  15. Rare endocrine cancers have novel genetic alterations

    Science.gov (United States)

    A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

  16. Altered gut microbiota in Rett syndrome.

    Science.gov (United States)

    Strati, Francesco; Cavalieri, Duccio; Albanese, Davide; De Felice, Claudio; Donati, Claudio; Hayek, Joussef; Jousson, Olivier; Leoncini, Silvia; Pindo, Massimo; Renzi, Daniela; Rizzetto, Lisa; Stefanini, Irene; Calabrò, Antonio; De Filippo, Carlotta

    2016-07-30

    The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status. Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles. We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT

  17. Synthesis of 2-phosphaadamantane derivatives

    International Nuclear Information System (INIS)

    Zemlyanoi, V.N.; Aleksandrov, A.M.; Kukhar', V.P.

    1986-01-01

    The authors describe the synthesis and properties of 2-phosphadamantane derivatives. For the synthesis of 2-phosphaadamantane derivatives they decided to use the methodology of the synthesis of 2-thiaadamantane. The IR spectra were determined on CHCl 3 solutions with a Specord 711R spectrometer, the PMR spectra were determined on Tesla BS-467 (60 MHz) and Bruker WP-200 (200 MHz) spectrometers, external standard hexamethyldisiloxane, the 31 P NMR spectra were determined on Tesla BS-487 C (30 MHz) and Bruker WP-200 (81 MHz) spectrometers, external standard 85% phosphoric acid, and the mass spectra were determined on an MS-1302 spectrometer

  18. Synthesis of C-vinylpyrroles

    International Nuclear Information System (INIS)

    Sobenina, Lyubov N; Demenev, Andrei P; Mikhaleva, Albina I; Trofimov, Boris A

    2002-01-01

    The latest advances in the synthesis of C-vinylpyrroles are generalised and systematised. Methods for the synthesis based on reactions of acylpyrroles and dicarbonyl compounds or their synthetic equivalents are still of most importance. New promising methods for the synthesis of C-vinylpyrroles are considered, among them the reactions of alkenyl ketone oximes with acetylene in the KOH-DMSO system and base-catalysed condensation of pyrrolecarbodithioates, which have recently become available, with CH-acids. The bibliography includes 195 references.

  19. Hypericin: chemical synthesis and biosynthesis.

    Science.gov (United States)

    Huang, Lin-Fang; Wang, Zeng-Hui; Chen, Shi-Lin

    2014-02-01

    Hypericin is one of the most important phenanthoperylene quinones extracted mainly from plants of the genus Hypericum belonging to the sections Euhypericum and Campylosporus of Keller's classification. Widespread attention to the antiviral and anti-tumor properties of hypericin has spurred investigations of the chemical synthesis and biosynthesis of this unique compound. However, the synthetic strategies are challenging for organic and biological chemists. In this review, specific significant advances in total synthesis, semi-synthesis, and biosynthesis in the past decades are summarized. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  20. PCR-based gene synthesis to produce recombinant proteins for crystallization

    Directory of Open Access Journals (Sweden)

    Byrne-Steele Miranda L

    2008-04-01

    Full Text Available Abstract Background Gene synthesis technologies are an important tool for structural biology projects, allowing increased protein expression through codon optimization and facilitating sequence alterations. Existing methods, however, can be complex and not always reproducible, prompting researchers to use commercial suppliers rather than synthesize genes themselves. Results A PCR-based gene synthesis method, referred to as SeqTBIO, is described to efficiently assemble the coding regions of two novel hyperthermophilic proteins, PAZ (Piwi/Argonaute/Zwille domain, a siRNA-binding domain of an Argonaute protein homologue and a deletion mutant of a family A DNA polymerase (PolA. The gene synthesis procedure is based on sequential assembly such that homogeneous DNA products can be obtained after each synthesis step without extensive manipulation or purification requirements. Coupling the gene synthesis procedure to in vivo homologous recombination techniques allows efficient subcloning and site-directed mutagenesis for error correction. The recombinant proteins of PAZ and PolA were subsequently overexpressed in E. coli and used for protein crystallization. Crystals of both proteins were obtained and they were suitable for X-ray analysis. Conclusion We demonstrate, by using PAZ and PolA as examples, the feasibility of integrating the gene synthesis, error correction and subcloning techniques into a non-automated gene to crystal pipeline such that genes can be designed, synthesized and implemented for recombinant expression and protein crystallization.

  1. Intestinal mucosa in diabetes: synthesis of total proteins and sucrase-isomaltase

    International Nuclear Information System (INIS)

    Olsen, W.A.; Perchellet, E.; Malinowski, R.L.

    1986-01-01

    The effects of insulin deficiency on nitrogen metabolism in muscle and liver have been extensively studied with recent in vivo demonstration of impaired protein synthesis in rats with streptozotocin-induced diabetes. Despite the significant contribution of small intestinal mucosa to overall protein metabolism, the effect of insulin deficiency on intestinal protein synthesis have not been completely defined. The authors studied the effects of streptozotocin-induced diabetes on total protein synthesis by small intestinal mucosa and on synthesis of a single enzyme protein of the enterocyte brush-border membrane sucrase-isomaltase. They used the flood-dose technique to minimize the difficulties of measuring specific radioactivity of precursor phenylalanine and determined incorporation into mucosal proteins and sucrase-isomaltase 20 min after injection of the labeled amino acid. Diabetes did not alter mucosal mass as determined by weight and content of protein and DNA during the 5 days after injection of streptozotocin. Increased rates of sucrase-isomaltase synthesis developed beginning on day 3, and those of total protein developed on day 5. Thus intestinal mucosal protein synthesis is not an insulin-sensitive process

  2. The solution combustion synthesis of nanophosphors

    Energy Technology Data Exchange (ETDEWEB)

    Tornga, Stephanie C [Los Alamos National Laboratory

    2009-01-01

    Nanophosphors are defined as nano-sized (1-100mn), insulating, inorganic materials that emit light under particle or electromagnetic excitation. Their unique luminescence properties provide an excellent potential for applications in radiation detection and imaging. Herein, solution combustion synthesis (SCS) is presented as a method to prepare nanophosphor powders, while X-ray diffraction (XRD), transmission electron microscopy (TEM), photoluminescence (PL), photoluminescence excitation (PLE), and other techniques were used to characterize their structural and optical properties. The goal of this work is to synthesize bright, high-quality powders of nanophosphors, consolidate them into bulk materials and study their structural and optical properties using XRD, TEM, PL, and PLE. SCS is of interest because it is a robust, inexpensive, and facile technique, which yields a significant amount of a wide variety of oxide materials, in a short amount of time. Several practical nanophosphors were synthesized and investigated in this work, including simple oxides such as Y{sub 2}O{sub 3}:Bi, Y{sub 2}O{sub 3}:Tb, Y{sub 2}O{sub 3}:Eu and Gd{sub 2}O{sub 3}:Eu, complex oxides such as Gd{sub 2}SiO{sub 5}:Ce, Y{sub 2}SiO{sub 5}:Ce, Lu{sub 2}SiO{sub 5}:Ce, Zn{sub 2}SiO{sub 4}:Mn, and Y{sub 3}Al{sub 5}O{sub 12}:Ce. Results demonstrate that altering the processing parameters such as water content of the precursor solution, ignition temperature, fuel type and amount, and post-synthesis annealing can significantly improve light output, and that it is possible to optimize the luminescence output of oxyorthosilicates by reducing the amount of silica in the precursor mixture.

  3. 28 CFR 36.403 - Alterations: Path of travel.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Path of travel. 36.403... Alterations: Path of travel. (a) General. An alteration that affects or could affect the usability of or... the maximum extent feasible, the path of travel to the altered area and the restrooms, telephones, and...

  4. Epigenetic alteration of sedimentary rocks at hydrogenic uranium deposit

    International Nuclear Information System (INIS)

    Ding Wanlie; Shen Kefeng

    2001-01-01

    The author introduces the concept, the recognition criteria, the genesis and classification of the epigenetic alteration of sedimentary rocks in brief, and expounds the mineral-geochemical indications and characteristics of oxidation and reduction alterations in different geochemical zones in detail, and proposes the two models of ore-controlling zonation of epigenetic alteration. The authors finally introduce research methods of epigenetic alteration

  5. Biochemical aspects of overtraining in endurance sports : the metabolism alteration process syndrome.

    Science.gov (United States)

    Petibois, Cyril; Cazorla, Georges; Poortmans, Jacques-Rémi; Déléris, Gérard

    2003-01-01

    Recent studies have shown that endurance overtraining could result from successive and cumulative alterations in metabolism, which become chronic during training. The onset of this process is a biochemical alteration in carbohydrate (saccharide) metabolism. During endurance exercises, the amount of saccharide chains from two blood glycoproteins (alpha(2)-macroglobulin and alpha(1)-acid glycoprotein) was found to have decreased, i.e. concentrations of these proteins remained unchanged but their quality changed. These saccharide chains were probably used for burning liver glycogen stores during exercise. This step was followed by alterations in lipid metabolism. The most relevant aspect of this step was that the mean chain length of blood fatty acids decreased, i.e. the same amount of fatty acids were found within the blood, but overtrained individuals presented shorter fatty acids than well-trained individuals. This suggests that alterations appeared in the liver synthesis of long-chain fatty acids or that higher peroxidation of blood lipoparticles occurred. For the final step of this overtraining process, it was found that these dysfunctions in carbohydrate/lipid metabolism led to the higher use of amino acids, which probably resulted from protein catabolism. The evolution of three protein concentrations (alpha(1)-acid glycoprotein, alpha(2)-macroglobulin and IgG(3)) correlated with this amino acid concentration increase, suggesting a specific catabolism of these proteins. At this time only, overtraining was clinically diagnosed through conventional symptoms. Therefore, this process described successive alterations in exercise metabolism that shifted from the main energetic stores of exercise (carbohydrates and lipids) towards molecular pools (proteins) normally not substantially used for the energetic supply of skeletal muscles. Now, a general biochemical model of the overtraining process may be proposed which includes most of the previously identified metabolic

  6. Synthesis of radium silicate

    International Nuclear Information System (INIS)

    Garibov, A.A; Agayev, T.N; Mansimov, Z.A

    2010-01-01

    Full text :One of the possible ways of implementation of the processes of molecular hydrogen radiologic of the elements in the differential heat of water as a catalyst for the collapse of the creation of a special nuclear reactors. A chemical process in radiation-4-oxide-silicon compounds, which is one of the radium, is of great importance. Research in the silicon-oxide-radiumun different activity-4 has been synthesized. As initial substances for the synthesis of tetra etiolate silicate and radium chloride solutions were used. At the same time to remove reaction products from the reaction intermediate in acetate acid was used. The intermediate product was reacted with ethyl alcohol ethyl acetate ether acetate acid that forms from the reaction of the temperature effect is broken. As a result, 4-oxide was initially pure silicon.

  7. The synthesis of clopidogrel

    Science.gov (United States)

    Huang, Yuanjun; Zhu, Qingxin

    2017-12-01

    Cardiac and cerebrovascular disease is a common disease. It is well recognized that antiplatelet agent is effective in the prevention and treatment of thrombosis. Clopidogrel is one of thieno pyridine derivatives, which can inhibit ADP-induced platelet aggregation. The preparation methods of Clopidogrel were reviewed and Clopidogrel was finally synthesized from 2-chlorobenzyl cyanide via bromination, condensation, hydrolyze, esterification, resolution, Finally with the sulfate, re-crystallization product of the target compound clopidogrel. The overall yield is 16%. Synthesis of the intermediate product and finally the structure of the product through ESI and 1H-NMR corroboration. The improved synthetic procedure has the advantage of low cost and is suitable for industrial production.

  8. Synthesis of cyclododeciptycene quinones.

    Science.gov (United States)

    Lou, Kaiyan; Prior, Allan M; Wiredu, Bernard; Desper, John; Hua, Duy H

    2010-12-15

    Cycloiptycenes are elusive and synthetically challenging molecules. We report the first synthesis of two substituted cyclododeciptycene tetraquinones via a sequence of intermolecular and intramolecular Diels-Alder reactions from cis,cis-heptiptycene tetraquinone 2 and substituted 7,16-dihydro-7,16-(o-benzeno)heptacenes 3. Heptiptycene tetraquinone 2 was made from triptycene bisquinone 4 and 1,4-dimethoxyanthracene in three steps, and 6,8,15,17-tetramethoxy-7,16-dihydro-7,16-(o-benzeno)heptacene (3a) was synthesized from triptycene bisquinone 4 and 1,4-dihydro-2,3-benzoxathiin-3-oxide in four steps. The structure of a cyclododeciptycene, 1a, was determined by a single-crystal X-ray analysis. The synthetic sequence is general and should allow the incorporation of various alkoxy and acetoxy substituents appended to the cycloiptycene framework.

  9. Thermodynamics of Organic Compound Alteration in Hydrothermal Systems

    Science.gov (United States)

    Shock, E. L.

    2005-12-01

    Organic compounds enter hydrothermal systems through infiltrating surface waters, zones of microbial productivity in the subsurface, extracts of organic matter in surrounding host rocks, and abiotic synthesis. Owing to variations in pH, oxidation state, composition, temperature, and pressure throughout the changing pathways of fluid migration over the duration of the system, organic compounds from all of these sources are introduced to conditions where their relative stabilities and reactivities can be dramatically transformed. If those transformations were predictable, then the extent to which organic alteration reactions have occurred could be used to reveal flowpaths and histories of hydrothermal systems. Speciation and mass transfer calculations permit some insight into the underlying thermodynamic driving forces that result in organic compound alteration. As an example, the speciation of many geochemist's canonical organic matter: CH2O depends strongly on oxidation state, temperature, and total concentration of dissolved organic matter. Calculations show that at oxidation states buffered by iron-bearing mineral assemblages, organic acids dominate the speciation of CH2O throughout hydrothermal systems, with acetic acid (itself equivalent to 2 CH2O by bulk composition) and propanoic acid generally the most abundant compounds. However, at more reduced conditions, which may prevail in organic-rich iron-poor sediments, the drive is to form ketones and especially alcohols at the expense of organic acids. The distribution of organic carbon among the various members of these compound classes is strongly dependent on the total concentration of dissolved organic matter. As an example, at a bulk concentration equivalent to average dissolved organic matter in seawater (45μm), the dominant alcohols at 100°C are small compounds like ethanol and 1-propanol. In contrast, at a higher bulk concentration of 500μm, there is a drive to shift large percentages of dissolved

  10. Genetic alterations in quadruple malignancies of a patient with multiple sclerosis: their role in malignancy development and response to therapy.

    Science.gov (United States)

    Milosevic, Zorica; Tanic, Nikola; Bankovic, Jasna; Stankovic, Tijana; Buta, Marko; Lavrnic, Dragana; Milovanovic, Zorka; Pupic, Gordana; Stojkovic, Sonja; Milinkovic, Vedrana; Ito, Yasuhiro; Dzodic, Radan

    2014-01-01

    Multiple cancers represent 2.42% of all human cancers and are mainly double or triple cancers. Many possible causes of multiple malignancies have been reported such as genetic alterations, exposure to anti-cancer chemotherapy, radiotherapy, immunosuppressive therapy and reduced immunologic response. We report a female patient with multiple sclerosis and quadruple cancers of different embryological origin. Patient was diagnosed with stage III (T3, N1a, MO) medullary thyroid carcinoma (MTC), multicentric micropapillary thyroid carcinoma, scapular and lumbar melanomas (Clark II, Breslow II), and lobular invasive breast carcinoma (T1a, NO, MO). All tumors present in our patient except micropapillary thyroid carcinomas were investigated for gene alterations known to have a key role in cancer promotion and progression. Tumor samples were screened for the p16 alterations (loss of heterozygosity and homozygous deletions), loss of heterozygosity of PTEN, p53 alterations (mutational status and loss of heterozygosity) and mutational status of RET, HRAS and KRAS. Each type of tumor investigated had specific pattern of analyzed genetic alterations. The most prominent genetic changes were mutual alterations in PTEN and p53 tumor suppressors present in breast cancer and two melanomas. These co-alterations could be crucial for promoting development of multiple malignancies. Moreover the insertion in 4(th) codon of HRAS gene was common for all tumor types investigated. It represents frameshift mutation introducing stop codon at position 5 which prevents synthesis of a full-length protein. Since the inactivated RAS enhances sensitivity to tamoxifen and radiotherapy this genetic alteration could be considered as a good prognostic factor for this patient.

  11. De Novo Glutamine Synthesis

    Science.gov (United States)

    He, Qiao; Shi, Xinchong; Zhang, Linqi; Yi, Chang; Zhang, Xuezhen

    2016-01-01

    Purpose: The aim of this study was to investigate the role of de novo glutamine (Gln) synthesis in the proliferation of C6 glioma cells and its detection with 13N-ammonia. Methods: Chronic Gln-deprived C6 glioma (0.06C6) cells were established. The proliferation rates of C6 and 0.06C6 cells were measured under the conditions of Gln deprivation along with or without the addition of ammonia or glutamine synthetase (GS) inhibitor. 13N-ammonia uptake was assessed in C6 cells by gamma counting and in rats with C6 and 0.06C6 xenografts by micro–positron emission tomography (PET) scanning. The expression of GS in C6 cells and xenografts was assessed by Western blotting and immunohistochemistry, respectively. Results: The Gln-deprived C6 cells showed decreased proliferation ability but had a significant increase in GS expression. Furthermore, we found that low concentration of ammonia was sufficient to maintain the proliferation of Gln-deprived C6 cells, and 13N-ammonia uptake in C6 cells showed Gln-dependent decrease, whereas inhibition of GS markedly reduced the proliferation of C6 cells as well as the uptake of 13N-ammoina. Additionally, microPET/computed tomography exhibited that subcutaneous 0.06C6 xenografts had higher 13N-ammonia uptake and GS expression in contrast to C6 xenografts. Conclusion: De novo Gln synthesis through ammonia–glutamate reaction plays an important role in the proliferation of C6 cells. 13N-ammonia can be a potential metabolic PET tracer for Gln-dependent tumors. PMID:27118759

  12. Enantioselective biotransformations of nitriles in organic synthesis.

    Science.gov (United States)

    Wang, Mei-Xiang

    2015-03-17

    other methods. Nitrile substrates are readily available, and the mild reaction conditions are specific toward cyano and amido functional groups without interfering with other reactive functional groups. I anticipate that further advances in this field will lead to new and engineered nitrile-hydrolyzing enzymes or catalytic systems with improved activity and altered selectivity. These advances will broaden the scope of these transformations and their applications in organic synthesis.

  13. Urinary acylcarnitines are altered in human kidney cancer.

    Science.gov (United States)

    Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

    2012-06-15

    Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

  14. Altering surface characteristics of polypropylene mesh via sodium hydroxide treatment.

    Science.gov (United States)

    Regis, Shawn; Jassal, Manisha; Mukherjee, Nilay; Bayon, Yves; Scarborough, Nelson; Bhowmick, Sankha

    2012-05-01

    Incisional hernias represent a serious and common complication following laparotomy. The use of synthetic (e.g. polypropylene) meshes to aid repair of these hernias has considerably reduced recurrence rates. While polypropylene is biocompatible and has a long successful clinical history in treating hernias and preventing reherniation, this material may suffer some limitations, particularly in challenging patients at risk of wound failure due to, for example, an exaggerated inflammation reaction, delayed wound healing, and infection. Surface modification of the polypropylene mesh without sacrificing its mechanical properties, critical for hernia repair, represents one way to begin to address these clinical complications. Our hypothesis is treatment of a proprietary polypropylene mesh with sodium hydroxide (NaOH) will increase in vitro NIH/3T3 cell attachment, predictive of earlier and improved cell colonization and tissue integration of polypropylene materials. Our goal is to achieve this altered surface functionality via enhanced removal of chemicals/oils used during material synthesis without compromising the mechanical properties of the mesh. We found that NaOH treatment does not appear to compromise the mechanical strength of the material, despite roughly a 10% decrease in fiber diameter. The treatment increases in vitro NIH/3T3 cell attachment within the first 72 h and this effect is sustained up to 7 days in vitro. This research demonstrates that sodium hydroxide treatment is an efficient way to modify the surface of polypropylene hernia meshes without losing the mechanical integrity of the material. This simple procedure could also allow the attachment of a variety of biomolecules to the polypropylene mesh that may aid in reducing the complications associated with polypropylene meshes today. Copyright © 2012 Wiley Periodicals, Inc.

  15. Vanillin Synthesis from 4-Hydroxybenzaldehyde

    Science.gov (United States)

    Taber, Douglass F.; Patel, Shweta; Hambleton, Travis M.; Winkel, Emma E.

    2007-01-01

    A regioselective, safe and efficient method for the synthesis of vanillin from 4-hydroxybenzaldehyde is being described. The vanillin derived from the process is cheap and can be used as a flavor or in the paper industry.

  16. Methyltrioctylammonium chloride catalysed sonochemical synthesis ...

    Indian Academy of Sciences (India)

    The greener, clean and efficient protocol for the synthesis of acridine diones derivatives has been achieved by reacting aromatic aldehyde, dimedone and amines using methyltrioctylammonium chloride (Aliquate 336) as a catalyst under ultrasonic irradiations.

  17. Green chemistry for nanoparticle synthesis.

    Science.gov (United States)

    Duan, Haohong; Wang, Dingsheng; Li, Yadong

    2015-08-21

    The application of the twelve principles of green chemistry in nanoparticle synthesis is a relatively new emerging issue concerning the sustainability. This field has received great attention in recent years due to its capability to design alternative, safer, energy efficient, and less toxic routes towards synthesis. These routes have been associated with the rational utilization of various substances in the nanoparticle preparations and synthetic methods, which have been broadly discussed in this tutorial review. This article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present several pivotal aspects of synthesis with environmental concerns, involving the selection and evaluation of nontoxic capping and reducing agents, the choice of innocuous solvents and the development of energy-efficient synthetic methods.

  18. Enzymatic synthesis of organophosphorus compounds

    International Nuclear Information System (INIS)

    Kolodiazhnyi, Oleg I

    2011-01-01

    Data on biocatalytic methods for the preparation of chiral organophosphorus compounds are generalized and described systematically. Various examples of enzymatic and microbiological synthesis of hydroxyphosphonates, aminophosphonates, phosphinites, phosphine oxides and tertiary phosphines are discussed. The bibliography includes 154 references.

  19. CLEAN CHEMICAL SYNTHESIS IN WATER

    Science.gov (United States)

    Newer green chemistry approach to accomplish chemical synthesis in water is summarized. Recent global developments pertaining to C-C bond forming reactions using metallic reagents and direct use of the renewable materials such as carbohydrates without derivatization are described...

  20. Gestural Control Of Wavefield synthesis

    DEFF Research Database (Denmark)

    Grani, Francesco; Di Carlo, Diego; Portillo, Jorge Madrid

    2016-01-01

    We present a report covering our preliminary research on the control of spatial sound sources in wavefield synthesis through gesture based interfaces. After a short general introduction on spatial sound and few basic concepts on wavefield synthesis, we presents a graphical application called sp......AAce which let users to con- trol real-time movements of sound sources by drawing tra- jectories on a screen. The first prototype of this application has been developed bound to WFSCollider, an open-source software based on Supercollider which let users control wavefield synthesis. The spAAce application has...... Wi- iMote game controller to “throw” sounding objects towards them. Aim of this project was to create a gestural interface for a game based on auditory cues only, and to investigate how convolution reverberation can affects people’s percep- tion of distance in a wavefield synthesis setup environment....

  1. Enzymatic synthesis of organophosphorus compounds

    Science.gov (United States)

    Kolodiazhnyi, Oleg I.

    2011-09-01

    Data on biocatalytic methods for the preparation of chiral organophosphorus compounds are generalized and described systematically. Various examples of enzymatic and microbiological synthesis of hydroxyphosphonates, aminophosphonates, phosphinites, phosphine oxides and tertiary phosphines are discussed. The bibliography includes 154 references.

  2. Alteration of consciousness in focal epilepsy: the global workspace alteration theory.

    Science.gov (United States)

    Bartolomei, Fabrice; McGonigal, Aileen; Naccache, Lionel

    2014-01-01

    Alteration of consciousness (AOC) is an important clinical manifestation of partial seizures that greatly impacts the quality of life of patients with epilepsy. Several theories have been proposed in the last fifty years. An emerging concept in neurology is the global workspace (GW) theory that postulates that access to consciousness (from several sensorial modalities) requires transient coordinated activity from associative cortices, in particular the prefrontal cortex and the posterior parietal associative cortex. Several lines of evidence support the view that partial seizures alter consciousness through disturbance of the GW. In particular, a nonlinear relation has been shown between excess of synchronization in the GW regions and the degree of AOC. Changes in thalamocortical synchrony occurring during the spreading of the ictal activity seem particularly involved in the mechanism of altered consciousness. This link between abnormal synchrony and AOC offers new perspectives in the treatment of the AOC since means of decreasing consciousness alteration in seizures could improve patients' quality of life. © 2013.

  3. Essentials of inorganic materials synthesis

    CERN Document Server

    Rao, C N R

    2015-01-01

    This compact handbook describes all the important methods of synthesis employed today for synthesizing inorganic materials. Some features: Focuses on modern inorganic materials with applications in nanotechnology, energy materials, and sustainability Synthesis is a crucial component of materials science and technology; this book provides a simple introduction as well as an updated description of methods Written in a very simple style, providing references to the literature to get details of the methods of preparation when required

  4. Levulinic acid in organic synthesis

    International Nuclear Information System (INIS)

    Timokhin, Boris V; Baransky, V A; Eliseeva, G D

    1999-01-01

    Data concerning the methods of synthesis, chemical transformations and application of levulinic acid are analysed and generalised. The wide synthetic potential of levulinic acid, particularly as a key compound in the synthesis of various heterocyclic systems, saturated and unsaturated ketones and diketones, difficultly accessible acids and other compounds is demonstrated. The accessibility of levulinic acid from hexose-containing wood-processing and agricultural wastes is noted. The bibliography includes 260 references.

  5. Diamond Synthesis Employing Nanoparticle Seeds

    Science.gov (United States)

    Uppireddi, Kishore (Inventor); Morell, Gerardo (Inventor); Weiner, Brad R. (Inventor)

    2014-01-01

    Iron nanoparticles were employed to induce the synthesis of diamond on molybdenum, silicon, and quartz substrates. Diamond films were grown using conventional conditions for diamond synthesis by hot filament chemical vapor deposition, except that dispersed iron oxide nanoparticles replaced the seeding. This approach to diamond induction can be combined with dip pen nanolithography for the selective deposition of diamond and diamond patterning while avoiding surface damage associated to diamond-seeding methods.

  6. Principles of digital image synthesis

    CERN Document Server

    Glassner, Andrew S

    1995-01-01

    Image synthesis, or rendering, is a field of transformation: it changesgeometry and physics into meaningful images. Because the most popularalgorithms frequently change, it is increasingly important for researchersand implementors to have a basic understanding of the principles of imagesynthesis. Focusing on theory, Andrew Glassner provides a comprehensiveexplanation of the three core fields of study that come together to formdigital image synthesis: the human visual system, digital signalprocessing, and the interaction of matter and light. Assuming no more thana basic background in calculus,

  7. Isolation and synthesis of curcumin

    OpenAIRE

    Zetterström, Susanna

    2012-01-01

    The aim of this thesis was to evaluate pre-existing methods for isolation and synthesis of curcumin. Two different isolation methods were used, where only the extraction step differs from each other. To obtain pure curcumin, column chromatography was needed to separate the compound from its analogues. As for the isolation the synthesis was also carried out by two different methods, the first in a conventional way and the second one by using irradiation of microwaves. The result of the experim...

  8. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  9. Synthesis of different pectinases by filamentous growing A. niger mutants.

    Science.gov (United States)

    Leuchtenberger, A; Mayer, G

    1991-01-01

    Mutants of A. niger K 69/26, prepared by multistep mutagenesis (UV, MNNG, heating) have been screened for pectinase activities. Mutants with altered levels of certain pectinases, such as endo- and exopolygalacturonase (PG vis, red), pectinesterase (PE) and pectinlyase (PL), were isolated. The enzyme activities of the best mutants M 1348/126 were increased 2-3-fold compared to the parent strain after a 6-d cultivation of filamentous mycelium on a shaker. Further mutagenesis of mutants with decreased pectinase activities (e.g. Se3) produced revertants. PG (vis) synthesis of revertant Se5 was increased 1.7 times compared to the control strain K 69/26. Independent of these increased rates, the general level of pectinase activities synthesized by the filamentous mycelium of A. niger mutants amounts to about 10-20% compared with those produced by aggregated mycelium. It appears that the enzyme synthesis related to mycelium structure is independent of the mechanism which regulates the level of pectinase synthesis within a specific morphological structure.

  10. Metabolic alterations in renal cell carcinoma.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Piva, Francesco; Modena, Alessandra; Bimbatti, Davide; Fantinel, Emanuela; Santini, Daniele; Cheng, Liang; Cascinu, Stefano; Montironi, Rodolfo; Tortora, Giampaolo

    2015-11-01

    Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  12. Epigenetic alterations of sedimentary rocks at deposits

    International Nuclear Information System (INIS)

    Komarova, G.V.; Kondrat'eva, I.A.; Zelenova, O.I.

    1980-01-01

    Notions are explained, and technique for studying epigenetic alterations of sedimentary rocks at uranium deposits is described. Main types of epigenetic transformations and their mineralogic-geochemical characteristics are considered. Rock alterations, accompanying uranium mineralization, can be related to 2 types: oxidation and reduction. The main mineralogic-geochemical property of oxidation transformations is epigenetic limonitization. Stratal limonitization in primary grey-coloured terrigenic rocks and in epigenetically reduced (pyritized) rocks, as well as in rock, subjected to epigenetic gleying, are characterized. Reduction type of epigenetic transformations is subdivided into sulphidic and non-sulphidic (gley) subtypes. Sulphidic transformations in grey-coloured terrigenic rocks with organic substance of carbonic row, in rocks, containing organic substance of oil row, sulphide transformations of sedimentary rocks, as well as gley transformations, are considered

  13. Siliceous microfossil extraction from altered Monterey rocks

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, C.O.; Casey, R.E.

    1986-04-01

    Samples of altered Monterey rocks of differing lithologies were processed by various methods to develop new techniques for extracting siliceous microfossils. The preliminary use of thin sections made from the same rocks reduced the number of probable samples (samples worth further processing) by about one-third. Most of the siliceous microfossils contained in altered Monterey rocks appear to be highly recrystallized and are extremely fragile; however, some contained silicified and silica-infilled radiolarians and planktonic and benthonic foraminifera, which are very tough. In general the most useful techniques were gently hydrochloric acid, hydrogen peroxide, formic acid, monosodium glutamate, and regular siliceous microfossil extraction techniques. Unsuccessful techniques and a new siliceous microfossil flotation technique are also documented.

  14. Altered Sensory Feedbacks in Pianist's Dystonia: the altered auditory feedback paradigm and the glove effect

    Directory of Open Access Journals (Sweden)

    Felicia Pei-Hsin Cheng

    2013-12-01

    Full Text Available Background: This study investigates the effect of altered auditory feedback (AAF in musician's dystonia (MD and discusses whether altered auditory feedback can be considered as a sensory trick in MD. Furthermore, the effect of AAF is compared with altered tactile feedback, which can serve as a sensory trick in several other forms of focal dystonia. Methods: The method is based on scale analysis (Jabusch et al. 2004. Experiment 1 employs synchronization paradigm: 12 MD patients and 25 healthy pianists had to repeatedly play C-major scales in synchrony with a metronome on a MIDI-piano with 3 auditory feedback conditions: 1. normal feedback; 2. no feedback; 3. constant delayed feedback. Experiment 2 employs synchronization-continuation paradigm: 12 MD patients and 12 healthy pianists had to repeatedly play C-major scales in two phases: first in synchrony with a metronome, secondly continue the established tempo without the metronome. There are 4 experimental conditions, among them 3 are the same altered auditory feedback as in Experiment 1 and 1 is related to altered tactile sensory input. The coefficient of variation of inter-onset intervals of the key depressions was calculated to evaluate fine motor control. Results: In both experiments, the healthy controls and the patients behaved very similarly. There is no difference in the regularity of playing between the two groups under any condition, and neither did AAF nor did altered tactile feedback have a beneficial effect on patients’ fine motor control. Conclusions: The results of the two experiments suggest that in the context of our experimental designs, AAF and altered tactile feedback play a minor role in motor coordination in patients with musicians' dystonia. We propose that altered auditory and tactile feedback do not serve as effective sensory tricks and may not temporarily reduce the symptoms of patients suffering from MD in this experimental context.

  15. Ocean acidification alters fish–jellyfish symbiosis

    Science.gov (United States)

    Nagelkerken, Ivan; Pitt, Kylie A.; Rutte, Melchior D.; Geertsma, Robbert C.

    2016-01-01

    Symbiotic relationships are common in nature, and are important for individual fitness and sustaining species populations. Global change is rapidly altering environmental conditions, but, with the exception of coral–microalgae interactions, we know little of how this will affect symbiotic relationships. We here test how the effects of ocean acidification, from rising anthropogenic CO2 emissions, may alter symbiotic interactions between juvenile fish and their jellyfish hosts. Fishes treated with elevated seawater CO2 concentrations, as forecast for the end of the century on a business-as-usual greenhouse gas emission scenario, were negatively affected in their behaviour. The total time that fish (yellowtail scad) spent close to their jellyfish host in a choice arena where they could see and smell their host was approximately three times shorter under future compared with ambient CO2 conditions. Likewise, the mean number of attempts to associate with jellyfish was almost three times lower in CO2-treated compared with control fish, while only 63% (high CO2) versus 86% (control) of all individuals tested initiated an association at all. By contrast, none of three fish species tested were attracted solely to jellyfish olfactory cues under present-day CO2 conditions, suggesting that the altered fish–jellyfish association is not driven by negative effects of ocean acidification on olfaction. Because shelter is not widely available in the open water column and larvae of many (and often commercially important) pelagic species associate with jellyfish for protection against predators, modification of the fish–jellyfish symbiosis might lead to higher mortality and alter species population dynamics, and potentially have flow-on effects for their fisheries. PMID:27358374

  16. Silychristin: Skeletal Alterations and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Biedermann, David; Buchta, M.; Holečková, Veronika; Sedlák, David; Valentová, Kateřina; Cvačka, Josef; Bednárová, Lucie; Křenková, Alena; Kuzma, Marek; Škuta, Ctibor; Peikerová, Žaneta; Bartůněk, Petr; Křen, Vladimír

    2016-01-01

    Roč. 79, č. 12 (2016), s. 3086-3092 ISSN 0163-3864 R&D Projects: GA ČR(CZ) GA15-03037S; GA MZd(CZ) NV16-27317A; GA MŠk LO1220; GA MŠk LM2015063; GA MŠk(CZ) LD15081 Institutional support: RVO:61388971 ; RVO:68378050 ; RVO:61388963 Keywords : Silychristin * skeletal alterations * biological activities Subject RIV: CC - Organic Chemistry Impact factor: 3.281, year: 2016

  17. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  18. Oncometabolites: linking altered metabolism with cancer

    Science.gov (United States)

    Yang, Ming; Soga, Tomoyoshi; Pollard, Patrick J.

    2013-01-01

    The discovery of cancer-associated mutations in genes encoding key metabolic enzymes has provided a direct link between altered metabolism and cancer. Advances in mass spectrometry and nuclear magnetic resonance technologies have facilitated high-resolution metabolite profiling of cells and tumors and identified the accumulation of metabolites associated with specific gene defects. Here we review the potential roles of such “oncometabolites” in tumor evolution and as clinical biomarkers for the detection of cancers characterized by metabolic dysregulation. PMID:23999438

  19. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Skilton, Rebeca [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Lavado, Ramon [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Thibaut, Remi [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Minier, Christophe [Laboratoire d' Ecotoxicologie, Universite du Havre, 25 rue Philippe Lebon, B.P. 540, F-76058 Le Havre (France); Porte, Cinta [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)]. E-mail: cpvqam@cid.csic.es

    2006-05-15

    Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17{beta}-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period.

  20. Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

    International Nuclear Information System (INIS)

    Martin-Skilton, Rebeca; Lavado, Ramon; Thibaut, Remi; Minier, Christophe; Porte, Cinta

    2006-01-01

    Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17β-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period

  1. The ecological limits of hydrologic alteration (ELOHA): A new framework for developing regional environmental flow standards

    Science.gov (United States)

    Poff, N.L.; Richter, B.D.; Arthington, A.H.; Bunn, S.E.; Naiman, R.J.; Kendy, E.; Acreman, M.; Apse, C.; Bledsoe, B.P.; Freeman, Mary C.; Henriksen, J.; Jacobson, R.B.; Kennen, J.G.; Merritt, D.M.; O'Keeffe, J. H.; Olden, J.D.; Rogers, K.; Tharme, R.E.; Warner, A.

    2010-01-01

    The flow regime is a primary determinant of the structure and function of aquatic and riparian ecosystems for streams and rivers. Hydrologic alteration has impaired riverine ecosystems on a global scale, and the pace and intensity of human development greatly exceeds the ability of scientists to assess the effects on a river-by-river basis. Current scientific understanding of hydrologic controls on riverine ecosystems and experience gained from individual river studies support development of environmental flow standards at the regional scale. 2. This paper presents a consensus view from a group of international scientists on a new framework for assessing environmental flow needs for many streams and rivers simultaneously to foster development and implementation of environmental flow standards at the regional scale. This framework, the ecological limits of hydrologic alteration (ELOHA), is a synthesis of a number of existing hydrologic techniques and environmental flow methods that are currently being used to various degrees and that can support comprehensive regional flow management. The flexible approach allows scientists, water-resource managers and stakeholders to analyse and synthesise available scientific information into ecologically based and socially acceptable goals and standards for management of environmental flows. 3. The ELOHA framework includes the synthesis of existing hydrologic and ecological databases from many rivers within a user-defined region to develop scientifically defensible and empirically testable relationships between flow alteration and ecological responses. These relationships serve as the basis for the societally driven process of developing regional flow standards. This is to be achieved by first using hydrologic modelling to build a 'hydrologic foundation' of baseline and current hydrographs for stream and river segments throughout the region. Second, using a set of ecologically relevant flow variables, river segments within the

  2. Alterations of brain activity in fibromyalgia patients.

    Science.gov (United States)

    Sawaddiruk, Passakorn; Paiboonworachat, Sahattaya; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-04-01

    Fibromyalgia is a chronic pain syndrome, characterized by widespread musculoskeletal pain with diffuse tenderness at multiple tender points. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Evidence shows that it could be due to changes in either the peripheral or central nervous system (CNS). For the CNS changes, alterations in the high brain area of fibromyalgia patients have been investigated but the definite mechanisms are still unclear. Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance (fMRI) have been used to gather evidence regarding the changes of brain morphologies and activities in fibromyalgia patients. Nevertheless, due to few studies, limited knowledge for alterations in brain activities in fibromyalgia is currently available. In this review, the changes in brain activity in various brain areas obtained from reports in fibromyalgia patients are comprehensively summarized. Changes of the grey matter in multiple regions such as the superior temporal gyrus, posterior thalamus, amygdala, basal ganglia, cerebellum, cingulate cortex, SII, caudate and putamen from the MRI as well as the increase of brain activities in the cerebellum, prefrontal cortex, anterior cingulate cortex, thalamus, somatosensory cortex, insula in fMRI studies are presented and discussed. Moreover, evidence from pharmacological interventions offering benefits for fibromyalgia patients by reducing brain activity is presented. Because of limited knowledge regarding the roles of brain activity alterations in fibromyalgia, this summarized review will encourage more future studies to elucidate the underlying mechanisms involved in the brains of these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Extracellular matrix alterations in the Peyronie's disease.

    Science.gov (United States)

    Watanabe, Marcelo Silva; Theodoro, Thérèse Rachel; Coelho, Natália Lima; Mendes, Aline; Leonel, Monica Luzia Pereira; Mader, Ana Maria; Nader, Helena Bonciani; Glina, Sidney; Pinhal, Maria Aparecida Silva

    2017-07-01

    Peyronie's disease is characterized by fibrous plaque formation of the tunica albuginea, causing penile deformity and fertility problems. The aim of the present study was to investigate alterations in the extracellular matrix in Peyronie's disease. The study used tissues collected by surgical procedure from individuals that presented a well-established disease, while control samples were obtained by biopsies of fresh cadavers. Immunohistochemistry analysis followed by digital quantification was performed to evaluate TGF-β, heparanases and metalloproteinases (MMPs). The profile of sulfated glycosaminoglycans, chondroitin sulfate and dermatan sulfate was determined by agarose gel electrophoresis, while hyaluronic acid quantification was obtained by an ELISA-like assay. The expression of mRNA was investigated for syndecan-1 proteoglycan (Syn-1), interleukine-6 (IL-6), hyaluronic acid synthases, and hyaluronidases. Pathologic features showed decreased apoptosis and blood vessel number in Peyronie's tissues. TGF-β and IL-6 were significantly enhanced in Peyronie's disease. There was an increased expression of heparanases, though no alteration was observed for MMPs. Hyaluronic acid as well as hyaluronic acid synthases, hyaluronidases, and dermatan sulfate were not changed, while the level of chondroitin sulfate was significantly ( P  = 0.008, Mann-Whitney test) increased in Peyronie's samples. Heparanases and sulfated glycosaminoglycans seem to be involved in extracellular matrix alterations in Peyronie's disease.

  4. Chromite alteration processes within Vourinos ophiolite

    Science.gov (United States)

    Grieco, Giovanni; Merlini, Anna

    2012-09-01

    The renewed interest in chromite ore deposits is directly related to the increase in Cr price ruled by international market trends. Chromite, an accessory mineral in peridotites, is considered to be a petrogenetic indicator because its composition reflects the degree of partial melting that the mantle experienced while producing the chromium spinel-bearing rock (Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993). However, the understanding of chromite alteration and metamorphic modification is still controversial (e.g. Evans and Frost in Geochim Cosmochim Acta 39:959-972, 1975; Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993; Oze et al. in Am J Sci 304:67-101, 2004). Metamorphic alteration leads to major changes in chromite chemistry and to the growth of secondary phases such as ferritchromite and chlorite. In this study, we investigate the Vourinos complex chromitites (from the mines of Rizo, Aetoraches, Xerolivado and Potamia) with respect to textural and chemical analyses in order to highlight the most important trend of alteration related to chromite transformation. The present study has been partially funded by the Aliakmon project in collaboration between the Public Power Corporation of Greece and Institute of Geology and Mineral Exploration of Kozani.

  5. Obesogenic diets alter metabolism in mice.

    Science.gov (United States)

    Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

    2018-01-01

    Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  6. Synthesis of ferroelectric nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Roervik, Per Martin

    2008-12-15

    The increasing miniaturization of electric and mechanical components makes the synthesis and assembly of nanoscale structures an important step in modern technology. Functional materials, such as the ferroelectric perovskites, are vital to the integration and utility value of nanotechnology in the future. In the present work, chemical methods to synthesize one-dimensional (1D) nanostructures of ferroelectric perovskites have been studied. To successfully and controllably make 1D nanostructures by chemical methods it is very important to understand the growth mechanism of these nanostructures, in order to design the structures for use in various applications. For the integration of 1D nanostructures into devices it is also very important to be able to make arrays and large-area designed structures from the building blocks that single nanostructures constitute. As functional materials, it is of course also vital to study the properties of the nanostructures. The characterization of properties of single nanostructures is challenging, but essential to the use of such structures. The aim of this work has been to synthesize high quality single-crystalline 1D nanostructures of ferroelectric perovskites with emphasis on PbTiO3 , to make arrays or hierarchical nanostructures of 1D nanostructures on substrates, to understand the growth mechanisms of the 1D nanostructures, and to investigate the ferroelectric and piezoelectric properties of the 1D nanostructures. In Paper I, a molten salt synthesis route, previously reported to yield BaTiO3 , PbTiO3 and Na2Ti6O13 nanorods, was re-examined in order to elucidate the role of volatile chlorides. A precursor mixture containing barium (or lead) and titanium was annealed in the presence of NaCl at 760 degrees Celsius or 820 degrees Celsius. The main products were respectively isometric nanocrystalline BaTiO3 and PbTiO3. Nanorods were also detected, but electron diffraction revealed that the composition of the nanorods was

  7. Synthesis document on the long life behavior of packages: reference operational document ''CSD-C'' 2004

    International Nuclear Information System (INIS)

    Helie, M.

    2004-12-01

    This document is realized in the framework of the law of 1991 on the radioactive wastes management. The 2004 synthesis document on long time behavior of standard packages of compacted wastes is constituted by two documents, the reference document and the operational document. This paper presents the operational model describing the packages alteration by the water and the associated radionuclide release. (A.L.B.)

  8. Synthesis of nanostructured polyaniline

    Science.gov (United States)

    Surwade, Sumedh P.

    The organization of my thesis is as follows: (a) Chapter III describes the synthesis of bulk quantities of polyaniline nanofibers in one step using a simple and versatile high ionic strength aqueous system (HCl/NaCl) that permits the use of pure H2O2 as a mild oxidant without any added metal or enzyme catalyst. Polyaniline nanofibers obtained are highly conducting, sigma˜1--5 S/cm, and spectroscopically similar to conventional polyaniline synthesized using stronger oxidants. The synthesis method is further extended to the synthesis of oligoanilines of controlled molecular weight, e.g., aniline tetramer, octamer, and hexadecamer. Microns long tetramer nanofibers are synthesized using this method. (b) Chapter IV describes the mechanism of nanofiber formation in polyaniline. It is proposed that the surfaces such as the walls of the reaction vessel and/or intentionally added surfaces play a dramatic role in the evolution of nanofibrillar morphology. Nucleation sites on surfaces promote the accumulation of aniline dimer that reacts further to yield aniline tetramer, which (surprisingly) is entirely in form of nanofibers and whose morphology is transcribed to the bulk by a double heterogeneous nucleation mechanism. This unexpected phenomenon could form the basis of nanofiber formation in all classes of precipitation polymerization systems. (c) Chapter V is the mechanistic study on the formation of oligoanilines during the chemical oxidation of aniline in weakly acidic, neutral or basic media using peroxydisulfate oxidant. It is proposed that the reaction proceeds via the intermediacy of benzoquinone monoimine that is formed as a result of a Boyland-Sims rearrangement of aniline. The initial role of peroxydisulfate is to provide a pathway for the formation of benzoquinone monoimine intermediate that is followed by a conjugate Michael-type addition reaction with aniline or sulfated anilines. The products isolated in pH 2.5--10.0 buffers are intermediate species at various

  9. Responsibility of regulatory gene expression and repressed protein synthesis for triacylglycerol accumulation on sulfur-starvation in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Atsushi eSato

    2014-09-01

    Full Text Available Triacylglycerol (TG synthesis is induced for energy and carbon storage in algal cells under nitrogen(N-starved conditions, and helps prevent reactive oxygen species production through fatty acid synthesis that consumes excessive reducing power. Here, the regulatory mechanism for the TG content in sulfur(S-starved cells of Chlamydomonas reinhardtii was examined, in comparison to that in N- or phosphorus(P-starved cells. S- and N-starved cells exhibited markedly increased TG contents with up-regulation of mRNA levels of diacylglycerol acyltransferase genes. S-Starvation also induced expression of the genes for phosphatidate synthesis. In contrast, P-starved cells exhibited little alteration of the TG content with almost no induction of these genes. The results implied deficient nutrient-specific regulation of the TG content. An arg9 disruptant defective in arginine synthesis, even without nutritional deficiencies, exhibited an increased TG content upon removal of supplemented arginine, which repressed protein synthesis. Repression of protein synthesis thus seemed crucial for TG accumulation in S- or N-starved cells. Meanwhile, the results of inhibitor experiments involving cells inferred that TG accumulation during S-starvation is supported by photosynthesis and de novo fatty acid synthesis. During S-starvation, sac1 and snrk2.2 disruptants, which are defective in the response to the ambient S-status, accumulated TG at lower and higher levels, respectively, than the wild type. The sac1 and snrk2.2 disruptants showed no or much greater up-regulation of diacylglycerol acyltransferase genes, respectively. In conclusion, TG synthesis would be activated in S-starved cells, through the diversion of metabolic carbon-flow from protein to TG synthesis, and simultaneously through up-regulation of the expression of a particular set of genes for TG synthesis at proper levels through the actions of SAC1 and SNRK2.2.

  10. Chemistry, mineralogy and alteration intensity of hydrothermal altered Mt Unzen conduit rocks (Shimabara/Japan)

    Science.gov (United States)

    Hess, Kai-Uwe; Yilmaz, Tim; Gilg, H. Albert; Janots, Emilie; Mayer, Klaus; Nakada, Setsuya; Dingwell, Donald

    2017-04-01

    Investigations were carried out on hydrothermally altered coherent dacitic dykes samples from (USDP-4) drill core at Mt Unzen stratovolcano (Shimabara/Japan). XRF, XRD, EMPA, C-O-isotope, hot-cathode CL and SEM analysis led to insights concerning chemistry, mineralogy, and intensity and type of alteration as well as the origin of carbonate-precipitating fluids. Additionally a textural characterization of the occurring replacement features in the volcanic conduit rocks was performed. The occurrence of the main secondary phases such as chlorite, pyrite, carbonates, and R1 (Reichweite parameter) illite-smectite and kaolinite group minerals indicate a weak to moderate propylitic to phyllic hydrothermal alteration. The dacitic samples of the dykes show different hydrothermal alteration features: (i) carbonate and chlorite pseudomorphs after hornblende as well as core and zonal textures due to replacement of plagioclase by R1 illite-smectite as well as kaolinite group minerals, (ii) colloform banded fracture fillings and fillings in dissolution vugs, and (iii) chlorite, R1 illite-smectite as well as kaolinite group minerals in the groundmass. Late chlorite veins crosscut precipitates of R1 illite-smectite as well as kaolinite group minerals. Carbonates in fractures and in pseudomorphs after hornblende comprise iron-rich dolomite solid solutions ("ankerite") and calcite. Isotopic values indicate a hydrothermal-magmatic origin for the carbonate formation. The chlorite-carbonate-pyrite index (CCPI) and the Ishikawa alteration index (AI), applied to the investigated samples show significant differences (CCPI=52.7-57.8; AI=36.1-40.6) indicating their different degree of alteration. According to Nakada et al., 2005, the C13 to C16 dykes represent the feeder dyke from the latest eruption (1991-1995) whereas C8 represents an earlier dyke feeder dyke from an older eruption. Weakest alteration, which was obtained in samples C16-1-5 and C13-2-5, correlates with the alteration

  11. Electrifying Organic Synthesis.

    Science.gov (United States)

    Wiebe, Anton; Gieshoff, Tile; Möhle, Sabine; Rodrigo, Eduardo; Zirbes, Michael; Waldvogel, Siegfried R

    2018-01-02

    The direct synthetic organic use of electricity is currently experiencing a renaissance. More synthetically oriented laboratories working in this area are exploiting both novel and more traditional concepts, paving the way to broader applications of this niche technology. As only electrons serve as reagents, the generation of reagent waste is efficiently avoided. Moreover, stoichiometric reagents can be regenerated and allow a transformation to be conducted in an electrocatalytic fashion. However, the application of electroorganic transformations is more than minimizing the waste footprint, it rather gives rise to inherently safe processes, reduces the number of steps of many syntheses, allows for milder reaction conditions, provides alternative means to access desired structural entities, and creates intellectual property (IP) space. When the electricity originates from renewable resources, this surplus might be directly employed as a terminal oxidizing or reducing agent, providing an ultra-sustainable and therefore highly attractive technique. This Review surveys recent developments in electrochemical synthesis that will influence the future of this area. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  12. Synthesis of P005091

    Directory of Open Access Journals (Sweden)

    Ping YU

    2016-06-01

    Full Text Available To improve the synthesis method of P005091 (1-(5-((2,3-dichlorophenyl thio-4-nitro-2-thienyl ethanone, with 2-chlorothiophene as the starting material, acetyl chloride as the acetylation reagent and aluminium trichloride as the catalyst, acetyl is introduced in the 5th position of 2-chlorothiophene to get 2-acetyl-5-chlorothiophene (compound 2, and the yield is 91%; then with concentrated sulfuric acid as solvent and mixed acid as nitrating agent, 5-acetyl-2-chloro-3-nitrothiophene (compound 3 is obtained by nitration reaction with compound 2, and the yield is 64%; thioetherfication reaction of compound 3 and 2,3-dichlorobenzenethiol in DMF solution under the function of potassium carbonate takes place to obtain the target product P005091, and the yield is 76%. The structure of P005091 is confirmed by mp, 1H-NMR, 13C-NMR and MS, and the overall yield is 44%. The improved method has the advantages of low cost, simple operation, and a milder reaction condition compared with the former references, avoiding using the reagent with higher toxicity, and high yield on the premise that the product purity is assured.

  13. Sickle erythrocytes inhibit human endothelial cell DNA synthesis

    International Nuclear Information System (INIS)

    Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K.

    1990-01-01

    Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling

  14. Phase alteration compensation in reflection digital holography

    International Nuclear Information System (INIS)

    Rincon, O; Amezquita, R; Monroy, F

    2011-01-01

    The phase maps obtained from digital holographic microscopy techniques carry information about the axial lengths of the object under study. Additionally, these phase maps have information of tilt and curvatures with origin in the off-axis geometry and the magnification lenses system, respectively. Only a complete compensation of these extra phases allows a correct interpretation of the phase information. In this article a numerical strategy to compensate for these alterations is designed, using a phase mask located in different planes. This strategy is applied in the measurement of a phase steps plate using a digital holography setup.

  15. Ethic's pedagogy: from responsibility to alterity

    Directory of Open Access Journals (Sweden)

    Eduardo S. Vila Merino

    2004-11-01

    Full Text Available Ethics, since the so-called 'linguistic turn' and the rise of the notion of discursive formations, has tended to combine the teleological and the deontological. That means that, if ethics is to be useful in understanding relationships and other social issues, or in building the common good, it ought to take a procedural position. We believe that the teaching of ethics should be based on the notions of responsibility and alterity. These two concepts are helpful in promoting mutual understanding and other-directedness.

  16. Clerics urge ban on altering germline cells.

    Science.gov (United States)

    Norman, C

    1983-06-24

    A resolution calling for a ban on genetic engineering of human reproductive cells has been signed by leaders of almost every major church group in the United States. Some of the religious leaders, while not certain that a total moratorium should be placed on altering germline cells, signed the statement in order to stimulate public debate on the issue. Legislation has recently been introduced in Congress to set up a committee to monitor genetic engineering and its human applications, but author Jeremy Rifkin, the impetus behind the church leaders' resolution, argues that such tampering threatens the gene pool and should be banned altogether.

  17. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

    Full Text Available Prior to 2009, 5-methylcytosine (5-mC was thought to be the only biologically significant cytosine modification in mammalian DNA. With the discovery of the TET enzymes, which convert 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, however, intense interest has emerged in determining the biological function of 5-hmC. Here, we review the techniques used to study 5-hmC and evidence that alterations to 5-hmC physiology play a functional role in the molecular pathogenesis of human cancers.

  18. Simultaneous Targeting of Multiple Gene Homeologs to Alter Seed Oil Production in Camelina sativa.

    Science.gov (United States)

    Aznar-Moreno, J A; Durrett, T P

    2017-07-01

    The ability to transform Camelina sativa easily with biosynthetic enzymes derived from other plants has made this oil seed crop an ideal platform for the production of unusual lipids valuable for different applications. However, in addition to expressing transgenic enzymes, the suppression of endogenous enzyme activity to reduce competition for common substrates or cofactors is also required to enhance the production of target compounds. As camelina possesses a relatively undifferentiated hexaploid genome, up to three gene homeologs can code for any particular enzymatic activity, complicating efforts to alter endogenous biosynthetic pathways. New genome editing technologies, such as that offered by the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) system, offer the capability to introduce mutations into specifically targeted genomic sites. Here, by using a carefully designed guide RNA identical to all three homeologs, we demonstrate the ability of the CRISPR/Cas genome editing system to introduce mutations in all three CsDGAT1 or CsPDAT1 homeologous genes important for triacylglycerol (TAG) synthesis in developing seeds. Sequence analysis from transgenic T1 plants revealed that each CsDGAT1 or each CsPDAT1 homeolog was altered by multiple mutations, resulting in a genetic mosaic in the plants. Interestingly, seed harvested from both CsDGAT1- and CsPDAT1-targeted lines was often shrunken and wrinkled. Further, lipid analysis revealed that many lines produced seed with reduced oil content and altered fatty acid composition, consistent with the role of the targeted genes in seed oil biosynthesis. The CRISPR/Cas system therefore represents a useful method to alter endogenous biosynthetic pathways efficiently in polyploid species such as camelina. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. A powerful enhancement to the DMAP alter capability

    Science.gov (United States)

    Pamidi, P. R.

    1989-01-01

    A powerful enhancement to the DMAP alter capability was developed and is available on all RPK-supported versions of COSMIC/NASTRAN. This enhancement involves the addition of two alter control cards, called INSERT and DELETE, to the Executive Control Deck. These cards allow for DMAP alters to be made by referencing DMAP statements by their module names rather than by their statement numbers in the rigid format DMAP sequence. This allows for increased user convenience and flexibility and makes alters more meaningful to the user. In addition, DMAP alter packages employing the alter control cards will be much less susceptible to future changes in rigid format DMAPs than alter packages employing the standard ALTER control cards. The usage of the cards is illustrated by examples.

  20. 28 CFR 36.404 - Alterations: Elevator exemption.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Alterations: Elevator exemption. 36.404... Alterations: Elevator exemption. (a) This section does not require the installation of an elevator in an... facility has an elevator. ...

  1. Synthesis of ammonia using sodium melt

    OpenAIRE

    Kawamura, Fumio; Taniguchi, Takashi

    2017-01-01

    Research into inexpensive ammonia synthesis has increased recently because ammonia can be used as a hydrogen carrier or as a next generation fuel which does not emit CO2. Furthermore, improving the efficiency of ammonia synthesis is necessary, because current synthesis methods emit significant amounts of CO2. To achieve these goals, catalysts that can effectively reduce the synthesis temperature and pressure, relative to those required in the Haber-Bosch process, are required. Although severa...

  2. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    Directory of Open Access Journals (Sweden)

    Johann eSteiner

    2014-11-01

    Full Text Available Clozapine has stronger systemic metabolic side effects than haloperidol and it was hypothesized that therapeutic antipsychotic and adverse metabolic effects might be related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production.Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT and monocarboxylate (MCT transporters was determined after 6h and 24h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed.Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside.Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  3. Morphology of altered layers of glasses

    Energy Technology Data Exchange (ETDEWEB)

    Deruelle, O. [CEA Saclay, Dept. d' Astrophysique, de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, 91 - Gif sur Yvette (France); Spalla, O.; Lambard, J. [CEA Saclay, Dept. de Recherche sur l' Etat Condense les Atomes et les Molecules, 91 - Gif sur Yvette (France); Barboux, Ph.; Ricol, St. [Ecole Polytechnique, PMC, 91 - Palaiseau (France); Ricol, St.; Vernaz, E. [CEA Valrho, Dir. de l' Energie Nucleaire, DEN, 30 - Marcoule (France)

    1997-07-01

    The alteration of the french nuclear waste glass R7T7 has been studied through chemical analysis, thermo-poro-metry and X-ray scattering. Pseudo-dynamic leaching was used, with daily renewal of the leaching solution. The behavior of the R77 glass has been compared to cesium borosilicate glasses with small amounts of Ca and Zr added. As compared to these simplified compositions, the R7T7 glass has a quasi-congruent leaching of Na, B and Si and strongly retains Ca and Zr. The altered layers are very porous (porosity > 40% ). The pore size increases with time to reach a constant value that is independent of the nature of the glass but that strongly depends on the method used for leaching. The pore radii are about 4 nm in pseudo-dynamic mode and 2 nm in static conditions. X-ray scattering indicate that the pores are compact with a sharp interface. Their origin is related to the quasi-equilibrium reaction of hydrolysis redeposition of silica. (authors)

  4. Origins of altered reinforcement effects in ADHD

    Directory of Open Access Journals (Sweden)

    Tripp Gail

    2009-02-01

    Full Text Available Abstract Attention-deficit/hyperactivity disorder (ADHD, characterized by hyperactivity, impulsiveness and deficient sustained attention, is one of the most common and persistent behavioral disorders of childhood. ADHD is associated with catecholamine dysfunction. The catecholamines are important for response selection and memory formation, and dopamine in particular is important for reinforcement of successful behavior. The convergence of dopaminergic mesolimbic and glutamatergic corticostriatal synapses upon individual neostriatal neurons provides a favorable substrate for a three-factor synaptic modification rule underlying acquisition of associations between stimuli in a particular context, responses, and reinforcers. The change in associative strength as a function of delay between key stimuli or responses, and reinforcement, is known as the delay of reinforcement gradient. The gradient is altered by vicissitudes of attention, intrusions of irrelevant events, lapses of memory, and fluctuations in dopamine function. Theoretical and experimental analyses of these moderating factors will help to determine just how reinforcement processes are altered in ADHD. Such analyses can only help to improve treatment strategies for ADHD.

  5. Hemorheological alterations related to training and overtraining.

    Science.gov (United States)

    Brun, Jean-Frédéric; Varlet-Marie, Emmanuelle; Connes, Philippe; Aloulou, Ikram

    2010-01-01

    Alterations of blood rheology related to muscular activity have been extensively studied over the last 20 years. It has been shown that exercise exerts a "triphasic" action on the rheological properties of blood. In the short term, exercise induces a transient hyperviscosity, mostly due to a rise in hematocrit and plasma viscosity, but also to alterations in erythrocyte rheology. Reversal of this hyperviscosity pattern over the following 24 h can be described as an "autohemodilution". Later, training results in several profiles of "hemorheologic fitness" with a low hematocrit reflecting an expansion in plasma volume, and improvements in red cell rheology (increased deformability, decreased aggregation, reduced disaggregation shear rate). Some specific aspects of these long-term adaptations have been described, such as the intriguing occurrence of a paradoxical improvement in RBC deformability during exercise in some athletes, and overtraining, which is associated with higher plasma viscosity. Given the variety of modes of exercise and the wide heterogeneity of their effects on blood rheology in the short and long term, many investigations remain to be performed in this area of clinical hemorheology.

  6. Auditory alterations for occupational exposition in musicians

    Directory of Open Access Journals (Sweden)

    Melo, Ana Dolores Passarelli

    2008-09-01

    Full Text Available Introduction: Exposure to music has become an interest among experts in hearing and acoustics, once it's related to the professional and social activity and to the high prevalence of Hearing Loss. Objective: To investigate musicians auditory health. Method: 30 musicians participated in the study and were submitted to specific interview, conventional and highfrequency tonal audiometry, tympanometry and transient-evoked and distortion-produced otoacoustic emissions. Results: 17% of the participants presented an audiogram that suggested Noise-Induced Hearing Loss, 7% normal with notch and 7% with other characteristics. The frequency thresholds average of 3, 4 and 6kHz presented a more intense level when compared to the one of 500, 1 and 2kHz; as well as the high frequency audiometry thresholds average when compared to the conventional audiometry. There was a threshold positive correlation with the age and time of profession. There hasn't been found transiently evoked otoacoustic emissions in 26,7% (right ear and 23,3% (left ear, as well as in isolated frequencies in distortion-produced evoked otoacoustic emissions. Conclusion: Alterations were observed in tests with no complaints of hearing difficulties; the otoacoustic emissions test presented more sensitivity in the early detection of hearing alterations; musicians present a significant risk of developing hearing loss.

  7. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-02-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  8. Thermal remediation alters soil properties - a review.

    Science.gov (United States)

    O'Brien, Peter L; DeSutter, Thomas M; Casey, Francis X M; Khan, Eakalak; Wick, Abbey F

    2018-01-15

    Contaminated soils pose a risk to human and ecological health, and thermal remediation is an efficient and reliable way to reduce soil contaminant concentration in a range of situations. A primary benefit of thermal treatment is the speed at which remediation can occur, allowing the return of treated soils to a desired land use as quickly as possible. However, this treatment also alters many soil properties that affect the capacity of the soil to function. While extensive research addresses contaminant reduction, the range and magnitude of effects to soil properties have not been explored. Understanding the effects of thermal remediation on soil properties is vital to successful reclamation, as drastic effects may preclude certain post-treatment land uses. This review highlights thermal remediation studies that have quantified alterations to soil properties, and it supplements that information with laboratory heating studies to further elucidate the effects of thermal treatment of soil. Notably, both heating temperature and heating time affect i) soil organic matter; ii) soil texture and mineralogy; iii) soil pH; iv) plant available nutrients and heavy metals; v) soil biological communities; and iv) the ability of the soil to sustain vegetation. Broadly, increasing either temperature or time results in greater contaminant reduction efficiency, but it also causes more severe impacts to soil characteristics. Thus, project managers must balance the need for contaminant reduction with the deterioration of soil function for each specific remediation project. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. [Hepatic alterations in patients with dengue].

    Science.gov (United States)

    Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

    2005-06-01

    Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

  10. Altered pharyngeal muscles in Parkinson disease.

    Science.gov (United States)

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

    2012-06-01

    Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

  11. Obesity Promotes Alterations in Iron Recycling

    Directory of Open Access Journals (Sweden)

    Marta Citelli

    2015-01-01

    Full Text Available Hepcidin is a key hormone that induces the degradation of ferroportin (FPN, a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1, FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

  12. Sustainable Process Synthesis-Intensification

    DEFF Research Database (Denmark)

    Babi, Deenesh Kavi; Holtbruegge, Johannes; Lutze, Philip

    2014-01-01

    Sustainable process design can be achieved by performing process synthesis and process intensification together. This approach first defines a design target through a sustainability analysis and then finds design alternatives that match the target through process intensification. A systematic......, multi-stage framework for process synthesis- intensification that identifies more sustainable process designs has been developed. At stages 1-2, the working scale is at the level of unit operations, where a base case design is identified and analyzed with respect to sustainability metrics. At stages 3......, a phenomena-based process synthesis method is applied, where the phenomena involved in each tasks are identified, manipulated and recombined to generate new and/or existing unit operations configured into flowsheets that are more sustainable from those found in the previous levels. An overview of the key...

  13. Synthesis through Trans-disciplinarity

    DEFF Research Database (Denmark)

    Hansen, Hanne Tine Ring

    2006-01-01

    , architecture and landscape provides a great architectural experience. Another is Jörn Utzon's church in Bagsvaerd, Denmark, where the treatment of construction, acoustics and daylight ingeniously fuses with the church's function and architectural expression, once again offering a unique architectural...... experience. In relation to ‘environmentally sustainable' architecture the importance of synthesis becomes even more apparent, however, as the success of the design depends on how, and if, a synthesis is achieved between technology and architectural design.[2] This understanding has led me to consider how...... synthesis is a requirement for creating successful ‘environmentally sustainable' architecture through the application of trans-disciplinarity, which leads to an increased awareness of the differences in decision-making as well as that of communication barriers between the different professions...

  14. Sustainable Process Synthesis-Intensification

    DEFF Research Database (Denmark)

    Babi, Deenesh Kavi; Holtbruegge, Johannes; Lutze, Philip

    2014-01-01

    Sustainable process design can be achieved by performing process synthesis and process intensification together. This approach first defines a design target through a sustainability analysis and then finds design alternatives that match the target through process intensification. A systematic, mu...... concepts and the framework are presented together with the results from a case study highlighting the application of the framework to the sustainable design of a production process for dimethyl carbonate.......Sustainable process design can be achieved by performing process synthesis and process intensification together. This approach first defines a design target through a sustainability analysis and then finds design alternatives that match the target through process intensification. A systematic......, multi-stage framework for process synthesis- intensification that identifies more sustainable process designs has been developed. At stages 1-2, the working scale is at the level of unit operations, where a base case design is identified and analyzed with respect to sustainability metrics. At stages 3...

  15. The KTH synthesis of singing

    Directory of Open Access Journals (Sweden)

    Johan Sundberg

    2006-01-01

    Full Text Available This is an overview of the work with synthesizing singing that has been carried out at the Speech Music Hearing Department, KTH since 1977. The origin of the work, a hardware synthesis machine, is described and some aspects of the control program, a modified version of a text-to-speech conversion system are reviewed. Three applications are described in which the synthesis system has paved the way for investigations of specific aspects of the singing voice. One concerns the perceptual relevance of the center frequency of the singer's formant, one deals with characteristics of an ugly voice, and one regards intonation. The article is accompanied by 18 sound examples, several of which were not published before. Finally, limitations and advantages of singing synthesis are discussed.

  16. Structural synthesis of parallel robots

    CERN Document Server

    Gogu, Grigore

    This book represents the fifth part of a larger work dedicated to the structural synthesis of parallel robots. The originality of this work resides in the fact that it combines new formulae for mobility, connectivity, redundancy and overconstraints with evolutionary morphology in a unified structural synthesis approach that yields interesting and innovative solutions for parallel robotic manipulators.  This is the first book on robotics that presents solutions for coupled, decoupled, uncoupled, fully-isotropic and maximally regular robotic manipulators with Schönflies motions systematically generated by using the structural synthesis approach proposed in Part 1.  Overconstrained non-redundant/overactuated/redundantly actuated solutions with simple/complex limbs are proposed. Many solutions are presented here for the first time in the literature. The author had to make a difficult and challenging choice between protecting these solutions through patents and releasing them directly into the public domain. T...

  17. In vivo effects of dexamethasone and indomethacin on neutrophil-induced alterations of nasal epithelial mucosubstances

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Portereiko, J.V.; Harkema, J.R.

    1988-01-01

    Previous studies have shown that neutrophils migrating through rat nasal mucosal epithelium, in response to intranasal instillation of endotoxin, induce a transient decrease in stored epithelial mucosubstances. Prostaglandins and leukotrienes can either increase or decrease mucous secretion of airway epithelia in vitro. In this study, rats were treated with indomethacin a specific inhibitor of prostaglandin synthesis, or with dexamethasone, a general inhibitor of arachidonic acid metabolism, and challenged with intranasally instilled endotoxin. Dexamethasone alone or in combination with indomethacin, but not indomethacin alone, significantly altered the neutrophil response to intranasally instilled endotoxin and may have inhibited the neutrophil-induced decrease in stored mucosubstances. These data suggest that leukotrienes and possibly prostaglandins play a significant role in the coordinated response of the nasal mucosal epitholium to an acute inflammatory stimulus. (author)

  18. A NASTRAN DMAP alter for the coupling of modal and physical coordinate substructures

    Science.gov (United States)

    Wilson, T. L.

    1977-01-01

    A method is described to derive a generalized coordinate model consisting of flexible cantilever modes and rigid body modes from a physical coordinate model using a direct matrix abstraction procedure alter to rigid format 3. This model can readily be coupled to other substructures using modal synthesis techniques. It allows the use of a reduced size model for structural analyses while maintaining the capability of recovering the accelerations, forces, stresses, etc., from the original, large, complex model. This output recovery is accomplished with the use of a loads transformation matrix which relates the output parameters to the modal coordinate accelerations. In addition, a method is described to synthesize structural models consisting of hybrid coordinates for use in dynamic response analyses where one structure is described using physical coordinates and the other using generalized modal coordinates.

  19. A Viral RNA Structural Element Alters Host Recognition of Nonself RNA

    Energy Technology Data Exchange (ETDEWEB)

    Hyde, J. L.; Gardner, C. L.; Kimura, T.; White, J. P.; Liu, G.; Trobaugh, D. W.; Huang, C.; Tonelli, M.; Paessler, S.; Takeda, K.; Klimstra, W. B.; Amarasinghe, G. K.; Diamond, M. S.

    2014-01-30

    Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.

  20. ALTER-GLOBALISM AND DEVELOPMENT IN MIGRATION CONDITIONS. THE CASE OF AN EAST EUROPEAN COUNTRY

    Directory of Open Access Journals (Sweden)

    Alina HALLER

    2017-12-01

    Full Text Available Globalisation is a process that brings advantages and disadvantages to all states, regardless of their stage of development. The relative deprivation, especially the financial one, of the developing countries is a reason of frustration, which motivates the emigration decision; hence our orientation to alter-globalism. In this paper, I intend to highlight by means of analysis, synthesis, deduction, induction, and statistic data, the causes and types of migration in Romania’s case, one of the main European countries where the immigrants originate from. We will see how globalisation manifests itself in a twofold manner in the economy and the society of a developing country, just like migration. We will show why a poor country is avoided by immigrants and deserted, as a result of immigration, by its own population, while, just like the developed states, it is likely to face the same demographic, economic and social problems, considering that the process of demographic transition is already manifested.

  1. Woodward's Synthesis of Vitamin B12

    Indian Academy of Sciences (India)

    The synthesis of this molecule was a landmark in organic synthesis. It involved the masterful control of shapes of molecules to create 9 chiral centres with known absolute and relative configurations. The concepts of absolute and induced asymmetric synthesis are here explained. Robert B. Woodward was one of the greatest ...

  2. STICS: surface-tethered iterative carbohydrate synthesis.

    Science.gov (United States)

    Pornsuriyasak, Papapida; Ranade, Sneha C; Li, Aixiao; Parlato, M Cristina; Sims, Charles R; Shulga, Olga V; Stine, Keith J; Demchenko, Alexei V

    2009-04-14

    A new surface-tethered iterative carbohydrate synthesis (STICS) technology is presented in which a surface functionalized 'stick' made of chemically stable high surface area porous gold allows one to perform cost efficient and simple synthesis of oligosaccharide chains; at the end of the synthesis, the oligosaccharide can be cleaved off and the stick reused for subsequent syntheses.

  3. Formal synthesis of naturally occurring norephedrine

    Indian Academy of Sciences (India)

    A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives has been achieved following classical organic transformations using commercially available chiral pools. The said derivatives were explored for the synthesis of naturally occurring bio-active small molecules. Formal synthesis of norephedrine, virolin ...

  4. Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression.

    Science.gov (United States)

    Borojevic, Radovan; Roela, Rosimeire A; Rodarte, Renato S; Thiago, Leandro S; Pasini, Fátima S; Conti, Fabiana M; Rossi, Maria Isabel D; Reis, Luiz F L; Lopes, Luiz F; Brentani, M Mitzi

    2004-08-01

    We studied bone marrow stromal cell cultures from patients with childhood myelodysplastic syndromes (MDS, refractory anemia with excess of blasts, RAEB) and from matched normal donors. Stromal cell monolayers were characterized as myofibroblasts by the expression of smooth muscle alpha-actin, collagen IV, laminin and fibronectin. When normal cord blood cells were plated onto myelodysplastic stromas, a pathologic cell differentiation was observed, indicating altered myelosupportive properties. cDNA array analysis showed that patient stromas expressed increased levels of thrombospondin-1, collagen-I alpha2-chain, osteoblast-specific factor-2 and osteonectin, indicating the presence of increased osteoblast content, as confirmed by enhanced alkaline phosphatase synthesis. Alterations in the myelodysplastic stroma environment might contribute to abnormal hematopoiesis in this pathology.

  5. 46 CFR 115.700 - Permission for repairs and alterations.

    Science.gov (United States)

    2010-10-01

    ... replacement in kind, of electrical wiring, fuel lines, tanks, boilers and other pressure vessels, and steering... 46 Shipping 4 2010-10-01 2010-10-01 false Permission for repairs and alterations. 115.700 Section... AND CERTIFICATION Repairs and Alterations § 115.700 Permission for repairs and alterations. (a...

  6. Bacterial infection affects protein synthesis in primary lymphoid tissues and circulating lymphocytes of rats.

    Science.gov (United States)

    Papet, Isabelle; Ruot, Benoît; Breuillé, Denis; Walrand, Stéphane; Farges, Marie-Chantal; Vasson, Marie-Paule; Obled, Christiane

    2002-07-01

    Bacterial infection alters whole-body protein homeostasis. Although immune cells are of prime importance for host defense, the effect of sepsis on their protein synthesis rates is poorly documented. We analyzed protein synthesis rates in rat primary lymphoid tissues and circulating lymphocytes after infection. Male Sprague-Dawley rats were studied 1, 2, 6 or 10 d after an intravenous injection of live Escherichia coli. Control healthy rats consumed food ad libitum (d 0) or were pair-fed to infected rats. Protein synthesis was quantified using a flooding dose of L-(4,4,4-(2)H(3))valine. Sepsis induced a delayed increase in total blood leukocytes and a rapid and persistent inversion of the counts. Basal fractional rates of protein synthesis (ks) were 117, 73 and 29%/d in bone marrow, thymus and circulating lymphocytes, respectively. Pair-feeding strongly depressed the absolute protein synthesis rates (ASR) of bone marrow (d 2 and 10) and thymus (d 2-10). The infection per se increased bone marrow, thymus and circulating lymphocyte ks but at various postinfection times. It decreased bone marrow (d 1) and thymus (d 1 and 2) ASR but increased lymphocyte (d 2 and 10) and bone marrow (d 10) ASR. Our results reflect the deleterious effect of anorexia on primary lymphoid tissues. The host defense against bacterial infection exhibited time- and tissue-dependent modifications of protein synthesis, indicating that blood lymphocyte protein data are not representative of the immune system as a whole. Optimization of nutritional supports would be facilitated by including protein synthesis measurements of the immune system.

  7. Ferroic materials synthesis and applications

    CERN Document Server

    Virk, Hardev Singh

    2015-01-01

    Ferroics is the generic name given to the study of ferromagnets, ferroelectrics, and ferroelastics. The basis of this study is to understand the large changes in physical characteristics that occur over a very narrow temperature range. In recent years, a new class of ferroic materials has been attracting increased interest. These multiferroics exhibit more than one ferroic property simultaneously in a single phase. The present volume: ""Ferroic Materials: Synthesis and Applications"" has ten Chapters, spread over areas as diverse as Magnetic Oxide Nanomaterials, Ferrites Synthesis, Hexaferrite

  8. Impaired glutathione synthesis in schizophrenia

    DEFF Research Database (Denmark)

    Gysin, René; Kraftsik, Rudolf; Sandell, Julie

    2007-01-01

    Schizophrenia is a complex multifactorial brain disorder with a genetic component. Convergent evidence has implicated oxidative stress and glutathione (GSH) deficits in the pathogenesis of this disease. The aim of the present study was to test whether schizophrenia is associated with a deficit...... of GSH synthesis. Cultured skin fibroblasts from schizophrenia patients and control subjects were challenged with oxidative stress, and parameters of the rate-limiting enzyme for the GSH synthesis, the glutamate cysteine ligase (GCL), were measured. Stressed cells of patients had a 26% (P = 0.......002) decreased GCL activity as compared with controls. This reduction correlated with a 29% (P schizophrenia in two...

  9. Sequential logic analysis and synthesis

    CERN Document Server

    Cavanagh, Joseph

    2007-01-01

    Until now, there was no single resource for actual digital system design. Using both basic and advanced concepts, Sequential Logic: Analysis and Synthesis offers a thorough exposition of the analysis and synthesis of both synchronous and asynchronous sequential machines. With 25 years of experience in designing computing equipment, the author stresses the practical design of state machines. He clearly delineates each step of the structured and rigorous design principles that can be applied to practical applications. The book begins by reviewing the analysis of combinatorial logic and Boolean a

  10. Tunable synthesis of copper nanotubes

    International Nuclear Information System (INIS)

    Kaniukov, E; Yakimchuk, D; Kozlovsky, A; Shlimas, D; Zdorovets, M; Kadyrzhanov, K

    2016-01-01

    Simple method of tunable synthesis of copper nanotubes based on template synthesis was developed. A comprehensive study of the structural, morphological and electrical characteristics of the obtained nanostructures was carried out. Characterization of structural features was made by methods of scanning electron microscopy, energy dispersive spectroscopy and X-ray diffractometry analysis. Evaluation of wall thickness is made by methods of gas permeability. Electrical conductivity of nanotubes was define in the study of their current-voltage characteristics. The possibility to control of copper nanotubes physical properties by variation of the deposition parameters was shown. (paper)

  11. A Short Synthesis of (+)-Cyclophellitol

    DEFF Research Database (Denmark)

    Hansen, Flemming Gundorph; Bundgaard, Eva; Madsen, Robert

    2005-01-01

    A new synthesis of (+)-cyclophellitol, a potent b-glucosidase inhibitor, has been completed in nine steps from D-xylose. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 5-deoxy-5-iodo-xylofuranoside followed by a highly diastereoselective indium-mediated c......-mediated coupling with ethyl 4-bromocrotonate. Subsequent ring-closing olefin metathesis, ester reduction, olefin epoxidation, and deprotection then afford the natural product. This constitutes the shortest synthesis of (+)-cyclophellitol reported to date....

  12. Synthesis of magnetic polymeric microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Gervald, A Yu; Gritskova, Inessa A; Prokopov, Nikolai I [M.V. Lomonosov Moscow State Academy of Fine Chemical Technology, Moscow (Russian Federation)

    2010-05-13

    The key types of magnetic polymeric microspheres are considered. Methods of synthesis of different types of magnetic nanoparticles and of preparation of stable magnetic fluids on their basis are outlined. The overview of the methods for the manufacture of magnetic polymeric microspheres is presented. The effect of the synthesis conditions on the characteristics of magnetic polymeric microspheres such as the diameter and the particle size distribution and the content of magnetic material is discussed by particular examples. The application fields of magnetic polymeric microspheres are briefly surveyed.

  13. Synthesis of magnetic polymeric microspheres

    International Nuclear Information System (INIS)

    Gervald, A Yu; Gritskova, Inessa A; Prokopov, Nikolai I

    2010-01-01

    The key types of magnetic polymeric microspheres are considered. Methods of synthesis of different types of magnetic nanoparticles and of preparation of stable magnetic fluids on their basis are outlined. The overview of the methods for the manufacture of magnetic polymeric microspheres is presented. The effect of the synthesis conditions on the characteristics of magnetic polymeric microspheres such as the diameter and the particle size distribution and the content of magnetic material is discussed by particular examples. The application fields of magnetic polymeric microspheres are briefly surveyed.

  14. Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

    International Nuclear Information System (INIS)

    Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

    1987-01-01

    The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

  15. Synthesis: Chapter 19

    Science.gov (United States)

    Pardo, L.H.; Geiser, L.H.; Fenn, M.E.; Driscoll, C.T.; Goodale, C.L.; Allen, E.B.; Baron, Jill S.; Bobbink, R.; Bowman, W.D.; Clark, C.M.; Emmett, B.; Gilliam, F.S.; Greaver, T.; Hall, S.J.; Lilleskov, E.A.; Liu, L.; Lynch, J.A.; Nadelhoffer, K.; Perakis, S.S.; Robin-Abbott, M. J.; Stoddard, J.L.; Weathers, K. C.

    2011-01-01

    Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition (Galloway et al. 2003). Because of past, and, in some regions, continuing increases in emissions (Lehmann et al. 2005, Nilles and Conley 2001), this N deposition has reached a level that has caused or is likely to cause alterations and damage in many ecosystems across the United States. In some ecoregions, the impact of N deposition has been severe and has changed the biotic community structure and composition of ecosystems. In the Mediterranean California ecoregion, for example (see Chapter 13), replacement of native by exotic invasive vegetation is accelerated because exotic species are often more productive under elevated N deposition than native species in some California grasslands, coastal sage scrub, and desert scrub (Fenn et al. 2010, Rao and Allen 2010, Rao et al. 2010, Weiss 1999, Yoshida and Allen 2004). Such shifts in plant community composition and species richness can have consequences beyond changes in ecosystem structure: shifts may lead to overall losses in biodiversity and further impair particular threatened or endangered species (Stevens et al. 2004). Th e extirpation of the endangered checkerspot butterfl y (Euphydryas editha bayensis), because the host plant for the larval stage disappears in N-enriched ecosystems (Fenn et al. 2010, Weiss 1999), is just one example of the detrimental impacts of elevated N deposition.

  16. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development

    Science.gov (United States)

    Caldwell, Katharine E.; Labrecque, Matthew T.; Solomon, Benjamin R.; Ali, Abdulmehdi; Allan, Andrea M.

    2015-01-01

    The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50 ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of

  17. Environmental Nutrient Supply Directly Alters Plant Traits but Indirectly Determines Virus Growth Rate

    Directory of Open Access Journals (Sweden)

    Christelle Lacroix

    2017-11-01

    Full Text Available Ecological stoichiometry and resource competition theory both predict that nutrient rates and ratios can alter infectious disease dynamics. Pathogens such as viruses hijack nutrient rich host metabolites to complete multiple steps of their epidemiological cycle. As the synthesis of these molecules requires nitrogen (N and phosphorus (P, environmental supply rates, and ratios of N and P to hosts can directly limit disease dynamics. Environmental nutrient supplies also may alter virus epidemiology indirectly by changing host phenotype or the dynamics of coinfecting pathogens. We tested whether host nutrient supplies and coinfection control pathogen growth within hosts and transmission to new hosts, either directly or through modifications of plant tissue chemistry (i.e., content and stoichiometric ratios of nutrients, host phenotypic traits, or among-pathogen interactions. We examined two widespread plant viruses (BYDV-PAV and CYDV-RPV in cultivated oats (Avena sativa grown along a range of N and of P supply rates. N and P supply rates altered plant tissue chemistry and phenotypic traits; however, environmental nutrient supplies and plant tissue content and ratios of nutrients did not directly alter virus titer. Infection with CYDV-RPV altered plant traits and resulted in thicker plant leaves (i.e., higher leaf mass per area and there was a positive correlation between CYDV-RPV titer and leaf mass per area. CYDV-RPV titer was reduced by the presence of a competitor, BYDV-PAV, and higher CYDV-RPV titer led to more severe chlorotic symptoms. In our experimental conditions, virus transmission was unaffected by nutrient supply rates, co-infection, plant stoichiometry, or plant traits, although nutrient supply rates have been shown to increase infection and coinfection rates. This work provides a robust test of the role of plant nutrient content and ratios in the dynamics of globally important pathogens and reveals a more complex relationship between

  18. β-Enaminonitriles in heterocylic synthesis: Synthesis of new ...

    Indian Academy of Sciences (India)

    WINTEC

    gicides and solvatochromatic dyes. Recently, a num- ber of papers and patents concerning the importance of β-enaminonitriles in the synthesis of biologically active compounds, dihydropyridines analogous to nifedipine and amlodipine as potential calcium channel blockers in the treatment of angina and hypertension have ...

  19. The Effect of Synthesis Parameters on the Catalytic Synthesis of ...

    African Journals Online (AJOL)

    NJD

    Synthesis of Multiwalled Carbon Nanotubes using. Fe-Co/CaCO. 3. Catalysts. Sabelo D. Mhlangaa,b, Kartick C. Mondala,b, Robin Cartera,b, Michael J. Witcombb,c and Neil J. Covillea,b*. aMolecular Sciences Institute and School of Chemistry, University of the Witwatersrand, Johannesburg, WITS 2050, South Africa.

  20. The effect of NGATHA altered activity in auxin signaling pathways within the Arabidopsis gynoecium

    Directory of Open Access Journals (Sweden)

    Irene eMartinez-Fernandez

    2014-05-01

    Full Text Available The four NGATHA genes (NGA form a small subfamily within the large family of B3-domain transcription factors of Arabidopsis thaliana. NGA genes act redundantly to direct the development of the apical tissues of the gynoecium, the style and the stigma. Previous studies indicate that NGA genes could exert this function at least partially by directing the synthesis of auxin at the distal end of the developing gynoecium through the upregulation of two different YUCCA genes, which encode flavin monooxygenases involved in auxin biosynthesis. We have compared three developing pistil transcriptome data sets from wildtype, nga quadruple mutants and a 35S::NGA3 line. The differentially expressed genes showed a significant enrichment for auxin-related genes, supporting the idea of NGA genes as major regulators of auxin accumulation and distribution within the developing gynoecium.We have introduced reporter lines for several of these differentially expressed genes involved in synthesis, transport and response to auxin in NGA gain- and loss-of-function backgrounds. We present here a detailed map of the response of these reporters to NGA misregulation that could help to clarify the role of NGA in auxin-mediated gynoecium morphogenesis. Our data point to a very reduced auxin synthesis in the developing apical gynoecium of nga mutants, likely responsible for the lack of DR5rev::GFP reporter activity observed in these mutants. In addition, NGA altered activity affects the expression of protein kinases that regulate the cellular localization of auxin efflux regulators, and thus likely impact auxin transport. Finally, protein accumulation in pistils of several ARFs was differentially affected by nga mutations or NGA overexpression, suggesting that these accumulation patterns depend not only on auxin distribution but could be also regulated by transcriptional networks involving NGA factors.

  1. Altered expression of keratinocyte growth factor and its receptor in psoriasis.

    Science.gov (United States)

    Finch, P W; Murphy, F; Cardinale, I; Krueger, J G

    1997-12-01

    One of the biological characteristics of psoriasis is excessive flaking of the skin. This is directly related to the marked hyperplasia of epidermal keratinocytes and to incomplete epidermal differentiation. Keratinocyte growth factor (KGF), a potent mitogen for human keratinocytes, is expressed by stromal cells. Alterations in the KGF signaling pathway might account for the epidermal hyperplasia associated with psoriasis. To test this hypothesis, we investigated the expression of KGF and its receptor (KGFR) in psoriasis tissue. KGF and KGFR mRNA levels were found to be frequently elevated in psoriatic skin specimens as compared with normal skin. Increased KGF transcript expression was localized to the dermal layer of the involved skin specimen using in situ hybridization. In contrast, KGFR transcript and protein expression was localized to the basal layer of keratinocytes in normal skin and to the basal and suprabasal layers of the psoriatic epidermis, coincident with the expanded proliferative keratinocyte pool. To identify molecules that might regulate KGFR expression we investigated the effects of various pharmacological agents and cytokines on KGFR synthesis by keratinocytes. Phorbol ester, interleukin-6, interferon-gamma, and ultraviolet B (UVB) treatment all led to substantial down-regulation of KGFR expression. The down-regulation of KGFR synthesis by UVB suggests a possible mechanism for the antiproliferative action of this agent in the treatment of psoriasis. Taken together, these results suggest that increased KGFR-mediated signaling in keratinocytes in the lesional epidermis might account in part for the epidermal hyperplasia in psoriasis.

  2. Tenascin-x deficiency mimics ehlers-danlos syndrome in mice through alteration of collagen deposition

    Energy Technology Data Exchange (ETDEWEB)

    Mao, J.R.; Taylor, G.; Dean, W.B.; Wagner, D.R.; Afzal, V.; Lotz, J.C.; Rubin, E.M.; Bristow, J.

    2002-03-01

    Tenascin-X is a large extracellular matrix protein of unknown function1-3. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome4,5, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens6. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme7-14, we suggested that tenascin-X might regulate collagen synthesis or deposition15. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.

  3. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.

    Science.gov (United States)

    Xiao, Yong-Tao; Cao, Yi; Zhou, Ke-Jun; Lu, Li-Na; Cai, Wei

    2016-12-15

    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.

  4. Maize (Zea mays) seeds can detect above-ground weeds; thiamethoxam alters the view.

    Science.gov (United States)

    Afifi, Maha; Lee, Elizabeth; Lukens, Lewis; Swanton, Clarence

    2015-09-01

    Far red light is known to penetrate soil and delay seed germination. Thiamethoxam as a seed treatment has been observed to enhance seed germination. No previous work has explored the effect of thiamethoxam on the physiological response of buried maize seed when germinating in the presence of above-ground weeds. We hypothesised that the changes in red:far red reflected from above-ground weeds would be detected by maize seed phytochrome and delay seed germination by decreasing the level of GA and increasing ABA. We further hypothesised that thiamethoxam would overcome this delay in germination. Thiamethoxam enhanced seed germination in the presence of above-ground weeds by increasing GA signalling and downregulating DELLA protein and ABA signalling genes. An increase in amylase activity and a degradation of starch were also observed. Far red reflected from the above-ground weeds was capable of penetrating below the soil surface and was detected by maize seed phytochrome. Thiamethoxam altered the effect of far red on seed germination by stimulating GA and inhibiting ABA synthesis. This is the first study to suggest that the mode of action of thiamethoxam involves both GA synthesis and ABA inhibition. © 2014 Society of Chemical Industry.

  5. Alterations in adipokines in feline hepatic lipidosis.

    Science.gov (United States)

    Mazaki-Tovi, M; Abood, S K; Segev, G; Schenck, P A

    2013-01-01

    Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. Serum concentrations of adiponectin and leptin are altered in feline HL. Client-owned cats: 55 healthy and 45 with liver disease. Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 μg/mL), HL and concurrent disease (4.4 μg/mL), or other liver disease (6.1 μg/mL), as compared with healthy cats (1.5 μg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  6. Alteration of serum adropin level in preeclampsia.

    Science.gov (United States)

    Wang, Huihua; Gao, Bo; Wu, Zaigui; Wang, Hanzhi; Dong, Minyue

    2017-04-01

    To clarify the alterations in serum adropin and preptin concentrations in preeclampsia, we determined serum adropin and preptin levels in 29 women with normal pregnancy and 32 women with preeclampsia. We found that maternal age, body mass index and fetal gender were not significantly different between two groups; however, blood pressure, gestational age and neonatal birth weight were significantly different. Serum adropin levels were significantly increased in women with preeclampsia compared with those with normal pregnancy but there were no significant differences in preptin levels. An increase in maternal serum adropin level was found in preeclampsia, and this may be a compensation for pregnancy complicated with preeclampsia. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  7. Aqueous alteration detection in Tikhonravov crater, Mars

    Science.gov (United States)

    Mancarella, F.; Fonti, S.; Alemanno, G.; Orofino, V.; Blanco, A.

    2018-03-01

    The existence of a wet period lasting long enough to allow the development of elementary forms of life on Mars has always been a very interesting issue. Given this perspective, the research for geological markers of such occurrences has been continually pursued. Once a favorable site is detected, effort should be spent to get as much information as possible aimed at a precise assessment of the genesis and evolution of the areas showing the selected markers. In this work, we discuss the recent finding of possible deposits pointing to the past existence of liquid water in Tikhonravov crater located in Arabia Terra. Comparison of CRISM spectra and those of laboratory minerals formed by aqueous alteration has led us to the conclusion that the studied areas within the impact crater host phyllosilicates deposits. In addition, analysis of the CRISM spectra has resulted in the tentative identification of carbonates mixed with phyllosilicates.

  8. Oral complications of cancer therapies. Mucosal alterations

    Energy Technology Data Exchange (ETDEWEB)

    Squier, C.A. (Univ. of Iowa, Iowa City (USA))

    1990-01-01

    The initial effect of anticancer therapy, such as radiation and chemotherapy, is on the rapidly proliferating cells of the oral epithelium. As a consequence, the epithelium may show atrophy and ulceration. The sites of these alterations are related to the rate of epithelial proliferation. Regions of rapid proliferation, such as the oral lining mucosa, show a greater frequency of ulceration than masticatory mucosa or skin. Subsequent changes in the mucosa reflect damage to connective tissue, including fibroblasts and blood vessels. This results in hyalinization of collagen, hypovascularity, and ischemia. Indirect effects of anticancer therapy may include granulocytopenia and reduced salivary secretion, so that the protective mucin coating of the epithelium is compromised. These changes result in tissue with reduced barrier function and impaired ability to heal and to resist entry of pathogens, thus increasing the risk of systemic infections.

  9. Frontal lobe alterations in schizophrenia: a review.

    Science.gov (United States)

    Mubarik, Ateeq; Tohid, Hassaan

    2016-01-01

    To highlight the changes in the frontal lobe of the human brain in people with schizophrenia. This was a qualitative review of the literature. Many schizophrenic patients exhibit functional, structural, and metabolic abnormalities in the frontal lobe. Some patients have few or no alterations, while some have more functional and structural changes than others. Magnetic resonance imaging (MRI) shows structural and functional changes in volume, gray matter, white matter, and functional activity in the frontal lobe, but the mechanisms underlying these changes are not yet fully understood. When schizophrenia is studied as an essential topic in the field of neuropsychiatry, neuroscientists find that the frontal lobe is the most commonly involved area of the human brain. A clear picture of how this lobe is affected in schizophrenia is still lacking. We therefore recommend that further research be conducted to improve understanding of the pathophysiology of this psychiatric dilemma.

  10. Bortezomib alters sour taste sensitivity in mice

    Directory of Open Access Journals (Sweden)

    Akihiro Ohishi

    Full Text Available Chemotherapy-induced taste disorder is one of the critical issues in cancer therapy. Bortezomib, a proteasome inhibitor, is a key agent in multiple myeloma therapy, but it induces a taste disorder. In this study, we investigated the characteristics of bortezomib-induced taste disorder and the underlying mechanism in mice. Among the five basic tastes, the sour taste sensitivity of mice was significantly increased by bortezomib administration. In bortezomib-administered mice, protein expression of PKD2L1 was increased. The increased sour taste sensitivity induced by bortezomib returned to the control level on cessation of its administration. These results suggest that an increase in protein expression of PKD2L1 enhances the sour taste sensitivity in bortezomib-administered mice, and this alteration is reversed on cessation of its administration. Keywords: Taste disorder, Bortezomib, Sour taste, Chemotherapy, Adverse effect

  11. Alterations in subspecific characters of groundnut

    International Nuclear Information System (INIS)

    Mouli, C.; Patil, S.H.; Kale, D.M.

    1983-01-01

    Recombination of beneficial characters associated in the cultivars of groundnut (Arachis hypogaea, L.) belonging to the two subspecies hypogaea and fastigiata had little success in conventional breeding programme. The cultures of ssp. hypogaea have the desirable characters for the crop improvement viz; various growth habits, profuse branching, large pod, seed dormancy and stress tolerance. Sequential flowering, early maturity, compact fruiting habit and high kernel outturn are the other useful characters present in ssp. fastigiata cultures. Mutation research in a popular variety, Spanish Improved belonging to ssp. fastigiata led to the selection of various mutants. One among the mutants had large pod, a characteristic of hypogaea ssp. Hybridization among the mutants and improved cultivars as well as radiation treatment of selected cultures resulted in the isolation of cultures having not only combinations and alterations of characters in both subspecies, but also modifications. These cultures are classified into major groups and their significance in the groundnut improvement is discussed. (author)

  12. DNA methylation alterations in Alzheimer's disease.

    Science.gov (United States)

    Yokoyama, Amy S; Rutledge, John C; Medici, Valentina

    2017-05-01

    The observation that Alzheimer's disease (AD) patients with similar and even identical genetic backgrounds often present with heterogeneous pathologies has prompted the hypothesis that epigenetics may contribute to AD. While the study of epigenetics encompasses a variety of modifications including histone modifications and non-coding RNAs, much of the research on how epigenetics might impact AD pathology has been focused on DNA methylation. To this end, several studies have characterized DNA methylation alterations in various brain regions of individuals with AD, with conflicting results. This review examines the results of studies analyzing both global and gene-specific DNA methylation changes in AD and also assesses the results of studies analyzing DNA hydroxymethylation in patients with AD.

  13. Saccadic Alterations in Severe Developmental Dyslexia

    Directory of Open Access Journals (Sweden)

    Stefano Pensiero

    2013-01-01

    Full Text Available It is not sure if persons with dyslexia have ocular motor deficits in addition to their deficits in rapid visual information processing. A 15-year-old boy afflicted by severe dyslexia was submitted to saccadic eye movement recording. Neurological and ophthalmic examinations were normal apart from the presence of an esophoria for near and slightly longer latencies of pattern visual evoked potentials. Subclinical saccadic alterations were present, which could be at the basis of the reading pathology: (1 low velocities (and larger durations of the adducting saccades of the left eye with undershooting and long-lasting postsaccadic onward drift, typical of the internuclear ophthalmoplegia; (2 saccades interrupted in mid-flight and fixation instability, which are present in cases of brainstem premotor disturbances.

  14. Altered erythrocyte cation permeability in familial pseudohyperkalaemia.

    Science.gov (United States)

    Dagher, G; Vantyghem, M C; Doise, B; Lallau, G; Racadot, A; Lefebvre, J

    1989-08-01

    1. Erythrocyte cation transport pathways have been investigated in a family with pseudohyperkalaemia. 2. Ouabain- and bumetanide-resistant Na+ and K+ effluxes in three pseudohyperkalaemic patients were not different from those of control subjects when assessed at 37 degrees C. 3. When the temperature was decreased to 20 degrees C and 9 degrees C, K+ passive permeability markedly increased and Na+ permeability remained unchanged in these patients. In contrast, in control subjects a reduction in temperature caused a marked reduction in Na+ and K+ passive permeability. 4. These findings could account for the marked increase in plasma K+ concentration observed at subphysiological temperatures. 5. The Na+-K+ co-transport pathway was reduced in all members of the family, but the Na+-K+ pump was reduced in only two of them. These alterations were independent from the pseudohyperkalaemic state.

  15. Peripheral myelin protein 22 alters membrane architecture

    Science.gov (United States)

    Mittendorf, Kathleen F.; Marinko, Justin T.; Hampton, Cheri M.; Ke, Zunlong; Hadziselimovic, Arina; Schlebach, Jonathan P.; Law, Cheryl L.; Li, Jun; Wright, Elizabeth R.; Sanders, Charles R.; Ohi, Melanie D.

    2017-01-01

    Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin. PMID:28695207

  16. Glaucoma alters the circadian timing system.

    Directory of Open Access Journals (Sweden)

    Elise Drouyer

    Full Text Available Glaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC and visual deficits associated with glaucoma have been extensively studied, we hypothesize that glaucoma will also lead to alteration of the circadian timing system. Circadian and non-visual responses to light are mediated by a specialized subset of melanopsin expressing RGCs that provide photic input to mammalian endogenous clock in the suprachiasmatic nucleus (SCN. In order to explore the molecular, anatomical and functional consequences of glaucoma we used a rodent model of chronic ocular hypertension, a primary causal factor of the pathology. Quantitative analysis of retinal projections using sensitive anterograde tracing demonstrates a significant reduction (approximately 50-70% of RGC axon terminals in all visual and non-visual structures and notably in the SCN. The capacity of glaucomatous rats to entrain to light was challenged by exposure to successive shifts of the light dark (LD cycle associated with step-wise decreases in light intensity. Although glaucomatous rats are able to entrain their locomotor activity to the LD cycle at all light levels, they require more time to re-adjust to a shifted LD cycle and show significantly greater variability in activity onsets in comparison with normal rats. Quantitative PCR reveals the novel finding that melanopsin as well as rod and cone opsin mRNAs are significantly reduced in glaucomatous retinas. Our findings demonstrate that glaucoma impacts on all these aspects of the circadian timing system. In light of these results, the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system.

  17. Wound trauma alters ionizing radiation dose assessment

    Directory of Open Access Journals (Sweden)

    Kiang Juliann G

    2012-06-01

    Full Text Available Abstract Background Wounding following whole-body γ-irradiation (radiation combined injury, RCI increases mortality. Wounding-induced increases in radiation mortality are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to bacterial infection. Among these factors, cytokines along with other biomarkers have been adopted for biodosimetric evaluation and assessment of radiation dose and injury. Therefore, wounding could complicate biodosimetric assessments. Results In this report, such confounding effects were addressed. Mice were given 60Co γ-photon radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, body-weight loss, and wound healing. Analyses of DNA damage in bone-marrow cells and peripheral blood mononuclear cells (PBMCs, changes in hematology and cytokine profiles, and fundamental clinical signs were evaluated. Early biomarkers (1 d after RCI vs. irradiation alone included significant decreases in survivin expression in bone marrow cells, enhanced increases in γ-H2AX formation in Lin+ bone marrow cells, enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood, and concomitant decreases in γ-H2AX formation in PBMCs and decreases in numbers of splenocytes, lymphocytes, and neutrophils. Intermediate biomarkers (7 – 10 d after RCI included continuously decreased γ-H2AX formation in PBMC and enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood. The clinical signs evaluated after RCI were increased water consumption, decreased body weight, and decreased wound healing rate and survival rate. Late clinical signs (30 d after RCI included poor survival and wound healing. Conclusion Results suggest that confounding factors such as wounding alters ionizing radiation dose assessment and agents inhibiting these responses may prove therapeutic for radiation combined

  18. Altered potassium homeostasis in Crohn's disease

    International Nuclear Information System (INIS)

    Schober, O.; Hundeshagen, H.; Bosaller, C.; Lehr, L.

    1983-01-01

    The total body potassium (TBK), serum potassium, and the number of red blood cell ouabain-binding sites was studied in 94 patients with Crohn's diease. TBK was measured by counting the endogenous 40 K in a whole body counter. TBK was 87%+-13% in 94 patients was Crohn's disease, while in control subjects, it was 97%+-12% (n=24). This significant reduction in TBK was accompanied by normal serum potassium levels (4.4+-0.5 mM). TBK was significantly correlated with the Crohn's disease activity index (r=0.79, n=113, P 3 H-ouabain showed a significant increse in the number of Na-K pumps in Crohn's disease (396+-65, n=27) compared with the control group. 290+-45 (n=24). These results support the suggestion that changes in TBK may regulate the synthesis of Na-K pump molecules. The total body potassium depletion and the need for a preoperative nutritional support in Crohn's disease are discussed. (orig.)

  19. Kinetics of viral deoxyribonucleic acid, protein, and infectious particle production and alterations in host macromolecular syntheses in equine abortion (herpes) virus-infected cells.

    Science.gov (United States)

    O'Callaghan, D J; Hyde, J M; Gentry, G A; Randall, C C

    1968-08-01

    Infection of exponential-phase suspension cultures of mouse fibroblast cells (L-M) with equine abortion virus (EAV) resulted in inhibition of cell growth and marked alterations in host metabolic processes. The synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid was inhibited within 4 hr after infection and was suppressed by more than 90% by the time of maximal virus replication (14 to 18 hr). The overall rate of protein synthesis, however, was similar in uninfected and virus-producing cells as determined by measurements of net protein and isotope incorporation. The time course of viral DNA and protein synthesis and assembly into mature virus was determined with the inhibitors 5-fluorodeoxyuridine (FUdR) and cycloheximide, respectively. Thus, viral DNA synthesis was essentially completed at 14 hr, and viral protein and infectious virus synthesis was completed at 18 hr. Although the number of plaque-forming units (PFU) produced by FUdR-treated cells (10(3) to 10(4) PFU/ml) was at least 3 logs less than that produced by untreated cells, the yield of physical particles (as determined by electron microscopy) was approximately the same at 30 hr after infection. Besides being relatively non-infective, the particles produced in FUdR-treated cells appeared morphologically incomplete as they contained little or no nucleoid material.

  20. Synthesis and supramolecular assembly of biomimetic polymers

    Science.gov (United States)

    Marciel, Amanda Brittany

    A grand challenge in materials chemistry is the synthesis of macromolecules and polymers with precise shapes and architectures. Polymer microstructure and architecture strongly affect the resulting functionality of advanced materials, yet understanding the static and dynamic properties of these complex macromolecules in bulk has been difficult due to their inherit polydispersity. Single molecule studies have provided a wealth of information on linear flexible and semi-flexible polymers in dilute solutions. However, few investigations have focused on industrially relevant complex topologies (e.g., star, comb, hyperbranched polymers) in industrially relevant solution conditions (e.g., semi-dilute, concentrated). Therefore, from this perspective there is a strong need to synthesize precision complex architectures for bulk studies as well as complex architectures compatible with current single molecule techniques to study static and dynamic polymer properties. In this way, we developed a hybrid synthetic strategy to produce branched polymer architectures based on chemically modified DNA. Overall, this approach enables control of backbone length and flexibility, as well as branch grafting density and chemical identity. We utilized a two-step scheme based on enzymatic incorporation of non-natural nucleotides containing bioorthogonal dibenzocyclooctyne (DBCO) functional groups along the main polymer backbone, followed by copper-free "click" chemistry to graft synthetic polymer branches or oligonucleotide branches to the DNA backbone, thereby allowing for the synthesis of a variety of polymer architectures, including three-arm stars, H-polymers, graft block copolymers, and comb polymers for materials assembly and single molecule studies. Bulk materials properties are also affected by industrial processing conditions that alter polymer morphology. Therefore, in an alternative strategy we developed a microfluidic-based approach to assemble highly aligned synthetic

  1. Development of a Matrix Alteration Model (MAM)

    International Nuclear Information System (INIS)

    Martinez Esparza, A.; Cunado, M. A.; Gago, J. A.; Quinones, J.; Iglesias, E.; Cobos, J.; Gonzalez de la Huebra, A.; Cera, E.; Merino, J.; Bruno, J.; Pablos, J. de; Casas, I.; Clarens, F.; Gimenez, J.

    2005-01-01

    The present report is a summary of the main tasks carried out within the WP4 of the SFS project (5th Framework Programme of the European Commission) by ENRESA and collaborators, mainly focused on the development of the so-called Matrix Alteration Model (MAM), a model to study the long-term oxidant dissolution of the spent fuel matrix under repository conditions. A variety of issues have been addressed: development of the MAM conceptual model, integration of a new matrix alteration mechanism in the radiolytic model, calibration and testing of the model, calculations for base case in Performance Assessment exercises, sensitivity analysis and an assessment of applicability of the MAM. The conceptual model for the UO2 oxidant dissolution is based on the processes expected to occur in the long term under repository conditions. Briefly, when water will enter in contact with the fuel surface, the first process we may expect is the radiolysis of water. Water radiolysis will generate reductant and oxidants and we may expect local oxidising conditions. Because of these local conditions, the surface of the fuel will be oxidized. The oxidation of the matrix and the attachment of aqueous ligands able to form strong complexes with its major component will favour the dissolution of the matrix. The integration of the matrix alteration (oxidation and dissolution) mechanism in the radiolytic model by means of elemental reactions has been mainly elucidated from the mechanistic models developed for non-irradiated UO2 dissolution experiments. Moreover, flow-through dissolution experiments with unirradiated UO2 have been used to calibrate the oxidative dissolution mechanism of UO2. The model developed has been able to reproduce experimental dissolution rates for pH > 5 and [HCO3 -] < 10-2 M when the oxidant is O2 at partial pressures lower than 21%, and 3 < pH < 9 and [HCO3 -] = 210-3 M and when the oxidant is H2O2 at concentrations below 10-4 M. These ranges cover the geochemical

  2. Expressing yeast SAMdc gene confers broad changes in gene expression and alters fatty acid composition in tomato fruit.

    Science.gov (United States)

    Kolotilin, Igor; Koltai, Hinanit; Bar-Or, Carmiya; Chen, Lea; Nahon, Sahadia; Shlomo, Haviva; Levin, Ilan; Reuveni, Moshe

    2011-07-01

    Tomato (Solanum lycopersicum) fruits expressing a yeast S-adenosyl methionine decarboxylase (ySAMdc) gene under control of a ripening-induced promoter show altered phytonutrient content and broad changes in gene expression. Genome-wide transcriptional alterations in pericarp tissues of the ySAMdc-expressing fruits are shown. Consistent with the ySAMdc expression pattern from the ripening-induced promoter, very minor transcriptional alterations were detected at the mature green developmental stage. At the breaker and red stages, altered levels of numerous transcripts were observed with a general tendency toward upregulation in the transgenic fruits. Ontological analysis of up- and downregulated transcript groups revealed various affected metabolic processes, mainly carbohydrate and amino acid metabolism, and protein synthesis, which appeared to be intensified in the ripening transgenic fruits. Other functional ontological categories of altered transcripts represented signal transduction, transcription regulation, RNA processing, molecular transport and stress response, as well as metabolism of lipids, glycans, xenobiotics, energy, cofactors and vitamins. In addition, transcript levels of genes encoding structural enzymes for several biosynthetic pathways showed strong correlations to levels of specific metabolites that displayed altered levels in transgenic fruits. Increased transcript levels of fatty acid biosynthesis enzymes were accompanied by a change in the fatty acid profile of transgenic fruits, most notably increasing ω-3 fatty acids at the expense of other lipids. Thus, SAMdc is a prime target in manipulating the nutritional value of tomato fruits. Combined with analyses of selected metabolites in the overripe fruits, a model of enhanced homeostasis of the pericarp tissue in the polyamine-accumulating tomatoes is proposed. Copyright © Physiologia Plantarum 2011.

  3. Plant mediated green synthesis: modified approaches

    Science.gov (United States)

    Das, Ratul Kumar; Brar, Satinder Kaur

    2013-10-01

    Plant mediated green synthesis of different metallic nanoparticles has emerged as one of the options for implementation of green chemistry principles, and successfully made an important contribution towards green nanotechnology. However, beyond the synthesis and application aspects, the science of green synthesis has carried some wrong perceptions in an unforeseen fashion. In this review, some of the key issues related to the green synthesis of metallic nanoparticles employing plants as reducing/capping agents have been addressed. Random selection of plants and its overall impact on the different aspects of green synthesis have been discussed. Emphasis is given to the setting of some standard selection criteria to be adopted for selecting a plant for use in green synthesis. How selection of a plant can positively or negatively influence both procedure and products of a green synthesis process is the prime concern of this article. In addition to selection, the key issue of biocompatibility associated with green synthesized metallic nanoparticles has been considered. Both selection of plant and biocompatibility were reconsidered for their minute details in terms of synthesis, analysis and data interpretation in the green synthesis approach. The key factors capable of fine tuning the core meaning of ``green'' in the synthesis of any metallic nanoparticles were taken into consideration. This article is an effort towards keeping the core meaning of green synthesis.

  4. Plant mediated green synthesis: modified approaches.

    Science.gov (United States)

    Das, Ratul Kumar; Brar, Satinder Kaur

    2013-11-07

    Plant mediated green synthesis of different metallic nanoparticles has emerged as one of the options for implementation of green chemistry principles, and successfully made an important contribution towards green nanotechnology. However, beyond the synthesis and application aspects, the science of green synthesis has carried some wrong perceptions in an unforeseen fashion. In this review, some of the key issues related to the green synthesis of metallic nanoparticles employing plants as reducing/capping agents have been addressed. Random selection of plants and its overall impact on the different aspects of green synthesis have been discussed. Emphasis is given to the setting of some standard selection criteria to be adopted for selecting a plant for use in green synthesis. How selection of a plant can positively or negatively influence both procedure and products of a green synthesis process is the prime concern of this article. In addition to selection, the key issue of biocompatibility associated with green synthesized metallic nanoparticles has been considered. Both selection of plant and biocompatibility were reconsidered for their minute details in terms of synthesis, analysis and data interpretation in the green synthesis approach. The key factors capable of fine tuning the core meaning of "green" in the synthesis of any metallic nanoparticles were taken into consideration. This article is an effort towards keeping the core meaning of green synthesis.

  5. Green chemistry for chemical synthesis

    Science.gov (United States)

    Li, Chao-Jun; Trost, Barry M.

    2008-01-01

    Green chemistry for chemical synthesis addresses our future challenges in working with chemical processes and products by inventing novel reactions that can maximize the desired products and minimize by-products, designing new synthetic schemes and apparati that can simplify operations in chemical productions, and seeking greener solvents that are inherently environmentally and ecologically benign. PMID:18768813

  6. Efficient synthesis of substituted dihydrotetraazapentacenes.

    Science.gov (United States)

    Seillan, Claire; Brisset, Hugues; Siri, Olivier

    2008-09-18

    We describe a versatile and very efficient synthesis of previously unknown substituted 5,14-dihydro-5,7,12,14-tetraazapentacenes (DHTAPs). A structural study by NMR spectroscopy showed that the conjugated pi-system of the pentacyclic skeleton rearranges depending on the electronic effect of the substituent(s).

  7. Analysis and synthesis of laughter

    Science.gov (United States)

    Sundaram, Shiva; Narayanan, Shrikanth

    2004-10-01

    There is much enthusiasm in the text-to-speech community for synthesis of emotional and natural speech. One idea being proposed is to include emotion dependent paralinguistic cues during synthesis to convey emotions effectively. This requires modeling and synthesis techniques of various cues for different emotions. Motivated by this, a technique to synthesize human laughter is proposed. Laughter is a complex mechanism of expression and has high variability in terms of types and usage in human-human communication. People have their own characteristic way of laughing. Laughter can be seen as a controlled/uncontrolled physiological process of a person resulting from an initial excitation in context. A parametric model based on damped simple harmonic motion to effectively capture these diversities and also maintain the individuals characteristics is developed here. Limited laughter/speech data from actual humans and synthesis ease are the constraints imposed on the accuracy of the model. Analysis techniques are also developed to determine the parameters of the model for a given individual or laughter type. Finally, the effectiveness of the model to capture the individual characteristics and naturalness compared to real human laughter has been analyzed. Through this the factors involved in individual human laughter and their importance can be better understood.

  8. Methyltrioctylammonium chloride catalysed sonochemical synthesis ...

    Indian Academy of Sciences (India)

    Methyltrioctylammonium chloride catalysed sonochemical synthesis of acridine diones. BHUPINDER KAUR and HARISH KUMAR. ∗. Department of Chemistry, Sant Longowal Institute of Engineering and Technology, Longowal 148 106, India e-mail: choprahk67@gmail.com. MS received 21 May 2012; revised 30 January ...

  9. SYNTHESIS, CHARACTERIZATION AND DENSITY FUNCTIONAL ...

    African Journals Online (AJOL)

    Preferred Customer

    KEY WORDS: Monoacyl aniline, Synthesis, Density functional theory, Rotation barrier. INTRODUCTION ... on the electron density in the phenyl ring and the respective accelerating and decelerating effects on the rate of ... compounds were determined using Nujol mulls and of liquids either in dichloromethane or chloroform ...

  10. Hydrothermal synthesis, characterization and luminescent ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 39; Issue 4. Hydrothermal synthesis, characterization and luminescent properties of lanthanide-doped NaLaF 4 nanoparticles. JIGMET LADOL HEENA KHAJURIA SONIKA KHAJURIA ... Keywords. Citric acid; X-ray diffraction; down-conversion emission; energy transfer.

  11. Methanol synthesis beyond chemical equilibrium

    NARCIS (Netherlands)

    van Bennekom, J. G.; Venderbosch, R. H.; Winkelman, J. G. M.; Wilbers, E.; Assink, D.; Lemmens, K. P. J.; Heeres, H. J.

    2013-01-01

    In commercial methanol production from syngas, the conversion is thermodynamically limited to 0.3-0.7 leading to large recycles of non-converted syngas. This problem can be overcome to a significant extent by in situ condensation of methanol during its synthesis which is possible nowadays due to the

  12. Total Synthesis of a Gene

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 12. Total Synthesis of a Gene. H G Khorana. Classics Volume 17 Issue 12 December 2012 pp 1174-1197 ... Author Affiliations. H G Khorana1. Professor of Biology and Chemestry, Massachusetts Institute of Technology, Cambridge 02139.

  13. Brassinosteroids: synthesis and biological activities

    Czech Academy of Sciences Publication Activity Database

    Oklešťková, Jana; Rárová, Lucie; Kvasnica, Miroslav; Strnad, Miroslav

    2015-01-01

    Roč. 14, č. 6 (2015), s. 1053-1072 ISSN 1568-7767 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Brassinosteroids * Chemical synthesis * Plant biological activity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.686, year: 2015

  14. Synthesis of partially stabilized leucite

    Czech Academy of Sciences Publication Activity Database

    Kloužková, A.; Mrázová, M.; Kohoutková, Martina

    2007-01-01

    Roč. 68, 5-6 (2007), s. 1207-1210 ISSN 0022-3697 R&D Projects: GA MPO 2A-1TP1/063 Institutional research plan: CEZ:AV0Z40320502 Keywords : ceramics * chemical synthesis * X-ray diffraction Subject RIV: CA - Inorganic Chemistry Impact factor: 0.899, year: 2007

  15. Methyltrioctylammonium chloride catalysed sonochemical synthesis ...

    Indian Academy of Sciences (India)

    of the researchers because of their use as drugs for car- diovascular diseases, such as angina pectoris,7 hyper- tension,8 antitumour agents,9–11 DNA-binding moieties and DNA-intercalating anticancer drugs.12,13 There- fore, the synthesis of ... properties of ionic liquids they are emerging as a 'green reaction media'. ∗.

  16. Protein synthesis controls phosphate homeostasis.

    Science.gov (United States)

    Pontes, Mauricio H; Groisman, Eduardo A

    2018-01-01

    Phosphorus is an essential element assimilated largely as orthophosphate (Pi). Cells respond to Pi starvation by importing Pi from their surroundings. We now report that impaired protein synthesis alone triggers a Pi starvation response even when Pi is plentiful in the extracellular milieu. In the bacterium Salmonella enterica serovar Typhimurium , this response entails phosphorylation of the regulatory protein PhoB and transcription of PhoB-dependent Pi transporter genes and is eliminated upon stimulation of adenosine triphosphate (ATP) hydrolysis. When protein synthesis is impaired due to low cytoplasmic magnesium (Mg 2+ ), Salmonella triggers the Pi starvation response because ribosomes are destabilized, which reduces ATP consumption and thus free cytoplasmic Pi. This response is transient because low cytoplasmic Mg 2+ promotes an uptake in Mg 2+ and a decrease in ATP levels, which stabilizes ribosomes, resulting in ATP consumption and Pi increase, thus ending the response. Notably, pharmacological inhibition of protein synthesis also elicited a Pi starvation response in the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae Our findings identify a regulatory connection between protein synthesis and Pi homeostasis that is widespread in nature. © 2018 Pontes and Groisman; Published by Cold Spring Harbor Laboratory Press.

  17. Phytochelatin synthesis in tomato cells

    International Nuclear Information System (INIS)

    Goldsbrough, P.; Gupta, S.; Huang, B.; Scheller, H.

    1987-01-01

    Tomato cells that are exposed to cadmium and other heavy metals synthesize phytochelatins (PCs), a family of peptides that bind heavy metals and are structurally related to glutathione (GSH). PCs have the structure (γ-glutamyl-cysteinyl) glycine; for PCs, n=2-10; GSH, n=1. GSH levels decline rapidly in tomato cells exposed to Cd 2+ . Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, prevents sustained synthesis of PC. However the addition of GSH to the medium of BSO-treated cells restores PC production. In vivo labeling studies indicate that 35 [S]-cysteine is incorporated into PC via GSH, rather than being added directly to GSH or pre-formed PC. Initial synthesis of PCs is not inhibited by cycloheximide. Tomato cell cultures that are tolerant of high levels of Cd 2+ contain large amounts of PCs. However, when sensitive and tolerant cells that have been grown in the absence of Cd 2+ are exposed to relatively low concentrations of Cd 2+ , they synthesize PCs at similar rates. These and other results suggest that, although PCs are necessary, increased PC synthesis is not sufficient for expression of the Cd 2+ tolerant phenotype

  18. Synthesis of Glucose Spiropiperazinone Derivatives

    OpenAIRE

    Vasiļjevs, D

    2013-01-01

    Piperazinone derivatives аге noticeable peptidometics; therefore, they сап replace peptides, such as RGD and Leu-enkephalin in different biological processes. Some piperazinone derivatives are anticoagulants, others act like neurotransmitters. Herein, we report an approach for the synthesis of поуеl piperazinone ring containing spiro-derivatives of glucose.

  19. Catalysis and prebiotic RNA synthesis

    Science.gov (United States)

    Ferris, James P.

    1993-01-01

    The essential role of catalysis for the origins of life is discussed. The status of the prebiotic synthesis of 2',5'- and 3'5'-linked oligomers of RNA is reviewed. Examples of the role of metal ion and mineral catalysis in RNA oligomer formation are discussed.

  20. SYNTHESIS AND CHARACTERIZATION OF FUNCTIONALIZED ...

    African Journals Online (AJOL)

    2016-07-30

    E-mail: b_mohtat@yahoo.com. This work is licensed under the Creative Commons ... Department of Chemistry, Islamic Azad University, Karaj Branch, Karaj, Iran. (Received July 30, 2016; revised ..... Chem. 2013, 9, 2846-2851. 7. Mohamed, K.S.; Soliman, M.A.; El-Remaily, M.A.A.; Abdel-Ghany, H. Eco-friendly synthesis of ...

  1. Northwest Forest Plan research synthesis.

    Science.gov (United States)

    Richard W. Haynes; Gloria E. Perez; [tech. eds.].

    2000-01-01

    This document synthesizes research accomplishments initiated and funded under the Northwest Forest Plan or the President’s Forest Plan (hereafter referred to as the Forest Plan) since its inception in 1994. Three major parts in this document cover, the context for this effort, eight Forest Plan research accomplishments, and a synthesis. The eight accomplishments...

  2. Multicomponent reactions in polymer synthesis.

    Science.gov (United States)

    Kakuchi, Ryohei

    2014-01-03

    More participants, yet efficient reactions: Multicomponent reactions (MCRs) have found application in polymer chemistry both in the synthesis of multifunctional monomers and in post-polymerization modification. Examples include the Passerini three-component reaction, the Ugi four-component reaction, and the copper-catalyzed MCR. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. IONOTHERMAL SYNTHESIS, STRUCTURES AND SUPRAMOLE

    African Journals Online (AJOL)

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    2Department of Chemistry, University of Aveiro, CICECO, 3810-193 Aveiro, Portugal. (Received October 14 ... The principal feature of ionothermal synthesis is that the ionic liquids (ILs) act as both the “designed” green solvents ... purification except [EMI]Br. [EMI]Br was synthesized from the reaction of ethylbromide with.

  4. Green chemistry for chemical synthesis

    OpenAIRE

    Li, Chao-Jun; Trost, Barry M.

    2008-01-01

    Green chemistry for chemical synthesis addresses our future challenges in working with chemical processes and products by inventing novel reactions that can maximize the desired products and minimize by-products, designing new synthetic schemes and apparati that can simplify operations in chemical productions, and seeking greener solvents that are inherently environmentally and ecologically benign.

  5. Green chemistry for chemical synthesis.

    Science.gov (United States)

    Li, Chao-Jun; Trost, Barry M

    2008-09-09

    Green chemistry for chemical synthesis addresses our future challenges in working with chemical processes and products by inventing novel reactions that can maximize the desired products and minimize by-products, designing new synthetic schemes and apparati that can simplify operations in chemical productions, and seeking greener solvents that are inherently environmentally and ecologically benign.

  6. Synthesis of [14C] alaproclate

    International Nuclear Information System (INIS)

    Gawell, Lars

    1986-01-01

    The synthesis of carbon-14 labelled alaproclate from [2- 14 C]acetone in three steps is described. The label is introduced by the reaction of a benzylic Grignard reagent with the ketone yielding a tertiary alcohol. Subsequent esterification with an α-bromocarboxylic acid chloride and amination produced the title compound in a 13% overall radiochemical yield. (author)

  7. The Total Synthesis of Chlorophyll

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 7. The Total Synthesis of Chlorophyll. Setty Mallikarjuna Babu Subramania Ranganathan. General Article Volume 19 Issue 7 July 2014 pp 645-648. Fulltext. Click here to view fulltext PDF. Permanent link:

  8. Organic Synthesis using Clay Catalysts

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 1. Organic Synthesis using Clay Catalysts - Clays for 'Green Chemistry'. Gopalpur Nagendrappa. General Article Volume 7 Issue 1 January 2002 pp 64-77. Fulltext. Click here to view fulltext PDF. Permanent link:

  9. Hydrothermal synthesis, characterization and luminescent ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 39; Issue 4. Hydrothermal synthesis, characterization and luminescent properties of lanthanide-doped NaLaF 4 nanoparticles. JIGMET LADOL HEENA KHAJURIA SONIKA KHAJURIA HAQ NAWAZ SHEIKH. Volume 39 Issue 4 August 2016 pp 943-952 ...

  10. The Total Synthesis of Strychnine

    Indian Academy of Sciences (India)

    IAS Admin

    The Total Synthesis of Strychnine. Edited by Setty Mallikarjuna Babu and Subramania Ranganathan. Keywords. Strychnine. N. N. O. H. H. H. H. O. H. Strychnine! No other molecule has captured the popular imagina- tion as strychnine, perhaps because thousands of writers of fiction have used it to dispatch the recipient and ...

  11. SYNTHESIS, STRUCTURE AND PHOTOLUMINESCENCE OF ...

    African Journals Online (AJOL)

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    dimensional supramolecular framework. ... The growing interest in the field of the crystal engineering of inorganic-organic hybrid materials .... Synthesis, structure and photoluminescence of (HgCl3)n(C6NO2H6)n(C6NO2H5)n nH2O. Bull. Chem.

  12. Haber Process for Ammonia Synthesis

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 16; Issue 12. Haber Process for Ammonia Synthesis. Jayant M Modak. Volume 16 Issue 12 December 2011 pp 1159-1167. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/016/12/1159-1167. Keywords.

  13. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  14. Microstructured Reactors for Electroorganic Synthesis

    Czech Academy of Sciences Publication Activity Database

    Bouzek, K.; Jiřičný, Vladimír; Kodým, R.; Křišťál, Jiří; Bystroň, T.

    2010-01-01

    Roč. 55, č. 7 (2010), s. 8172-8181 ISSN 0013-4686. [Annual Meeting of ISE /60./. Beijing, 16.08.2009-21.08.2009] Institutional research plan: CEZ:AV0Z40720504 Keywords : microstructured reactor * bipolar * electroorganic synthesis Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 3.642, year: 2010

  15. Inhibition of skeletal muscle protein synthesis in septic intra-abdominal abscess

    International Nuclear Information System (INIS)

    Vary, T.C.; Siegel, J.H.; Tall, B.D.; Morris, J.G.; Smith, J.A.

    1988-01-01

    Chronic sepsis is always associated with profound wasting leading to increased release of amino acids from skeletal muscle. Net protein catabolism may be due to decreased rate of synthesis, increased rate of degradation, or both. To determine whether protein synthesis is altered in chronic sepsis, the rate of protein synthesis in vivo was estimated by measuring the incorporation of [ 3 H]-phenylalanine in skeletal muscle protein in a chronic (5-day) septic rat model induced by creation of a stable intra-abdominal abscess using an E. coli + B. fragilis-infected sterile fecal-agar pellet as foreign body nidus. Septic rats failed to gain weight at rates similar to control animals, therefore control animals were weight matched to the septic animals. The skeletal muscle protein content in septic animals was significantly reduced relative to control animals (0.18 +/- 0.01 vs. 0.21 +/- 0.01 mg protein/gm wet wt; p less than 0.02). The rate of incorporation of [ 3 H]-phenylalanine into skeletal muscle protein from control animals was 39 +/- 4 nmole/gm wet wt/hr or a fractional synthetic rate of 5.2 +/- 0.5%/day. In contrast to control animals, the fractional synthetic rate in septic animals (2.6 +/- 0.2%/day) was reduced by 50% compared to control animals (p less than 0.005). The decreased rate of protein synthesis in sepsis was not due to an energy deficit, as high-energy phosphates and ATP/ADP ratio were not altered. This decrease in protein synthesis occurred even though septic animals consumed as much food as control animals

  16. Different modes of diaminopimelate synthesis and their role in cell wall integrity: a study with Corynebacterium glutamicum.

    Science.gov (United States)

    Wehrmann, A; Phillipp, B; Sahm, H; Eggeling, L

    1998-06-01

    In eubacteria, there are three slightly different pathways for the synthesis of m-diaminopimelate (m-DAP), which is one of the key linking units of peptidoglycan. Surprisingly, for unknown reasons, some bacteria use two of these pathways together. An example is Corynebacterium glutamicum, which uses both the succinylase and dehydrogenase pathways for m-DAP synthesis. In this study, we clone dapD and prove by enzyme experiments that this gene encodes the succinylase (M(r) = 24082), initiating the succinylase pathway of m-DAP synthesis. By using gene-directed mutation, dapD, as well as dapE encoding the desuccinylase, was inactivated, thereby forcing C. glutamicum to use only the dehydrogenase pathway of m-DAP synthesis. The mutants are unable to grow on organic nitrogen sources. When supplied with low ammonium concentrations but excess carbon, their morphology is radically altered and they are less resistant to mechanical stress than the wild type. Since the succinylase has a high affinity toward its substrate and uses glutamate as the nitrogen donor, while the dehydrogenase has a low affinity and incorporates ammonium directly, the m-DAP synthesis is another example of twin activities present in bacteria for access to important metabolites such as the well-known twin activities for the synthesis of glutamate or for the uptake of potassium.

  17. Smectite alteration by anaerobic iron corrosion

    International Nuclear Information System (INIS)

    Sanders, D.; Kaufhold, S.; Hassel, A.W.; Dohrmann, R.

    2010-01-01

    Document available in extended abstract form only. The interaction of smectites with corroding steel/iron represents a crucial topic in the estimation of the long term confinement properties of clay barriers for the encasement of steel/iron containers. Especially in case of engineered clay barriers a possible deterioration of favourable smectite properties as response to corrosion could reduce the barrier capacity. The extent of this reduction is unknown, yet. The essential properties of bentonite clays in this context are on the one hand the relatively high swelling pressure together with low hydraulic conductivity, which results from the well known expandability of smectite interlayers in aqueous environments. On the other hand smectites are cation exchangers being able to long term encase radioactive cations in a way that negative charges of silicate layers are compensated by easily exchangeable hydrated cations. Both properties are directly related to the crystal and chemical composition of smectites. The nature of the corrosion of steel canisters in clay barriers will - after a first short aerobic phase - predominantly be anaerobic resulting in the formation of Fe(II) and two equivalents of hydroxide ions. In a set of exposition experiments anaerobic corroding iron in bentonite gels was studied in order to determine alteration of the smectite fraction. During the exposition a green coloration of the bentonite neighbouring to corroding iron was observed. Upon contact to oxygen in a humid state the bentonite turned reddish indicating the oxidation of Fe(II) to Fe(III). This observation is in accordance with reported results indicating the formation of an iron rich smectite. Chemical analysis of the 'green bentonite' reveals an increase of iron fraction e.g. from 3.4% mass to 9.3% mass . The adsorbed iron is predominantly Fe(II) which was proven by chromato-metric titration. The estimated ratio between silicon to increased iron content is Si: Fe ≅ 2

  18. Alterations in cell function with ischemia and shock and their correction.

    Science.gov (United States)

    Chaudry, I H; Clemens, M G; Baue, A E

    1981-10-01

    Progressive cell injury occurs with shock and ischemia, beginning with functional changes in the cell and cell membrane. Membrane transport and potential decrease, Na+ enters and K+ leaves cells; N+-K+ adenosine triphosphatase is activated, adenosine triphosphate (ATP) is used, and mitochondria are stimulated as increased lactate produces acidosis. Energy and cyclic adenosine monophosphate levels decrease, Ca2+ regulation is compromised, and nuclear function and protein synthesis are depressed. The cell swells, and further membrane changes occur with altered hormonal effects and mitochondrial uncoupling. Finally, lysosomes leak, intracellular and mitochondria disruption occurs, and the cell is destroyed. Based on these changes, attempts were made to directly support cell function during low-flow states. After volume replacement and vasoactive agents, other modalities, eg, substrates, membrane-stabilizing solutions, osmotic agents, and energy compounds were used. The use of ATP-MgCl2 was helpful in many experimental low-flow states, with an improvement in cell function mediated by micro-circulatory, cell membrane, or energy-recycling effects. Clinical examples of altered cell and organ function with ischemia and shock are numerous and play a critical role in the development of multiple systems failure. The potential for biochemical support and correction of these problems is now recognized. Benefits have already been achieved in myocardial preservation during cardiac operations, kidney preservation for transplantation, and circulatory and metabolic support of the injured and septic patient.

  19. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  20. Altered minor-groove hydrogen bonds in DNA block transcription elongation by T7 RNA polymerase.

    Science.gov (United States)

    Tanasova, Marina; Goeldi, Silvan; Meyer, Fabian; Hanawalt, Philip C; Spivak, Graciela; Sturla, Shana J

    2015-05-26

    DNA transcription depends upon the highly efficient and selective function of RNA polymerases (RNAPs). Modifications in the template DNA can impact the progression of RNA synthesis, and a number of DNA adducts, as well as abasic sites, arrest or stall transcription. Nonetheless, data are needed to understand why certain modifications to the structure of DNA bases stall RNA polymerases while others are efficiently bypassed. In this study, we evaluate the impact that alterations in dNTP/rNTP base-pair geometry have on transcription. T7 RNA polymerase was used to study transcription over modified purines and pyrimidines with altered H-bonding capacities. The results suggest that introducing wobble base-pairs into the DNA:RNA heteroduplex interferes with transcriptional elongation and stalls RNA polymerase. However, transcriptional stalling is not observed if mismatched base-pairs do not H-bond. Together, these studies show that RNAP is able to discriminate mismatches resulting in wobble base-pairs, and suggest that, in cases of modifications with minor steric impact, DNA:RNA heteroduplex geometry could serve as a controlling factor for initiating transcription-coupled DNA repair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Xyloglucan Deficiency Disrupts Microtubule Stability and Cellulose Biosynthesis in Arabidopsis, Altering Cell Growth and Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Chaowen; Zhang, Tian; Zheng, Yunzhen; Cosgrove, Daniel J.; Anderson, Charles T.

    2015-11-02

    Xyloglucan constitutes most of the hemicellulose in eudicot primary cell walls and functions in cell wall structure and mechanics. Although Arabidopsis (Arabidopsis thaliana) xxt1 xxt2 mutants lacking detectable xyloglucan are viable, they display growth defects that are suggestive of alterations in wall integrity. To probe the mechanisms underlying these defects, we analyzed cellulose arrangement, microtubule patterning and dynamics, microtubule- and wall-integrity-related gene expression, and cellulose biosynthesis in xxt1 xxt2 plants. We found that cellulose is highly aligned in xxt1 xxt2 cell walls, that its three-dimensional distribution is altered, and that microtubule patterning and stability are aberrant in etiolated xxt1 xxt2 hypocotyls. We also found that the expression levels of microtubule-associated genes, such as MAP70-5 and CLASP, and receptor genes, such as HERK1 and WAK1, were changed in xxt1 xxt2 plants and that cellulose synthase motility is reduced in xxt1 xxt2 cells, corresponding with a reduction in cellulose content. Our results indicate that loss of xyloglucan affects both the stability of the microtubule cytoskeleton and the production and patterning of cellulose in primary cell walls. These findings establish, to our knowledge, new links between wall integrity, cytoskeletal dynamics, and wall synthesis in the regulation of plant morphogenesis.

  2. Rhein inhibits glucose uptake in Ehrlich ascites tumor cells by alteration of membrane-associated functions.

    Science.gov (United States)

    Castiglione, S; Fanciulli, M; Bruno, T; Evangelista, M; Del Carlo, C; Paggi, M G; Chersi, A; Floridi, A

    1993-06-01

    Rhein (RH), 4,5 dihydroxyanthraquinone-2-carboxylic acid, is known to inhibit the glycolysis of neoplastic cells by impairing glucose uptake. In order to establish whether this might be due to a selective interaction of the carrier with the drug or to functional modifications of the cell membrane, the effect of RH on glucose uptake in Ehrlich ascites tumor cells has been investigated. RH strongly inhibits the uptake of both 2-deoxyglucose and 3-O-methylglucose, so the reduced influx therefore cannot be ascribed to an effect on glucose phosphorylation. The inhibition of glucose transport does not depend on a reduction of the number of the carriers as indicated by the inability of the drug to interfere with the synthesis of the transporter. Moreover, the extent of total binding of cytochalasin B, as well as the fact that glucose specificity is not altered, indicate that the intrinsic activity of the glucose carrier is not affected. We therefore conclude that the inhibition of glucose uptake must be ascribed to an interaction of the drug with cell membranes that results in an alteration of membrane-associated functions.

  3. Manipulating thyroid status alters endoplasmic reticulum calcium homeostasis in rat cerebellum.

    Science.gov (United States)

    Cole, J T; McMullen, D C; Kean, W S; Yarnell, A M; Lucky, J J; Selak, M A; Buonora, J E; Grunberg, N E; Verma, A; Watson, W D

    2012-01-01

    Thyroid-related hormones regulate the efficiency and expression of sarco-endoplasmic reticulum calcium ATPases in cardiac and skeletal muscle. However, little is known about the relationship between thyroid hormones and calcium (Ca2+) homeostasis in the brain. It is hypothesized that manipulating rat thyroid hormone levels would induce significant brain Ca2+ adaptations consistent with clinical findings. Adult male Sprague-Dawley rats were assigned to one of three treatment groups for 28 days: control, hypothyroid (6-n-propyl-2-thiouracil (PTU), an inhibitor of thyroxine (T4) synthesis), and hyperthyroid (T4). Throughout, rats were given weekly behavioral tests. Ca2+ accumulation decreased in the cerebellum in both hyper- and hypothyroid animals. This was specific to different ER pools of calcium with regional heterogeneity in the response to thyroid hormone manipulation. Behavioral tasks demonstrated sensitivity to thyroid manipulation, and corresponded to alterations in calcium homeostasis. Ca2+ accumulation heterogeneity in chronic hyper- and hypothyroid animals potentially explains clinical manifestations of altered thyroid status.

  4. Altered gene regulation and synaptic morphology in Drosophila learning and memory mutants

    Science.gov (United States)

    Guan, Zhuo; Buhl, Lauren K.; Quinn, William G.; Littleton, J. Troy

    2011-01-01

    Genetic studies in Drosophila have revealed two separable long-term memory pathways defined as anesthesia-resistant memory (ARM) and long-lasting long-term memory (LLTM). ARM is disrupted in radish (rsh) mutants, whereas LLTM requires CREB-dependent protein synthesis. Although the downstream effectors of ARM and LLTM are distinct, pathways leading to these forms of memory may share the cAMP cascade critical for associative learning. Dunce, which encodes a cAMP-specific phosphodiesterase, and rutabaga, which encodes an adenylyl cyclase, both disrupt short-term memory. Amnesiac encodes a pituitary adenylyl cyclase-activating peptide homolog and is required for middle-term memory. Here, we demonstrate that the Radish protein localizes to the cytoplasm and nucleus and is a PKA phosphorylation target in vitro. To characterize how these plasticity pathways may manifest at the synaptic level, we assayed synaptic connectivity and performed an expression analysis to detect altered transcriptional networks in rutabaga, dunce, amnesiac, and radish mutants. All four mutants disrupt specific aspects of synaptic connectivity at larval neuromuscular junctions (NMJs). Genome-wide DNA microarray analysis revealed ∼375 transcripts that are altered in these mutants, suggesting defects in multiple neuronal signaling pathways. In particular, the transcriptional target Lapsyn, which encodes a leucine-rich repeat cell adhesion protein, localizes to synapses and regulates synaptic growth. This analysis provides insights into the Radish-dependent ARM pathway and novel transcriptional targets that may contribute to memory processing in Drosophila. PMID:21422168

  5. Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

    Directory of Open Access Journals (Sweden)

    Heidi O Nousiainen

    Full Text Available Prostatic acid phosphatase (PAP, the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG, but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP in the brain by utilizing mice deficient in TMPAP (PAP-/- mice. Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.

  6. Near-field/altered-zone models report

    Energy Technology Data Exchange (ETDEWEB)

    Hardin, E. L., LLNL

    1998-03-01

    nonlithophysal and lower lithophysal units. These units are made up of moderately to densely welded, devitrified, fractured tuff. The rock's chemical composition is comparable to that of typical granite, but has textural features and mineralogical characteristics of large-scale, silicic volcanism. Because the repository horizon will be approximately 300 m below the ground surface and 200 m above the water table, the repository will be partially saturated. The welded tuff matrix in the host units is highly impermeable, but water and gas flow readily through fractures. The degree of fracturing in these units is highly variable, and the hydrologic significance of fracturing is an important aspect of site investigation. This report describes the characterization and modeling of a region around the potential repository--the altered zone--a region in which the temperature will be increased significantly by waste-generated heat. Numerical simulation has shown that, depending on the boundary conditions, rock properties, and repository design features incorporated in the models, the altered zone (AZ) may extend from the water table to the ground surface. This report also describes models of the near field, the region comprising the repository emplacement drifts and the surrounding rock, which are critical to the performance of engineered components. Investigations of near-field and altered-zone (NF/AZ) processes support the design of underground repository facilities and engineered barriers and also provide constraint data for probabilistic calculations of waste-isolation performance (i.e., performance assessment). The approach to investigation, which is an iterative process involving hypothesis testing and experimentation, has relied on conceptualizing engineered barriers and on performance analysis. This report is a collection, emphasizing conceptual and numerical models, of the recent results contributed from studies of NF/AZ processes and of quantitative measures of NF

  7. Altered whole-brain connectivity in albinism.

    Science.gov (United States)

    Welton, Thomas; Ather, Sarim; Proudlock, Frank A; Gottlob, Irene; Dineen, Robert A

    2017-02-01

    Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Mutation of the little finger domain in human DNA polymerase η alters fidelity when copying undamaged DNA.

    Science.gov (United States)

    Beardslee, Renee A; Suarez, Samuel C; Toffton, Shannon M; McCulloch, Scott D

    2013-10-01

    DNA polymerase η (pol η) synthesizes past cyclobutane pyrimidine dimer and possibly 7,8-dihydro-8-oxoguanine (8-oxoG) lesions during DNA replication. Loss of pol η is associated with an increase in mutation rate, demonstrating its indispensable role in mutation suppression. It has been recently reported that β-strand 12 (amino acids 316-324) of the little finger region correctly positions the template strand with the catalytic core of the enzyme. The authors hypothesized that modification of β-strand 12 residues would disrupt correct enzyme-DNA alignment and alter pol η's activity and fidelity. To investigate this, the authors purified proteins containing the catalytic core of the polymerase, incorporated single amino acid changes to select β-strand 12 residues, and evaluated DNA synthesis activity for each pol η. Lesion bypass efficiencies and replication fidelities when copying DNA-containing cis-syn cyclobutane thymine-thymine dimer and 8-oxoG lesions were determined and compared with the corresponding values for the wild-type polymerase. The results confirm the importance of the β-strand in polymerase function and show that fidelity is most often altered when undamaged DNA is copied. Additionally, it is shown that DNA-protein contacts distal to the active site can significantly affect the fidelity of synthesis. Copyright © 2013 Wiley Periodicals, Inc.

  9. Altered regulation of lipid biosynthesis in a mutant of Arabidopsis deficient in chloroplast glycerol-3-phosphate acyltransferase activity

    International Nuclear Information System (INIS)

    Kunst, L.; Browse, J.; Somerville, C.

    1988-01-01

    The leaf membrane lipids of many plant species, including Arabidopsis thaliana (L.) Heynh., are synthesized by two complementary pathways that are associated with the chloroplast and the endoplasmic reticulum. By screening directly for alterations in lipid acyl-group composition, the authors have identified several mutants of Arabidopsis that lack the plastid pathway because of a deficiency in activity of the first enzyme in the plastid pathway of glycerolipid synthesis, acyl-ACP:sn-glycerol-3-phosphate acyltransferase. The lesion results in an increased synthesis of lipids by the cytoplasmic pathway that largely compensates for the loss of the plastid pathway and provides nearly normal amounts of all the lipids required for chloroplast biogenesis. However, the fatty acid composition of the leaf membrane lipids of the mutants is altered because the acyltransferases associated with the two pathways normally exhibit different substrate specificities. The remarkable flexibility of the system provides an insight into the nature of the regulatory mechanisms that allocate lipids for membrane biogenesis

  10. Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

    Science.gov (United States)

    2016-01-01

    The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis. PMID:27120289

  11. Measurement of Heme Synthesis Levels in Mammalian Cells.

    Science.gov (United States)

    Hooda, Jagmohan; Alam, Maksudul; Zhang, Li

    2015-07-09

    Heme serves as the prosthetic group for a wide variety of proteins known as hemoproteins, such as hemoglobin, myoglobin and cytochromes. It is involved in various molecular and cellular processes such as gene transcription, translation, cell differentiation and cell proliferation. The biosynthesis levels of heme vary across different tissues and cell types and is altered in diseased conditions such as anemia, neuropathy and cancer. This technique uses [4-(14)C] 5-aminolevulinic acid ([(14)C] 5-ALA), one of the early precursors in the heme biosynthesis pathway to measure the levels of heme synthesis in mammalian cells. This assay involves incubation of cells with [(14)C] 5-ALA followed by extraction of heme and measurement of the radioactivity incorporated into heme. This procedure is accurate and quick. This method measures the relative levels of heme biosynthesis rather than the total heme content. To demonstrate the use of this technique the levels of heme biosynthesis were measured in several mammalian cell lines.

  12. Facile synthesis of hollow silica nanospheres employing anionic PMANa templates

    Science.gov (United States)

    Shi, Yan; Takai, Chika; Shirai, Takashi; Fuji, Masayoshi

    2015-05-01

    This article presents a facile and green route to the synthesis of hollow silica particles by means of anionic particles of poly(sodium methacrylate) (PMANa) as templates. This method was composed of the following three steps: formation of PMANa particles in ethanol by nanoprecipitation, the deposition of silica shell on the polymer cores through sol-gel process of tetraethylorthosilicate under catalysis of ammonia, and removal of the polymer templates by washing with water. The templates' size can be controlled in the range of about 70-140 nm by altering the ratio of ethanol to water, the polymer solution concentration, the ethanol amount in polymer solution, and the silica shell thickness can be adjusted between 15 and 30 nm by varying the ratio of silica precursor to the polymer cores. A tentative interpretation about the silica-coating process on the anionic PMANa particles was also proposed according to the experimental results.

  13. Genetic alterations and epigenetic changes in hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Luz Stella Hoyos Giraldo

    2007-02-01

    Full Text Available

    Hepatocarcinogenesis as hepatocellular carcinoma (HCC is associated with background of chronic liver disease usually in association with cirrhosis, marked hepatic fibrosis, hepatitis B virus (HBV and/or hepatitis virus (HCV infection, chronic inflammation, Aflatoxin B1(AFB1 exposure, chronic alcoholism, metabolic disorder of the liver and necroinflamatory liver disease. Hepatocarcinogenesis involve two mechanisms, genetic alterations (with changes in the cell's DNA sequence and epigenetic changes (without changes in the cell's DNA sequence, but changes in the pattern of gene expression that can persist through one or more generations (somatic sense. Hepatocarcinogenesis is associated with activation of oncogenes and decreased expression of tumor suppressor genes (TSG; include those involved in cell cycle control, apoptosis, DNA repair, immortalization and angiogenesis. AFB1 is metabolized in the liver into a potent carcinogen, aflatoxin 8, 9-epoxide, which is detoxified by epoxide hydrolase (EPHX and glutathione S-transferase M1 (GSTM1.

    A failure of detoxification processes can allow to mutagenic metabolite to bind to DNA and inducing P53 mutation. Genetic polymorphism of EPHX and GSTM1 can make individuals more susceptible to AFB1. Epigenetic inactivation of GSTP1 by promoter hypermethylation plays a role in the development of HCC because, it leads that electrophilic metabolite increase DNA damage and mutations. HBV DNA integration into the host chromosomal DNA of hepatocytes has been detected in HBV-related HCC.

    DNA tumor viruses cause cancer mainly by interfering with cell cycle controls, and activating the cell's replication machinery by blocking the action of key TSG. HBx protein is a

  14. Iron status alters murine systemic lupus erythematosus.

    Science.gov (United States)

    Leiter, L M; Reuhl, K R; Racis, S P; Sherman, A R

    1995-03-01

    The effect of Fe status on murine systemic lupus erythematosus was investigated. Weanling female MRL/MPJ-lpr/lpr mice (systemic lupus erythematosus strain) were fed diets with the following levels (mg Fe/kg diet): 3 (severely deficient), 10 (moderately deficient), 35 (control) and 250 (supplemented). A fifth group was pair fed the control diet in the amounts consumed by the severely deficient group. C3H/Hej mice fed the same diets were used as non-lupus controls. Anemia was more severe in severely deficient mice than in all other MRL groups and C3H severely deficient mice. Incidence of skin lesions was highest in MRL severely and moderately deficient mice compared with pair-fed, control and supplemented mice. By 22 wk of age, mortality was higher in supplemented and severely deficient mice than in moderately deficient, pair-fed and control MRL mice. Anti-dsDNA activity in serum was not altered by Fe. In a second experiment, kidney function was examined in mice fed severely deficient, control, supplemented and pair-fed diets. Urine protein concentration was highest in supplemented mice at 14 wk of age. Serum urea nitrogen was significantly higher in MRL severely deficient mice than in pair-fed and control mice at 18 wk of age. Glomerular filtration rate, measured by creatinine clearance, was significantly lower in MRL severely deficient mice than in pair-fed and Fe supplemented mice at 16 wk of age and pair-fed and control mice at 18 wk of age. Renal histopathology was more severe in Fe supplemented mice than in pair-fed and control mice, and more severe in severely deficient and pair-fed mice than in control mice. Fluorescent staining of kidneys with anti-Ig G and anti-C3 fluorescein-conjugated antibodies was most intense in severely deficient mice, and the concentration of circulating immune complexes in serum was significantly higher in severely deficient mice than in all other groups. These data demonstrate that systemic lupus erythematosus in MRL

  15. Pyrogenic organic matter can alter microbial communication

    Science.gov (United States)

    Masiello, Caroline; Gao, Xiaodong; Cheng, Hsiao-Ying; Silberg, Jonathan

    2016-04-01

    Soil microbes communicate with each other to manage a large range of processes that occur more efficiently when microbes are able to act simultaneously. This coordination occurs through the continuous production of signaling compounds that are easily diffused into and out of cells. As the number of microbes in a localized environment increases, the internal cellular concentration of these signaling compounds increases, and when a threshold concentration is reached, gene expression shifts, leading to altered (and coordinated) microbial behaviors. Many of these coordinated behaviors have biogeochemically important outcomes. For example, methanogenesis, denitrification, biofilm formation, and the development of plant-rhizobial symbioses are all regulated by a simple class of cell-cell signaling molecules known as acyl homoserine lactones (AHLs). Pyrogenic organic matter in soils can act to disrupt microbial communication through multiple pathways. In the case of AHLs, charcoal's very high surface area can sorb these signaling compounds, preventing microbes from detecting each others' presence (Masiello et al., 2014). In addition, the lactone ring in AHLs is vulnerable to pH increases accompanying PyOM inputs, with soil pH values higher than 7-8 leading to ring opening and compound destabilization. Different microbes use different classes of signaling compounds, and not all microbial signaling compounds are pH-vulnerable. This implies that PyOM-driven pH increases may trigger differential outcomes for Gram negative bacteria vs fungi, for example. A charcoal-driven reduction in microbes' ability to detect cell-cell communication compounds may lead to a shift in the ability of microbes to participate in key steps of C and N cycling. For example, an increase in an archaeon-specific AHL has been shown to lead to a cascade of metabolic processes that eventually results in the upregulation of CH4 production (Zhang et al., 2012). Alterations in similar AHL compounds leads to

  16. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Séverine Cruet-Hennequart

    Full Text Available While human mesenchymal stem cells (hMSCs, either in the bone marrow or in tumour microenvironment could be targeted by radiotherapy, their response is poorly understood. The oxic effects on radiosensitivity, cell cycle progression are largely unknown, and the radiation effects on hMSCs differentiation capacities remained unexplored. Here we analysed hMSCs viability and cell cycle progression in 21% O2 and 3% O2 conditions after medical X-rays irradiation. Differentiation towards osteogenesis and chondrogenesis after irradiation was evaluated through an analysis of differentiation specific genes. Finally, a 3D culture model in hypoxia was used to evaluate chondrogenesis in conditions mimicking the natural hMSCs microenvironment. The hMSCs radiosensitivity was not affected by O2 tension. A decreased number of cells in S phase and an increase in G2/M were observed in both O2 tensions after 16 hours but hMSCs released from the G2/M arrest and proliferated at day 7. Osteogenesis was increased after irradiation with an enhancement of mRNA expression of specific osteogenic genes (alkaline phosphatase, osteopontin. Osteoblastic differentiation was altered since matrix deposition was impaired with a decreased expression of collagen I, probably through an increase of its degradation by MMP-3. After induction in monolayers, chondrogenesis was altered after irradiation with an increase in COL1A1 and a decrease in both SOX9 and ACAN mRNA expression. After induction in a 3D culture in hypoxia, chondrogenesis was altered after irradiation with a decrease in COL2A1, ACAN and SOX9 mRNA amounts associated with a RUNX2 increase. Together with collagens I and II proteins decrease, associated to a MMP-13 expression increase, these data show a radiation-induced impairment of chondrogenesis. Finally, a radiation-induced impairment of both osteogenesis and chondrogenesis was characterised by a matrix composition alteration, through inhibition of synthesis and

  17. Overexpression of tomato SlNAC1 transcription factor alters fruit pigmentation and softening.

    Science.gov (United States)

    Ma, Nana; Feng, Hailong; Meng, Xia; Li, Dong; Yang, Dongyue; Wu, Changai; Meng, Qingwei

    2014-12-10

    Fruit maturation and ripening are genetically regulated processes that involve a complex interplay of plant hormones, growth regulators and multiple biological and environmental factors. Tomato (Solanum lycopersicum) has been used as a model of biological and genetic studies on the regulation of specific ripening pathways, including ethylene, carotenoid and cell wall metabolism. This model has also been used to investigate the functions of upstream signalling and transcriptional regulators. Thus far, many ripening-associated transcription factors that influence fruit development and ripening have been reported. NAC transcription factors are plant specific and play important roles in many stages of plant growth and development, such as lateral root formation, secondary cell wall synthesis, and embryo, floral organ, vegetative organ and fruit development. Tissue-specific analysis by quantitative real-time PCR showed that SlNAC1 was highly accumulated in immature green fruits; the expression of SlNAC1 increased with fruit ripening till to the highest level at 7 d after the breaker stage. The overexpression of SlNAC1 resulted in reduced carotenoids by altering carotenoid pathway flux and decreasing ethylene synthesis mediated mainly by the reduced expression of ethylene biosynthetic genes of system-2, thus led to yellow or orange mature fruits. The results of yeast one-hybrid experiment demonstrated that SlNAC1 can interact with the regulatory regions of genes related lycopene and ethylene synthesis. These results also indicated that SlNAC1 inhibited fruit ripening by affecting ethylene synthesis and carotenoid accumulation in SlNAC1 overexpression lines. In addition, the overexpression of SlNAC1 reduced the firmness of the fruits and the thickness of the pericarp and produced more abscisic acid, resulting in the early softening of fruits. Hence, in SlNAC1 overexpression lines, both ethylene-dependent and abscisic acid-dependent pathways are regulated by SlNAC1 in

  18. Altered structural connectome in temporal lobe epilepsy.

    Science.gov (United States)

    DeSalvo, Matthew N; Douw, Linda; Tanaka, Naoaki; Reinsberger, Claus; Stufflebeam, Steven M

    2014-03-01

    To study differences in the whole-brain structural connectomes of patients with left temporal lobe epilepsy (TLE) and healthy control subjects. This study was approved by the institutional review board, and all individuals gave signed informed consent. Sixty-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) magnetic resonance imaging volumes were analyzed in 24 patients with left TLE and in 24 healthy control subjects. MP-RAGE volumes were segmented into 1015 regions of interest (ROIs) spanning the entire brain. Deterministic white matter tractography was performed after voxelwise tensor calculation. Weighted structural connectivity matrices were generated by using the pairwise density of connecting fibers between ROIs. Graph theoretical measures of connectivity networks were compared between groups by using linear models with permutation testing. Patients with TLE had 22%-45% reduced (P < .01) distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with that in healthy subjects. However, local connectivity, as measured by means of network efficiency, was increased by 85%-270% (P < .01) in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE as compared with healthy subjects. This study suggests that TLE involves altered structural connectivity in a network that reaches beyond the temporal lobe, especially in the default mode network.

  19. Perinatal TCDD exposure alters developmental neuroendocrine system.

    Science.gov (United States)

    Ahmed, R G

    2011-06-01

    This study tested whether maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may disrupt the development of neuroendocrine system of their offspring during the perinatal period. TCDD (0.2 or 0.4 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1 to lactation day (LD) 30. Potential effects on neuroendocrine function were evaluated by measuring serum thyroid hormone levels in pregnant rats and their offspring and measuring some biochemical parameters in cerebellum of these offspring on GD 16 and 19, and LD 10, 20, and 30. In both treated groups, a decrease in serum thyroxine (T4), triiodothyronine (T3) and increase in thyrotropin (TSH) levels were noticed during the tested days in dams and offspring, as well as GH levels were decreased in offspring with respect to control group. In cerebellum of control offspring, the levels of monoamines, γ-aminobutyric acid (GABA) and acetylcholinesterase (AchE) were found to be increased from GD 16 to LD 30. The hypothyroid conditions due to both maternal administrations of TCDD produced inhibitory effects on monoamines and AchE, and stimulatory actions on GABA in cerebellum of offspring. These alterations were dose and age dependent. Overall, these results suggest that TCDD may act as neuroendocrine disruptor. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  20. Cerebral blood volume alterations during fractional pneumoencephalography

    International Nuclear Information System (INIS)

    Voigt, K.; Greitz, T.

    1976-01-01

    Simultaneous and continuous measurements of the cerebral blood volume (CBV), cerebrospinal fluid (CSF) and blood pressure were carried out in six patients during fractional pneumoencephalography in order to examine intracranial volumetric interactions. Three patients (Group A) showed normal encephalographic findings, and in three patients (Group B) communicating hydrocephalus with convexity block was found encephalographically. In all patients the injection of air was followed by an immediate increase of CSF pressure and blood pressure and a concomitant decrease of CBV. The initial CSF pressure was invariably re-established within 3 to 3.5 min. During this time interval the CBV of the patients of Group B decreased significantly and 30 percent more than that of Group A. Furthermore, after restoration of the original CSF pressure, CBV returned to its initial level in all patients of Group A, whereas it remained unchanged or showed a further decrease in the patients of Group B. Removal of an amount of CSF corresponding to half of the amount of injected air was followed by a significant reactive hyperemic response in two normal patients. The intracranial volumetric alterations during fractional pneumoencephalography are discussed in detail with respect to the underlying physiologic mechanisms and are suggested as a model for acute and low pressure hydrocephalus

  1. Altered default network activity in obesity.

    Science.gov (United States)

    Tregellas, Jason R; Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Jesse; Kronberg, Eugene; Cordes, Dietmar; Cornier, Marc-Andre

    2011-12-01

    The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. To better understand the neurobiology of this process and how it may be dysfunctional in obesity, this study examined activity of the brain's "default network" in reduced-obese (RO) as compared to lean individuals. The default network is a group of functionally connected brain regions thought to play an important role in internally directed cognitive activity and the interplay between external and internal sensory processing. Functional magnetic resonance imaging was performed in 24 lean and 18 RO individuals in the fasted state after 2 days of eucaloric energy intake and after 2 days of 30% overfeeding in a counterbalanced design. Scanning was performed while subjects passively viewed images of food and nonfood objects. Independent component analysis was used to identify the default network component. In the eucaloric state, greater default network activity was observed in RO compared to lean individuals in the lateral inferior parietal and posterior cingulate cortices. Activity was positively correlated with appetite. Overfeeding resulted in increased default network activity in lean but not RO individuals. These findings suggest that the function of the default network, a major contributor to intrinsic neuronal activity, is altered in obesity and/or obese-prone individuals. Future studies of the network's function and its relationship to other brain networks may improve our understanding of the mechanisms and treatment of obesity.

  2. Can bread processing conditions alter glycaemic response?

    Science.gov (United States)

    Lau, Evelyn; Soong, Yean Yean; Zhou, Weibiao; Henry, Jeyakumar

    2015-04-15

    Bread is a staple food that is traditionally made from wheat flour. This study aimed to compare the starch digestibility of western baked bread and oriental steamed bread. Four types of bread were prepared: western baked bread (WBB) and oriental steamed bread (OSB), modified baked bread (MBB) made with the OSB recipe and WBB processing, and modified steamed bread (MSB) made with the WBB recipe and OSB processing. MBB showed the highest starch digestibility in vitro, followed by WBB, OSB and MSB. A similar trend was observed for glycaemic response in vivo. MBB, WBB, OSB and MSB had a glycaemic index of 75±4, 71±5, 68±5 and 65±4, respectively. Processing differences had a more pronounced effect on starch digestibility in bread, and steamed bread was healthier in terms of glycaemic response. The manipulation of processing conditions could be an innovative route to alter the glycaemic response of carbohydrate-rich foods. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Stabilization of LCD devices via geometric alteration.

    Science.gov (United States)

    Jeon, Il; Yoon, MinSung; Lee, Je-Hoon

    2013-02-20

    Glass bending in LCD displays is an inherent problem that has challenged many engineers. As a solution to this problem, we propose a methodology that can tackle the root of the phenomenon in terms of linear elastic beam theory. Using this hypothesis, we devised a background theory and a solution. In this paper, we present a glass panel to which geometrical changes, such as furrow, groove, and curb have been applied. These geometrical changes are applied to the nonactive area of the glass panel. To confirm the validity of our approach, we conducted simulation tests as well as hands-on experiments to observe the thermo-mechanical behavior of the device under various conditions. The simulation results using the Ansys simulator show that the proposed technique can reduce the deformation level of panel bending by 40%. In the experiment using a bare cell with polarizer films attached and with performing the high temperature reliability test, the deformation level of panel bending is reduced by half compared to the reference glass panel without any geometric alteration.

  4. Taurine depletion alters vascular reactivity in rats.

    Science.gov (United States)

    Abebe, Worku; Mozaffari, Mahmood S

    2003-09-01

    We recently showed that chronic taurine supplementation is associated with attenuation of contractile responses of rat aorta to norepinephrine and potassium chloride. However, the potential involvement of endogenous taurine in modulation of vascular reactivity is not known. Therefore, we examined the effect of beta-alanine-induced taurine depletion on the in vitro reactivity of rat aorta to selected vasoactive agents. The data indicate that both norepinephrine- and potassium-chloride-induced maximum contractile responses of endothelium-denuded aortae were enhanced in taurine-depleted rats compared with control animals. However, taurine depletion did not affect tissue sensitivity to either norepinephrine or potassium chloride. By contrast, sensitivity of the endothelium-denuded aortae to sodium nitroprusside was attenuated by taurine depletion. Similarly, taurine deficiency reduced the relaxant responses of endothelium-intact aortic rings elicited by submaximal concentrations of acetylcholine, and this effect was associated with decreased nitric oxide production. Taken together, the data suggest that taurine depletion augments contractility but attenuates relaxation of vascular smooth muscle in a nonspecific manner. Impairment of endothelium-dependent responses, which is at least in part associated with reduced nitric oxide generation, may contribute to the attenuation of the vasorelaxant responses. These vascular alterations could be of potential consequence in pathological conditions associated with taurine deficiency.

  5. Paternal Age Alters Social Development in Offspring.

    Science.gov (United States)

    Janecka, Magdalena; Haworth, Claire M A; Ronald, Angelica; Krapohl, Eva; Happé, Francesca; Mill, Jonathan; Schalkwyk, Leonard C; Fernandes, Cathy; Reichenberg, Abraham; Rijsdijk, Frühling

    2017-05-01

    Advanced paternal age (APA) at conception has been linked with autism and schizophrenia in offspring, neurodevelopmental disorders that affect social functioning. The current study explored the effects of paternal age on social development in the general population. We used multilevel growth modeling to investigate APA effects on socioemotional development from early childhood until adolescence, as measured by the Strengths and Difficulties Questionnaire (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated genetic and environmental underpinnings of the paternal age effects on development, using the Additive genetics, Common environment, unique Environment (ACE) and gene-environment (GxE) models. In the general population, both very young and advanced paternal ages were associated with altered trajectory of social development (intercept: p = .01; slope: p = .03). No other behavioral domain was affected by either young or advanced age at fatherhood, suggesting specificity of paternal age effects. Increased importance of genetic factors in social development was recorded in the offspring of older but not very young fathers, suggesting distinct underpinnings of the paternal age effects at these two extremes. Our findings highlight that the APA-related deficits that lead to autism and schizophrenia are likely continuously distributed in the population. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Percent tissue altered and corneal ectasia.

    Science.gov (United States)

    Santhiago, Marcony R

    2016-07-01

    This article reviews the association of a novel metric, percentage tissue altered (PTA), with the occurrence of ectasia after laser in-situ keratomileusis in eyes with normal corneal topography, and analyses the influence of the variables that comprise it, and its role on eyes with suspicious topography. PTA is derived from [PTA = (FT + AD)/CCT] where FT = flap thickness, AD = ablation depth, and CCT = preoperative central corneal thickness. Our studies revealed that there is a robust relationship between high PTA and ectasia risk in eyes with normal preoperative topography. PTA higher or equal to 40% presented the highest odds ratio and highest predictive capabilities for ectasia risk than each of the variables that comprise it, residual stromal bed or age. Average thicker flaps alone were insufficient to create ectasia unless coupled with greater ablation depths, meaning a high PTA. In eyes with suspicious topography, even low PTA value is sufficient to induce ectasia. This new metric, PTA, should be taken into account when screening patients for refractive surgery. Patients with normal topography or tomography, presenting a PTA higher or equal to 40% should be considered at higher risk for post laser in-situ keratomileusis ectasia.

  7. Genetic alterations during radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  8. Plant growth conditions alter phytolith carbon

    Directory of Open Access Journals (Sweden)

    Kimberley L Gallagher

    2015-09-01

    Full Text Available Many plants, including grasses and some important human food sources, accumulate and precipitate silica in their cells to form opaline phytoliths. These phytoliths contain small amounts of organic matter (OM that are trapped during the process of silicification. Previous work has suggested that plant silica is associated with compounds such as proteins, lipids, lignin and carbohydrate complexes. It is not known whether these compounds are cellular components passively encapsulated as the cell silicifies, polymers actively involved in the precipitation process or random compounds assimilated by the plant and discarded into a glass wastebasket. Here, we used Raman spectroscopy to map the distribution of OM in phytoliths, and to analyze individual phytoliths isolated from Sorghum bicolor plants grown under different laboratory treatments. Using mapping, we showed that OM in phytoliths is distributed throughout the silica and is not related to dark spots visible in light microscopy, previously assumed to be the repository for phytolith OM. The Raman spectra exhibited common bands indicative of C-H stretching modes of general OM, and further more diagnostic bands consistent with carbohydrates, lignins and other OM. These Raman spectra exhibited variability of spectral signatures and of relative intensities between sample treatments indicating that differing growth conditions altered the phytolith carbon. This may have strong implications for understanding the mechanism of phytolith formation, and for use of phytolith carbon isotope values in dating or paleoclimate reconstruction.

  9. Shadows alter facial expressions of Noh masks.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Kawai

    Full Text Available BACKGROUND: A Noh mask, worn by expert actors during performance on the Japanese traditional Noh drama, conveys various emotional expressions despite its fixed physical properties. How does the mask change its expressions? Shadows change subtly during the actual Noh drama, which plays a key role in creating elusive artistic enchantment. We here describe evidence from two experiments regarding how attached shadows of the Noh masks influence the observers' recognition of the emotional expressions. METHODOLOGY/PRINCIPAL FINDINGS: In Experiment 1, neutral-faced Noh masks having the attached shadows of the happy/sad masks were recognized as bearing happy/sad expressions, respectively. This was true for all four types of masks each of which represented a character differing in sex and age, even though the original characteristics of the masks also greatly influenced the evaluation of emotions. Experiment 2 further revealed that frontal Noh mask images having shadows of upward/downward tilted masks were evaluated as sad/happy, respectively. This was consistent with outcomes from preceding studies using actually tilted Noh mask images. CONCLUSIONS/SIGNIFICANCE: Results from the two experiments concur that purely manipulating attached shadows of the different types of Noh masks significantly alters the emotion recognition. These findings go in line with the mysterious facial expressions observed in Western paintings, such as the elusive qualities of Mona Lisa's smile. They also agree with the aesthetic principle of Japanese traditional art "yugen (profound grace and subtlety", which highly appreciates subtle emotional expressions in the darkness.

  10. Triclosan alterations of estuarine phytoplankton community structure.

    Science.gov (United States)

    Pinckney, James L; Thompson, Laura; Hylton, Sarah

    2017-06-15

    Antimicrobial additives in pharmaceutical and personal care products are a major environmental concern due to their potential ecological impacts on aquatic ecosystems. Triclosan (TCS) has been used as an antiseptic, disinfectant, and preservative in various media. The sublethal and lethal effects of TCS on estuarine phytoplankton community composition were investigated using bioassays of natural phytoplankton communities to measure phytoplankton responses to different concentrations of TCS ranging from 1 to 200μgl -1 . The EC 50 (the concentration of an inhibitor where the growth is reduced by half) for phytoplankton groups (diatoms, chlorophytes, cryptophytes) examined in this ranged from 10.7 to 113.8μg TCS l -1 . Exposures resulted in major shifts in phytoplankton community composition at concentrations as low as 1.0μg TCS l -1 . This study demonstrates estuarine ecosystem sensitivity to TCS exposure and highlights potential alterations in phytoplankton community composition at what are typically environmental concentrations of TCS in urbanized estuaries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  12. Pulmonary biochemical alterations resulting from ozone exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mustafa, M.G.; Lee, S.D.

    1976-07-01

    Metabolic response of lung tissue to ozone was studied in rats and monkeys after exposure of animals to various levels of ozone (0.1 to 0.8 ppM) for 1 to 30 days. In rats, 0.8 ppM ozone exposure resulted in a 40 to 50 percent augmentation of oxygen utilization in lung homogenate in the presence of an added substrate (e.g., succinate or 2-oxoglutarate). Activities of marker enzymes, viz. mitochondrial succinate-cytochrome c reductase; microsomal NADPH-cytochrome c reductase and cytosolic glucose-6-phosphate dehydrogenase, increased maximally (40 to 70 percent over control) after 3 to 4 days of exposure, and remained elevated throughout the 0.8 ppM ozone exposure for 30 days. In monkeys, the observations were the same except that the magnitude of biochemical changes was relatively smaller. Exposure of animals to lower levels of ozone resulted in proportionately smaller biochemical changes in the lung, and ozone effects were detectable up to the 0.2 ppM level. While 0.1 ppM ozone exposure was ineffective, dietary deficiency of vitamin E, a natural antioxidant, increased the sensitivity of rat lungs to this concentration of ozone. The results suggest that low-level ozone exposures may cause metabolic alterations in the lung, and that dietary supplementation of vitamin E may offer protection against oxidant stress.

  13. Alterated integrin expression in lichen planopilaris

    Directory of Open Access Journals (Sweden)

    Erriquez Roberta

    2007-02-01

    Full Text Available Abstract Background Lichen planopilaris (LPP is an inflammatory disease characterized by a lymphomononuclear infiltrate surrounding the isthmus and infundibulum of the hair follicle of the scalp, that evolves into atrophic/scarring alopecia. In the active phase of the disease hairs are easily plucked with anagen-like hair-roots. In this study we focused on the expression of integrins and basement membrane components of the hair follicle in active LPP lesions. Methods Scalp biopsies were taken in 10 patients with LPP and in 5 normal controls. Using monoclonal antibodies against α3β1 and α6β4 integrins we showed the expression of these integrins and of the basement membrane components of the hair follicle in active LPP lesions and in healthy scalp skin. Results In the LPP involved areas, α3β1 was distributed in a pericellular pattern, the α6 subunit was present with a basolateral distribution while the β4 subunit showed discontinuous expression at the basal pole and occasionally, basolateral staining of the hair follicle. Conclusion: An altered distribution of the integrins in active LPP lesions can explain the phenomenon of easy pulling-out of the hair with a "gelatinous" root-sheath.

  14. Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

    Science.gov (United States)

    Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

    2017-11-01

    The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

  15. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  16. Great Lakes rivermouth ecosystems: scientific synthesis and management implications

    Science.gov (United States)

    Larson, James H.; Trebitz, Anett S.; Steinman, Alan D.; Wiley, Michael J.; Carlson Mazur, Martha; Pebbles, Victoria; Braun, Heather A.; Seelbach, Paul W.

    2013-01-01

    At the interface of the Great Lakes and their tributary rivers lies the rivermouths, a class of aquatic ecosystem where lake and lotic processes mix and distinct features emerge. Many rivermouths are the focal point of both human interaction with the Great Lakes and human impacts to the lakes; many cities, ports, and beaches are located in rivermouth ecosystems, and these human pressures often degrade key ecological functions that rivermouths provide. Despite their ecological uniqueness and apparent economic importance, there has been relatively little research on these ecosystems as a class relative to studies on upstream rivers or the open-lake waters. Here we present a synthesis of current knowledge about ecosystem structure and function in Great Lakes rivermouths based on studies in both Laurentian rivermouths, coastal wetlands, and marine estuarine systems. A conceptual model is presented that establishes a common semantic framework for discussing the characteristic spatial features of rivermouths. This model then is used to conceptually link ecosystem structure and function to ecological services provided by rivermouths. This synthesis helps identify the critical gaps in understanding rivermouth ecology. Specifically, additional information is needed on how rivermouths collectively influence the Great Lakes ecosystem, how human alterations influence rivermouth functions, and how ecosystem services provided by rivermouths can be managed to benefit the surrounding socioeconomic networks.

  17. Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

    Science.gov (United States)

    Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

    2018-02-10

    Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Nano crystals-Related Synthesis, Assembly, and Energy Applications

    International Nuclear Information System (INIS)

    Dai, Q.; Hu, M.Z.; Yu, B.Z.; William, W.; Seo, J.

    2011-01-01

    Fundamental material properties have been dramatically altered in the nano scale regime because of quantum confinement effect. The unique size-tunable functionalities of nano materials make them involved in an extensive variety of energy applications, such as light-emitting diodes and solar cells. These applications have been demonstrated to cut energy consumption. In response to the ever-growing energy demands as well as the concerns of global warming, researchers are actively placing their enormous emphasis on the exploration of energy savings. During this exploration, the primary stage requires the design of appropriate strategies for the synthesis of high-quality nano crystals in terms of size uniformity and superior optical/electronic properties. Especially, there is a need to seek green-chemistry approaches for the synthesis of environmentally benign and user-friendly nano crystals. Another recent area of focus is the use of individual nano crystals as building blocks for self-assembly, providing new opportunities to improve the nano crystal performance

  19. Pushing the threshold: how NMDAR antagonists induce homeostasis through protein synthesis to remedy depression

    Science.gov (United States)

    Raab-Graham, Kimberly F.; Workman, Emily R.; Namjoshi, Sanjeev; Niere, Farr

    2016-01-01

    Healthy neurons have an optimal operating range, coded globally by the frequency of action potentials or locally by calcium. The maintenance of this range is governed by homeostatic plasticity. Here, we discuss how new approaches to treat depression alter synaptic activity. These approaches induce the neuron to recruit homeostatic mechanisms to relieve depression. Homeostasis generally implies that the direction of activity necessary to restore the neuron’s critical operating range is opposite in direction to its current activity pattern. Unconventional antidepressant therapies deep brain stimulation and NMDAR antagonists alter the neuron’s “depressed” state by pushing the neuron’s current activity in the same direction but to the extreme edge. These therapies rally the intrinsic drive of neurons in the opposite direction, thereby allowing the cell to return to baseline activity, form new synapses, and restore proper communication. In this review, we discuss seminal studies on protein synthesis dependent homeostatic plasticity and their contribution to our understanding of molecular mechanisms underlying the effectiveness of NMDAR antagonists as rapid antidepressants. Rapid antidepressant efficacy is likely to require a cascade of mRNA translational regulation. Emerging evidence suggests that changes in synaptic strength or intrinsic excitability converge on the same protein synthesis pathways, relieving depressive symptoms. Thus, we address the question: Are there multiple homeostatic mechanisms that induce the neuron and neuronal circuits to self-correct to regulate mood in vivo? Targeting alternative ways to induce homeostatic protein synthesis may provide, faster, safer, and longer lasting antidepressants. PMID:27125595

  20. TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy

    DEFF Research Database (Denmark)

    Zimmermann, Christine; Santos, Aline; Gable, Kenneth

    2013-01-01

    Very long chain fatty acids (VLCFAs) are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell's metabolic demand remains unknown. The goal...... of autophagy. Together, our data reveal a function for TORC1 and GSK3 in the regulation of VLCFA synthesis that has important implications for autophagy and cell homeostasis....... of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated by phosphorylation. Elo2 phosphorylation is induced upon inhibition of TORC1 and requires GSK3. Expression of nonphosphorylatable Elo2 profoundly alters...