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Sample records for tissue-specific alternative pre-mrna

  1. Strengths and weaknesses of EST-based prediction of tissue-specific alternative splicing

    Directory of Open Access Journals (Sweden)

    Vingron Martin

    2004-09-01

    Full Text Available Abstract Background Alternative splicing contributes significantly to the complexity of the human transcriptome and proteome. Computational prediction of alternative splice isoforms are usually based on EST sequences that also allow to approximate the expression pattern of the related transcripts. However, the limited number of tissues represented in the EST data as well as the different cDNA construction protocols may influence the predictive capacity of ESTs to unravel tissue-specifically expressed transcripts. Methods We predict tissue and tumor specific splice isoforms based on the genomic mapping (SpliceNest of the EST consensus sequences and library annotation provided in the GeneNest database. We further ascertain the potentially rare tissue specific transcripts as the ones represented only by ESTs derived from normalized libraries. A subset of the predicted tissue and tumor specific isoforms are then validated via RT-PCR experiments over a spectrum of 40 tissue types. Results Our strategy revealed 427 genes with at least one tissue specific transcript as well as 1120 genes showing tumor specific isoforms. While our experimental evaluation of computationally predicted tissue-specific isoforms revealed a high success rate in confirming the expression of these isoforms in the respective tissue, the strategy frequently failed to detect the expected restricted expression pattern. The analysis of putative lowly expressed transcripts using normalized cDNA libraries suggests that our ability to detect tissue-specific isoforms strongly depends on the expression level of the respective transcript as well as on the sensitivity of the experimental methods. Especially splice isoforms predicted to be disease-specific tend to represent transcripts that are expressed in a set of healthy tissues rather than novel isoforms. Conclusions We propose to combine the computational prediction of alternative splice isoforms with experimental validation for

  2. Investigation of tissue-specific human orthologous alternative splice events in pig

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Jørgensen, Claus Bøttcher; Salicio, Susanna Cirera

    2010-01-01

    Alternative splicing of pre-mRNA can contribute to differences between tissues or cells either by regulating gene expression or creating proteins with various functions encoded by one gene. The number of investigated alternative splice events in pig has so far been limited. In this study we have ...... in preservation of open reading frame are indicative of a functional significance of the splice variants of the gene....

  3. Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster.

    Science.gov (United States)

    Liu, Xiaochuan; Freitas, Jaime; Zheng, Dinghai; Oliveira, Marta S; Hoque, Mainul; Martins, Torcato; Henriques, Telmo; Tian, Bin; Moreira, Alexandra

    2017-12-01

    Alternative polyadenylation (APA) is a mechanism that generates multiple mRNA isoforms with different 3'UTRs and/or coding sequences from a single gene. Here, using 3' region extraction and deep sequencing (3'READS), we have systematically mapped cleavage and polyadenylation sites (PASs) in Drosophila melanogaster , expanding the total repertoire of PASs previously identified for the species, especially those located in A-rich genomic sequences. Cis -element analysis revealed distinct sequence motifs around fly PASs when compared to mammalian ones, including the greater enrichment of upstream UAUA elements and the less prominent presence of downstream UGUG elements. We found that over 75% of mRNA genes in Drosophila melanogaster undergo APA. The head tissue tends to use distal PASs when compared to the body, leading to preferential expression of APA isoforms with long 3'UTRs as well as with distal terminal exons. The distance between the APA sites and intron location of PAS are important parameters for APA difference between body and head, suggesting distinct PAS selection contexts. APA analysis of the RpII215 C4 mutant strain, which harbors a mutant RNA polymerase II (RNAPII) with a slower elongation rate, revealed that a 50% decrease in transcriptional elongation rate leads to a mild trend of more usage of proximal, weaker PASs, both in 3'UTRs and in introns, consistent with the "first come, first served" model of APA regulation. However, this trend was not observed in the head, suggesting a different regulatory context in neuronal cells. Together, our data expand the PAS collection for Drosophila melanogaster and reveal a tissue-specific effect of APA regulation by RNAPII elongation rate. © 2017 Liu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  4. Alternative Splicing and Tissue-specific Elastin Misassembly Act as Biological Modifiers of Human Elastin Gene Frameshift Mutations Associated with Dominant Cutis Laxa*

    Science.gov (United States)

    Sugitani, Hideki; Hirano, Eiichi; Knutsen, Russell H.; Shifren, Adrian; Wagenseil, Jessica E.; Ciliberto, Christopher; Kozel, Beth A.; Urban, Zsolt; Davis, Elaine C.; Broekelmann, Thomas J.; Mecham, Robert P.

    2012-01-01

    Elastin is the extracellular matrix protein in vertebrates that provides elastic recoil to blood vessels, the lung, and skin. Because the elastin gene has undergone significant changes in the primate lineage, modeling elastin diseases in non-human animals can be problematic. To investigate the pathophysiology underlying a class of elastin gene mutations leading to autosomal dominant cutis laxa, we engineered a cutis laxa mutation (single base deletion) into the human elastin gene contained in a bacterial artificial chromosome. When expressed as a transgene in mice, mutant elastin was incorporated into elastic fibers in the skin and lung with adverse effects on tissue function. In contrast, only low levels of mutant protein incorporated into aortic elastin, which explains why the vasculature is relatively unaffected in this disease. RNA stability studies found that alternative exon splicing acts as a modifier of disease severity by influencing the spectrum of mutant transcripts that survive nonsense-mediated decay. Our results confirm the critical role of the C-terminal region of tropoelastin in elastic fiber assembly and suggest tissue-specific differences in the elastin assembly pathway. PMID:22573328

  5. [Tissue-specific nucleoprotein complexes].

    Science.gov (United States)

    Riadnova, I Iu; Shataeva, L K; Khavinson, V Kh

    2000-01-01

    A method of isolation of native nucleorprotein complexes from cattle cerebral cortex, thymus, and liver was developed. Compositions of these complexes were studied by means of gel-chromatography and ion-exchange chromatography. These preparations were shown to consist of several fractions of proteins and their complexes differ by molecular mass and electro-chemical properties. Native nucleoprotein complexes revealed high tissue specific activity, which was not species-specific.

  6. Description of electrophoretic loci and tissue specific gene ...

    African Journals Online (AJOL)

    Protein electrophoresis was used to study the distributions and tissue specificity of gene expression of enzymes encoded by 42 loci in Rhinolophus clivosus and R. landeri, the genetically most divergent of the ten species of southern African horseshoe bats. No differences in gene expression were found between R.

  7. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

  8. Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L

    2010-06-01

    Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed.

  9. Heritability and tissue specificity of expression quantitative trait loci

    Czech Academy of Sciences Publication Activity Database

    Petretto, E.; Mangion, J.; Dickens, N. J.; Cook, S.A.; Kumaran, M. K.; Lu, H.; Fischer, J.; Maatz, H.; Křen, Vladimír; Pravenec, Michal; Hubner, N.; Aitman, T. J.

    2006-01-01

    Roč. 2, č. 10 (2006), s. 1625-1633 ISSN 1553-7390 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/06/0028; GA ČR(CZ) GA301/04/0390 Grant - others:HHMI(US) 55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : expression QTL * heritability * tissue specificity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.671, year: 2006

  10. Predicting Tissue-Specific Enhancers in the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  11. Predicting tissue-specific expressions based on sequence characteristics

    KAUST Repository

    Paik, Hyojung; Ryu, Tae Woo; Heo, Hyoungsam; Seo, Seungwon; Lee, Doheon; Hur, Cheolgoo

    2011-01-01

    In multicellular organisms, including humans, understanding expression specificity at the tissue level is essential for interpreting protein function, such as tissue differentiation. We developed a prediction approach via generated sequence features from overrepresented patterns in housekeeping (HK) and tissue-specific (TS) genes to classify TS expression in humans. Using TS domains and transcriptional factor binding sites (TFBSs), sequence characteristics were used as indices of expressed tissues in a Random Forest algorithm by scoring exclusive patterns considering the biological intuition; TFBSs regulate gene expression, and the domains reflect the functional specificity of a TS gene. Our proposed approach displayed better performance than previous attempts and was validated using computational and experimental methods.

  12. Predicting tissue-specific expressions based on sequence characteristics

    KAUST Repository

    Paik, Hyojung

    2011-04-30

    In multicellular organisms, including humans, understanding expression specificity at the tissue level is essential for interpreting protein function, such as tissue differentiation. We developed a prediction approach via generated sequence features from overrepresented patterns in housekeeping (HK) and tissue-specific (TS) genes to classify TS expression in humans. Using TS domains and transcriptional factor binding sites (TFBSs), sequence characteristics were used as indices of expressed tissues in a Random Forest algorithm by scoring exclusive patterns considering the biological intuition; TFBSs regulate gene expression, and the domains reflect the functional specificity of a TS gene. Our proposed approach displayed better performance than previous attempts and was validated using computational and experimental methods.

  13. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

    Science.gov (United States)

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  14. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

    Science.gov (United States)

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-01-01

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

  15. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

    Science.gov (United States)

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-04-21

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

  16. Repressor-mediated tissue-specific gene expression in plants

    Science.gov (United States)

    Meagher, Richard B [Athens, GA; Balish, Rebecca S [Oxford, OH; Tehryung, Kim [Athens, GA; McKinney, Elizabeth C [Athens, GA

    2009-02-17

    Plant tissue specific gene expression by way of repressor-operator complexes, has enabled outcomes including, without limitation, male sterility and engineered plants having root-specific gene expression of relevant proteins to clean environmental pollutants from soil and water. A mercury hyperaccumulation strategy requires that mercuric ion reductase coding sequence is strongly expressed. The actin promoter vector, A2pot, engineered to contain bacterial lac operator sequences, directed strong expression in all plant vegetative organs and tissues. In contrast, the expression from the A2pot construct was restricted primarily to root tissues when a modified bacterial repressor (LacIn) was coexpressed from the light-regulated rubisco small subunit promoter in above-ground tissues. Also provided are analogous repressor operator complexes for selective expression in other plant tissues, for example, to produce male sterile plants.

  17. Tissue specific regulation of lipogenesis by thyroid hormone

    Energy Technology Data Exchange (ETDEWEB)

    Blennemann, B.; Freake, H. (Univ. of Connecticut, Storrs (United States))

    1990-02-26

    Thyroid hormone stimulates long chain fatty acid synthesis in rat liver by increasing the amounts of key lipogenic enzymes. Sparse and conflicting data exist concerning its action on this pathway in other tissues. The authors recently showed that, in contrast to liver, hypothyroidism stimulates lipogenesis in brown adipose tissue and have now systematically examined the effects of thyroid state on fatty acid synthesis in other rat tissues. Lipogenesis was assessed by tritiated water incorporation. Euthyroid hepatic fatty acid synthesis (16.6um H/g/h) was reduced to 30% in hypothyroid rats and increased 3 fold in hyperthyroidism. Lipogenesis was detected in euthyroid kidney and heart and these levels were also stimulated by thyroid hormone treatment. Brown adipose tissue was unique in showing increased lipogenesis in the hypothyroid state. Hyperthyroid levels were not different from euthyroid. Effects in white adipose tissue were small and inconsistent. Brain, skin and lung were all lipogenically active, but did not respond to changes in thyroid state. Low but detectable levels of fatty acid synthesis were measured in muscle, which also were non-responsive. A wide spectrum of responses to thyroid hormone are seen in different rat tissues and thus the pathway of long chain fatty acid synthesis would appear to be an excellent model for examining the tissue specific regulation of gene expression by thyroid hormone.

  18. Tissue specific regulation of lipogenesis by thyroid hormone

    International Nuclear Information System (INIS)

    Blennemann, B.; Freake, H.

    1990-01-01

    Thyroid hormone stimulates long chain fatty acid synthesis in rat liver by increasing the amounts of key lipogenic enzymes. Sparse and conflicting data exist concerning its action on this pathway in other tissues. The authors recently showed that, in contrast to liver, hypothyroidism stimulates lipogenesis in brown adipose tissue and have now systematically examined the effects of thyroid state on fatty acid synthesis in other rat tissues. Lipogenesis was assessed by tritiated water incorporation. Euthyroid hepatic fatty acid synthesis (16.6um H/g/h) was reduced to 30% in hypothyroid rats and increased 3 fold in hyperthyroidism. Lipogenesis was detected in euthyroid kidney and heart and these levels were also stimulated by thyroid hormone treatment. Brown adipose tissue was unique in showing increased lipogenesis in the hypothyroid state. Hyperthyroid levels were not different from euthyroid. Effects in white adipose tissue were small and inconsistent. Brain, skin and lung were all lipogenically active, but did not respond to changes in thyroid state. Low but detectable levels of fatty acid synthesis were measured in muscle, which also were non-responsive. A wide spectrum of responses to thyroid hormone are seen in different rat tissues and thus the pathway of long chain fatty acid synthesis would appear to be an excellent model for examining the tissue specific regulation of gene expression by thyroid hormone

  19. Tissue-specific expression of type IX collagen

    International Nuclear Information System (INIS)

    Nishimura, I.; Muragaki, Y.; Ninomiya, Y.; Olsen, B.R.; Hayashi, M.

    1990-01-01

    This paper reports on the tissue-specific expression of type IX collagen, a major component of cartilage fibrils. It contains molecules with three genetically distinct subunits. The subunits form three triple-helical (CO) domains separated by non-triple-helical (NC) sequences. One of the subunits in cartilage, α1(IX), contains a large amino-terminal globular domain, NC4, while a second subunit, α2(IX), contains a covalently attached chondroitin sulfate chain. The site of attachment for this chain is located within the non-triple-helical sequence NC3, which separates the amino-terminal and central triple-helical domains of the type IX molecules. The NC3 region is 5 amino acid residues longer in the α2(IX) chain than in the α1(IX) and α3(IX) chains. This may explain why type IX molecules tend to show a sharp angle in the NC3 region, and why monoclonal antibody molecules that are specific for the stub left after chondroitinase ABC digestion of the chondroitin sulfate side chain always are located on the outside of the angle

  20. Tissue-specific 5' heterogeneity of PPARα transcripts and their differential regulation by leptin.

    Directory of Open Access Journals (Sweden)

    Emma S Garratt

    Full Text Available The genes encoding nuclear receptors comprise multiple 5'untranslated exons, which give rise to several transcripts encoding the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR α genes have multiple promoters, although their function is unknown. Here we have characterised the rat PPARα promoter region and have identified three alternative PPARα transcripts, which have different transcription start sites owing to the utilisation of distinct first exons. Moreover these alternative PPARα transcripts were differentially expressed between adipose tissue and liver. We show that while the major adipose (P1 and liver (P2 transcripts were both induced by dexamethasone, they were differentially regulated by the PPARα agonist, clofibric acid, and leptin. Leptin had no effect on the adipose-specific P1 transcript, but induced liver-specific P2 promoter activity via a STAT3/Sp1 mechanism. Moreover in Wistar rats, leptin treatment between postnatal day 3-13 led to an increase in P2 but not P1 transcription in adipose tissue which was sustained into adulthood. This suggests that the expression of the alternative PPARα transcripts are in part programmed by early life exposure to leptin leading to persistent change in adipose tissue fatty acid metabolism through specific activation of a quiescent PPARα promoter. Such complexity in the regulation of PPARα may allow the expression of PPARα to be finely regulated in response to environmental factors.

  1. Tissue-Specific 5′ Heterogeneity of PPARα Transcripts and Their Differential Regulation by Leptin

    Science.gov (United States)

    Garratt, Emma S.; Vickers, Mark H.; Gluckman, Peter D.; Hanson, Mark A.

    2013-01-01

    The genes encoding nuclear receptors comprise multiple 5′untranslated exons, which give rise to several transcripts encoding the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR) α genes have multiple promoters, although their function is unknown. Here we have characterised the rat PPARα promoter region and have identified three alternative PPARα transcripts, which have different transcription start sites owing to the utilisation of distinct first exons. Moreover these alternative PPARα transcripts were differentially expressed between adipose tissue and liver. We show that while the major adipose (P1) and liver (P2) transcripts were both induced by dexamethasone, they were differentially regulated by the PPARα agonist, clofibric acid, and leptin. Leptin had no effect on the adipose-specific P1 transcript, but induced liver-specific P2 promoter activity via a STAT3/Sp1 mechanism. Moreover in Wistar rats, leptin treatment between postnatal day 3–13 led to an increase in P2 but not P1 transcription in adipose tissue which was sustained into adulthood. This suggests that the expression of the alternative PPARα transcripts are in part programmed by early life exposure to leptin leading to persistent change in adipose tissue fatty acid metabolism through specific activation of a quiescent PPARα promoter. Such complexity in the regulation of PPARα may allow the expression of PPARα to be finely regulated in response to environmental factors. PMID:23825665

  2. SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

    International Nuclear Information System (INIS)

    Short, Stephen; Malartre, Marianne; Sharpe, Colin

    2005-01-01

    SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT

  3. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

    Science.gov (United States)

    Chausse, Bruno; Vieira-Lara, Marcel A; Sanchez, Angélica B; Medeiros, Marisa H G; Kowaltowski, Alicia J

    2015-01-01

    Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

  4. Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

    Directory of Open Access Journals (Sweden)

    Bruno Chausse

    Full Text Available Intermittent fasting (IF is a dietary intervention often used as an alternative to caloric restriction (CR and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

  5. Tissue-specific alternative splicing and expression of ATP1B2 gene

    African Journals Online (AJOL)

    user6

    2012-05-15

    May 15, 2012 ... retention; these isoforms were found in liver, kidney, muscle and breast tissues. ... lower levels than the complete ATP1B2 gene transcript in all the ... temperature. ... growth, differentiation, and disease (Zhou et al., 2002;.

  6. Tissue-specific alternative splicing and expression of ATP1B2 gene

    African Journals Online (AJOL)

    user6

    2012-05-15

    May 15, 2012 ... The Na+-K+-ATPase is an essential transport enzyme expressed in all animal tissues, where it generates ion gradients to maintain membrane potential and drive the transport of other solutes. It also balances metabolism and body temperature. In this study, the characterization of three novel bovine ...

  7. Tissue-specific alternative splicing and expression of ATP1B2 gene ...

    African Journals Online (AJOL)

    After heat-stress, the expression levels of the different transcripts were lower in different tissues; however, the expression of the ATP1B2-complete transcript increased in heart and lung tissues. The results of this research provide some useful information for further studies into the function of the bovine ATP1B2 gene.

  8. Tissue-specific RNA expression marks distant-acting developmental enhancers.

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    Han Wu

    2014-09-01

    Full Text Available Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks.

  9. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

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    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

  10. Tissue-specific functional networks for prioritizing phenotype and disease genes.

    Directory of Open Access Journals (Sweden)

    Yuanfang Guan

    Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

  11. Isolation of two tissue-specific Drosophila paired box genes, Pox meso and Pox neuro.

    OpenAIRE

    Bopp, D; Jamet, E; Baumgartner, S; Burri, M; Noll, M

    1989-01-01

    Two new paired domain genes of Drosophila, Pox meso and Pox neuro, are described. In contrast to the previously isolated paired domain genes, paired and gooseberry, which contain both a paired and a homeo-domain (PHox genes), Pox meso and Pox neuro possess no homeodomain. Evidence suggesting that the new genes encode tissue-specific transcriptional factors and belong to the same regulatory cascade as the other paired domain genes includes (i) tissue-specific expression of Pox meso in the soma...

  12. TiGER: a database for tissue-specific gene expression and regulation.

    Science.gov (United States)

    Liu, Xiong; Yu, Xueping; Zack, Donald J; Zhu, Heng; Qian, Jiang

    2008-06-09

    Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation. The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation). The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM) detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes. We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.

  13. TiGER: A database for tissue-specific gene expression and regulation

    Directory of Open Access Journals (Sweden)

    Zack Donald J

    2008-06-01

    Full Text Available Abstract Background Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation. Results The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation. The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes. Conclusion We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at 1.

  14. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

    Science.gov (United States)

    Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

    2017-03-23

    Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

  15. Tissue-specific Proteogenomic Analysis of Plutella xylostella Larval Midgut Using a Multialgorithm Pipeline.

    Science.gov (United States)

    Zhu, Xun; Xie, Shangbo; Armengaud, Jean; Xie, Wen; Guo, Zhaojiang; Kang, Shi; Wu, Qingjun; Wang, Shaoli; Xia, Jixing; He, Rongjun; Zhang, Youjun

    2016-06-01

    The diamondback moth, Plutella xylostella (L.), is the major cosmopolitan pest of brassica and other cruciferous crops. Its larval midgut is a dynamic tissue that interfaces with a wide variety of toxicological and physiological processes. The draft sequence of the P. xylostella genome was recently released, but its annotation remains challenging because of the low sequence coverage of this branch of life and the poor description of exon/intron splicing rules for these insects. Peptide sequencing by computational assignment of tandem mass spectra to genome sequence information provides an experimental independent approach for confirming or refuting protein predictions, a concept that has been termed proteogenomics. In this study, we carried out an in-depth proteogenomic analysis to complement genome annotation of P. xylostella larval midgut based on shotgun HPLC-ESI-MS/MS data by means of a multialgorithm pipeline. A total of 876,341 tandem mass spectra were searched against the predicted P. xylostella protein sequences and a whole-genome six-frame translation database. Based on a data set comprising 2694 novel genome search specific peptides, we discovered 439 novel protein-coding genes and corrected 128 existing gene models. To get the most accurate data to seed further insect genome annotation, more than half of the novel protein-coding genes, i.e. 235 over 439, were further validated after RT-PCR amplification and sequencing of the corresponding transcripts. Furthermore, we validated 53 novel alternative splicings. Finally, a total of 6764 proteins were identified, resulting in one of the most comprehensive proteogenomic study of a nonmodel animal. As the first tissue-specific proteogenomics analysis of P. xylostella, this study provides the fundamental basis for high-throughput proteomics and functional genomics approaches aimed at deciphering the molecular mechanisms of resistance and controlling this pest. © 2016 by The American Society for Biochemistry and

  16. Tissue-specific Proteogenomic Analysis of Plutella xylostella Larval Midgut Using a Multialgorithm Pipeline*

    Science.gov (United States)

    Zhu, Xun; Xie, Shangbo; Armengaud, Jean; Xie, Wen; Guo, Zhaojiang; Kang, Shi; Wu, Qingjun; Wang, Shaoli; Xia, Jixing; He, Rongjun; Zhang, Youjun

    2016-01-01

    The diamondback moth, Plutella xylostella (L.), is the major cosmopolitan pest of brassica and other cruciferous crops. Its larval midgut is a dynamic tissue that interfaces with a wide variety of toxicological and physiological processes. The draft sequence of the P. xylostella genome was recently released, but its annotation remains challenging because of the low sequence coverage of this branch of life and the poor description of exon/intron splicing rules for these insects. Peptide sequencing by computational assignment of tandem mass spectra to genome sequence information provides an experimental independent approach for confirming or refuting protein predictions, a concept that has been termed proteogenomics. In this study, we carried out an in-depth proteogenomic analysis to complement genome annotation of P. xylostella larval midgut based on shotgun HPLC-ESI-MS/MS data by means of a multialgorithm pipeline. A total of 876,341 tandem mass spectra were searched against the predicted P. xylostella protein sequences and a whole-genome six-frame translation database. Based on a data set comprising 2694 novel genome search specific peptides, we discovered 439 novel protein-coding genes and corrected 128 existing gene models. To get the most accurate data to seed further insect genome annotation, more than half of the novel protein-coding genes, i.e. 235 over 439, were further validated after RT-PCR amplification and sequencing of the corresponding transcripts. Furthermore, we validated 53 novel alternative splicings. Finally, a total of 6764 proteins were identified, resulting in one of the most comprehensive proteogenomic study of a nonmodel animal. As the first tissue-specific proteogenomics analysis of P. xylostella, this study provides the fundamental basis for high-throughput proteomics and functional genomics approaches aimed at deciphering the molecular mechanisms of resistance and controlling this pest. PMID:26902207

  17. Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

    Directory of Open Access Journals (Sweden)

    Chen Xiaoyu

    2007-12-01

    Full Text Available Abstract Background In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression. Results We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure. Conclusion Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.

  18. Tissue specific MR contrast media role in the differential diagnosis of cirrhotic liver nodules.

    Science.gov (United States)

    Lupescu, Ioana Gabriela; Capsa, Razvan A; Gheorghe, Liana; Herlea, Vlad; Georgescu, Serban A

    2008-09-01

    State-of-the-art magnetic resonance (MR) imaging using tissue specific contrast media facilitates detection and characterization in most cases of hepatic nodules. According to the currently used nomenclature, in liver cirrhosis there are only two major types of hepatocellular nodular lesions: regenerative lesions and dysplastic or neoplastic lesions. The purpose of this clinical imaging review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the hepatobiliary and reticuloendothelial systems during the carcinogenesis in liver cirrhosis.

  19. Tissue-specific regulation of mouse MicroRNA genes in endoderm-derived tissues

    OpenAIRE

    Gao, Yan; Schug, Jonathan; McKenna, Lindsay B.; Le Lay, John; Kaestner, Klaus H.; Greenbaum, Linda E.

    2010-01-01

    MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here, we determine the entire microRNAome of three endoderm-derived tissues, liver, jejunum and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After...

  20. Involvement of an ent-copalyl diphosphate synthase in tissue-specific accumulation of specialized diterpenes in Andrographis paniculata.

    Science.gov (United States)

    Misra, Rajesh Chandra; Garg, Anchal; Roy, Sudeep; Chanotiya, Chandan Singh; Vasudev, Prema G; Ghosh, Sumit

    2015-11-01

    Ent-labdane-related diterpene (ent-LRD) specialized (i.e. secondary) metabolites of the medicinal plant kalmegh (Andrographis paniculata) have long been known for several pharmacological activities. However, our understanding of the ent-LRD biosynthetic pathway has remained largely incomplete. Since ent-LRDs accumulate in leaves, we carried out a comparative transcriptional analysis using leaf and root tissues, and identified 389 differentially expressed transcripts, including 223 transcripts that were preferentially expressed in leaf tissue. Analysis of the transcripts revealed various specialized metabolic pathways, including transcripts of the ent-LRD biosynthetic pathway. Two class II diterpene synthases (ApCPS1 and ApCPS2) along with one (ApCPS1') and two (ApCPS2' and ApCPS2″) transcriptional variants that were the outcomes of alternative splicing of the precursor mRNA and alternative transcriptional termination, respectively, were identified. ApCPS1 and ApCPS2 encode for 832- and 817-amino acids proteins, respectively, and are phylogenetically related to the dicotyledons ent-copalyl diphosphate synthases (ent-CPSs). The spatio-temporal patterns of ent-LRD metabolites accumulation and gene expression suggested a likely role for ApCPS1 in general (i.e. primary) metabolism, perhaps by providing precursor for the biosynthesis of phytohormone gibberellin (GA). However, ApCPS2 is potentially involved in tissue-specific accumulation of ent-LRD specialized metabolites. Bacterially expressed recombinant ApCPS2 catalyzed the conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP), the general precursor of diterpenes to ent-copalyl diphosphate (ent-CPP), the precursor of ent-LRDs. Taken together, these results advance our understanding of the tissue-specific accumulation of specialized ent-LRDs of medicinal importance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Concordance of gene expression in human protein complexes reveals tissue specificity and pathology

    DEFF Research Database (Denmark)

    Börnigen, Daniela; Pers, Tune Hannes; Thorrez, Lieven

    2013-01-01

    Disease-causing variants in human genes usually lead to phenotypes specific to only a few tissues. Here, we present a method for predicting tissue specificity based on quantitative deregulation of protein complexes. The underlying assumption is that the degree of coordinated expression among prot...

  2. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    NARCIS (Netherlands)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.; Acha, Moshe Ray; Newton-Cheh, Christopher; Pfeufer, Arne; Lyneh, Stacey N.; Olesen, Soren-Peter; Brunak, Soren; Ellinor, Patrick T.; Jukema, J. Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W.; Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.; Nathoe, Hendrik M.; Spiering, Wilko; Daly, Mark J.; Asselbergs, Ikea W.; van der Harst, Pim; Milan, David J.; de Bakker, Paul I. W.; Lage, Kasper; Olsen, Jesper V.

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes

  3. Tissue Specific Roles of Dynein Light Chain 1 in Regulating Germ Cell Apoptosis in Ceanorhabditis elegans

    DEFF Research Database (Denmark)

    Morthorst, Tine Hørning

    2015-01-01

    in the etiology of many diseases, including cancer, neurodegenerative, cardiovascular and autoimmune diseases. Several of the first genes found to regulate apoptosis were discovered in the nematode Caenorhabditis elegans. In this project, two different and tissue specific roles of C. elegans dynein light chain 1...

  4. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

    2013-01-01

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

  5. Analysis of tissue-specific region in sericin 1 gene promoter of Bombyx mori

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Liu [College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027 (China); Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Lian, Yu [College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027 (China); Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310029 (China); Xiuyang, Guo [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Tingqing, Guo [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shengpeng, Wang [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Changde, Lu [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2006-03-31

    The gene encoding sericin 1 (Ser1) of silkworm (Bombyx mori) is specifically expressed in the middle silk gland cells. To identify element involved in this transcription-dependent spatial restriction, truncation of the 5' terminal from the sericin 1 (Ser1) promoter is studied in vivo. A 209 bp DNA sequence upstream of the transcriptional start site (-586 to -378) is found to be responsible for promoting tissue-specific transcription. Analysis of this 209 bp region by overlapping deletion studies showed that a 25 bp region (-500 to -476) suppresses the ectopic expression of the Ser1 promoter. An unknown factor abundant in fat body nuclear extracts is shown to bind to this 25 bp fragment. These results suggest that this 25 bp region and the unknown factor are necessary for determining the tissue-specificity of the Ser1 promoter.

  6. Tissue-Specific Peroxisome Proliferator Activated Receptor Gamma Expression and Metabolic Effects of Telmisartan

    Czech Academy of Sciences Publication Activity Database

    Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Landa, Vladimír; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

    2013-01-01

    Roč. 26, č. 6 (2013), s. 829-835 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : telmisartan * metabolic effects * tissue-specific Pparg knockout mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

  7. Species and tissues specific differentiation of processed animal proteins in aquafeeds using proteomics tools.

    Science.gov (United States)

    Rasinger, J D; Marbaix, H; Dieu, M; Fumière, O; Mauro, S; Palmblad, M; Raes, M; Berntssen, M H G

    2016-09-16

    The rapidly growing aquaculture industry drives the search for sustainable protein sources in fish feed. In the European Union (EU) since 2013 non-ruminant processed animal proteins (PAP) are again permitted to be used in aquafeeds. To ensure that commercial fish feeds do not contain PAP from prohibited species, EU reference methods were established. However, due to the heterogeneous and complex nature of PAP complementary methods are required to guarantee the safe use of this fish feed ingredient. In addition, there is a need for tissue specific PAP detection to identify the sources (i.e. bovine carcass, blood, or meat) of illegal PAP use. In the present study, we investigated and compared different protein extraction, solubilisation and digestion protocols on different proteomics platforms for the detection and differentiation of prohibited PAP. In addition, we assessed if tissue specific PAP detection was feasible using proteomics tools. All work was performed independently in two different laboratories. We found that irrespective of sample preparation gel-based proteomics tools were inappropriate when working with PAP. Gel-free shotgun proteomics approaches in combination with direct spectral comparison were able to provide quality species and tissue specific data to complement and refine current methods of PAP detection and identification. To guarantee the safe use of processed animal protein (PAP) in aquafeeds efficient PAP detection and monitoring tools are required. The present study investigated and compared various proteomics workflows and shows that the application of shotgun proteomics in combination with direct comparison of spectral libraries provides for the desired species and tissue specific classification of this heat sterilized and pressure treated (≥133°C, at 3bar for 20min) protein feed ingredient. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples.

    Science.gov (United States)

    Gorelick, Daniel A; Iwanowicz, Luke R; Hung, Alice L; Blazer, Vicki S; Halpern, Marnie E

    2014-04-01

    Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  9. Pyrosequencing data reveals tissue-specific expression of lineage-specific transcripts in chickpea

    OpenAIRE

    Garg, Rohini; Jain, Mukesh

    2011-01-01

    Chickpea is a very important crop legume plant, which provides a protein-rich supplement to cereal-based diets and has the ability to fix atmospheric nitrogen. Despite its economic importance, the functional genomic resources for chickpea are very limited. Recently, we reported the complete transcriptome of chickpea using next generation sequencing technologies. We analyzed the tissue-specific expression of chickpea transcripts based on RNA-seq data. In addition, we identified two sets of lin...

  10. The role of the endocrine system in feeding-induced tissue-specific circadian entrainment.

    Science.gov (United States)

    Sato, Miho; Murakami, Mariko; Node, Koichi; Matsumura, Ritsuko; Akashi, Makoto

    2014-07-24

    The circadian clock is entrained to environmental cycles by external cue-mediated phase adjustment. Although the light input pathway has been well defined, the mechanism of feeding-induced phase resetting remains unclear. The tissue-specific sensitivity of peripheral entrainment to feeding suggests the involvement of multiple pathways, including humoral and neuronal signals. Previous in vitro studies with cultured cells indicate that endocrine factors may function as entrainment cues for peripheral clocks. However, blood-borne factors that are well characterized in actual feeding-induced resetting have yet to be identified. Here, we report that insulin may be involved in feeding-induced tissue-type-dependent entrainment in vivo. In ex vivo culture experiments, insulin-induced phase shift in peripheral clocks was dependent on tissue type, which was consistent with tissue-specific insulin sensitivity, and peripheral entrainment in insulin-sensitive tissues involved PI3K- and MAPK-mediated signaling pathways. These results suggest that insulin may be an immediate early factor in feeding-mediated tissue-specific entrainment. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    Science.gov (United States)

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Simple and high yielding method for preparing tissue specific extracellular matrix coatings for cell culture.

    Science.gov (United States)

    DeQuach, Jessica A; Mezzano, Valeria; Miglani, Amar; Lange, Stephan; Keller, Gordon M; Sheikh, Farah; Christman, Karen L

    2010-09-27

    The native extracellular matrix (ECM) consists of a highly complex, tissue-specific network of proteins and polysaccharides, which help regulate many cellular functions. Despite the complex nature of the ECM, in vitro cell-based studies traditionally assess cell behavior on single ECM component substrates, which do not adequately mimic the in vivo extracellular milieu. We present a simple approach for developing naturally derived ECM coatings for cell culture that provide important tissue-specific cues unlike traditional cell culture coatings, thereby enabling the maturation of committed C2C12 skeletal myoblast progenitors and human embryonic stem cells differentiated into cardiomyocytes. Here we show that natural muscle-specific coatings can (i) be derived from decellularized, solubilized adult porcine muscle, (ii) contain a complex mixture of ECM components including polysaccharides, (iii) adsorb onto tissue culture plastic and (iv) promote cell maturation of committed muscle progenitor and stem cells. This versatile method can create tissue-specific ECM coatings, which offer a promising platform for cell culture to more closely mimic the mature in vivo ECM microenvironment.

  13. Thyroid Hormone Effects on Whole-Body Energy Homeostasis and Tissue-Specific Fatty Acid Uptake in Vivo

    NARCIS (Netherlands)

    Klieverik, Lars P.; Coomans, Claudia P.; Endert, Erik; Sauerwein, Hans P.; Havekes, Louis M.; Voshol, Peter J.; Rensen, Patrick C. N.; Romijn, Johannes A.; Kalsbeek, Andries; Fliers, Eric

    2009-01-01

    The effects of thyroid hormone (TH) status on energy metabolism and tissue-specific substrate supply in vivo are incompletely understood. To study the effects of TH status on energy metabolism and tissue-specific fatty acid (FA) fluxes, we used metabolic cages as well as C-14-labeled FA and

  14. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    Science.gov (United States)

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  15. Diet-induced obesity alters protein synthesis: Tissue-specific effects in fasted vs. fed mice

    OpenAIRE

    Anderson, Stephanie R.; Gilge, Danielle A.; Steiber, Alison L.; Previs, Stephen F.

    2008-01-01

    The influence of obesity on protein dynamics is not clearly understood. We have designed experiments to test the hypothesis that obesity impairs the stimulation of tissue-specific protein synthesis following nutrient ingestion. C57BL/6J mice were randomized into two groups: group 1 (control, n = 16) were fed a low-fat, high-carbohydrate diet and group 2 (experimental, n = 16) were fed a high-fat, low-carbohydrate diet ad libitum for 9 weeks. On the experiment day, all mice were fasted for 6 h...

  16. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  17. Novel strong tissue specific promoter for gene expression in human germ cells

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    Kuzmin Denis

    2010-08-01

    Full Text Available Abstract Background Tissue specific promoters may be utilized for a variety of applications, including programmed gene expression in cell types, tissues and organs of interest, for developing different cell culture models or for use in gene therapy. We report a novel, tissue-specific promoter that was identified and engineered from the native upstream regulatory region of the human gene NDUFV1 containing an endogenous retroviral sequence. Results Among seven established human cell lines and five primary cultures, this modified NDUFV1 upstream sequence (mNUS was active only in human undifferentiated germ-derived cells (lines Tera-1 and EP2102, where it demonstrated high promoter activity (~twice greater than that of the SV40 early promoter, and comparable to the routinely used cytomegaloviral promoter. To investigate the potential applicability of the mNUS promoter for biotechnological needs, a construct carrying a recombinant cytosine deaminase (RCD suicide gene under the control of mNUS was tested in cell lines of different tissue origin. High cytotoxic effect of RCD with a cell-death rate ~60% was observed only in germ-derived cells (Tera-1, whereas no effect was seen in a somatic, kidney-derived control cell line (HEK293. In further experiments, we tested mNUS-driven expression of a hyperactive Sleeping Beauty transposase (SB100X. The mNUS-SB100X construct mediated stable transgene insertions exclusively in germ-derived cells, thereby providing further evidence of tissue-specificity of the mNUS promoter. Conclusions We conclude that mNUS may be used as an efficient promoter for tissue-specific gene expression in human germ-derived cells in many applications. Our data also suggest that the 91 bp-long sequence located exactly upstream NDUFV1 transcriptional start site plays a crucial role in the activity of this gene promoter in vitro in the majority of tested cell types (10/12, and an important role - in the rest two cell lines.

  18. Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

    Science.gov (United States)

    Xiao, Yinghong; Dolan, Patrick Timothy; Goldstein, Elizabeth Faul; Li, Min; Farkov, Mikhail; Brodsky, Leonid; Andino, Raul

    2017-08-29

    RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues.

  19. Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

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    Dasgupta Dipayan

    2005-05-01

    Full Text Available Abstract Background Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group. Results In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes. Conclusion The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

  20. Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds

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    Yuxiao Yao

    2017-09-01

    Full Text Available The zebrafish is a prominent vertebrate model for low-cost in vivo whole organism screening. In our recent screening of the distribution patterns of fluorescent compounds in live zebrafish larvae, fifteen compounds with tissue-specific distributions were identified. Several compounds were observed to accumulate in tissues where they were reported to induce side-effects, and compounds with similar structures tended to be enriched in the same tissues, with minor differences. In particular, we found three novel red fluorescent bone-staining dyes: purpurin, lucidin and 3-hydroxy-morindone; purpurin can effectively label bones in both larval and adult zebrafish, as well as in postnatal mice, without significantly affecting bone mass and density. Moreover, two structurally similar chemotherapeutic compounds, doxorubicin and epirubicin, were observed to have distinct distribution preferences in zebrafish. Epirubicin maintained a relatively higher concentration in the liver, and performed better in inhibiting hepatic hyperplasia caused by the over-expression of krasG12V. In total, our study suggests that the transparent zebrafish larvae serve as valuable tools for identifying tissue-specific distributions of fluorescent compounds.

  1. Laminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.

    Science.gov (United States)

    Merna, Nick; Wong, Andrew K; Barahona, Victor; Llanos, Pierre; Kunar, Balvir; Palikuqi, Brisa; Ginsberg, Michael; Rafii, Shahin; Rabbany, Sina Y

    2018-04-17

    Endothelial cells form vascular beds in all organs and are exposed to a range of mechanical forces that regulate cellular phenotype. We sought to determine the role of endothelial luminal surface stiffness in tissue-specific mechanotransduction of laminar shear stress in microvascular mouse cells and the role of arachidonic acid in mediating this response. Microvascular mouse endothelial cells were subjected to laminar shear stress at 4 dynes/cm 2 for 12 hours in parallel plate flow chambers that enabled real-time optical microscopy and atomic force microscopy measurements of cell stiffness. Lung endothelial cells aligned parallel to flow, while cardiac endothelial cells did not. This rapid alignment was accompanied by increased cell stiffness. The addition of arachidonic acid to cardiac endothelial cells increased alignment and stiffness in response to shear stress. Inhibition of arachidonic acid in lung endothelial cells and embryonic stem cell-derived endothelial cells prevented cellular alignment and decreased cell stiffness. Our findings suggest that increased endothelial luminal surface stiffness in microvascular cells may facilitate mechanotransduction and alignment in response to laminar shear stress. Furthermore, the arachidonic acid pathway may mediate this tissue-specific process. An improved understanding of this response will aid in the treatment of organ-specific vascular disease. © 2018 John Wiley & Sons Ltd.

  2. Tissue-specific mRNA expression profiling in grape berry tissues

    Science.gov (United States)

    Grimplet, Jerome; Deluc, Laurent G; Tillett, Richard L; Wheatley, Matthew D; Schlauch, Karen A; Cramer, Grant R; Cushman, John C

    2007-01-01

    Background Berries of grape (Vitis vinifera) contain three major tissue types (skin, pulp and seed) all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin) and mesocarp (pulp), not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions. Results Overall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater) differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell wall function and

  3. Tissue-specific mRNA expression profiling in grape berry tissues

    Directory of Open Access Journals (Sweden)

    Cramer Grant R

    2007-06-01

    Full Text Available Abstract Background Berries of grape (Vitis vinifera contain three major tissue types (skin, pulp and seed all of which contribute to the aroma, color, and flavor characters of wine. The pericarp, which is composed of the exocarp (skin and mesocarp (pulp, not only functions to protect and feed the developing seed, but also to assist in the dispersal of the mature seed by avian and mammalian vectors. The skin provides volatile and nonvolatile aroma and color compounds, the pulp contributes organic acids and sugars, and the seeds provide condensed tannins, all of which are important to the formation of organoleptic characteristics of wine. In order to understand the transcriptional network responsible for controlling tissue-specific mRNA expression patterns, mRNA expression profiling was conducted on each tissue of mature berries of V. vinifera Cabernet Sauvignon using the Affymetrix GeneChip® Vitis oligonucleotide microarray ver. 1.0. In order to monitor the influence of water-deficit stress on tissue-specific expression patterns, mRNA expression profiles were also compared from mature berries harvested from vines subjected to well-watered or water-deficit conditions. Results Overall, berry tissues were found to express approximately 76% of genes represented on the Vitis microarray. Approximately 60% of these genes exhibited significant differential expression in one or more of the three major tissue types with more than 28% of genes showing pronounced (2-fold or greater differences in mRNA expression. The largest difference in tissue-specific expression was observed between the seed and pulp/skin. Exocarp tissue, which is involved in pathogen defense and pigment production, showed higher mRNA abundance relative to other berry tissues for genes involved with flavonoid biosynthesis, pathogen resistance, and cell wall modification. Mesocarp tissue, which is considered a nutritive tissue, exhibited a higher mRNA abundance of genes involved in cell

  4. Tissue-specific expression of insulin-like growth factor II mRNAs with distinct 5' untranslated regions

    International Nuclear Information System (INIS)

    Irminger, J.C.; Rosen, K.M.; Humble, R.E.; Villa-Komaroff, L.

    1987-01-01

    The authors have used RNA from human hypothalamus as template for the production of cDNAs encoding insulin-like growth factor II (IGF-II). The prohormone coding sequence of brain IGF-II RNA is identical to that found in liver; however, the 5' untranslated sequence of the brain cDNA has no homology to the 5' untranslated sequence of the previously reported liver cDNAs. By using hybridization to specific probes as well as a method based on the properties of RNase H, they found that the human IGF-II gene has at least three exons that encode alternative 5' untranslated regions and that are expressed in a tissue-specific manner. A probe specific to the brain cDNA 5' untranslated region hybridizes to a 6.0-kilobase transcript present in placenta, hypothalamus, adrenal gland, kidney, Wilms tumor, and a pheochromocytoma. The 5' untranslated sequence of the brain cDNA does not hybridize to a 5.3-kilobase transcript found in liver or to a 5.0-kb transcript found in pheochromocytoma. By using RNase H to specifically fragment the IGF-II transcripts into 3' and 5' fragments, they found that the RNAs vary in size due to differences in the 5' end but not the 3' end

  5. Structural evolution and tissue-specific expression of tetrapod-specific second isoform of secretory pathway Ca2+-ATPase

    International Nuclear Information System (INIS)

    Pestov, Nikolay B.; Dmitriev, Ruslan I.; Kostina, Maria B.; Korneenko, Tatyana V.; Shakhparonov, Mikhail I.; Modyanov, Nikolai N.

    2012-01-01

    Highlights: ► Full-length secretory pathway Ca-ATPase (SPCA2) cloned from rat duodenum. ► ATP2C2 gene (encoding SPCA2) exists only in genomes of Tetrapoda. ► Rat and pig SPCA2 are expressed in intestines, lung and some secretory glands. ► Subcellular localization of SPCA2 may depend on tissue type. ► In rat duodenum, SPCA2 is localized in plasma membrane-associated compartments. -- Abstract: Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2 gene radiated from ATP2C1 (encoding SPCA1) during adaptation of tetrapod ancestors to terrestrial habitats.

  6. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders

    Science.gov (United States)

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.; Law, Amanda J.

    2018-01-01

    Objective Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I–IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. Method NRG3 isoform classes I–IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. Results NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Conclusions

  7. Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

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    Srivastava Mousami

    2012-11-01

    Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

  8. Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1.

    Science.gov (United States)

    Galeone, Antonio; Han, Seung Yeop; Huang, Chengcheng; Hosomi, Akira; Suzuki, Tadashi; Jafar-Nejad, Hamed

    2017-08-04

    Mutations in the human N- glycanase 1 ( NGLY1 ) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N -glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N -glycanase enzyme.

  9. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

    Science.gov (United States)

    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  10. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    DEFF Research Database (Denmark)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes...... involved in the Mendelian disorder long QT syndrome (LOTS). We integrated the LOTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LOTS protein...... network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy...

  11. Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

    Science.gov (United States)

    Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

    2017-11-01

    Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

  12. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

    Science.gov (United States)

    Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

    2013-02-15

    During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

  13. Linking salinity stress tolerance with tissue-specific Na+ sequestration in wheat roots

    Directory of Open Access Journals (Sweden)

    Honghong eWu

    2015-02-01

    Full Text Available Salinity stress tolerance is a physiologically complex trait that is conferred by the large array of interacting mechanisms. Among these, vacuolar Na+ sequestration has always been considered as one of the key components differentiating between sensitive and tolerant species and genotypes. However, vacuolar Na+ sequestration has been rarely considered in the context of the tissue-specific expression and regulation of appropriate transporters contributing to Na+ removal from the cytosol. In this work, six bread wheat varieties contrasting in their salinity tolerance (three tolerant and three sensitive were used to understand the essentiality of vacuolar Na+ sequestration between functionally different root tissues, and link it with the overall salinity stress tolerance in this species. Roots of 4-d old wheat seedlings were treated with 100 mM NaCl for 3 days, and then Na+ distribution between cytosol and vacuole was quantified by CoroNa Green fluorescent dye imaging. Our major observations were as follows: 1 salinity stress tolerance correlated positively with vacuolar Na+ sequestration ability in the mature root zone but not in the root apex; 2 Contrary to expectations, cytosolic Na+ levels in root meristem were significantly higher in salt tolerant than sensitive group, while vacuolar Na+ levels showed an opposite trend. These results are interpreted as meristem cells playing a role of the salt sensor; 3 No significant difference in the vacuolar Na+ sequestration ability was found between sensitive and tolerant group in either transition or elongation zones; 4 The overall Na+ accumulation was highest in the elongation zone, suggesting its role in osmotic adjustment and turgor maintenance required to drive root expansion growth. Overall, the reported results suggest high tissue-specificity of Na+ uptake, signalling, and sequestration in wheat root. The implications of these findings for plant breeding for salinity stress tolerance are discussed.

  14. Depleted uranium induces sex- and tissue-specific methylation patterns in adult zebrafish

    International Nuclear Information System (INIS)

    Gombeau, Kewin; Pereira, Sandrine; Ravanat, Jean-Luc; Camilleri, Virginie; Cavalie, Isabelle; Bourdineaud, Jean-Paul; Adam-Guillermin, Christelle

    2016-01-01

    We examined the effects of chronic exposure to different concentrations (2 and 20 μg L"−"1) of environmentally relevant waterborne depleted uranium (DU) on the DNA methylation patterns both at HpaII restriction sites (5′-CCGG-3′) and across the whole genome in the zebrafish brain, gonads, and eyes. We first identified sex-dependent differences in the methylation level of HpaII sites after exposure. In males, these effects were present as early as 7 days after exposure to 20 μg L"−"1 DU, and were even more pronounced in the brain, gonads, and eyes after 24 days. However, in females, hypomethylation was only observed in the gonads after exposure to 20 μg L"−"1 DU for 24 days. Sex-specific effects of DU were also apparent at the whole-genome level, because in males, exposure to 20 μg L"−"1 DU for 24 days resulted in cytosine hypermethylation in the brain and eyes and hypomethylation in the gonads. In contrast, in females, hypermethylation was observed in the brain after exposure to both concentrations of DU for 7 days. Based on our current knowledge of uranium toxicity, several hypotheses are proposed to explain these findings, including the involvement of oxidative stress, alteration of demethylation enzymes and the calcium signaling pathway. This study reports, for the first time, the sex- and tissue-specific epigenetic changes that occur in a nonhuman organism after exposure to environmentally relevant concentrations of uranium, which could induce transgenerational epigenetic effects. - Highlights: • This study demonstrates a sex-related effect of DU exposure on DNA methylation patterns. • Impacts on DNA methylation patterns revealed a tissue-specific effect of DU exposure. • The MS–AFLP and HPLC–MS/MS sensitively and complementarily demonstrated the responses to environmental concentrations of DU.

  15. Tissue- Specific Expression Analysis of Anthocyanin Biosynthetic Genes in White- and Red-Fleshed Grape Cultivars

    Directory of Open Access Journals (Sweden)

    Sha Xie

    2015-12-01

    Full Text Available Yan73, a teinturier (dyer grape variety in China, is one of the few Vitis vinifera cultivars with red-coloured berry flesh. To examine the tissue-specific expression of genes associated with berry colour in Yan73, we analysed the differential accumulation of anthocyanins in the skin and flesh tissues of two red-skinned grape varieties with either red (Yan73 or white flesh (Muscat Hamburg based on HPLC-MS analysis, as well as the differential expression of 18 anthocyanin biosynthesis genes in both varieties by quantitative RT-PCR. The results revealed that the transcripts of GST, OMT, AM3, CHS3, UFGT, MYBA1, F3′5′H, F3H1 and LDOX were barely detectable in the white flesh of Muscat Hamburg. In particular, GST, OMT, AM3, CHS3 and F3H1 showed approximately 50-fold downregulation in the white flesh of Muscat Hamburg compared to the red flesh of Yan73. A correlation analysis between the accumulation of different types of anthocyanins and gene expression indicated that the cumulative expression of GST, F3′5′H, LDOX and MYBA1 was more closely associated with the acylated anthocyanins and the 3′5′-OH anthocyanins, while OMT and AM3 were more closely associated with the total anthocyanins and methoxylated anthocyanins. Therefore, the transcripts of OMT, AM3, GST, F3′5′H, LDOX and MYBA1 explained most of the variation in the amount and composition of anthocyanins in skin and flesh of Yan73. The data suggest that the specific localization of anthocyanins in the flesh tissue of Yan73 is most likely due to the tissue-specific expression of OMT, AM3, GST, F3′5′H, LDOX and MYBA1 in the flesh.

  16. Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

    Science.gov (United States)

    Getzenberg, R H; Coffey, D S

    1990-09-01

    The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

  17. Development of a GAL4-VP16/UAS trans-activation system for tissue specific expression in Medicago truncatula.

    Directory of Open Access Journals (Sweden)

    Amélie Sevin-Pujol

    Full Text Available Promoters with tissue-specific activity are very useful to address cell-autonomous and non cell autonomous functions of candidate genes. Although this strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific regulation of root symbiotic interactions in legumes has only started recently. Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric transcription factor that can bind short upstream activation sequences (UAS is an efficient way to target and enhance the expression of any gene of interest. Here, we developed a collection of promoters with different root cell layers specific activities in Medicago truncatula and tested their abilities to drive the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation UAS: β-Glucuronidase (GUS reporter gene system. By developing a binary vector devoted to modular Golden Gate cloning together with a collection of adapted tissue specific promoters and coding sequences we could test the activity of four of these promoters in trans-activation GAL4/UAS systems and compare them to "classical" promoter GUS fusions. Roots showing high levels of tissue specific expression of the GUS activity could be obtained with this trans-activation system. We therefore provide the legume community with new tools for efficient modular Golden Gate cloning, tissue specific expression and a trans-activation system. This study provides the ground work for future development of stable transgenic lines in Medicago truncatula.

  18. Endometrial natural killer (NK) cells reveal a tissue-specific receptor repertoire.

    Science.gov (United States)

    Feyaerts, D; Kuret, T; van Cranenbroek, B; van der Zeeuw-Hingrez, S; van der Heijden, O W H; van der Meer, A; Joosten, I; van der Molen, R G

    2018-02-13

    Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. NK cells are important for successful pregnancy. After implantation, NK cells encounter extravillous trophoblast cells and regulate trophoblast invasion. NK cell activity is amongst others regulated by C-type lectin heterodimer (CD94/NKG2) and killer cell immunoglobulin-like (KIR) receptors. KIR expression on decidual NK cells is affected by the presence of maternal HLA-C and biased towards KIR2D expression. However, little is known about NKR expression on eNK cells prior to pregnancy. In this study, matched peripheral and menstrual blood (a source of endometrial cells) was obtained from 25 healthy females with regular menstrual cycles. Menstrual blood was collected during the first 36 h of menstruation using a menstrual cup, a non-invasive technique to obtain endometrial cells. KIR and NKG2 receptor expression on eNK cells was characterized by 10-color flow cytometry, and compared to matched pbNK cells of the same female. KIR and HLA-C genotypes were determined by PCR-SSOP techniques. Anti-CMV IgG antibodies in plasma were measured by chemiluminescence immunoassay. KIR expression patterns of eNK cells collected from the same female do not differ over consecutive menstrual cycles. The percentage of NK cells expressing KIR2DL2/L3/S2, KIR2DL3, KIR2DL1, LILRB1 and/or NKG2A was significantly higher in eNK cells compared to pbNK cells, while no significant difference was observed for NKG2C, KIR2DL1/S1, and KIR3DL1. The NKR repertoire of eNK cells was clearly different from pbNK cells, with eNK cells co-expressing more than three NKR simultaneously. In addition, outlier analysis revealed 8 and 15 NKR

  19. Tissue-specific MR contrast agents. Impact on imaging diagnosis and future prospects

    International Nuclear Information System (INIS)

    Yoshimitsu, Kengo; Nakayama, Tomohiro; Kakihara, Daisuke; Irie, Hiroyuki; Tajima, Tsuyoshi; Asayama, Yoshiki; Hirakawa, Masakazu; Ishigami, Kousei; Honda, Hiroshi

    2005-01-01

    Superparamagnetic iron oxide (SPIO) is the only tissue-specific MR agent currently available in Japan. It is quickly taken up by Kupffer cells at the first pass (either arterial or portal) and becomes clustered in the lysosome, providing characteristic T2 * and T2 shortening effects that suppresses the signal of normal or non-tumorous liver tissue. SPIO has dramatically changed the diagnostic algorithm of liver metastasis in clinical practice, now serving as the gold standard instead of CT during arterial portography (CTAP). Its role in the diagnosis of hepatocellular carcinoma (HCC), however, is somewhat complicated, owing to its heterogeneous uptake by the background cirrhotic liver, as well as by some of the HCCs themselves. It has been shown to be useful in the diagnosis of pseudolesions (arterioportal shunts) and some benign hepatocellular lesions (focal nodular hyperplasia or adenoma) by their complete or partial uptake of SPIO, in contrast to an absence of uptake by true liver lesions. It has also been suggested that the histological grade of HCC affects the degree of SPIO uptake. Thus, SPIO serves as a complementary tool to the primary modalities of vascular survey, namely, dynamic CT/MR and CT during hepatic arteriography (CTHA)/CTAP, in the diagnosis of HCC. Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a novel hepatobiliary contrast agent that is not yet available but is supposed to be approved by the Ministry of Health, Labour, and Welfare of Japan in the near future. It is taken up by hepatocytes and excreted into the bile, providing a T1-shortening effect that enhances the normal or non-tumorous liver tissue. It has also been shown to have the effect of positive enhancement of hypervascular liver tumors on the arterial phase, just like the usual extracellular contrast agent (gadopentetate dimeglumine: Gd-DTPA). Thus, Gd-EOB-DTPA was once thought to be an ideal contrast agent for liver tumors, providing information on both

  20. Whole-organ isolation approach as a basis for tissue-specific analyses in Schistosoma mansoni.

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    Steffen Hahnel

    Full Text Available BACKGROUND: Schistosomiasis is one of the most important parasitic diseases worldwide, second only to malaria. Schistosomes exhibit an exceptional reproductive biology since the sexual maturation of the female, which includes the differentiation of the reproductive organs, is controlled by pairing. Pathogenicity originates from eggs, which cause severe inflammation in their hosts. Elucidation of processes contributing to female maturation is not only of interest to basic science but also considering novel concepts combating schistosomiasis. METHODOLOGY/PRINCIPAL FINDINGS: To get direct access to the reproductive organs, we established a novel protocol using a combined detergent/protease-treatment removing the tegument and the musculature of adult Schistosoma mansoni. All steps were monitored by scanning electron microscopy (SEM and bright-field microscopy (BF. We focused on the gonads of adult schistosomes and demonstrated that isolated and purified testes and ovaries can be used for morphological and structural studies as well as sources for RNA and protein of sufficient amounts for subsequent analyses such as RT-PCR and immunoblotting. To this end, first exemplary evidence was obtained for tissue-specific transcription within the gonads (axonemal dynein intermediate chain gene SmAxDynIC; aquaporin gene SmAQP as well as for post-transcriptional regulation (SmAQP. CONCLUSIONS/SIGNIFICANCE: The presented method provides a new way of getting access to tissue-specific material of S. mansoni. With regard to many still unanswered questions of schistosome biology, such as elucidating the molecular processes involved in schistosome reproduction, this protocol provides opportunities for, e.g., sub-transcriptomics and sub-proteomics at the organ level. This will promote the characterisation of gene-expression profiles, or more specifically to complete knowledge of signalling pathways contributing to differentiation processes, so discovering involved

  1. De novo assembly and characterization of tissue specific transcriptomes in the emerald notothen, Trematomus bernacchii.

    Science.gov (United States)

    Huth, Troy J; Place, Sean P

    2013-11-20

    The notothenioids comprise a diverse group of fishes that rapidly radiated after isolation by the Antarctic Circumpolar Current approximately 14-25 million years ago. Given that evolutionary adaptation has led to finely tuned traits with narrow physiological limits in these organisms, this system provides a unique opportunity to examine physiological trade-offs and limits of adaptive responses to environmental perturbation. As such, notothenioids have a rich history with respect to studies attempting to understand the vulnerability of polar ecosystems to the negative impacts associated with global climate change. Unfortunately, despite being a model system for understanding physiological adaptations to extreme environments, we still lack fundamental molecular tools for much of the Nototheniidae family. Specimens of the emerald notothen, Trematomus bernacchii, were acclimated for 28 days in flow-through seawater tanks maintained near ambient seawater temperatures (-1.5°C) or at +4°C. Following acclimation, tissue specific cDNA libraries for liver, gill and brain were created by pooling RNA from n = 5 individuals per temperature treatment. The tissue specific libraries were bar-coded and used for 454 pyrosequencing, which yielded over 700 thousand sequencing reads. A de novo assembly and annotation of these reads produced a functional transcriptome library of T. bernacchii containing 30,107 unigenes, 13,003 of which possessed significant homology to a known protein product. Digital gene expression analysis of these extremely cold adapted fish reinforced the loss of an inducible heat shock response and allowed the preliminary exploration into other elements of the cellular stress response. Preliminary exploration of the transcriptome of T. bernacchii under elevated temperatures enabled a semi-quantitative comparison to prior studies aimed at characterizing the thermal response of this endemic fish whose size, abundance and distribution has established it as a

  2. Regulating expressin of cell and tissue-specific genes by modifying transcription

    Energy Technology Data Exchange (ETDEWEB)

    Beachy, Roger N. [Donald Danforth Plant Science Center, St. Louis, MO (United States); Dai, Shunhong [Donald Danforth Plant Science Center, St. Louis, MO (United States)

    2009-12-15

    Transcriptional regulation is the primary step to control gene expression, therefore function. Such regulation is achieved primarily via a combination of the activities of the promoter cis regulatory DNA elements and trans regulatory proteins that function through binding to these DNA elements. Our research supported by this program has led to the identification of rice bZIP transcription factors RF2a, RF2b and RLP1 that play key roles in regulating the activity of a vascular tissue specific promoter isolated from Rice Tungro Bacilliform Virus (RTBV) through their interactions with the Box II essential cis element located in the promoter. RF2a, RF2b and RLP1 possess multiple regulatory domains. Functional characterization reveals that those domains can activate or repress the activity of the RTBV promoter. Studies of transcriptional regulation of the RTBV promoter by this group of bZIP proteins not only provide insights about gene expression in the vascular tissue, but also insights about general mechanisms of transcription activation and repression. The knowledge gained from this research will also enable us to develop a well-described set of tools that can be used to control expression of multiple genes in transgenic plants and to improve biofuel feedstock.

  3. Tissue-Specific Ablation of Prkar1a Causes Schwannomas by Suppressing Neurofibromatosis Protein Production

    Directory of Open Access Journals (Sweden)

    Georgette N. Jones

    2008-11-01

    Full Text Available Signaling events leading to Schwann cell tumor initiation have been extensively characterized in the context of neurofibromatosis (NF. Similar tumors are also observed in patients with the endocrine neoplasia syndrome Carney complex, which results from inactivating mutations in PRKAR1A. Loss of PRKAR1A causes enhanced protein kinase A activity, although the pathways leading to tumorigenesis are not well characterized. Tissue-specific ablation of Prkar1a in neural crest precursor cells (TEC3KO mice causes schwannomas with nearly 80% penetrance by 10 months. These heterogeneous neoplasms were clinically characterized as genetically engineered mouse schwannomas, grades II and III. At the molecular level, analysis of the tumors revealed almost complete loss of both NF proteins, despite the fact that transcript levels were increased, implying posttranscriptional regulation. Although Erk and Akt signaling are typically enhanced in NF-associated tumors, we observed no activation of either of these pathways in TEC3KO tumors. Furthermore, the small G proteins Ras, Rac1, and RhoA are all known to be involved with NF signaling. In TEC3KO tumors, all three molecules showed modest increases in total protein, but only Rac1 showed significant activation. These data suggest that dysregulated protein kinase A activation causes tumorigenesis through pathways that overlap but are distinct from those described in NF tumorigenesis.

  4. Knowledge Enrichment Analysis for Human Tissue- Specific Genes Uncover New Biological Insights

    Directory of Open Access Journals (Sweden)

    Gong Xiu-Jun

    2012-06-01

    Full Text Available The expression and regulation of genes in different tissues are fundamental questions to be answered in biology. Knowledge enrichment analysis for tissue specific (TS and housekeeping (HK genes may help identify their roles in biological process or diseases and gain new biological insights.In this paper, we performed the knowledge enrichment analysis for 17,343 genes in 84 human tissues using Gene Set Enrichment Analysis (GSEA and Hypergeometric Analysis (HA against three biological ontologies: Gene Ontology (GO, KEGG pathways and Disease Ontology (DO respectively.The analyses results demonstrated that the functions of most gene groups are consistent with their tissue origins. Meanwhile three interesting new associations for HK genes and the skeletal muscle tissuegenes are found. Firstly, Hypergeometric analysis against KEGG database for HK genes disclosed that three disease terms (Parkinson’s disease, Huntington’s disease, Alzheimer’s disease are intensively enriched.Secondly, Hypergeometric analysis against the KEGG database for Skeletal Muscle tissue genes shows that two cardiac diseases of “Hypertrophic cardiomyopathy (HCM” and “Arrhythmogenic right ventricular cardiomyopathy (ARVC” are heavily enriched, which are also considered as no relationship with skeletal functions.Thirdly, “Prostate cancer” is intensively enriched in Hypergeometric analysis against the disease ontology (DO for the Skeletal Muscle tissue genes, which is a much unexpected phenomenon.

  5. A novel CpG island set identifies tissue-specific methylation at developmental gene loci.

    Directory of Open Access Journals (Sweden)

    Robert Illingworth

    2008-01-01

    Full Text Available CpG islands (CGIs are dense clusters of CpG sequences that punctuate the CpG-deficient human genome and associate with many gene promoters. As CGIs also differ from bulk chromosomal DNA by their frequent lack of cytosine methylation, we devised a CGI enrichment method based on nonmethylated CpG affinity chromatography. The resulting library was sequenced to define a novel human blood CGI set that includes many that are not detected by current algorithms. Approximately half of CGIs were associated with annotated gene transcription start sites, the remainder being intra- or intergenic. Using an array representing over 17,000 CGIs, we established that 6%-8% of CGIs are methylated in genomic DNA of human blood, brain, muscle, and spleen. Inter- and intragenic CGIs are preferentially susceptible to methylation. CGIs showing tissue-specific methylation were overrepresented at numerous genetic loci that are essential for development, including HOX and PAX family members. The findings enable a comprehensive analysis of the roles played by CGI methylation in normal and diseased human tissues.

  6. Tissue Specificity of a Response of the Pro- and Antioxidative System After Resuscitation

    Directory of Open Access Journals (Sweden)

    A. G. Zhukova

    2005-01-01

    Full Text Available This investigation was undertaken to study the resistance of membrane structures and the level of the intracellular defense systems of the heart, brain, and liver in animals with active versus passive behavior in different periods (days 7 and 30 after resuscitation made 10 minutes following systemic circulatory arrest. All the animals in which systemic circulation had been stopped were survivors with the cession of neurological deficit. The activity of antioxidative defense enzymes, such as cata-lase and superoxide dismutase, in cardiac, cerebral, and hepatic tissues was assayed by spectrophotometry using the conventional methods. The level of stress-induced protein HSP70 was measured in the tissue cytosolic fraction by the Western blotting assay. The activity of Ca2+ transport in the myocardial sarcoplasmic reticulum was determined on an Orion EA 940 ionomer («Orion Research», USA having a Ca2+-selective electrode. The findings show a significant tissue specificity in different postresuscitative periods (days 7 and 30 and varying (protective to damaging cardiac, cerebral, and hepatic responses in active and passive animals to hypoxia.

  7. Fusarium oxysporum Triggers Tissue-Specific Transcriptional Reprogramming in Arabidopsis thaliana

    Science.gov (United States)

    Lyons, Rebecca; Stiller, Jiri; Powell, Jonathan; Rusu, Anca; Manners, John M.; Kazan, Kemal

    2015-01-01

    Some of the most devastating agricultural diseases are caused by root-infecting pathogens, yet the majority of studies on these interactions to date have focused on the host responses of aerial tissues rather than those belowground. Fusarium oxysporum is a root-infecting pathogen that causes wilt disease on several plant species including Arabidopsis thaliana. To investigate and compare transcriptional changes triggered by F. oxysporum in different Arabidopsis tissues, we infected soil-grown plants with F. oxysporum and subjected root and leaf tissue harvested at early and late timepoints to RNA-seq analyses. At least half of the genes induced or repressed by F. oxysporum showed tissue-specific regulation. Regulators of auxin and ABA signalling, mannose binding lectins and peroxidases showed strong differential expression in root tissue. We demonstrate that ARF2 and PRX33, two genes regulated in the roots, promote susceptibility to F. oxysporum. In the leaves, defensins and genes associated with the response to auxin, cold and senescence were strongly regulated while jasmonate biosynthesis and signalling genes were induced throughout the plant. PMID:25849296

  8. Fusarium oxysporum triggers tissue-specific transcriptional reprogramming in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Rebecca Lyons

    Full Text Available Some of the most devastating agricultural diseases are caused by root-infecting pathogens, yet the majority of studies on these interactions to date have focused on the host responses of aerial tissues rather than those belowground. Fusarium oxysporum is a root-infecting pathogen that causes wilt disease on several plant species including Arabidopsis thaliana. To investigate and compare transcriptional changes triggered by F. oxysporum in different Arabidopsis tissues, we infected soil-grown plants with F. oxysporum and subjected root and leaf tissue harvested at early and late timepoints to RNA-seq analyses. At least half of the genes induced or repressed by F. oxysporum showed tissue-specific regulation. Regulators of auxin and ABA signalling, mannose binding lectins and peroxidases showed strong differential expression in root tissue. We demonstrate that ARF2 and PRX33, two genes regulated in the roots, promote susceptibility to F. oxysporum. In the leaves, defensins and genes associated with the response to auxin, cold and senescence were strongly regulated while jasmonate biosynthesis and signalling genes were induced throughout the plant.

  9. Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

    International Nuclear Information System (INIS)

    Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu

    2004-01-01

    Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

  10. ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Blow, Matthew J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Ren, Bing; Rubin, Edward M.; Pennacchio, Len A.

    2009-02-01

    A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

  11. Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome

    Science.gov (United States)

    Pinter, Stefan F.; Colognori, David; Beliveau, Brian J.; Sadreyev, Ruslan I.; Payer, Bernhard; Yildirim, Eda; Wu, Chao-ting; Lee, Jeannie T.

    2015-01-01

    In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease. PMID:25858912

  12. Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.

    Science.gov (United States)

    Sack, Laura Magill; Davoli, Teresa; Li, Mamie Z; Li, Yuyang; Xu, Qikai; Naxerova, Kamila; Wooten, Eric C; Bernardi, Ronald J; Martin, Timothy D; Chen, Ting; Leng, Yumei; Liang, Anthony C; Scorsone, Kathleen A; Westbrook, Thomas F; Wong, Kwok-Kin; Elledge, Stephen J

    2018-04-05

    Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes regulate proliferation, with most performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in somatic copy number changes (SCNAs) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue-type-specific genetic network architectures underlie SCNA and driver selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive insights about the genetic network architecture of aneuploidy in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes.

    Science.gov (United States)

    Bastiani, Michele; Liu, Libin; Hill, Michelle M; Jedrychowski, Mark P; Nixon, Susan J; Lo, Harriet P; Abankwa, Daniel; Luetterforst, Robert; Fernandez-Rojo, Manuel; Breen, Michael R; Gygi, Steven P; Vinten, Jorgen; Walser, Piers J; North, Kathryn N; Hancock, John F; Pilch, Paul F; Parton, Robert G

    2009-06-29

    Polymerase I and transcript release factor (PTRF)/Cavin is a cytoplasmic protein whose expression is obligatory for caveola formation. Using biochemistry and fluorescence resonance energy transfer-based approaches, we now show that a family of related proteins, PTRF/Cavin-1, serum deprivation response (SDR)/Cavin-2, SDR-related gene product that binds to C kinase (SRBC)/Cavin-3, and muscle-restricted coiled-coil protein (MURC)/Cavin-4, forms a multiprotein complex that associates with caveolae. This complex can constitutively assemble in the cytosol and associate with caveolin at plasma membrane caveolae. Cavin-1, but not other cavins, can induce caveola formation in a heterologous system and is required for the recruitment of the cavin complex to caveolae. The tissue-restricted expression of cavins suggests that caveolae may perform tissue-specific functions regulated by the composition of the cavin complex. Cavin-4 is expressed predominantly in muscle, and its distribution is perturbed in human muscle disease associated with Caveolin-3 dysfunction, identifying Cavin-4 as a novel muscle disease candidate caveolar protein.

  14. Extensive tissue-specific transcriptomic plasticity in maize primary roots upon water deficit.

    Science.gov (United States)

    Opitz, Nina; Marcon, Caroline; Paschold, Anja; Malik, Waqas Ahmed; Lithio, Andrew; Brandt, Ronny; Piepho, Hans-Peter; Nettleton, Dan; Hochholdinger, Frank

    2016-02-01

    Water deficit is the most important environmental constraint severely limiting global crop growth and productivity. This study investigated early transcriptome changes in maize (Zea mays L.) primary root tissues in response to moderate water deficit conditions by RNA-Sequencing. Differential gene expression analyses revealed a high degree of plasticity of the water deficit response. The activity status of genes (active/inactive) was determined by a Bayesian hierarchical model. In total, 70% of expressed genes were constitutively active in all tissues. In contrast, deficit-responsive genes (1915) were consistently regulated in all tissues, while >75% (1501 genes) were specifically regulated in a single root tissue. Water deficit-responsive genes were most numerous in the cortex of the mature root zone and in the elongation zone. The most prominent functional categories among differentially expressed genes in all tissues were 'transcriptional regulation' and 'hormone metabolism', indicating global reprogramming of cellular metabolism as an adaptation to water deficit. Additionally, the most significant transcriptomic changes in the root tip were associated with cell wall reorganization, leading to continued root growth despite water deficit conditions. This study provides insight into tissue-specific water deficit responses and will be a resource for future genetic analyses and breeding strategies to develop more drought-tolerant maize cultivars. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. Tissue-specific concentrations and patterns of perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears.

    Science.gov (United States)

    Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Born, Erik W

    2012-11-06

    Several perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs) of varying chain length are bioaccumulative in biota. However, wildlife reports have focused on liver and with very little examination of other tissues, and thus there is a limited understanding of their distribution and potential effects in the mammalian body. In the present study, the comparative accumulation of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, and select precursors were examined in the liver, blood, muscle, adipose, and brain of 20 polar bears (Ursus maritimus) from Scoresby Sound, Central East Greenland. Overall, PFSA and PFCA concentrations were highest in liver followed by blood > brain > muscle ≈ adipose. Liver and blood samples contained proportionally more of the shorter/medium chain length (C(6) to C(11)) PFCAs, whereas adipose and brain samples were dominated by longer chain (C(13) to C(15)) PFCAs. PFCAs with lower lipophilicities accumulated more in the liver, whereas the brain accumulated PFCAs with higher lipophilicities. The concentration ratios (±SE) between perfluorooctane sulfonate and its precursor perfluorooctane sulfonamide varied among tissues from 9 (±1):1 (muscle) to 36 (±7):1 (liver). PFCA and PFSA patterns in polar bears indicate that the pharmacokinetics of these compounds are to some extent tissue-specific, and are the result of several factors that may include differing protein interactions throughout the body.

  16. Tissue-Specific Fatty Acids Response to Different Diets in Common Carp (Cyprinus carpio L.)

    Science.gov (United States)

    Böhm, Markus; Schultz, Sebastian; Koussoroplis, Apostolos-Manuel; Kainz, Martin J.

    2014-01-01

    Fish depend on dietary fatty acids (FA) to support their physiological condition and health. Exploring the FA distribution in common carp (Cyprinus carpio), one of the world's most consumed freshwater fish, is important to understand how and where FA of different sources are allocated. We investigated diet effects on the composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively) in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine, eyes, liver and adipose tissue) of common carp. Two-year old carp were exposed to three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds containing vegetable, VO, or fish oil, FO) with different FA composition. The PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only marginally influenced by dietary FA, whereas the NLFA composition strongly reflected dietary FA profiles. However, the NLFA composition in carp tissues varied considerably at low NLFA mass ratios, suggesting that carp is able to regulate the NLFA composition and thus FA quality in its tissues when NLFA contents are low. Finally, this study shows that FO were 3X more retained than VO as NLFA particularly in muscle tissues, indicating that higher nutritional quality feeds are selectively allocated into tissues and thus available for human consumption. PMID:24733499

  17. Tissue-Specific Apocarotenoid Glycosylation Contributes to Carotenoid Homeostasis in Arabidopsis Leaves1

    Science.gov (United States)

    Hübner, Michaela; Matsubara, Shizue; Beyer, Peter

    2015-01-01

    Attaining defined steady-state carotenoid levels requires balancing of the rates governing their synthesis and metabolism. Phytoene formation mediated by phytoene synthase (PSY) is rate limiting in the biosynthesis of carotenoids, whereas carotenoid catabolism involves a multitude of nonenzymatic and enzymatic processes. We investigated carotenoid and apocarotenoid formation in Arabidopsis (Arabidopsis thaliana) in response to enhanced pathway flux upon PSY overexpression. This resulted in a dramatic accumulation of mainly β-carotene in roots and nongreen calli, whereas carotenoids remained unchanged in leaves. We show that, in chloroplasts, surplus PSY was partially soluble, localized in the stroma and, therefore, inactive, whereas the membrane-bound portion mediated a doubling of phytoene synthesis rates. Increased pathway flux was not compensated by enhanced generation of long-chain apocarotenals but resulted in higher levels of C13 apocarotenoid glycosides (AGs). Using mutant lines deficient in carotenoid cleavage dioxygenases (CCDs), we identified CCD4 as being mainly responsible for the majority of AGs formed. Moreover, changed AG patterns in the carotene hydroxylase mutants lutein deficient1 (lut1) and lut5 exhibiting altered leaf carotenoids allowed us to define specific xanthophyll species as precursors for the apocarotenoid aglycons detected. In contrast to leaves, carotenoid hyperaccumulating roots contained higher levels of β-carotene-derived apocarotenals, whereas AGs were absent. These contrasting responses are associated with tissue-specific capacities to synthesize xanthophylls, which thus determine the modes of carotenoid accumulation and apocarotenoid formation. PMID:26134165

  18. Tissue-specific fatty acids response to different diets in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Böhm, Markus; Schultz, Sebastian; Koussoroplis, Apostolos-Manuel; Kainz, Martin J

    2014-01-01

    Fish depend on dietary fatty acids (FA) to support their physiological condition and health. Exploring the FA distribution in common carp (Cyprinus carpio), one of the world's most consumed freshwater fish, is important to understand how and where FA of different sources are allocated. We investigated diet effects on the composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively) in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine, eyes, liver and adipose tissue) of common carp. Two-year old carp were exposed to three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds containing vegetable, VO, or fish oil, FO) with different FA composition. The PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only marginally influenced by dietary FA, whereas the NLFA composition strongly reflected dietary FA profiles. However, the NLFA composition in carp tissues varied considerably at low NLFA mass ratios, suggesting that carp is able to regulate the NLFA composition and thus FA quality in its tissues when NLFA contents are low. Finally, this study shows that FO were 3X more retained than VO as NLFA particularly in muscle tissues, indicating that higher nutritional quality feeds are selectively allocated into tissues and thus available for human consumption.

  19. Tissue-specific fatty acids response to different diets in common carp (Cyprinus carpio L..

    Directory of Open Access Journals (Sweden)

    Markus Böhm

    Full Text Available Fish depend on dietary fatty acids (FA to support their physiological condition and health. Exploring the FA distribution in common carp (Cyprinus carpio, one of the world's most consumed freshwater fish, is important to understand how and where FA of different sources are allocated. We investigated diet effects on the composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine, eyes, liver and adipose tissue of common carp. Two-year old carp were exposed to three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds containing vegetable, VO, or fish oil, FO with different FA composition. The PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only marginally influenced by dietary FA, whereas the NLFA composition strongly reflected dietary FA profiles. However, the NLFA composition in carp tissues varied considerably at low NLFA mass ratios, suggesting that carp is able to regulate the NLFA composition and thus FA quality in its tissues when NLFA contents are low. Finally, this study shows that FO were 3X more retained than VO as NLFA particularly in muscle tissues, indicating that higher nutritional quality feeds are selectively allocated into tissues and thus available for human consumption.

  20. Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects.

    Science.gov (United States)

    Wang, L; Chang, S; Guan, J; Shangguan, S; Lu, X; Wang, Z; Wu, L; Zou, J; Zhao, H; Bao, Y; Qiu, Z; Niu, B; Zhang, T

    2015-01-01

    Epigenetic regulation of long interspersed nucleotide element-1 (LINE-1) retrotransposition events plays crucial roles during early development. Previously we showed that LINE-1 hypomethylation in neuronal tissues is associated with pathogenesis of neural tube defect (NTD). Herein, we further evaluated LINE-1 Homo sapiens (L1Hs) methylation in tissues derived from three germ layers of stillborn NTD fetuses, to define patterns of tissue specific methylation and site-specific hypomethylation at CpG sites within an L1Hs promoter region. Stable, tissue-specific L1Hs methylation patterns throughout three germ layer lineages of the fetus, placenta, and maternal peripheral blood were observed. Samples from maternal peripheral blood exhibited the highest level of L1Hs methylation (64.95%) and that from placenta showed the lowest (26.82%). Between samples from NTDs and controls, decrease in L1Hs methylation was only significant in NTD-affected brain tissue at 7.35%, especially in females (8.98%). L1Hs hypomethylation in NTDs was also associated with a significant increase in expression level of an L1Hs-encoded transcript in females (r = -0.846, p = 0.004). This could be due to genomic DNA instability and alternation in chromatins accessibility resulted from abnormal L1Hs hypomethylation, as showed in this study with HCT-15 cells treated with methylation inhibitor 5-Aza.

  1. Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

    Science.gov (United States)

    Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

    2013-11-01

    To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

  2. Tissue-Specific Expression of Monocarboxylate Transporters during Fasting in Mice

    Science.gov (United States)

    Schutkowski, Alexandra; Wege, Nicole; Stangl, Gabriele I.; König, Bettina

    2014-01-01

    Monocarboxylates such as pyruvate, lactate and ketone bodies are crucial for energy supply of all tissues, especially during energy restriction. The transport of monocarboxylates across the plasma membrane of cells is mediated by monocarboxylate transporters (MCTs). Out of 14 known mammalian MCTs, six isoforms have been functionally characterized to transport monocarboxylates and short chain fatty acids (MCT1-4), thyroid hormones (MCT8, -10) and aromatic amino acids (MCT10). Knowledge on the regulation of the different MCT isoforms is rare. In an attempt to get more insights in regulation of MCT expression upon energy deprivation, we carried out a comprehensive analysis of tissue specific expression of five MCT isoforms upon 48 h of fasting in mice. Due to the crucial role of peroxisome proliferator-activated receptor (PPAR)-α as a central regulator of energy metabolism and as known regulator of MCT1 expression, we included both wildtype (WT) and PPARα knockout (KO) mice in our study. Liver, kidney, heart, small intestine, hypothalamus, pituitary gland and thyroid gland of the mice were analyzed. Here we show that the expression of all examined MCT isoforms was markedly altered by fasting compared to feeding. Expression of MCT1, MCT2 and MCT10 was either increased or decreased by fasting dependent on the analyzed tissue. MCT4 and MCT8 were down-regulated by fasting in all examined tissues. However, PPARα appeared to have a minor impact on MCT isoform regulation. Due to the fundamental role of MCTs in transport of energy providing metabolites and hormones involved in the regulation of energy homeostasis, we assumed that the observed fasting-induced adaptations of MCT expression seem to ensure an adequate energy supply of tissues during the fasting state. Since, MCT isoforms 1–4 are also necessary for the cellular uptake of drugs, the fasting-induced modifications of MCT expression have to be considered in future clinical care algorithms. PMID:25390336

  3. Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in MutaMouse.

    Science.gov (United States)

    Chen, Guosheng; Gingerich, John; Soper, Lynda; Douglas, George R; White, Paul A

    2008-10-01

    3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected in diesel exhaust, airborne particulate matter, and urban soil. We investigated the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic MutaMouse following acute single dose or 28-day repeated-dose oral administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant frequency was observed in bone marrow and colonic epithelium, but not in liver and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant frequency was observed in bone marrow and liver (2- and 4-fold increase above control), but not in lung or intestinal epithelium. In addition, a concentration-dependent increase in mutant frequency (8.5-fold above control) was observed for MutaMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3-NBA reductase, and acetyltransferase activities were measured in a variety of MutaMouse specimens in an effort to link metabolic activation and mutagenicity. High 3-NBA nitroreductase activities were observed in lung, liver, colon and bladder, and detectable N-acetyltransferase activities were found in all tissues except bone marrow. The relatively high 3-NBA nitroreductase activity in MutaMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase levels in liver and colon are consistent with the elevated lacZ mutant frequency values, and previously noted inductions of hepatic DNA adducts. Despite an absence of induced lacZ mutations, the highest 3-NBA reductase activity was detected in lung. Further studies are warranted, especially following inhalation or intratracheal exposures. Published 2008 Wiley-Liss, Inc.

  4. A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jürgen Hench

    Full Text Available The majority of metabolic principles are evolutionarily conserved from nematodes to humans. Caenorhabditis elegans has widely accelerated the discovery of new genes important to maintain organismic metabolic homeostasis. Various methods exist to assess the metabolic state in worms, yet they often require large animal numbers and tend to be performed as bulk analyses of whole worm homogenates, thereby largely precluding a detailed studies of metabolic changes in specific worm tissues. Here, we have adapted well-established histochemical methods for the use on C. elegans fresh frozen sections and demonstrate their validity for analyses of morphological and metabolic changes on tissue level in wild type and various mutant strains. We show how the worm presents on hematoxylin and eosin (H&E stained sections and demonstrate their usefulness in monitoring and the identification of morphological abnormalities. In addition, we demonstrate how Oil-Red-O staining on frozen worm cross-sections permits quantification of lipid storage, avoiding the artifact-prone fixation and permeabilization procedures of traditional whole-mount protocols. We also adjusted standard enzymatic stains for respiratory chain subunits (NADH, SDH, and COX to monitor metabolic states of various C. elegans tissues. In summary, the protocols presented here provide technical guidance to obtain robust, reproducible and quantifiable tissue-specific data on worm morphology as well as carbohydrate, lipid and mitochondrial energy metabolism that cannot be obtained through traditional biochemical bulk analyses of worm homogenates. Furthermore, analysis of worm cross-sections overcomes the common problem with quantification in three-dimensional whole-mount specimens.

  5. Tissue-specific transcriptome profiling of Plutella xylostella third instar larval midgut.

    Science.gov (United States)

    Xie, Wen; Lei, Yanyuan; Fu, Wei; Yang, Zhongxia; Zhu, Xun; Guo, Zhaojiang; Wu, Qingjun; Wang, Shaoli; Xu, Baoyun; Zhou, Xuguo; Zhang, Youjun

    2012-01-01

    The larval midgut of diamondback moth, Plutella xylostella, is a dynamic tissue that interfaces with a diverse array of physiological and toxicological processes, including nutrient digestion and allocation, xenobiotic detoxification, innate and adaptive immune response, and pathogen defense. Despite its enormous agricultural importance, the genomic resources for P. xylostella are surprisingly scarce. In this study, a Bt resistant P. xylostella strain was subjected to the in-depth transcriptome analysis to identify genes and gene networks putatively involved in various physiological and toxicological processes in the P. xylostella larval midgut. Using Illumina deep sequencing, we obtained roughly 40 million reads containing approximately 3.6 gigabases of sequence data. De novo assembly generated 63,312 ESTs with an average read length of 416 bp, and approximately half of the P. xylostella sequences (45.4%, 28,768) showed similarity to the non-redundant database in GenBank with a cut-off E-value below 10(-5). Among them, 11,092 unigenes were assigned to one or multiple GO terms and 16,732 unigenes were assigned to 226 specific pathways. In-depth analysis identified genes putatively involved in insecticide resistance, nutrient digestion, and innate immune defense. Besides conventional detoxification enzymes and insecticide targets, novel genes, including 28 chymotrypsins and 53 ABC transporters, have been uncovered in the P. xylostella larval midgut transcriptome; which are potentially linked to the Bt toxicity and resistance. Furthermore, an unexpectedly high number of ESTs, including 46 serpins and 7 lysozymes, were predicted to be involved in the immune defense.As the first tissue-specific transcriptome analysis of P. xylostella, this study sheds light on the molecular understanding of insecticide resistance, especially Bt resistance in an agriculturally important insect pest, and lays the foundation for future functional genomics research. In addition, current

  6. Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death.

    Directory of Open Access Journals (Sweden)

    Mohamed I Husseiny

    Full Text Available The onset of metabolic dysregulation in type 1 diabetes (T1D occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy.

  7. Tissue-specific expression and regulatory networks of pig microRNAome.

    Directory of Open Access Journals (Sweden)

    Paolo Martini

    Full Text Available BACKGROUND: Despite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date. RESULTS: We applied a novel computational approach to predict species-specific and conserved miRNAs in the pig genome, which were then subjected to experimental validation. We experimentally identified candidate miRNAs sequences grouped in high-confidence (424 and medium-confidence (353 miRNAs according to RNA-seq results. A group of miRNAs was also validated by PCR experiments. We established the subtle variability in expression of isomiRs and miRNA-miRNA star couples supporting a biological function for these molecules. Finally, miRNA and mRNA expression profiles produced from the same sample of 20 different tissue of the animal were combined, using a correlation threshold to filter miRNA-target predictions, to identify tissue-specific regulatory networks. CONCLUSIONS: Our data represent a significant progress in the current understanding of miRNAome in pig. The identification of miRNAs, their target mRNAs, and the construction of regulatory circuits will provide new insights into the complex biological networks in several tissues of this important animal model.

  8. Construction and Development of a Cardiac Tissue-Specific and Hypoxia-Inducible Expression Vector

    Directory of Open Access Journals (Sweden)

    Shahrooz Ghaderi

    2018-03-01

    Full Text Available Purpose: Cardiovascular gene therapy is a sophisticated approach, thanks to the safety of vectors, stable transgene expression, delivery method, and different layers of the heart. To date, numerous expression vectors have been introduced in biotechnology and biopharmacy industries in relation to genetic manipulation. Despite the rapid growth of these modalities, they must be intelligently designed, addressing the cardiac-specific transgene expression and less side effects. Herein, we conducted a pilot project aiming to design a cardiac-specific hypoxia-inducible expression cassette. Methods: We explored a new approach to design an expression cassette containing cardiac specific enhancer, hypoxia response elements (HRE, cardiac specific promoter, internal ribosome entry site (IRES, and beta globin poly A sequence to elicit specific and inducible expression of the gene of interest. Enhanced green fluorescent protein (eGFP was sub-cloned by BglII and NotI into the cassette. The specificity and inducible expression of the cassette was determined in both mouse myoblast C2C12 and mammary glandular tumor 4T1 as ‘twin’ cells. eGFP expression was evaluated by immunofluorescence microscope and flow cytometry at 520 nm emission peak. Results: Our data revealed that the designed expression cassette provided tissue specific and hypoxia inducible (O2<1% transgene expression. Conclusion: It is suggested that cardiac-specific enhancer combined with cardiac-specific promoter are efficient for myoblast specific gene expression. As well, this is for the first time that HRE are derived from three well known hypoxia-regulated promoters. Therefore, there is no longer need to overlap PCR process for one repeated sequence just in one promoter.

  9. Tissue-Specific Transcriptome Profiling of Plutella Xylostella Third Instar Larval Midgut

    Science.gov (United States)

    Xie, Wen; Lei, Yanyuan; Fu, Wei; Yang, Zhongxia; Zhu, Xun; Guo, Zhaojiang; Wu, Qingjun; Wang, Shaoli; Xu, Baoyun; Zhou, Xuguo; Zhang, Youjun

    2012-01-01

    The larval midgut of diamondback moth, Plutella xylostella, is a dynamic tissue that interfaces with a diverse array of physiological and toxicological processes, including nutrient digestion and allocation, xenobiotic detoxification, innate and adaptive immune response, and pathogen defense. Despite its enormous agricultural importance, the genomic resources for P. xylostella are surprisingly scarce. In this study, a Bt resistant P. xylostella strain was subjected to the in-depth transcriptome analysis to identify genes and gene networks putatively involved in various physiological and toxicological processes in the P. xylostella larval midgut. Using Illumina deep sequencing, we obtained roughly 40 million reads containing approximately 3.6 gigabases of sequence data. De novo assembly generated 63,312 ESTs with an average read length of 416bp, and approximately half of the P. xylostella sequences (45.4%, 28,768) showed similarity to the non-redundant database in GenBank with a cut-off E-value below 10-5. Among them, 11,092 unigenes were assigned to one or multiple GO terms and 16,732 unigenes were assigned to 226 specific pathways. In-depth analysis indentified genes putatively involved in insecticide resistance, nutrient digestion, and innate immune defense. Besides conventional detoxification enzymes and insecticide targets, novel genes, including 28 chymotrypsins and 53 ABC transporters, have been uncovered in the P. xylostella larval midgut transcriptome; which are potentially linked to the Bt toxicity and resistance. Furthermore, an unexpectedly high number of ESTs, including 46 serpins and 7 lysozymes, were predicted to be involved in the immune defense. As the first tissue-specific transcriptome analysis of P. xylostella, this study sheds light on the molecular understanding of insecticide resistance, especially Bt resistance in an agriculturally important insect pest, and lays the foundation for future functional genomics research. In addition, current

  10. Detection of neuronal tissue in meat using tissue specific DNA modifications

    Directory of Open Access Journals (Sweden)

    Harris N.

    2004-01-01

    Full Text Available A method has been developed to differentiate between non-muscle tissues such as liver, kidney and heart and that of muscle in meat samples using tissue specific DNA detection. Only muscle tissue is considered meat from the point of view of labelling (Food Labelling [Amendment] (England Regulations 2003 and Quantitative Ingredient Declaration (QUID, and also certain parts of the carcass are prohibited to be used in raw meat products (Meat Products [England] Regulations 2003. Included in the prohibited offal are brain and spinal cord. The described methodology has therefore been developed primarily to enforce labelling rules but also to contribute to the enforcement of BSE legislation on the detection of Central Nervous System (CNS tissue. The latter requires the removal of Specified Risk Material (SRM, such as bovine and ovine brain and spinal cord, from the food chain. Current methodologies for detection of CNS tissue include histological examination, analysis of cholesterol content and immunodetection. These can potentially be time consuming, less applicable to processed samples and may not be readily adapted to high throughput sample analysis. The objective of this work was therefore to develop a DNAbased detection assay that exploits the sensitivity and specificity of PCR and is potentially applicable to more highly processed food samples. For neuronal tissue, the DNA target selected was the promoter for Glial Fibrillary Acidic Protein (GFAP, a gene whose expression is restricted to astroglial cells within CNS tissue. The promoter fragments from both cattle and sheep have been isolated and key differences in the methylation patterns of certain CpG dinucleotides in the sequences from bovine and sheep brain and spinal cord and the corresponding skeletal muscle identified. These have been used to design a PCR assay exploiting Methylation Specific PCR (MSP to specifically amplify the neuronal tissue derived sequence and therefore identify the

  11. Reprimo tissue-specific expression pattern is conserved between zebrafish and human.

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    Ricardo J Figueroa

    Full Text Available Reprimo (RPRM, a member of the RPRM gene family, is a tumor-suppressor gene involved in the regulation of the p53-mediated cell cycle arrest at G2/M. RPRM has been associated with malignant tumor progression and proposed as a potential biomarker for early cancer detection. However, the expression and role of RPRM, as well as its family, are poorly understood and their physiology is as yet unstudied. In this scenario, a model system like the zebrafish could serve to dissect the role of the RPRM family members in vivo. Phylogenetic analysis reveals that RPRM and RPRML have been differentially retained by most species throughout vertebrate evolution, yet RPRM3 has been retained only in a small group of distantly related species, including zebrafish. Herein, we characterized the spatiotemporal expression of RPRM (present in zebrafish as an infraclass duplication rprma/rprmb, RPRML and RPRM3 in the zebrafish. By whole-mount in situ hybridization (WISH and fluorescent in situ hybridization (FISH, we demonstrate that rprm (rprma/rprmb and rprml show a similar spatiotemporal expression profile during zebrafish development. At early developmental stages rprmb is expressed in somites. After one day post-fertilization, rprm (rprma/rprmb and rprml are expressed in the notochord, brain, blood vessels and digestive tube. On the other hand, rprm3 shows the most unique expression profile, being expressed only in the central nervous system (CNS. We assessed the expression patterns of RPRM gene transcripts in adult zebrafish and human RPRM protein product in tissue samples by RT-qPCR and immunohistochemistry (IHC staining, respectively. Strikingly, tissue-specific expression patterns of the RPRM transcripts and protein are conserved between zebrafish and humans. We propose the zebrafish as a powerful tool to elucidate the both physiological and pathological roles of the RPRM gene family.

  12. Tissue-Specific Transcriptomics of the Exotic Invasive Insect Pest Emerald Ash Borer (Agrilus planipennis)

    Science.gov (United States)

    Mittapalli, Omprakash; Bai, Xiaodong; Bonello, Pierluigi; Herms, Daniel A.

    2010-01-01

    Background The insect midgut and fat body represent major tissue interfaces that deal with several important physiological functions including digestion, detoxification and immune response. The emerald ash borer (Agrilus planipennis), is an exotic invasive insect pest that has killed millions of ash trees (Fraxinus spp.) primarily in the Midwestern United States and Ontario, Canada. However, despite its high impact status little knowledge exists for A. planipennis at the molecular level. Methodology and Principal Findings Newer-generation Roche-454 pyrosequencing was used to obtain 126,185 reads for the midgut and 240,848 reads for the fat body, which were assembled into 25,173 and 37,661 high quality expressed sequence tags (ESTs) for the midgut and the fat body of A. planipennis larvae, respectively. Among these ESTs, 36% of the midgut and 38% of the fat body sequences showed similarity to proteins in the GenBank nr database. A high number of the midgut sequences contained chitin-binding peritrophin (248)and trypsin (98) domains; while the fat body sequences showed high occurrence of cytochrome P450s (85) and protein kinase (123) domains. Further, the midgut transcriptome of A. planipennis revealed putative microbial transcripts encoding for cell-wall degrading enzymes such as polygalacturonases and endoglucanases. A significant number of SNPs (137 in midgut and 347 in fat body) and microsatellite loci (317 in midgut and 571 in fat body) were predicted in the A. planipennis transcripts. An initial assessment of cytochrome P450s belonging to various CYP clades revealed distinct expression patterns at the tissue level. Conclusions and Significance To our knowledge this study is one of the first to illuminate tissue-specific gene expression in an invasive insect of high ecological and economic consequence. These findings will lay the foundation for future gene expression and functional studies in A. planipennis. PMID:21060843

  13. Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis.

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    Yannan Fan

    Full Text Available The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet knock-in context (Del-R26(Met reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an

  14. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

    2008-01-01

    to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also......Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...

  15. Andrographis paniculata transcriptome provides molecular insights into tissue-specific accumulation of medicinal diterpenes.

    Science.gov (United States)

    Garg, Anchal; Agrawal, Lalit; Misra, Rajesh Chandra; Sharma, Shubha; Ghosh, Sumit

    2015-09-02

    Kalmegh (Andrographis paniculata) has been widely exploited in traditional medicine for the treatment of infectious diseases and health disorders. Ent-labdane-related diterpene (ent-LRD) specialized (i.e., secondary) metabolites of kalmegh such as andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide, are known for variety of pharmacological activities. However, due to the lack of genomic and transcriptomic information, underlying molecular basis of ent-LRDs biosynthesis has remained largely unknown. To identify candidate genes of the ent-LRD biosynthetic pathway, we performed comparative transcriptome analysis using leaf and root tissues that differentially accumulate ent-LRDs. De novo assembly of Illumina HiSeq2000 platform-generated paired-end sequencing reads resulted into 69,011 leaf and 64,244 root transcripts which were assembled into a total of 84,628 unique transcripts. Annotation of these transcripts to the Uniprot, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active Enzymes (CAZy) databases identified candidate transcripts of the ent-LRD biosynthetic pathway. These included transcripts that encode enzymes of the plastidial 2C-methyl-D-erythritol-4-phosphate pathway which provides C5 isoprenoid precursors for the ent-LRDs biosynthesis, geranylgeranyl diphosphate synthase, class II diterpene synthase (diTPS), cytochrome P450 monooxygenase and glycosyltransferase. Three class II diTPSs (ApCPS1, ApCPS2 and ApCPS3) that showed distinct tissue-specific expression profiles and are phylogenetically related to the dicotyledon ent-copalyl diphosphate synthases, are identified. ApCPS1, ApCPS2 and ApCPS3 encode for 832-, 817- and 797- amino acids proteins of 55-63 % identity, respectively. Spatio-temporal patterns of transcripts and ent-LRDs accumulation are consistent with the involvement of ApCPS1 in general (i.e., primary) metabolism for the biosynthesis of phytohormone gibberellin, ApCPS2 in leaf specialized ent

  16. Tissue specific responses to cadmium-based quantum dots in the marine mussel Mytilus galloprovincialis

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Thiago Lopes [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Gomes, Tânia [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, NO-0349 Oslo (Norway); Mestre, Nélia C.; Cardoso, Cátia [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Bebianno, Maria João, E-mail: mbebian@ualg.pt [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2015-12-15

    Highlights: • Mussel gills are the main target for oxidative stress induced by Cd-based QDs. • Antioxidants responses induced by Cd-based QDs and dissolved Cd are mediated by different mechanisms. • CdTe QDs are more pro-oxidant Cd form when compared to dissolved Cd. • Differential tissue response indicated nano-specific effects. - Abstract: In recent years, Cd-based quantum dots (QDs) have generated interest from the life sciences community due to their potential applications in nanomedicine, biology and electronics. However, these engineered nanomaterials can be released into the marine environment, where their environmental health hazards remain unclear. This study investigated the tissue-specific responses related to alterations in the antioxidant defense system induced by CdTe QDs, in comparison with its dissolved counterpart, using the marine mussel Mytilus galloprovincialis. Mussels were exposed to CdTe QDs and dissolved Cd for 14 days at 10 μgCd L{sup −1} and biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (total, Se-independent and Se-dependent GPx) and glutathione-S-transferase (GST) activities] were analyzed along with Cd accumulation in the gills and digestive gland of mussels. Results show that both Cd forms changed mussels’ antioxidant responses with distinct modes of action (MoA). There were tissue- and time-dependent differences in the biochemical responses to each Cd form, wherein QDs are more pro-oxidant when compared to dissolved Cd. The gills are the main tissue affected by QDs, with effects related to the increase of SOD, GST and GPx activities, while those of dissolved Cd was associated to the increase of CAT activity, Cd accumulation and exposure time. Digestive gland is a main tissue for accumulation of both Cd forms, but changes in antioxidant enzyme activities are smaller than in gills. A multivariate analysis revealed that the antioxidant patterns are tissue dependent

  17. Tissue-specific features of the X chromosome and nucleolus spatial dynamics in a malaria mosquito, Anopheles atroparvus.

    Science.gov (United States)

    Bondarenko, Semen M; Artemov, Gleb N; Sharakhov, Igor V; Stegniy, Vladimir N

    2017-01-01

    Spatial organization of chromosome territories is important for maintenance of genomic stability and regulation of gene expression. Recent studies have shown tissue-specific features of chromosome attachments to the nuclear envelope in various organisms including malaria mosquitoes. However, other spatial characteristics of nucleus organization, like volume and shape of chromosome territories, have not been studied in Anopheles. We conducted a thorough analysis of tissue-specific features of the X chromosome and nucleolus volume and shape in follicular epithelium and nurse cells of the Anopheles atroparvus ovaries using a modern open-source software. DNA of the polytene X chromosome from ovarian nurse cells was obtained by microdissection and was used as a template for amplification with degenerate oligo primers. A fluorescently labeled X chromosome painting probe was hybridized with formaldehyde-fixed ovaries of mosquitoes using a 3D-FISH method. The nucleolus was stained by immunostaining with an anti-fibrillarin antibody. The analysis was conducted with TANGO-a software for a chromosome spatial organization analysis. We show that the volume and position of the X chromosome have tissue-specific characteristics. Unlike nurse cell nuclei, the growth of follicular epithelium nuclei is not accompanied with the proportional growth of the X chromosome. However, the shape of the X chromosome does not differ between the tissues. The dynamics of the X chromosome attachment regions location is tissue-specific and it is correlated with the process of nucleus growth in follicular epithelium and nurse cells.

  18. Prediction of disease-related genes based on weighted tissue-specific networks by using DNA methylation.

    Science.gov (United States)

    Li, Min; Zhang, Jiayi; Liu, Qing; Wang, Jianxin; Wu, Fang-Xiang

    2014-01-01

    Predicting disease-related genes is one of the most important tasks in bioinformatics and systems biology. With the advances in high-throughput techniques, a large number of protein-protein interactions are available, which make it possible to identify disease-related genes at the network level. However, network-based identification of disease-related genes is still a challenge as the considerable false-positives are still existed in the current available protein interaction networks (PIN). Considering the fact that the majority of genetic disorders tend to manifest only in a single or a few tissues, we constructed tissue-specific networks (TSN) by integrating PIN and tissue-specific data. We further weighed the constructed tissue-specific network (WTSN) by using DNA methylation as it plays an irreplaceable role in the development of complex diseases. A PageRank-based method was developed to identify disease-related genes from the constructed networks. To validate the effectiveness of the proposed method, we constructed PIN, weighted PIN (WPIN), TSN, WTSN for colon cancer and leukemia, respectively. The experimental results on colon cancer and leukemia show that the combination of tissue-specific data and DNA methylation can help to identify disease-related genes more accurately. Moreover, the PageRank-based method was effective to predict disease-related genes on the case studies of colon cancer and leukemia. Tissue-specific data and DNA methylation are two important factors to the study of human diseases. The same method implemented on the WTSN can achieve better results compared to those being implemented on original PIN, WPIN, or TSN. The PageRank-based method outperforms degree centrality-based method for identifying disease-related genes from WTSN.

  19. Acquisition and evolution of plant pathogenesis-associated gene clusters and candidate determinants of tissue-specificity in xanthomonas.

    Directory of Open Access Journals (Sweden)

    Hong Lu

    Full Text Available Xanthomonas is a large genus of plant-associated and plant-pathogenic bacteria. Collectively, members cause diseases on over 392 plant species. Individually, they exhibit marked host- and tissue-specificity. The determinants of this specificity are unknown.To assess potential contributions to host- and tissue-specificity, pathogenesis-associated gene clusters were compared across genomes of eight Xanthomonas strains representing vascular or non-vascular pathogens of rice, brassicas, pepper and tomato, and citrus. The gum cluster for extracellular polysaccharide is conserved except for gumN and sequences downstream. The xcs and xps clusters for type II secretion are conserved, except in the rice pathogens, in which xcs is missing. In the otherwise conserved hrp cluster, sequences flanking the core genes for type III secretion vary with respect to insertion sequence element and putative effector gene content. Variation at the rpf (regulation of pathogenicity factors cluster is more pronounced, though genes with established functional relevance are conserved. A cluster for synthesis of lipopolysaccharide varies highly, suggesting multiple horizontal gene transfers and reassortments, but this variation does not correlate with host- or tissue-specificity. Phylogenetic trees based on amino acid alignments of gum, xps, xcs, hrp, and rpf cluster products generally reflect strain phylogeny. However, amino acid residues at four positions correlate with tissue specificity, revealing hpaA and xpsD as candidate determinants. Examination of genome sequences of xanthomonads Xylella fastidiosa and Stenotrophomonas maltophilia revealed that the hrp, gum, and xcs clusters are recent acquisitions in the Xanthomonas lineage.Our results provide insight into the ancestral Xanthomonas genome and indicate that differentiation with respect to host- and tissue-specificity involved not major modifications or wholesale exchange of clusters, but subtle changes in a small

  20. Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid

    Directory of Open Access Journals (Sweden)

    Christopher J. Petzold

    2013-10-01

    bone cofactor was identified as a lipid containing a ceramide phosphate, a single chained glycerol lipid and a linker. Tendon uses a different cofactor made up of two fatty acid chains linked directly to the phosphate yielding a molecule about half the size. Moreover, adding the tendon factor/cofactor to osteosarcoma cells causes them to stop growing, which is opposite to its role with tendon cells. Thus, the cofactor is cell type specific both in composition and in the triggered response. Further support of its proposed role came from frozen sections from 5 week old mice where an antibody to the factor stained strongly at the growing ends of the tendon as predicted. In conclusion, the molecule needed for cell density signaling is a small protein bound to a unique, tissue-specific phospholipid yielding a membrane associated but diffusible molecule. Signal transduction is postulated to occur by an increased ordering of the plasma membrane as the concentration of this protein/lipid increases with cell density.

  1. Tissue specific promoters improve the localization of radiation-inducible gene expression

    International Nuclear Information System (INIS)

    Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph

    1996-01-01

    expression was quantified in vascular endothelial cells from large vessel (HUVEC) and small vessels (HMEC). We found cell-type specificity of radiation-induction. The promoter region from the ELAM gene gave no expression in cells that were not of endothelial cell origin and x-ray-induction of ELAM in the endothelium required the NFkB binding cis-acting element. ELAM induction was achieved at doses as low as 1 Gy, whereas induction of other radiation inducible genes required 5 to 10 Gy. Cells transfected with the minimal promoter (plasmid pTK-CAT) demonstrated no radiation induction. Expression of the CMV-LacZ genetic construct that was used as a negative control in each transfection was not altered by x-irradiation. Moreover, intravenous administration of liposomes containing a reporter gene linked to the ELAM promoter and a transcriptional amplification system were induced specifically at sites of x-irradiation in an animal model. Conclusions: Activation of transcription of the ELAM-1 promoter by ionizing radiation is a means of activating gene therapy within the vascular endothelium and demonstrates the feasibility of treating vascular lesions with noninvasive procedures. Tissue specific promoters (e. g., ELAM-1) combined with radiation inducible gene therapy improves the localization of gene therapy expression. These results have applications in intravascular brachytherapy for the prevention of blood vessel restenosis

  2. Tissue-specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat

    OpenAIRE

    1991-01-01

    Fibronectin isoforms are generated by the alternative splicing of a primary transcript derived from a single gene. In rat at least three regions of the molecule are involved: EIIIA, EIIIB, and V. This study investigated the splicing patterns of these regions during development and aging, by means of ribonuclease protection analysis. Between fetal and adult rat, the extent of inclusion of the EIIIA and/or EIIIB region in fibronectin mRNA varied according to the type of tissue analyzed; but the...

  3. Identification of CTLA2A, DEFB29, WFDC15B, SERPINA1F and MUP19 as Novel Tissue-Specific Secretory Factors in Mouse.

    Directory of Open Access Journals (Sweden)

    Jibin Zhang

    Full Text Available Secretory factors in animals play an important role in communication between different cells, tissues and organs. Especially, the secretory factors with specific expression in one tissue may reflect important functions and unique status of that tissue in an organism. In this study, we identified potential tissue-specific secretory factors in the fat, muscle, heart, lung, kidney and liver in the mouse by analyzing microarray data from NCBI's Gene Expression Omnibus (GEO public repository and searching and predicting their subcellular location in GeneCards and WoLF PSORT, and then confirmed tissue-specific expression of the genes using semi-quantitative PCR reactions. With this approach, we confirmed 11 lung, 7 liver, 2 heart, 1 heart and muscle, 7 kidney and 2 adipose and liver-specific secretory factors. Among these genes, 1 lung-specific gene--CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha, 3 kidney-specific genes--SERPINA1F (serpin peptidase inhibitor, Clade A, member 1F, WFDC15B (WAP four-disulfide core domain 15B and DEFB29 (defensin beta 29 and 1 liver-specific gene--MUP19 (major urinary protein 19 have not been reported as secretory factors. These genes were tagged with hemagglutinin at the 3'end and then transiently transfected to HEK293 cells. Through protein detection in cell lysate and media using Western blotting, we verified secretion of the 5 genes and predicted the potential pathways in which they may participate in the specific tissue through data analysis of GEO profiles. In addition, alternative splicing was detected in transcripts of CTLA2A and SERPINA1F and the corresponding proteins were found not to be secreted in cell culture media. Identification of novel secretory factors through the current study provides a new platform to explore novel secretory factors and a general direction for further study of these genes in the future.

  4. Tissue-specifically regulated site-specific excision of selectable marker genes in bivalent insecticidal, genetically-modified rice.

    Science.gov (United States)

    Hu, Zhan; Ding, Xuezhi; Hu, Shengbiao; Sun, Yunjun; Xia, Liqiu

    2013-12-01

    Marker-free, genetically-modified rice was created by the tissue-specifically regulated Cre/loxP system, in which the Cre recombinase gene and hygromycin phosphotransferase gene (hpt) were flanked by two directly oriented loxP sites. Cre expression was activated by the tissue-specific promoter OsMADS45 in flower or napin in seed, resulting in simultaneous excision of the recombinase and marker genes. Segregation of T1 progeny was performed to select recombined plants. The excision was confirmed by PCR, Southern blot and sequence analyses indicating that efficiency varied from 10 to 53 % for OsMADS45 and from 12 to 36 % for napin. The expression of cry1Ac and vip3A was detected by RT-PCR analysis in marker-free transgenic rice. These results suggested that our tissue-specifically regulated Cre/loxP system could auto-excise marker genes from transgenic rice and alleviate public concerns about the security of GM crops.

  5. Expression analysis of five tobacco EIN3 family members in relation to tissue-specific ethylene responses.

    Science.gov (United States)

    Rieu, I; Mariani, C; Weterings, K

    2003-10-01

    Ethylene induces different sets of genes in different tissues and at different stages of development. To investigate whether these differential responses are caused by differential expression of members of the EIN3 family transcription factors, five tobacco family members were isolated. They can be divided into three subgroups, which is probably due to the amphidiploid nature of tobacco. In phylogenetic analysis, each of the subgroups clustered with one of the three tomato EIL proteins and all NtEILs proved to be most homologous to Arabidopsis EIN3 and EIL1. Although organ-specific ethylene responses have been observed before, northern blot analysis showed that all NtEILs were expressed in all organs. To study differential NtEIL expression at the cellular level, in situ hybridization was used on the tobacco ovary. It was found that different ovary tissues displayed variable ethylene-induced expression of two ethylene-responsive marker genes. By contrast, no differences were found in expression level or tissue-specificity for any of the NtEILs in the ovary, before or after ethylene treatment. This indicates that the organ and tissue-specific ethylene responses are not caused by differential expression of NtEIL family members. These results support a model in which the developmental signals that regulate the tissue-specific responses are integrated with the ethylene signal downstream of a common primary ethylene-signalling pathway.

  6. Tissue specific responses alter the biomass accumulation in wheat under gradual and sudden salt stress

    Directory of Open Access Journals (Sweden)

    Yumurtaci A.

    2012-11-01

    Full Text Available Salinity is one the major limiting environmental factors which has negative side effects on crop production. The purpose of this study was to investigate the differences between the gradual and sudden salt stress effects on biomass accumulation associated with whole plant development in three different tissues of two wheat species ( Triticum aestivum and Triticum durum under hydroponic conditions in the long term. Considering the effects of sudden and gradual stress for biomass accumulation, while importance of salinity x genotype interaction for fresh weights was 5%, association for salinity x tissue type was found as 1% important. Interestingly, root branching and development of lateral roots were much more negatively affected by gradual stress rather than sudden salt application. Our results demonstrated that root and leaf were both critical tissues to test the salt tolerance by physiologically but sheath tissue might be used as an alternative source of variation for solving the interactions between root and leaves in wheat.

  7. A Novel Collection of snRNA-Like Promoters with Tissue-Specific Transcription Properties

    Directory of Open Access Journals (Sweden)

    Aldo Pagano

    2012-09-01

    Full Text Available We recently identified a novel dataset of snRNA-like trascriptional units in the human genome. The investigation of a subset of these elements showed that they play relevant roles in physiology and/or pathology. In this work we expand our collection of small RNAs taking advantage of a newly developed algorithm able to identify genome sequence stretches with RNA polymerase (pol III type 3 promoter features thus constituting putative pol III binding sites. The bioinformatic analysis of a subset of these elements that map in introns of protein-coding genes in antisense configuration suggest their association with alternative splicing, similarly to other recently characterized small RNAs. Interestingly, the analysis of the transcriptional activity of these novel promoters shows that they are active in a cell-type specific manner, in accordance with the emerging body of evidence of a tissue/cell-specific activity of pol III.

  8. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

    Directory of Open Access Journals (Sweden)

    Girgis Hani Z

    2012-02-01

    Full Text Available Abstract Background Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF binding sites (TFBSs. Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. Results We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was

  9. Evaluating the Application of Tissue-Specific Dose Kernels Instead of Water Dose Kernels in Internal Dosimetry : A Monte Carlo Study

    NARCIS (Netherlands)

    Moghadam, Maryam Khazaee; Asl, Alireza Kamali; Geramifar, Parham; Zaidi, Habib

    2016-01-01

    Purpose: The aim of this work is to evaluate the application of tissue-specific dose kernels instead of water dose kernels to improve the accuracy of patient-specific dosimetry by taking tissue heterogeneities into consideration. Materials and Methods: Tissue-specific dose point kernels (DPKs) and

  10. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2 defects predicts differential effects on aminoacylation

    Directory of Open Access Journals (Sweden)

    Liliya eEuro

    2015-02-01

    Full Text Available The accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs and the mitochondrial DNA-encoded tRNAs. The recent advances in whole-exome sequencing have revealed the importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19 is now recognized as a disease gene for mitochondrial disease. Typically, defects in each mtARS have been identified in one tissue-specific disease, most commonly affecting the brain, or in one syndrome. However, mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS have been reported both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. We present here an investigation of the effects of the described mutations on the structure of the synthetase, in an effort to understand the tissue-specific outcomes of the different mutations.The mtAlaRS differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged with incorrect amino acids. We show that the cardiomyopathy phenotype results from a single allele, causing an amino acid change p.R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. Nevertheless, our structural analysis predicts that all mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. According to our model, the cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. These predictions provide a hypothesis for the molecular basis of the distinct tissue-specific phenotypic outcomes.

  11. A minimal set of tissue-specific hypomethylated CpGs constitute epigenetic signatures of developmental programming.

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    Alejandro Colaneri

    Full Text Available Cell specific states of the chromatin are programmed during mammalian development. Dynamic DNA methylation across the developing embryo guides a program of repression, switching off genes in most cell types. Thus, the majority of the tissue specific differentially methylated sites (TS-DMS must be un-methylated CpGs.Comparison of expanded Methyl Sensitive Cut Counting data (eMSCC among four tissues (liver, testes, brain and kidney from three C57BL/6J mice, identified 138,052 differentially methylated sites of which 23,270 contain CpGs un-methylated in only one tissue (TS-DMS. Most of these CpGs were located in intergenic regions, outside of promoters, CpG islands or their shores, and up to 20% of them overlapped reported active enhancers. Indeed, tissue-specific enhancers were up to 30 fold enriched in TS-DMS. Testis showed the highest number of TS-DMS, but paradoxically their associated genes do not appear to be specific to the germ cell functions, but rather are involved in organism development. In the other tissues the differentially methylated genes are associated with tissue-specific physiological or anatomical functions. The identified sets of TS-DMS quantify epigenetic distances between tissues, generated during development. We applied this concept to measure the extent of reprogramming in the liver of mice exposed to in utero or early postnatal nutritional stress. Different protocols of food restriction reprogrammed the liver methylome in different but reproducible ways.Thus, each identified set of differentially methylated sites constituted an epigenetic signature that traced the developmental programing or the early nutritional reprogramming of each exposed mouse. We propose that our approach has the potential to outline a number of disease-associated epigenetic states. The composition of differentially methylated CpGs may vary with each situation, behaving as a composite variable, which can be used as a pre-symptomatic marker for

  12. mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.

    Science.gov (United States)

    Saada, Ann; Shaag, Avraham; Elpeleg, Orly

    2003-05-01

    Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.

  13. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori

    2016-01-01

    control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired...... C57BL/6 mice were analyzed at either 6 hours or 24 hours. ROS-production was simultaneously measured in brain samples using fluorometry.Septic brain tissue exhibited an early increased uncoupling of respiration. Temporal changes between the two time points were diminutive and no difference in ROS...

  14. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko

    2015-12-23

    Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

  15. Tissue-specific bioaccumulation and oxidative stress responses in juvenile Japanese flounder ( Paralichthys olivaceus) exposed to mercury

    Science.gov (United States)

    Huang, Wei; Cao, Liang; Ye, Zhenjiang; Lin, Longshan; Chen, Quanzhen; Dou, Shuozeng

    2012-07-01

    To understand mercury (Hg) toxicity in marine fish, we measured Hg accumulation in juvenile Japanese flounder ( Paralichthys olivaceus) and assessed the effects on growth and antioxidant responses. After Hg exposure (control, 5, 40, and 160 μg/L Hg) for 28 d, fish growth was significantly reduced. The accumulation of Hg in fish was dose-dependent and tissue-specific, with the maximum accumulation in kidney and liver, followed by gills, bone, and muscle. Different antioxidants responded differently to Hg exposure to cope with the induction of lipid peroxidation (LPO), which was also tissue-specific and dosedependent. As Hg concentration increased, superoxide dismutase (SOD) and catalase (CAT) activities increased significantly, whereas glutathione S -transferase (GST) activity and glutathione (GSH) levels decreased significantly in the gills. SOD and glutathione peroxidase (GPx) activities and the GSH level increased significantly in the liver. SOD activity and GSH levels increased significantly, but CAT activity decreased significantly with an increase in Hg concentration in the kidney. LPO was induced significantly by elevated Hg in the gills and kidney but was least affected in the liver. Therefore, oxidative stress biomarkers in gills were more sensitive than those in the liver and kidney to Hg exposure. Thus, the gills have potential as bioindicators for evaluating Hg toxicity in juvenile flounder.

  16. Tissue-specific congener composition of organohalogen and metabolite contaminants in East Greenland polar bears (Ursus maritimus)

    International Nuclear Information System (INIS)

    Gebbink, Wouter A.; Sonne, Christian; Dietz, Rune; Kirkegaard, Maja; Riget, Frank F.; Born, Erik W.; Muir, Derek C.G.; Letcher, Robert J.

    2008-01-01

    Congener patterns of the major organohalogen contaminant classes of PCBs, PBDEs and their metabolites and/or by-products (OH-PCBs, MeSO 2 -PCBs, OH-PBDEs and MeO-PBDEs) were examined in adipose tissue, liver, brain and blood of East Greenland polar bears (Ursus maritimus). PCB, OH-PCB, MeSO 2 -PCB and PBDE congener patterns showed significant differences (p ≤ 0.05) mainly in the liver and the brain relative to the adipose tissue and the blood. OH-PBDEs and MeO-PBDEs were not detected in the brain and liver, but had different patterns in blood versus the adipose tissue. Novel OH-polybrominated biphenyls (OH-PBBs), one tri- and two tetra-brominated OH-PBBs were detected in all tissues and blood. Congener pattern differences among tissues and blood are likely due to a combination of factors, e.g., biotransformation and retention in the liver, retention in the blood and blood-brain barrier transport. Our findings suggest that different congener pattern exposures to these classes of contaminants should be considered with respect to potential target tissue-specific effects in East Greenland polar bears. - Tissues-specific (adipose tissue, liver, brain and blood) differences exist for the congener patterns of PCBs, PBDEs and their metabolites/degradation products in East Greenland polar bears

  17. Tissue-Specific Contributions of Paternally Expressed Gene 3 in Lactation and Maternal Care of Mus musculus.

    Directory of Open Access Journals (Sweden)

    Wesley D Frey

    Full Text Available Paternally Expressed Gene 3 (Peg3 is an imprinted gene that controls milk letdown and maternal-caring behaviors. In this study, a conditional knockout allele has been developed in Mus musculus to further characterize these known functions of Peg3 in a tissue-specific manner. The mutant line was first crossed with a germline Cre. The progeny of this cross displayed growth retardation phenotypes. This is consistent with those seen in the previous mutant lines of Peg3, confirming the usefulness of the new mutant allele. The mutant line was subsequently crossed individually with MMTV- and Nkx2.1-Cre lines to test Peg3's roles in the mammary gland and hypothalamus, respectively. According to the results, the milk letdown process was impaired in the nursing females with the Peg3 mutation in the mammary gland, but not in the hypothalamus. This suggests that Peg3's roles in the milk letdown process are more critical in the mammary gland than in the hypothalamus. In contrast, one of the maternal-caring behaviors, nest-building, was interrupted in the females with the mutation in both MMTV- and Nkx2.1-driven lines. Overall, this is the first study to introduce a conditional knockout allele of Peg3 and to further dissect its contribution to mammalian reproduction in a tissue-specific manner.

  18. Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype.

    Science.gov (United States)

    Zhang, Yuanyuan; He, Yujiang; Bharadwaj, Shantaram; Hammam, Nevin; Carnagey, Kristen; Myers, Regina; Atala, Anthony; Van Dyke, Mark

    2009-08-01

    Recent studies have shown that extracellular matrix (ECM) substitutes can have a dramatic impact on cell growth, differentiation and function. However, these ECMs are often applied generically and have yet to be developed for specific cell types. In this study, we developed tissue-specific ECM-based coating substrates for skin, skeletal muscle and liver cell cultures. Cellular components were removed from adult skin, skeletal muscle, and liver tissues, and the resulting acellular matrices were homogenized and dissolved. The ECM solutions were used to coat culture dishes. Tissue matched and non-tissue matched cell types were grown on these coatings to assess adhesion, proliferation, maintenance of phenotype and cell function at several time points. Each cell type showed better proliferation and differentiation in cultures containing ECM from their tissue of origin. Although subtle compositional differences in the three ECM types were not investigated in this study, these results suggest that tissue-specific ECMs provide a culture microenvironment that is similar to the in vivo environment when used as coating substrates, and this new culture technique has the potential for use in drug development and the development of cell-based therapies.

  19. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  20. Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid and glucose uptake in mice.

    Science.gov (United States)

    Rottman, Jeffrey N; Bracy, Deanna; Malabanan, Carlo; Yue, Zou; Clanton, Jeff; Wasserman, David H

    2002-07-01

    Isotopic techniques were used to test the hypothesis that exercise and nitric oxide synthase (NOS) inhibition have distinct effects on tissue-specific fatty acid and glucose uptakes in a conscious, chronically catheterized mouse model. Uptakes were measured using the radioactive tracers (125)I-labeled beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) and deoxy-[2-(3)H]glucose (DG) during treadmill exercise with and without inhibition of NOS. [(125)I]BMIPP uptake at rest differed substantially among tissues with the highest levels in heart. With exercise, [(125)I]BMIPP uptake increased in both heart and skeletal muscles. In sedentary mice, NOS inhibition induced by nitro-L-arginine methyl ester (L-NAME) feeding increased heart and soleus [(125)I]BMIPP uptake. In contrast, exercise, but not L-NAME feeding, resulted in increased heart and skeletal muscle [2-(3)H]DG uptake. Significant interactions were not observed in the effects of combined exercise and L-NAME feeding on [(125)I]BMIPP and [2-(3)H]DG uptakes. In the conscious mouse, exercise and NOS inhibition produce distinct patterns of tissue-specific fatty acid and glucose uptake; NOS is not required for important components of exercise-associated metabolic signaling, or other mechanisms compensate for the absence of this regulatory mechanism.

  1. Tissue Discrimination by Uncorrected Autofluorescence Spectra: A Proof-of-Principle Study for Tissue-Specific Laser Surgery

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    Katja Tangermann-Gerk

    2013-10-01

    Full Text Available Laser surgery provides a number of advantages over conventional surgery. However, it implies large risks for sensitive tissue structures due to its characteristic non-tissue-specific ablation. The present study investigates the discrimination of nine different ex vivo tissue types by using uncorrected (raw autofluorescence spectra for the development of a remote feedback control system for tissue-selective laser surgery. Autofluorescence spectra (excitation wavelength 377 ± 50 nm were measured from nine different ex vivo tissue types, obtained from 15 domestic pig cadavers. For data analysis, a wavelength range between 450 nm and 650 nm was investigated. Principal Component Analysis (PCA and Quadratic Discriminant Analysis (QDA were used to discriminate the tissue types. ROC analysis showed that PCA, followed by QDA, could differentiate all investigated tissue types with AUC results between 1.00 and 0.97. Sensitivity reached values between 93% and 100% and specificity values between 94% and 100%. This ex vivo study shows a high differentiation potential for physiological tissue types when performing autofluorescence spectroscopy followed by PCA and QDA. The uncorrected autofluorescence spectra are suitable for reliable tissue discrimination and have a high potential to meet the challenges necessary for an optical feedback system for tissue-specific laser surgery.

  2. Tissue-specific and cation/anion-specific DNA methylation variations occurred in C. virgata in response to salinity stress.

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    Xiang Gao

    Full Text Available Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3 and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations.

  3. Tissue-specific and cation/anion-specific DNA methylation variations occurred in C. virgata in response to salinity stress.

    Science.gov (United States)

    Gao, Xiang; Cao, Donghui; Liu, Jie; Wang, Xiaoping; Geng, Shujuan; Liu, Bao; Shi, Decheng

    2013-01-01

    Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3) and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations.

  4. Structural evolution and tissue-specific expression of tetrapod-specific second isoform of secretory pathway Ca{sup 2+}-ATPase

    Energy Technology Data Exchange (ETDEWEB)

    Pestov, Nikolay B., E-mail: korn@mail.ibch.ru [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Dmitriev, Ruslan I.; Kostina, Maria B. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Korneenko, Tatyana V. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States); Shakhparonov, Mikhail I. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117871 (Russian Federation); Modyanov, Nikolai N., E-mail: nikolai.modyanov@utoledo.edu [Department of Physiology and Pharmacology, University of Toledo College of Medicine, 3000 Arlington Ave., Toledo, OH 43614 (United States)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Full-length secretory pathway Ca-ATPase (SPCA2) cloned from rat duodenum. Black-Right-Pointing-Pointer ATP2C2 gene (encoding SPCA2) exists only in genomes of Tetrapoda. Black-Right-Pointing-Pointer Rat and pig SPCA2 are expressed in intestines, lung and some secretory glands. Black-Right-Pointing-Pointer Subcellular localization of SPCA2 may depend on tissue type. Black-Right-Pointing-Pointer In rat duodenum, SPCA2 is localized in plasma membrane-associated compartments. -- Abstract: Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2

  5. The Genetics of PTPN1 and Obesity: Insights from Mouse Models of Tissue-Specific PTP1B Deficiency

    Directory of Open Access Journals (Sweden)

    Ryan C. Tsou

    2012-01-01

    Full Text Available The protein tyrosine phosphatase PTP1B is a negative regulator of both insulin and leptin signaling and is involved in the control of glucose homeostasis and energy expenditure. Due to its prominent role in regulating metabolism, PTP1B is a promising therapeutic target for the treatment of human obesity and type 2 diabetes. The PTP1B protein is encoded by the PTPN1 gene on human chromosome 20q13, a region that shows linkage with insulin resistance, type 2 diabetes, and obesity in human populations. In this paper, we summarize the genetics of the PTPN1 locus and associations with metabolic disease. In addition, we discuss the tissue-specific functions of PTP1B as gleaned from genetic mouse models.

  6. Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo

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    Xiaofen Li

    2013-01-01

    Full Text Available Gambogic acid (GA is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues but low in many normal tissues, GA could therefore produce tissue-specific proteasome inhibition and tumor-specific toxicity, with clinical significance for designing novel strategies for cancer treatment.

  7. Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome

    DEFF Research Database (Denmark)

    Feizi, Amir; Gatto, Francesco; Uhlén, Mathias

    2017-01-01

    Protein secretory pathway in eukaryal cells is responsible for delivering functional secretory proteins. The dysfunction of this pathway causes a range of important human diseases from congenital disorders to cancer. Despite the piled-up knowledge on the molecular biology and biochemistry level...... in specific gene families of the secretory pathway. We also inspected the potential functional link between detected extreme genes and the corresponding tissues enriched secretome. As a result, the detected extreme genes showed correlation with the enrichment of the nature and number of specific post......-translational modifications in each tissue's secretome. Our findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined gene families to support the diversity of secreted proteins and their modifications....

  8. Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice

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    Gue-Tae Chae

    1992-01-01

    Full Text Available RIPK 2 is adapter molecule in the signal pathway involved in Toll-like receptors. However, there has been no reported association between receptor-interacting serine/threonine kinase 2 (RIPK 2 expression and the infectious diseases involving mycobacterial infection. This study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of Mycobacterium leprae-infected nu/nu mice compared with those of the M. leprae non-infected nu/nu mice. It was observed that the interlukin-12p40 and interferon-γ genes involved in the susceptibility of M. leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection.

  9. Adiponectin receptor 2 is regulated by nutritional status, leptin and pregnancy in a tissue-specific manner.

    Science.gov (United States)

    González, Carmen Ruth; Caminos, Jorge Eduardo; Gallego, Rosalía; Tovar, Sulay; Vázquez, María Jesús; Garcés, María Fernanda; Lopez, Miguel; García-Caballero, Tomás; Tena-Sempere, Manuel; Nogueiras, Rubén; Diéguez, Carlos

    2010-01-12

    The aim of the present work was to study the regulation of circulating adiponectin levels and the expression of adiponectin receptor 2 (Adipo-R2) in several rat tissues in relation to fasting, leptin challenge, pregnancy, and chronic undernutrition. Using real-time PCR, we found Adipo-R2 mRNA expression in the liver, stomach, white and brown adipose tissues (WAT and BAT) of adult rats. Immunohistochemical studies confirmed protein expression in the same tissues. Adipo-R2 mRNA levels were decreased in liver after fasting, with no changes in the other tissues. Leptin decreased Adipo-R2 expression in liver and stomach, but increased its expression in WAT and BAT. Chronic caloric restriction in normal rats increased Adipo-R2 gene expression in stomach, while it decreased hepatic Adipo-R2 levels in pregnant rats. Using radioimmunoassay, we found that plasma adiponectin levels were diminished by fasting and leptin. Conversely, circulating adiponectin was increased in food-restricted rats, whereas its levels decreased in food-restricted pregnant rats by the end of gestation. In conclusion our findings provide the first evidence that (a) Adipo-R2 mRNA is regulated in a tissue-specific manner by fasting, but leptin is not responsible for those changes; (b) chronic caloric restriction in normal and pregnant rats also regulate Adipo-R2 mRNA in a tissue-specific manner; and (c) Adipo-R2 mRNA does not show a clear correlation with plasma adiponectin levels.

  10. BaP-metals co-exposure induced tissue-specific antioxidant defense in marine mussels Mytilus coruscus.

    Science.gov (United States)

    Chen, Siyu; Qu, Mengjie; Ding, Jiawei; Zhang, Yifei; Wang, Yi; Di, Yanan

    2018-04-18

    Both benzo(α)pyrene (BaP) and metals are frequently found in marine ecosystem and can cause detrimental effects in marine organism, especially the filter feeder-marine mussels. Although the biological responses in mussels have been well-studied upon the single metal or BaP exposure, the information about antioxidant defense, especially in different tissues of mussels, are still limited. Considering the variety of contaminants existing in the actual marine environment, single BaP (56 μg/L) and the co-exposure with Cu, Cd and Pb (50 μg/L, 50 μg/L and 3 mg/L respectively) were applied in a 6 days exposure followed by 6 days depuration experiment. The alterations of superoxide dismutase (SOD), catalase (CAT) activities and total antioxidant capacity (TAC) level were assessed in haemolymph, gills and digestive glands of marine mussels, Mytilus coruscus. An unparalleled change in antioxidant biomarkers was observed in all cells/tissues, with the SOD activity showing higher sensitivity to exposure. A tissue-specific response showing unique alteration in gill was investigated, indicating the different function of tissues during stress responses. Depressed antioxidant effects were induced by BaP-metals co-exposure, indicating the interaction may alter the intact properties of BaP. To our knowledge, this is the first research to explore the antioxidant defense induced by combined exposure of BaP-metals regarding to tissue-specific responses in marine mussels. The results and experimental model will provide valuable information and can be utilized in the investigation of stress response mechanisms, especially in relation to tissue functions in marine organism in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Organ-specific gene expression: the bHLH protein Sage provides tissue specificity to Drosophila FoxA.

    Science.gov (United States)

    Fox, Rebecca M; Vaishnavi, Aria; Maruyama, Rika; Andrew, Deborah J

    2013-05-01

    FoxA transcription factors play major roles in organ-specific gene expression, regulating, for example, glucagon expression in the pancreas, GLUT2 expression in the liver, and tyrosine hydroxylase expression in dopaminergic neurons. Organ-specific gene regulation by FoxA proteins is achieved through cooperative regulation with a broad array of transcription factors with more limited expression domains. Fork head (Fkh), the sole Drosophila FoxA family member, is required for the development of multiple distinct organs, yet little is known regarding how Fkh regulates tissue-specific gene expression. Here, we characterize Sage, a bHLH transcription factor expressed exclusively in the Drosophila salivary gland (SG). We show that Sage is required for late SG survival and normal tube morphology. We find that many Sage targets, identified by microarray analysis, encode SG-specific secreted cargo, transmembrane proteins, and the enzymes that modify these proteins. We show that both Sage and Fkh are required for the expression of Sage target genes, and that co-expression of Sage and Fkh is sufficient to drive target gene expression in multiple cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage-Fkh targets, and Sage, Fkh and Sens colocalize on SG chromosomes. Importantly, expression of Sage-Fkh target genes appears to simply add to the tissue-specific gene expression programs already established in other cell types, and Sage and Fkh cannot alter the fate of most embryonic cell types even when expressed early and continuously.

  12. Regulation of the number of cell division rounds by tissue-specific transcription factors and Cdk inhibitor during ascidian embryogenesis.

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    Mami Kuwajima

    Full Text Available Mechanisms that regulate the number of cell division rounds during embryogenesis have remained largely elusive. To investigate this issue, we used the ascidian, which develops into a tadpole larva with a small number of cells. The embryonic cells divide 11.45 times on average from fertilization to hatching. The number of cell division rounds varies depending on embryonic lineages. Notochord and muscle consist of large postmitotic cells and stop dividing early in developing embryos. Here we show that conversion of mesenchyme to muscle cell fates by inhibition of inductive FGF signaling or mis-expression of a muscle-specific key transcription factor for muscle differentiation, Tbx6, changed the number of cell divisions in accordance with the altered fate. Tbx6 likely activates a putative mechanism to halt cell division at a specific stage. However, precocious expression of Tbx6 has no effect on progression of the developmental clock itself. Zygotic expression of a cyclin-dependent kinase inhibitor, CKI-b, is initiated in muscle and then in notochord precursors. CKI-b is possibly downstream of tissue-specific key transcription factors of notochord and muscle. In the two distinct muscle lineages, postmitotic muscle cells are generated after 9 and 8 rounds of cell division depending on lineage, but the final cell divisions occur at a similar developmental stage. CKI-b gene expression starts simultaneously in both muscle lineages at the 110-cell stage, suggesting that CKI-b protein accumulation halts cell division at a similar stage. The difference in the number of cell divisions would be due to the cumulative difference in cell cycle length. These results suggest that muscle cells do not count the number of cell division rounds, and that accumulation of CKI-b protein triggered by tissue-specific key transcription factors after cell fate determination might act as a kind of timer that measures elapsed time before cell division termination.

  13. Diffuse reflectance spectroscopy for optical soft tissue differentiation as remote feedback control for tissue-specific laser surgery.

    Science.gov (United States)

    Stelzle, Florian; Tangermann-Gerk, Katja; Adler, Werner; Zam, Azhar; Schmidt, Michael; Douplik, Alexandre; Nkenke, Emeka

    2010-04-01

    Laser surgery does not provide haptic feedback for operating layer-by-layer and thereby preserving vulnerable anatomical structures like nerve tissue or blood vessels. Diffuse reflectance spectra can facilitate remote optical tissue differentiation. It is the aim of the study to use this technique on soft tissue samples, to set a technological basis for a remote optical feedback system for tissue-specific laser surgery. Diffuse reflectance spectra (wavelength range: 350-650 nm) of ex vivo types of soft tissue (a total of 10,800 spectra) of the midfacial region of domestic pigs were remotely measured under reduced environmental light conditions and analyzed in order to differentiate between skin, mucosa, muscle, subcutaneous fat, and nerve tissue. We performed a principal components (PC) analysis (PCA) to reduce the number of variables. Linear discriminant analysis (LDA) was utilized for classification. For the tissue differentiation, we calculated the specificity and sensitivity by receiver operating characteristic (ROC) analysis and the area under curve (AUC). Six PCs were found to be adequate for tissue differentiation with diffuse reflectance spectra using LDA. All of the types of soft tissue could be differentiated with high specificity and sensitivity. Only the tissue pairs nervous tissue/fatty tissue and nervous tissue/mucosa showed a decline of differentiation due to bio-structural similarity. However, both of these tissue pairs could still be differentiated with a specificity and sensitivity of more than 90%. Analyzing diffuse reflectance spectroscopy with PCA and LDA allows for remote differentiation of biological tissue. Considering the limitations of the ex vivo conditions, the obtained results are promising and set a basis for the further development of a feedback system for tissue-specific laser surgery. (c) 2010 Wiley-Liss, Inc.

  14. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

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    Sandrine Peruchon

    Full Text Available BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART. Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.. We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-CD27(+ B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid

  15. Mouse Nkrp1-Clr gene cluster sequence and expression analyses reveal conservation of tissue-specific MHC-independent immunosurveillance.

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    Qiang Zhang

    Full Text Available The Nkrp1 (Klrb1-Clr (Clec2 genes encode a receptor-ligand system utilized by NK cells as an MHC-independent immunosurveillance strategy for innate immune responses. The related Ly49 family of MHC-I receptors displays extreme allelic polymorphism and haplotype plasticity. In contrast, previous BAC-mapping and aCGH studies in the mouse suggest the neighboring and related Nkrp1-Clr cluster is evolutionarily stable. To definitively compare the relative evolutionary rate of Nkrp1-Clr vs. Ly49 gene clusters, the Nkrp1-Clr gene clusters from two Ly49 haplotype-disparate inbred mouse strains, BALB/c and 129S6, were sequenced. Both Nkrp1-Clr gene cluster sequences are highly similar to the C57BL/6 reference sequence, displaying the same gene numbers and order, complete pseudogenes, and gene fragments. The Nkrp1-Clr clusters contain a strikingly dissimilar proportion of repetitive elements compared to the Ly49 clusters, suggesting that certain elements may be partly responsible for the highly disparate Ly49 vs. Nkrp1 evolutionary rate. Focused allelic polymorphisms were found within the Nkrp1b/d (Klrb1b, Nkrp1c (Klrb1c, and Clr-c (Clec2f genes, suggestive of possible immune selection. Cell-type specific transcription of Nkrp1-Clr genes in a large panel of tissues/organs was determined. Clr-b (Clec2d and Clr-g (Clec2i showed wide expression, while other Clr genes showed more tissue-specific expression patterns. In situ hybridization revealed specific expression of various members of the Clr family in leukocytes/hematopoietic cells of immune organs, various tissue-restricted epithelial cells (including intestinal, kidney tubular, lung, and corneal progenitor epithelial cells, as well as myocytes. In summary, the Nkrp1-Clr gene cluster appears to evolve more slowly relative to the related Ly49 cluster, and likely regulates innate immunosurveillance in a tissue-specific manner.

  16. TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples.

    Science.gov (United States)

    Bandyopadhyay, Sanghamitra; Mitra, Ramkrishna

    2009-10-15

    Prediction of microRNA (miRNA) target mRNAs using machine learning approaches is an important area of research. However, most of the methods suffer from either high false positive or false negative rates. One reason for this is the marked deficiency of negative examples or miRNA non-target pairs. Systematic identification of non-target mRNAs is still not addressed properly, and therefore, current machine learning approaches are compelled to rely on artificially generated negative examples for training. In this article, we have identified approximately 300 tissue-specific negative examples using a novel approach that involves expression profiling of both miRNAs and mRNAs, miRNA-mRNA structural interactions and seed-site conservation. The newly generated negative examples are validated with pSILAC dataset, which elucidate the fact that the identified non-targets are indeed non-targets.These high-throughput tissue-specific negative examples and a set of experimentally verified positive examples are then used to build a system called TargetMiner, a support vector machine (SVM)-based classifier. In addition to assessing the prediction accuracy on cross-validation experiments, TargetMiner has been validated with a completely independent experimental test dataset. Our method outperforms 10 existing target prediction algorithms and provides a good balance between sensitivity and specificity that is not reflected in the existing methods. We achieve a significantly higher sensitivity and specificity of 69% and 67.8% based on a pool of 90 feature set and 76.5% and 66.1% using a set of 30 selected feature set on the completely independent test dataset. In order to establish the effectiveness of the systematically generated negative examples, the SVM is trained using a different set of negative data generated using the method in Yousef et al. A significantly higher false positive rate (70.6%) is observed when tested on the independent set, while all other factors are kept the

  17. Tissue specific distribution of pyrimidine deoxynucleoside salvage enzymes shed light on the mechanism of mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L; Eriksson, S

    2010-06-01

    Deficiency in thymidine kinase 2 (TK2) activity due to genetic alterations caused tissue specific mitochondrial DNA (mtDNA) depletion syndrome with symptoms resembling these of AIDS patients treated with nucleoside analogues. Mechanisms behind this mitochondrial effects is still not well understood. With rat as a model we isolated mitochondrial and cytosolic fractions from major organs and studied enzymes involved in thymidine (dT) and deoxycytidine (dC) phosphorylation by using ionic exchange column chromatography. A cytosolic form of TK2 was identified in all tested tissues in addition to mitochondrial TK2. TK1 was detected in liver and spleen cytosolic extracts while dCK was found in liver, spleen and lung cytosolic extracts. Thus, the nature of dT and dC salvage enzymes in each tissue type was determined. In most tissues TK2 is the only salvage enzyme present except liver and spleen. These results may help to explain the mechanisms of mitochondrial toxicity of antiviral nucleoside analogues and mtDNA depletion caused by TK2 deficiency.

  18. Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.

    Science.gov (United States)

    Szabo, Linda; Morey, Robert; Palpant, Nathan J; Wang, Peter L; Afari, Nastaran; Jiang, Chuan; Parast, Mana M; Murry, Charles E; Laurent, Louise C; Salzman, Julia

    2015-06-16

    The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.

  19. Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies

    Directory of Open Access Journals (Sweden)

    Joan K Ho

    2016-01-01

    Full Text Available Analysis of the tissue distribution of plasmid DNA after administration of nonviral gene delivery systems is best accomplished using quantitative real-time polymerase chain reaction (qPCR, although published strategies do not allow determination of the absolute mass of plasmid delivered to different tissues. Generally, data is expressed as the mass of plasmid relative to the mass of genomic DNA (gDNA in the sample. This strategy is adequate for comparisons of efficiency of delivery to a single site but it does not allow direct comparison of delivery to multiple tissues, as the mass of gDNA extracted per unit mass of each tissue is different. We show here that by constructing qPCR standard curves for each tissue it is possible to determine the dose of intact plasmid remaining in each tissue, which is a more useful parameter when comparing the fates of different formulations of DNA. We exemplify the use of this tissue-specific qPCR method by comparing the delivery of naked DNA, cationic DNA complexes, and neutral PEGylated DNA complexes after intramuscular injection. Generally, larger masses of intact plasmid were present 24 hours after injection of DNA complexes, and neutral complexes resulted in delivery of a larger mass of intact plasmid to the spleen.

  20. Assembled genomic and tissue-specific transcriptomic data resources for two genetically distinct lines of Cowpea ( Vigna unguiculata (L.) Walp).

    Science.gov (United States)

    Spriggs, Andrew; Henderson, Steven T; Hand, Melanie L; Johnson, Susan D; Taylor, Jennifer M; Koltunow, Anna

    2018-02-09

    Cowpea ( Vigna unguiculata (L.) Walp) is an important legume crop for food security in areas of low-input and smallholder farming throughout Africa and Asia. Genetic improvements are required to increase yield and resilience to biotic and abiotic stress and to enhance cowpea crop performance. An integrated cowpea genomic and gene expression data resource has the potential to greatly accelerate breeding and the delivery of novel genetic traits for cowpea. Extensive genomic resources for cowpea have been absent from the public domain; however, a recent early release reference genome for IT97K-499-35 ( Vigna unguiculata  v1.0, NSF, UCR, USAID, DOE-JGI, http://phytozome.jgi.doe.gov/) has now been established in a collaboration between the Joint Genome Institute (JGI) and University California (UC) Riverside. Here we release supporting genomic and transcriptomic data for IT97K-499-35 and a second transformable cowpea variety, IT86D-1010. The transcriptome resource includes six tissue-specific datasets for each variety, with particular emphasis on reproductive tissues that extend and support the V. unguiculata v1.0 reference. Annotations have been included in our resource to allow direct mapping to the v1.0 cowpea reference. Access to this resource provided here is supported by raw and assembled data downloads.

  1. Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats

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    CAROLYNE D.S. SANTOS

    Full Text Available ABSTRACT Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT, Brown Adipose Tissue (BAT, and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation. After birth, only male offspring (F1 were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA. According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.

  2. Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner.

    Science.gov (United States)

    de Jong, Simone; Chepelev, Iouri; Janson, Esther; Strengman, Eric; van den Berg, Leonard H; Veldink, Jan H; Ophoff, Roel A

    2012-09-06

    Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. Two divergent MAPT haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns across the region reflecting the inversion status at this locus. The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease and Alzheimer's disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability. In this study, we investigate the effect of the inversion on the expression of genes in the 17q21.31 region. We find the expression of several genes in and at the borders of the inversion to be affected; specific either to whole blood or different regions of the human brain. The H1 haplotype was found to be associated with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1. Studies thus far have focused on the expression of MAPT in the inversion region. However, our results show that the inversion status affects expression of other genes in the 17q21.31 region as well. Given the link between the inversion status and different neurological diseases, these genes may also be involved in disease pathology, possibly in a tissue-specific manner.

  3. Tissue-specific expression of silkmoth chorion genes in vivo using Bombyx mori nuclear polyhedrosis virus as a transducing vector.

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    Iatrou, K; Meidinger, R G

    1990-01-01

    A pair of silkmoth chorion chromosomal genes, HcA.12-HcB.12, was inserted into a baculovirus transfer vector, pBmp2, derived from the nuclear polyhedrosis virus of Bombyx mori. This vector, which permits the insertion of foreign genetic material in the vicinity of a mutationally inactivated polyhedrin gene, was used to acquire the corresponding recombinant virus. Injection of mutant silkmoth pupae that lack all Hc chorion genes with the recombinant virus resulted in the infection of all internal organs including follicular tissue. Analysis of RNA from infected tissues has demonstrated that the two chorion genes present in the viral genome are correctly transcribed under the control of their own promoter in follicular cells, the tissue in which chorion genes are normally expressed. The chorion primary transcripts are also correctly processed in the infected follicular cells and yield mature mRNAs indistinguishable from authentic chorion mRNAs present in wild-type follicles. These results demonstrate that recombinant nuclear polyhedrosis viruses can be used as transducing vectors for introducing genetic material of host origin into the cells of the organism and that the transduced genes are transiently expressed in a tissue-specific manner under the control of their resident regulatory sequences. Thus we show the in vivo expression of cloned genes under cellular promoter control in an insect other than Drosophila melanogaster. The approach should be applicable to all insect systems that are subject to nuclear polyhedrosis virus infection. Images PMID:2187186

  4. Adipocyte dysfunction in a mouse model of polycystic ovary syndrome (PCOS: evidence of adipocyte hypertrophy and tissue-specific inflammation.

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    Joseph S Marino

    Full Text Available Clinical research shows an association between polycystic ovary syndrome (PCOS and chronic inflammation, a pathological state thought to contribute to insulin resistance. The underlying pathways, however, have not been defined. The purpose of this study was to characterize the inflammatory state of a novel mouse model of PCOS. Female mice lacking leptin and insulin receptors in pro-opiomelanocortin neurons (IR/LepR(POMC mice and littermate controls were evaluated for estrous cyclicity, ovarian and adipose tissue morphology, and body composition by QMR and CT scan. Tissue-specific macrophage infiltration and cytokine mRNA expression were measured, as well as circulating cytokine levels. Finally, glucose regulation during pregnancy was evaluated as a measure of risk for diabetes development. Forty-five percent of IR/LepR(POMC mice showed reduced or absent ovulation. IR/LepR(POMC mice also had increased fat mass and adipocyte hypertrophy. These traits accompanied elevations in macrophage accumulation and inflammatory cytokine production in perigonadal adipose tissue, liver, and ovary. These mice also exhibited gestational hyperglycemia as predicted. This report is the first to show the presence of inflammation in IR/LepR(POMC mice, which develop a PCOS-like phenotype. Thus, IR/LepR(POMC mice may serve as a new mouse model to clarify the involvement of adipose and liver tissue in the pathogenesis and etiology of PCOS, allowing more targeted research on the development of PCOS and potential therapeutic interventions.

  5. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

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    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F. (Hagedorn Research Laboratory, Gentofte (Denmark))

    1988-09-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.

  6. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo

    International Nuclear Information System (INIS)

    Madsen, O.D.; Andersen, L.C.; Michelsen, B.; Owerbach, D.; Larsson, L.I.; Lernmark, A.; Steiner, D.F.

    1988-01-01

    The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissue-specific insulin gene enhancer elements are conserved between rat and human insulin genes. The authors propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression

  7. Tissue-Specific Control of the Endocycle by the Anaphase Promoting Complex/Cyclosome Inhibitors UVI4 and DEL1.

    Science.gov (United States)

    Heyman, Jefri; Polyn, Stefanie; Eekhout, Thomas; De Veylder, Lieven

    2017-09-01

    The endocycle represents a modified mitotic cell cycle that in plants is often coupled to cell enlargement and differentiation. Endocycle onset is controlled by activity of the Anaphase Promoting Complex/Cyclosome (APC/C), a multisubunit E3 ubiquitin ligase targeting cell-cycle factors for destruction. CELL CYCLE SWITCH52 (CCS52) proteins represent rate-limiting activator subunits of the APC/C. In Arabidopsis ( Arabidopsis thaliana ), mutations in either CCS52A1 or CCS52A2 activators result in a delayed endocycle onset, whereas their overexpression triggers increased DNA ploidy levels. Here, the relative contribution of the APC/C CCS52A1 and APC/C CCS52A2 complexes to different developmental processes was studied through analysis of their negative regulators, being the ULTRAVIOLET-B-INSENSITIVE4 protein and the DP-E2F-Like1 transcriptional repressor, respectively. Our data illustrate cooperative activity of the APC/C CCS52A1 and APC/C CCS52A2 complexes during root and trichome development, but functional interdependency during leaf development. Furthermore, we found APC/C CCS52A1 activity to control CCS52A2 expression. We conclude that interdependency of CCS52A-controlled APC/C activity is controlled in a tissue-specific manner. © 2017 American Society of Plant Biologists. All Rights Reserved.

  8. Blood as a surrogate marker for tissue-specific DNA methylation and changes due to folate depletion in post-partum female mice.

    Science.gov (United States)

    McKay, Jill A; Xie, Long; Harris, Sarah; Wong, Yi K; Ford, Dianne; Mathers, John C

    2011-07-01

    DNA methylation patterns are tissue specific and may influence tissue-specific gene regulation. Human studies investigating DNA methylation in relation to environmental factors primarily use blood-derived DNA as a surrogate for DNA from target tissues. It is therefore important to know if DNA methylation changes in blood in response to environmental changes reflect those in target tissues. Folate intake can influence DNA methylation, via altered methyl donor supply. Previously, manipulations of maternal folate intake during pregnancy altered the patterns of DNA methylation in offspring but, to our knowledge, the consequences for maternal DNA methylation are unknown. Given the increased requirement for folate during pregnancy, mothers may be susceptible to aberrant DNA methylation due to folate depletion. Female mice were fed folate-adequate (2 mg folic acid/kg diet) or folate-deplete (0.4 mg folic acid/kg diet) diets prior to mating and during pregnancy and lactation. Following weaning, dams were killed and DNA methylation was assessed by pyrosequencing® in blood, liver, and kidney at the Esr1, Igf2 differentially methylated region (DMR)1, Igf2 DMR2, Slc39a4CGI1, and Slc39a4CGI2 loci. We observed tissue-specific differences in methylation at all loci. Folate depletion reduced Igf2 DMR1 and Slc39a4CGI1 methylation across all tissues and altered Igf2 DMR2 methylation in a tissue-specific manner (pmethylation measurements may not always reflect methylation within other tissues. Further measurements of blood-derived and tissue-specific methylation patterns are warranted to understand the complexity of tissue-specific responses to altered nutritional exposure. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Dissecting Tissue-Specific Transcriptomic Responses from Leaf and Roots under Salt Stress in Petunia hybrida Mitchell

    Science.gov (United States)

    Villarino, Gonzalo H.; Hu, Qiwen; Scanlon, Michael J.; Mueller, Lukas; Mattson, Neil S.

    2017-01-01

    One of the primary objectives of plant biotechnology is to increase resistance to abiotic stresses, such as salinity. Salinity is a major abiotic stress and increasing crop resistant to salt continues to the present day as a major challenge. Salt stress disturbs cellular environment leading to protein misfolding, affecting normal plant growth and causing agricultural losses worldwide. The advent of state-of-the-art technologies such as high throughput mRNA sequencing (RNA-seq) has revolutionized whole-transcriptome analysis by allowing, with high precision, to measure changes in gene expression. In this work, we used tissue-specific RNA-seq to gain insight into the Petunia hybrida transcriptional responses under NaCl stress using a controlled hydroponic system. Roots and leaves samples were taken from a continuum of 48 h of acute 150 mM NaCl. This analysis revealed a set of tissue and time point specific differentially expressed genes, such as genes related to transport, signal transduction, ion homeostasis as well as novel and undescribed genes, such as Peaxi162Scf00003g04130 and Peaxi162Scf00589g00323 expressed only in roots under salt stress. In this work, we identified early and late expressed genes in response to salt stress while providing a core of differentially express genes across all time points and tissues, including the trehalose-6-phosphate synthase 1 (TPS1), a glycosyltransferase reported in salt tolerance in other species. To test the function of the novel petunia TPS1 allele, we cloned and showed that TPS1 is a functional plant gene capable of complementing the trehalose biosynthesis pathway in a yeast tps1 mutant. The list of candidate genes to enhance salt tolerance provided in this work constitutes a major effort to better understand the detrimental effects of salinity in petunia with direct implications for other economically important Solanaceous species. PMID:28771200

  10. Dynamic Metabolic Profiles and Tissue-Specific Source Effects on the Metabolome of Developing Seeds of Brassica napus.

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    Helin Tan

    Full Text Available Canola (Brassica napus is one of several important oil-producing crops, and the physiological processes, enzymes, and genes involved in oil synthesis in canola seeds have been well characterized. However, relatively little is known about the dynamic metabolic changes that occur during oil accumulation in seeds, as well as the mechanistic origins of metabolic changes. To explore the metabolic changes that occur during oil accumulation, we isolated metabolites from both seed and silique wall and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS. The results showed that a total of 443 metabolites were identified from four developmental stages. Dozens of these metabolites were differentially expressed during seed ripening, including 20 known to be involved in seed development. To investigate the contribution of tissue-specific carbon sources to the biosynthesis of these metabolites, we examined the metabolic changes of silique walls and seeds under three treatments: leaf-detachment (Ld, phloem-peeling (Pe, and selective silique darkening (Sd. Our study demonstrated that the oil content was independent of leaf photosynthesis and phloem transport during oil accumulation, but required the metabolic influx from the silique wall. Notably, Sd treatment resulted in seed senescence, which eventually led to a severe reduction of the oil content. Sd treatment also caused a significant accumulation of fatty acids (FA, organic acids and amino acids. Furthermore, an unexpected accumulation of sugar derivatives and organic acid was observed in the Pe- and Sd-treated seeds. Consistent with this, the expression of a subset of genes involved in FA metabolism, sugar and oil storage was significantly altered in Pe and Sd treated seeds. Taken together, our studies suggest the metabolite profiles of canola seeds dynamically varied during the course of oil accumulation, which may provide a new insight into the mechanisms

  11. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice.

    Science.gov (United States)

    Liu, Yawei; Teige, Anna; Mondoc, Emma; Ibrahim, Saleh; Holmdahl, Rikard; Issazadeh-Navikas, Shohreh

    2011-01-01

    NKT cells in the mouse recognize antigen in the context of the MHC class I-like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707-721), was not associated with either MHC class I or II. Activation of CD1d-restricted mCII707-721-specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707-721-specific NKT cells induced T cell death through Fas/FasL, in an IL-17A-independent fashion. Moreover, mCII707-721-specific NKT cells suppressed a range of in vivo inflammatory conditions, including delayed-type hypersensitivity, antigen-induced airway inflammation, collagen-induced arthritis, and EAE, which were all ameliorated by mCII707-721 vaccination. The findings presented here offer new insight into the intrinsic roles of NKT cells in health and disease. Given the results, endogenous collagen peptide activators of NKT cells may offer promise as novel therapeutics in tissue-specific autoimmune and inflammatory diseases.

  12. Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

    Science.gov (United States)

    Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

    2015-09-01

    Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

  13. Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

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    Therése Andersson

    Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

  14. Combinatorial binding leads to diverse regulatory responses: Lmd is a tissue-specific modulator of Mef2 activity.

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    Paulo M F Cunha

    2010-07-01

    Full Text Available Understanding how complex patterns of temporal and spatial expression are regulated is central to deciphering genetic programs that drive development. Gene expression is initiated through the action of transcription factors and their cofactors converging on enhancer elements leading to a defined activity. Specific constellations of combinatorial occupancy are therefore often conceptualized as rigid binding codes that give rise to a common output of spatio-temporal expression. Here, we assessed this assumption using the regulatory input of two essential transcription factors within the Drosophila myogenic network. Mutations in either Myocyte enhancing factor 2 (Mef2 or the zinc-finger transcription factor lame duck (lmd lead to very similar defects in myoblast fusion, yet the underlying molecular mechanism for this shared phenotype is not understood. Using a combination of ChIP-on-chip analysis and expression profiling of loss-of-function mutants, we obtained a global view of the regulatory input of both factors during development. The majority of Lmd-bound enhancers are co-bound by Mef2, representing a subset of Mef2's transcriptional input during these stages of development. Systematic analyses of the regulatory contribution of both factors demonstrate diverse regulatory roles, despite their co-occupancy of shared enhancer elements. These results indicate that Lmd is a tissue-specific modulator of Mef2 activity, acting as both a transcriptional activator and repressor, which has important implications for myogenesis. More generally, this study demonstrates considerable flexibility in the regulatory output of two factors, leading to additive, cooperative, and repressive modes of co-regulation.

  15. Tissue-Specific Reduction in Splicing Efficiency of IKBKAP Due to the Major Mutation Associated with Familial Dysautonomia

    Science.gov (United States)

    Cuajungco, Math P.; Leyne, Maire; Mull, James; Gill, Sandra P.; Lu, Weining; Zagzag, David; Axelrod, Felicia B.; Maayan, Channa; Gusella, James F.; Slaugenhaupt, Susan A.

    2003-01-01

    We recently identified a mutation in the I-κB kinase associated protein (IKBKAP) gene as the major cause of familial dysautonomia (FD), a recessive sensory and autonomic neuropathy. This alteration, located at base pair 6 of the intron 20 donor splice site, is present on >99.5% of FD chromosomes and results in tissue-specific skipping of exon 20. A second FD mutation, a missense change in exon 19 (R696P), was seen in only four patients heterozygous for the major mutation. Here, we have further characterized the consequences of the major mutation by examining the ratio of wild-type to mutant (WT:MU) IKBKAP transcript in EBV-transformed lymphoblast lines, primary fibroblasts, freshly collected blood samples, and postmortem tissues from patients with FD. We consistently found that WT IKBKAP transcripts were present, albeit to varying extents, in all cell lines, blood, and postmortem FD tissues. Further, a corresponding decrease in the level of WT protein is seen in FD cell lines and tissues. The WT:MU ratio in cultured lymphoblasts varied with growth phase but not with serum concentration or inclusion of antibiotics. Using both densitometry and real-time quantitative polymerase chain reaction, we found that relative WT:MU IKBKAP RNA levels were highest in cultured patient lymphoblasts and lowest in postmortem central and peripheral nervous tissues. These observations suggest that the relative inefficiency of WT IKBKAP mRNA production from the mutant alleles in the nervous system underlies the selective degeneration of sensory and autonomic neurons in FD.Therefore, exploration of methods to increase the WT:MU IKBKAP transcript ratio in the nervous system offers a promising approach for developing an effective therapy for patients with FD. PMID:12577200

  16. Assessment of tissue-specific accumulation and effects of cadmium in a marine fish fed contaminated commercially produced diet

    International Nuclear Information System (INIS)

    Dang Fei; Wang Wenxiong

    2009-01-01

    Commercially produced fish diet is now widely used in fish farming but it often contains elevated levels of cadmium (Cd). However, the adverse effects on fish are poorly understood. In this study, farm-raised marine grunts, Terapon jarbua, were fed Cd-contaminated diet or exposed to waterborne Cd for 4 weeks. Tissue-specific Cd bioaccumulation and its effects were subsequently examined. We found that Cd was accumulated in different fish tissues (digestive tracts, gills or livers). At the end of the exposure, Cd accumulation peaked in the fishes' livers (5.0-6.3 μg g -1 ), followed by the digestive tracts (0.83-3.16 μg g -1 ) and gills (0.27-2.74 μg g -1 ). Endpoints such as the survival rate, specific growth rate, condition factor, and superoxide dismutase activity were not significantly affected by Cd exposure. In contrast, metallothionein (MT) induction and subcellular Cd distribution indicated that there were possible sublethal effects of Cd exposure. MT was induced in response to Cd accumulation, but it returned to the control levels after a longer exposure period, except for hepatic MT induction resulting from waterborne or low dietary Cd exposure. The Cd percentage in the metallothionein-like protein (MTLP) fraction increased over exposure time, and it accounted for more than 57% Cd in the fishes' livers and 80% Cd in their digestive tracts by the end of the exposure period. Overall, although Cd in commercial fish diet did not have significant lethality to T. jarbua, sensitive responses such as hepatic MT induction and subcellular Cd distribution revealed that the Cd-induced storage and detoxification in T. jarbua may increase fish's tolerance to toxic metals.

  17. Sex- and Tissue-Specific Expression Profiles of Odorant Binding Protein and Chemosensory Protein Genes in Bradysia odoriphaga (Diptera: Sciaridae

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    Yunhe Zhao

    2018-04-01

    Full Text Available Bradysia odoriphaga is an agricultural pest insect affecting the production of Chinese chive and other liliaceous vegetables in China, and it is significantly attracted by sex pheromones and the volatiles derived from host plants. Despite verification of this chemosensory behavior, however, it is still unknown how B. odoriphaga recognizes these volatile compounds on the molecular level. Many of odorant binding proteins (OBPs and chemosensory proteins (CSPs play crucial roles in olfactory perception. Here, we identified 49 OBP and 5 CSP genes from the antennae and body transcriptomes of female and male adults of B. odoriphaga, respectively. Sequence alignment and phylogenetic analysis among Dipteran OBPs and CSPs were analyzed. The sex- and tissue-specific expression profiles of 54 putative chemosensory genes among different tissues were investigated by quantitative real-time PCR (qRT-PCR. qRT-PCR analysis results suggested that 22 OBP and 3 CSP genes were enriched in the antennae, indicating they might be essential for detection of general odorants and pheromones. Among these antennae-enriched genes, nine OBPs (BodoOBP2/4/6/8/12/13/20/28/33 were enriched in the male antennae and may play crucial roles in the detection of sex pheromones. Moreover, some OBP and CSP genes were enriched in non-antennae tissues, such as in the legs (BodoOBP3/9/19/21/34/35/38/39/45 and BodoCSP1, wings (BodoOBP17/30/32/37/44, abdomens and thoraxes (BodoOBP29/36, and heads (BodoOBP14/23/31 and BodoCSP2, suggesting that these genes might be involved in olfactory, gustatory, or other physiological processes. Our findings provide a starting point to facilitate functional research of these chemosensory genes in B. odoriphaga at the molecular level.

  18. Tissue-specific transcript profiling for ABC transporters in the sequestering larvae of the phytophagous leaf beetle Chrysomela populi.

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    Anja S Strauss

    Full Text Available Insects evolved ingenious adaptations to use extraordinary food sources. Particularly, the diet of herbivores enriched with noxious plant secondary metabolites requires detoxification mechanisms. Sequestration, which involves the uptake, transfer, and concentration of occasionally modified phytochemicals into specialized tissues or hemolymph, is one of the most successful detoxification strategies found in most insect orders. Due to the ability of ATP-binding cassette (ABC carriers to transport a wide range of molecules including phytochemicals and xenobiotics, it is highly likely that they play a role in this sequestration process. To shed light on the role of ABC proteins in sequestration, we describe an inventory of putative ABC transporters in various tissues in the sequestering juvenile poplar leaf beetle, Chrysomela populi.In the transcriptome of C. populi, we predicted 65 ABC transporters. To link the proteins with a possible function, we performed comparative phylogenetic analyses with ABC transporters of other insects and of humans. While tissue-specific profiling of each ABC transporter subfamily suggests that ABCB, C and G influence the plant metabolite absorption in the gut, ABCC with 14 members is the preferred subfamily responsible for the excretion of these metabolites via Malpighian tubules. Moreover, salicin, which is sequestered from poplar plants, is translocated into the defensive glands for further deterrent production. In these glands and among all identified ABC transporters, an exceptionally high transcript level was observed only for Cpabc35 (Cpmrp. RNAi revealed the deficiency of other ABC pumps to compensate the function of CpABC35, demonstrating its key role during sequestration.We provide the first comprehensive phylogenetic study of the ABC family in a phytophagous beetle species. RNA-seq data from different larval tissues propose the importance of ABC pumps to achieve a homeostasis of plant-derived compounds and

  19. Dissecting Tissue-Specific Transcriptomic Responses from Leaf and Roots under Salt Stress in Petunia hybrida Mitchell

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    Gonzalo H. Villarino

    2017-08-01

    Full Text Available One of the primary objectives of plant biotechnology is to increase resistance to abiotic stresses, such as salinity. Salinity is a major abiotic stress and increasing crop resistant to salt continues to the present day as a major challenge. Salt stress disturbs cellular environment leading to protein misfolding, affecting normal plant growth and causing agricultural losses worldwide. The advent of state-of-the-art technologies such as high throughput mRNA sequencing (RNA-seq has revolutionized whole-transcriptome analysis by allowing, with high precision, to measure changes in gene expression. In this work, we used tissue-specific RNA-seq to gain insight into the Petunia hybrida transcriptional responses under NaCl stress using a controlled hydroponic system. Roots and leaves samples were taken from a continuum of 48 h of acute 150 mM NaCl. This analysis revealed a set of tissue and time point specific differentially expressed genes, such as genes related to transport, signal transduction, ion homeostasis as well as novel and undescribed genes, such as Peaxi162Scf00003g04130 and Peaxi162Scf00589g00323 expressed only in roots under salt stress. In this work, we identified early and late expressed genes in response to salt stress while providing a core of differentially express genes across all time points and tissues, including the trehalose-6-phosphate synthase 1 (TPS1, a glycosyltransferase reported in salt tolerance in other species. To test the function of the novel petunia TPS1 allele, we cloned and showed that TPS1 is a functional plant gene capable of complementing the trehalose biosynthesis pathway in a yeast tps1 mutant. The list of candidate genes to enhance salt tolerance provided in this work constitutes a major effort to better understand the detrimental effects of salinity in petunia with direct implications for other economically important Solanaceous species.

  20. Tissue-specific regulation of CXCL9/10/11 chemokines in keratinocytes: Implications for oral inflammatory disease.

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    Alison Marshall

    Full Text Available The IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 play a key role in many inflammatory conditions, particularly those mediated by T cells. Therefore, the production of these chemokines in peripheral tissues could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus (OLP. In the present study, we assessed the production of keratinocyte-derived CXCL9/10/11 under basal and inflammatory conditions and investigated whether these chemokines were involved in the pathogenesis of OLP. We used semi-quantitative PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting (FACS to assess the expression and functional role of CXCL9/10/11 in oral keratinocytes (three strains of normal human oral keratinocytes (NHOK, and the H357 oral cancer cell line in the presence or absence of IFN-γ. CXCL9/10/11 were also assessed in tissues from normal patients and those with oral lichen planus (OLP. The time course study in oral keratinocytes treated with IFN-γ showed that expression of CXCL9/10/11 chemokines was significantly enhanced by IFN-γ in a time-dependent manner. In particular, CXCL10, a prominent chemokine that was overexpressed by IFN-γ-stimulated NHOK, was able to effectively recruit CD4 lymphocytes, mainly CD4+CD45RA- cells. Significantly higher levels of CXCL9/10/11 were found in tissues from patients with OLP compared to normal oral mucosa. Taken together, the results demonstrate that normal oral keratinocytes produce chemotactic molecules that mediate T cell recruitment. This study furthers understanding of chemokine production in oral keratinocytes and their role in the pathophysiology of oral mucosa, with particular relevance to OLP.

  1. Modulation of differentiation and self-renewal of tissue specific stem cells for effective mitigation of radiation injury

    International Nuclear Information System (INIS)

    Bandekar, Mayuri; Patwardhan, R.S.; Maurya, Dharmendra K.; Bhilwade, Hari N.; Sharma, Deepak; Sandur, Santosh Kumar

    2017-01-01

    The use of stem cells in regenerative medicine for the treatment of various human diseases is one of the active research areas. The aim of regenerative medicine is to restore normal tissue functions by replenishing injured tissues using either cell-based therapy or by inducing certain factors that can aid endogenous repair and regeneration. The approach for inducing endogenous repair and regeneration requires in vivo modulation of tissue-specific stem cells by therapeutic agents and enhance their abundance through activation, proliferation, differentiation, or reprogramming. Here we describe three different approaches to enhance the abundance of hematopoietic stem cells in vivo for mitigation of radiation induced toxicity. Baicalein, a flavonoid derived from Chinese and Indian medicinal plants like Scutellaria baicalensis and Terminalia ariuna enhanced the abundance of hematopoietic stem cells through activation of Nrf-2 in the lineage negative cells. Another anti-oxidant, chlorophyllin derived from green plant pigment, chlorophyll also enhanced the abundance of hematopoietic stem cells through modulation of cell cycle in cells of the bone marrow. Treatment of mice with Cobaltus chloride (CoCl_2), a well-known activator of hypoxia inducible factor-1α (HIP-1α), also led to increase in the number of hematopoietic stem cells in the bone marrow. Whereas chlorophyllin offered up to 100 % protection against whole body irradiation (WBI, 8 Gy) induced mortality in mice, baicalein offered up to70%protection. Cobaltus chloride treatment offered 40% protection against 8 Gy of WBI. These studies indicate potential use of stem cell modulating agents as effective mitigators of radiation induced toxicity in vivo. (author)

  2. Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

    Science.gov (United States)

    Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

    2009-03-11

    Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene

  3. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

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    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  4. Multiple POU-binding motifs, recognized by tissue-specific nuclear factors, are important for Dll1 gene expression in neural stem cells

    International Nuclear Information System (INIS)

    Nakayama, Kohzo; Nagase, Kazuko; Tokutake, Yuriko; Koh, Chang-Sung; Hiratochi, Masahiro; Ohkawara, Takeshi; Nakayama, Noriko

    2004-01-01

    We cloned the 5'-flanking region of the mouse homolog of the Delta gene (Dll1) and demonstrated that the sequence between nucleotide position -514 and -484 in the 5'-flanking region of Dll1 played a critical role in the regulation of its tissue-specific expression in neural stem cells (NSCs). Further, we showed that multiple POU-binding motifs, located within this short sequence of 30 bp, were essential for transcriptional activation of Dll1 and also that multiple tissue-specific nuclear factors recognized these POU-binding motifs in various combinations through differentiation of NSCs. Thus, POU-binding factors may play an important role in Dll1 expression in developing NSCs

  5. Tissue-Specific Upregulation of MDS/EVI Gene Transcripts in the Intestine by Thyroid Hormone during Xenopus Metamorphosis

    Science.gov (United States)

    Hasebe, Takashi; Fu, Liezhen; Heimeier, Rachel A.; Das, Biswajit; Ishizuya-Oka, Atsuko; Shi, Yun-Bo

    2013-01-01

    Background Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells. Methodology/Principal Findings The T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium. Conclusions/Significance Our results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells. PMID:23383234

  6. CXCR6, a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal, identifies more aggressive human melanoma cancer stem cells.

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    Rouzbeh Taghizadeh

    2010-12-01

    Full Text Available A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+.We defined CXCR6 as a new biomarker for tissue-specific stem cell asymmetric self-renewal. Thus, the relationship between melanoma formation and ABCG2 and CXCR6 expression was investigated. Consistent with their non-metastatic character, unsorted IGR39 cells formed significantly smaller tumors than unsorted IGR37 cells. In addition, ABCG2+ cells produced tumors that had a 2-fold greater mass than tumors produced by unsorted cells or ABCG2- cells. CXCR6+ cells produced more aggressive tumors. CXCR6 identifies a more discrete subpopulation of cultured human melanoma cells with a more aggressive MCSC phenotype than cells selected on the basis of the ABCG2+ phenotype alone.The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

  7. hSAGEing: an improved SAGE-based software for identification of human tissue-specific or common tumor markers and suppressors.

    Science.gov (United States)

    Yang, Cheng-Hong; Chuang, Li-Yeh; Shih, Tsung-Mu; Chang, Hsueh-Wei

    2010-12-17

    SAGE (serial analysis of gene expression) is a powerful method of analyzing gene expression for the entire transcriptome. There are currently many well-developed SAGE tools. However, the cross-comparison of different tissues is seldom addressed, thus limiting the identification of common- and tissue-specific tumor markers. To improve the SAGE mining methods, we propose a novel function for cross-tissue comparison of SAGE data by combining the mathematical set theory and logic with a unique "multi-pool method" that analyzes multiple pools of pair-wise case controls individually. When all the settings are in "inclusion", the common SAGE tag sequences are mined. When one tissue type is in "inclusion" and the other types of tissues are not in "inclusion", the selected tissue-specific SAGE tag sequences are generated. They are displayed in tags-per-million (TPM) and fold values, as well as visually displayed in four kinds of scales in a color gradient pattern. In the fold visualization display, the top scores of the SAGE tag sequences are provided, along with cluster plots. A user-defined matrix file is designed for cross-tissue comparison by selecting libraries from publically available databases or user-defined libraries. The hSAGEing tool provides a combination of friendly cross-tissue analysis and an interface for comparing SAGE libraries for the first time. Some up- or down-regulated genes with tissue-specific or common tumor markers and suppressors are identified computationally. The tool is useful and convenient for in silico cancer transcriptomic studies and is freely available at http://bio.kuas.edu.tw/hSAGEing.

  8. hSAGEing: an improved SAGE-based software for identification of human tissue-specific or common tumor markers and suppressors.

    Directory of Open Access Journals (Sweden)

    Cheng-Hong Yang

    Full Text Available BACKGROUND: SAGE (serial analysis of gene expression is a powerful method of analyzing gene expression for the entire transcriptome. There are currently many well-developed SAGE tools. However, the cross-comparison of different tissues is seldom addressed, thus limiting the identification of common- and tissue-specific tumor markers. METHODOLOGY/PRINCIPAL FINDINGS: To improve the SAGE mining methods, we propose a novel function for cross-tissue comparison of SAGE data by combining the mathematical set theory and logic with a unique "multi-pool method" that analyzes multiple pools of pair-wise case controls individually. When all the settings are in "inclusion", the common SAGE tag sequences are mined. When one tissue type is in "inclusion" and the other types of tissues are not in "inclusion", the selected tissue-specific SAGE tag sequences are generated. They are displayed in tags-per-million (TPM and fold values, as well as visually displayed in four kinds of scales in a color gradient pattern. In the fold visualization display, the top scores of the SAGE tag sequences are provided, along with cluster plots. A user-defined matrix file is designed for cross-tissue comparison by selecting libraries from publically available databases or user-defined libraries. CONCLUSIONS/SIGNIFICANCE: The hSAGEing tool provides a combination of friendly cross-tissue analysis and an interface for comparing SAGE libraries for the first time. Some up- or down-regulated genes with tissue-specific or common tumor markers and suppressors are identified computationally. The tool is useful and convenient for in silico cancer transcriptomic studies and is freely available at http://bio.kuas.edu.tw/hSAGEing.

  9. Simultaneous inference of phenotype-associated genes and relevant tissues from GWAS data via Bayesian integration of multiple tissue-specific gene networks.

    Science.gov (United States)

    Wu, Mengmeng; Lin, Zhixiang; Ma, Shining; Chen, Ting; Jiang, Rui; Wong, Wing Hung

    2017-12-01

    Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the advanced analysis of the vast volume of existing and anticipated genetic data. Towards this goal, gene-level integrative GWAS analysis with the assumption that genes associated with a phenotype tend to be enriched in biological gene sets or gene networks has recently attracted much attention, due to such advantages as straightforward interpretation, less multiple testing burdens, and robustness across studies. However, existing methods in this category usually exploit non-tissue-specific gene networks and thus lack the ability to utilize informative tissue-specific characteristics. To overcome this limitation, we proposed a Bayesian approach called SIGNET (Simultaneously Inference of GeNEs and Tissues) to integrate GWAS data and multiple tissue-specific gene networks for the simultaneous inference of phenotype-associated genes and relevant tissues. Through extensive simulation studies, we showed the effectiveness of our method in finding both associated genes and relevant tissues for a phenotype. In applications to real GWAS data of 14 complex phenotypes, we demonstrated the power of our method in both deciphering genetic basis and discovering biological insights of a phenotype. With this understanding, we expect to see SIGNET as a valuable tool for integrative GWAS analysis, thereby boosting the prevention, diagnosis, and treatment of human inherited diseases and eventually facilitating precision medicine.

  10. Green tissue-specific co-expression of chitinase and oxalate oxidase 4 genes in rice for enhanced resistance against sheath blight.

    Science.gov (United States)

    Karmakar, Subhasis; Molla, Kutubuddin Ali; Chanda, Palas K; Sarkar, Sailendra Nath; Datta, Swapan K; Datta, Karabi

    2016-01-01

    Green tissue-specific simultaneous overexpression of two defense-related genes ( OsCHI11 & OsOXO4 ) in rice leads to significant resistance against sheath blight pathogen ( R. solani ) without distressing any agronomically important traits. Overexpressing two defense-related genes (OsOXO4 and OsCHI11) cloned from rice is effective at enhancing resistance against sheath blight caused by Rhizoctonia solani. These genes were expressed under the control of two different green tissue-specific promoters, viz. maize phosphoenolpyruvate carboxylase gene promoter, PEPC, and rice cis-acting 544-bp DNA element, immediately upstream of the D54O translational start site, P D54O-544 . Putative T0 transgenic rice plants were screened by PCR and integration of genes was confirmed by Southern hybridization of progeny (T1) rice plants. Successful expression of OsOXO4 and OsCHI11 in all tested plants was confirmed. Expression of PR genes increased significantly following pathogen infection in overexpressing transgenic plants. Following infection, transgenic plants exhibited elevated hydrogen peroxide levels, significant changes in activity of ROS scavenging enzymes and reduced membrane damage when compared to their wild-type counterpart. In a Rhizoctonia solani toxin assay, a detached leaf inoculation test and an in vivo plant bioassay, transgenic plants showed a significant reduction in disease symptoms in comparison to non-transgenic control plants. This is the first report of overexpression of two different PR genes driven by two green tissue-specific promoters providing enhanced sheath blight resistance in transgenic rice.

  11. Supplementary Material for: Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

    2015-01-01

    Abstract Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis

  12. Tissue-specific signatures in the transcriptional response to Anaplasma phagocytophilum infection of Ixodes scapularis and Ixodes ricinus tick cell lines

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    Pilar eAlberdi

    2016-02-01

    Full Text Available Anaplasma phagocytophilum are transmitted by Ixodes spp. ticks and have become one of the most common and relevant tick-borne pathogens due to their impact on human and animal health. Recent results have increased our understanding of the molecular interactions between Ixodes scapularis and A. phagocytophilum through the demonstration of tissue-specific molecular pathways that ensure pathogen infection, development and transmission by ticks. However, little is known about the Ixodes ricinus genes and proteins involved in the response to A. phagocytophilum infection. The tick species I. scapularis and I. ricinus are evolutionarily closely related and therefore similar responses are expected in A. phagocytophilum-infected cells. However, differences may exist between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cells associated with tissue-specific signatures of these cell lines. To address this hypothesis, the transcriptional response to A. phagocytophilum infection was characterized by RNA sequencing and compared between I. scapularis ISE6 and I. ricinus IRE/CTVM20 tick cell lines. The transcriptional response to infection of I. scapularis ISE6 cells resembled that of tick hemocytes while the response in I. ricinus IRE/CTVM20 cells was more closely related to that reported previously in infected tick midguts. The inhibition of cell apoptosis by A. phagocytophilum appears to be a key adaptation mechanism to facilitate infection of both vertebrate and tick cells and was used to investigate further the tissue-specific response of tick cell lines to pathogen infection. The results supported a role for the intrinsic pathway in the inhibition of cell apoptosis by A. phagocytophilum infection of I. scapularis ISE6 cells. In contrast, the results in I. ricinus IRE/CTVM20 cells were similar to those obtained in tick midguts and suggested a role for the JAK/STAT pathway in the inhibition of apoptosis in tick cells infected with A. phagocytophilum

  13. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

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    Bryan C. Au

    2016-02-01

    Full Text Available Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag-specific responses through direct injections of recombinant lentivectors (LVs that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.

  14. Small RNA analysis in Petunia hybrida identifies unusual tissue-specific expression patterns of conserved miRNAs and of a 24mer RNA

    Science.gov (United States)

    Tedder, Philip; Zubko, Elena; Westhead, David R.; Meyer, Peter

    2009-01-01

    Two pools of small RNAs were cloned from inflorescences of Petunia hybrida using a 5′-ligation dependent and a 5′-ligation independent approach. The two libraries were integrated into a public website that allows the screening of individual sequences against 359,769 unique clones. The library contains 15 clones with 100% identity and 53 clones with one mismatch to miRNAs described for other plant species. For two conserved miRNAs, miR159 and miR390, we find clear differences in tissue-specific distribution, compared with other species. This shows that evolutionary conservation of miRNA sequences does not necessarily include a conservation of the miRNA expression profile. Almost 60% of all clones in the database are 24-nucleotide clones. In accordance with the role of 24mers in marking repetitive regions, we find them distributed across retroviral and transposable element sequences but other 24mers map to promoter regions and to different transcript regions. For one target region we observe tissue-specific variation of matching 24mers, which demonstrates that, as for 21mers, 24mer concentrations are not necessarily identical in different tissues. Asymmetric distribution of a putative novel miRNA in the two libraries suggests that the cloning method can be selective for the representation of certain small RNAs in a collection. PMID:19369427

  15. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

    Science.gov (United States)

    Au, Bryan C; Lee, Chyan-Jang; Lopez-Perez, Orlay; Foltz, Warren; Felizardo, Tania C; Wang, James C M; Huang, Ju; Fan, Xin; Madden, Melissa; Goldstein, Alyssa; Jaffray, David A; Moloo, Badru; McCart, J Andrea; Medin, Jeffrey A

    2016-02-19

    Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months-the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an "off-the-shelf" anti-cancer vaccine that could be made at large scale and injected into patients-even on an out-patient basis.

  16. Tissue-Specific Floral Transcriptome Analysis of the Sexually Deceptive Orchid Chiloglottis trapeziformis Provides Insights into the Biosynthesis and Regulation of Its Unique UV-B Dependent Floral Volatile, Chiloglottone 1

    Directory of Open Access Journals (Sweden)

    Darren C. J. Wong

    2017-07-01

    pathways (e.g., AP2/ERF given a strong co-regulation with FA biosynthesis/β-oxidation genes. Possible alternative biosynthetic routes for precursors (e.g., aldehyde dehydrogenases were also indicated. Our comprehensive study constitutes the first step toward understanding the biosynthetic pathways involved in chiloglottone 1 production in Chiloglottis trapeziformis – supporting the roles of FA metabolism in planta, gene duplication as a potential source of new genes, and co-regulation of novel pathway genes in a tissue-specific manner. This study also provides a new and valuable resource for future discovery and comparative studies in plant specialized metabolism of other orchids and non-model plants.

  17. A four step model for the IL-6 amplifier, a regulator of chromic inflammations in tissue specific MHC class II-associated autoimmune diseases

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    Masaaki eMurakami

    2011-06-01

    Full Text Available It is thought autoimmune diseases are caused by the breakdown of self-tolerance, which suggests the recognition of specific antigens by autoreactive CD4+ T cells contribute to the specificity of autoimmune diseases. In several cases, however, even for diseases associated with class II MHC alleles, the causative tissue-specific antigens recognized by memory/activated CD4+ T cells have not been established. Rheumatoid arthritis (RA and arthritis in F759 knock-in mouse line (F759 mice are such examples, even though evidences support a pathogenic role for CD4+ T cells in both diseases. We have recently shown local events such as microbleeding together with an accumulation of activated CD4+ T cells in a manner independent of tissue antigen-recognitions induces arthritis in the joints of F759 mice. For example, local microbleeding-mediated CCL20 expression induced such an accumulation, causing arthritis development via chronic activation of an IL-17A-dependent IL-6 signaling amplification loop in type 1 collagen+ cells that is triggered by CD4+ T cell-derived cytokine(s such as IL-17A, which leads to the synergistic activation of STAT3 and NFκB in non hematopoietic cells in the joint. We named this loop the IL-6-mediated inflammation amplifier, or IL-6 amplifier. Thus, certain class II MHC–associated, tissue-specific autoimmune diseases may be induced by local events that cause an antigen-independent accumulation of effector CD4+ T cells followed by the induction of the IL-6 amplifier in the affected tissue. To explain this hypothesis, we have proposed a Four Step Model for MHC class II associated autoimmune diseases. The interaction of four local events results in chronic activation of the IL-6 amplifier, leading to the manifestation of autoimmune diseases. Thus, we have concluded the IL-6 amplifier is a critical regulator of chromic inflammations in tissue specific MHC class II-associated autoimmune diseases.

  18. Development of transgenic rats producing human β-amyloid precursor protein as a model for Alzheimer's disease: Transgene and endogenous APP genes are regulated tissue-specifically

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    Chan Anthony WS

    2008-02-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a devastating neurodegenerative disorder that affects a large and growing number of elderly individuals. In addition to idiopathic disease, AD is also associated with autosomal dominant inheritance, which causes a familial form of AD (FAD. Some instances of FAD have been linked to mutations in the β-amyloid protein precursor (APP. Although there are numerous mouse AD models available, few rat AD models, which have several advantages over mice, have been generated. Results Fischer 344 rats expressing human APP driven by the ubiquitin-C promoter were generated via lentiviral vector infection of Fischer 344 zygotes. We generated two separate APP-transgenic rat lines, APP21 and APP31. Serum levels of human amyloid-beta (Aβ40 were 298 pg/ml for hemizygous and 486 pg/ml for homozygous APP21 animals. Serum Aβ42 levels in APP21 homozygous rats were 135 pg/ml. Immunohistochemistry in brain showed that the human APP transgene was expressed in neurons, but not in glial cells. These findings were consistent with independent examination of enhanced green fluorescent protein (eGFP in the brains of eGFP-transgenic rats. APP21 and APP31 rats expressed 7.5- and 3-times more APP mRNA, respectively, than did wild-type rats. Northern blots showed that the human APP transgene, driven by the ubiquitin-C promoter, is expressed significantly more in brain, kidney and lung compared to heart and liver. A similar expression pattern was also seen for the endogenous rat APP. The unexpected similarity in the tissue-specific expression patterns of endogenous rat APP and transgenic human APP mRNAs suggests regulatory elements within the cDNA sequence of APP. Conclusion This manuscript describes the generation of APP-transgenic inbred Fischer 344 rats. These are the first human AD model rat lines generated by lentiviral infection. The APP21 rat line expresses high levels of human APP and could be a useful model for AD. Tissue-specific

  19. α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

    Directory of Open Access Journals (Sweden)

    Yuan-Fei Peng

    Full Text Available RNA interference (RNAi has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment.Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1 was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3 and non-HCC cell lines (L-02, Hela and SW1116 were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5 was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo.The AFP-miRNA system could silence target gene (Beclin 1 but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1 in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo.An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA was successfully established. The system provides a usable tool for HCC-specific RNAi

  20. [Influence of tissue-specific superoxide dismutase genes expression in brain cells on Drosophila melanogaster sensitivity to oxidative stress and viability].

    Science.gov (United States)

    Vitushynska, M V; Matiytsiv, N P; Chernyk, Y

    2015-01-01

    The study has shown that both functional gene knockout Sodl and Sod2 and their overexpression in neurons and glial tissue increase the sensitivity of Drosophila melanogaster to oxidative stress (OS) conditions. The lowest survival rate was only 20.5% in insects with Sod2 knockout in neurons. Comparative analysis of the survival curves showed that adults with altered tissue-specific expression of the studied genes had reduced average and maximum life span. Under OS conditions induced by 5% hydrogen peroxide the life spans of wild type Oregon R and transgenic insects were significantly reduced. Altered Sod gene expression in glial tissue leads to degenerative changes in Drosophila brain at the young age. During the aging of insects and the action of pro-oxidants increasing of neurodegenerative phenotype is observed.

  1. Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

    DEFF Research Database (Denmark)

    Zuber, Verena; Bettella, Francesco; Witoelar, Aree

    2017-01-01

    progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC...

  2. Release of Tissue-specific Proteins into Coronary Perfusate as a Model for Biomarker Discovery in Myocardial Ischemia/Reperfusion Injury

    DEFF Research Database (Denmark)

    Cordwell, Stuart; Edwards, Alistair; Liddy, Kiersten

    2012-01-01

    -rich plasma, in which the wide dynamic range of the native protein complement hinders classical proteomic investigations. We employed an ex vivo rabbit model of myocardial ischemia/reperfusion (I/R) injury using Langendorff buffer perfusion. Nonrecirculating perfusate was collected over a temporal profile...... reperfusion post-15I. Proteins released during irreversible I/R (60I/60R) were profiled using gel-based (2-DE and one-dimensional gel electrophoresis coupled to liquid chromatography and tandem mass spectrometry; geLC–MS) and gel-free (LC–MS/MS) methods. A total of 192 tissue-specific proteins were identified...... release using ex vivo buffer perfused tissue to limit the presence of obfuscating plasma proteins may identify candidates for further study in humans....

  3. Protein profiles of Taenia solium cysts obtained from skeletal muscles and the central nervous system of pigs: Search for tissue-specific proteins.

    Science.gov (United States)

    Navarrete-Perea, José; Moguel, Bárbara; Bobes, Raúl José; Villalobos, Nelly; Carrero, Julio César; Sciutto, Edda; Soberón, Xavier; Laclette, Juan Pedro

    2017-01-01

    Taeniasis/cysticercosis caused by the tapeworm Taenia solium is a parasite disease transmitted among humans and pigs, the main intermediate host. The larvae/cysts can lodge in several tissues of the pig, i.e. skeletal muscles and different locations of the central nervous system. The molecular mechanisms associated to tissue preferences of the cysts remain poorly understood. The major public health concern about this zoonosis is due to the human infections by the larval form in the central nervous system, causing a highly pleomorphic and debilitating disease known as neurocysticercosis. This study was aimed to explore the 2DE protein maps of T. solium cysts obtained from skeletal muscles and central nervous system of naturally infected pigs. The gel images were analyzed through a combination of PDQuest™ and multivariate analysis. Results showed that differences in the protein patterns of cysts obtained from both tissues were remarkably discrete. Only 7 protein spots were found specifically associated to the skeletal muscle localization of the cysts; none was found significantly associated to the central nervous system. The use of distinct protein fractions of cysts allowed preliminary identification of several tissue-specific antigenic bands. The implications of these findings are discussed, as well as several strategies directed to achieve the complete characterization of this parasite's proteome, in order to extend our understanding of the molecular mechanisms underlying tissue localization of the cysts and to open avenues for the development of immunological tissue-specific diagnosis of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effects of chronic exposure to waterborne copper and nickel in binary mixture on tissue-specific metal accumulation and reproduction in fathead minnow (Pimephales promelas).

    Science.gov (United States)

    Driessnack, Melissa K; Jamwal, Ankur; Niyogi, Som

    2017-10-01

    The current study evaluated the interactive effects of chronic waterborne copper (Cu) and nickel (Ni) exposure on tissue-specific metal accumulation and reproductive performance in fathead minnow (Pimephales promelas). Fish trios (1 male: 2 female; n = 5-6) were exposed for 21 days to: (i) control (no added Cu or Ni), (ii) waterborne Cu (45 μg/L), (iii) waterborne Ni (270 μg/L), and (iv) binary mixture of waterborne Cu and Ni (45 and 270 μg/L, respectively). Fish fecundity (cumulative egg production) was found to be the most sensitive reproductive endpoint, and the interaction of Cu and Ni elicited an additive effect on egg production. Tissue-specific accumulation of both metals was not influenced by the interaction of Cu and Ni, except an increased Cu and Ni burden in the carcass and ovary, respectively, were recorded. The expressions of hepatic estrogen receptor genes (ER-α and ER-β) and the circulating estradiol level in females were also not affected by the metal-mixture treatment. However, co-exposure to waterborne Cu and Ni resulted in a significant downregulation of the hepatic vitellogenin gene in females, which was associated with the maximum upregulation of the hepatic metallothionein gene. In addition, a significant alteration of ovarian histopathology (decreased abundance of post-vitellogenic follicles, and increased follicular atresia) was also observed only in females exposed to Cu and Ni in mixture. Collectively, these observations suggest that chronic waterborne exposure to Cu and Ni in binary mixture may impair fish reproductive capacity by inducing histopathological damage in ovarian tissue, and disrupting of energy homeostasis in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Assessment of tissue-specific cortisol activity with regard to degeneration of the suspensory ligaments in horses with pituitary pars intermedia dysfunction.

    Science.gov (United States)

    Hofberger, Sina C; Gauff, Felicia; Thaller, Denise; Morgan, Ruth; Keen, John A; Licka, Theresia F

    2018-02-01

    OBJECTIVE To identify signs of tissue-specific cortisol activity in samples of suspensory ligament (SL) and neck skin tissue from horses with and without pituitary pars intermedia dysfunction (PPID). SAMPLE Suspensory ligament and neck skin tissue samples obtained from 26 euthanized horses with and without PPID. PROCEDURES Tissue samples were collected from 12 horses with and 14 horses without PPID (controls). Two control horses had received treatment with dexamethasone; data from those horses were not used in statistical analyses. The other 12 control horses were classified as old horses (≥ 14 years old) and young horses (≤ 9 years old). Standard histologic staining, staining for proteoglycan accumulation, and immunostaining of SL and neck skin tissue sections for glucocorticoid receptors, insulin, 11β hydroxysteroid dehydrogenase type 1, and 11β hydroxysteroid dehydrogenase type 2 were performed. Findings for horses with PPID were compared with findings for young and old horses without PPID. RESULTS Compared with findings for old and young control horses, there were significantly more cells stained for glucocorticoid receptors in SL samples and for 11 β hydroxysteroid dehydrogenase type 1 in SL and skin tissue samples from horses with PPID. Insulin could not be detected in any of the SL or skin tissue samples. Horses with PPID had evidence of SL degeneration with significantly increased proteoglycan accumulation. Neck skin tissue was found to be significantly thinner in PPID-affected horses than in young control horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that tissue-specific dysregulation of cortisol metabolism may contribute to the SL degeneration associated with PPID in horses.

  6. An Integrated “Multi-Omics” Comparison of Embryo and Endosperm Tissue-Specific Features and Their Impact on Rice Seed Quality

    Directory of Open Access Journals (Sweden)

    Marc Galland

    2017-11-01

    Full Text Available Although rice is a key crop species, few studies have addressed both rice seed physiological and nutritional quality, especially at the tissue level. In this study, an exhaustive “multi-omics” dataset on the mature rice seed was obtained by combining transcriptomics, label-free shotgun proteomics and metabolomics from embryo and endosperm, independently. These high-throughput analyses provide a new insight on the tissue-specificity related to rice seed quality. Foremost, we pinpointed that extensive post-transcriptional regulations occur at the end of rice seed development such that the embryo proteome becomes much more diversified than the endosperm proteome. Secondly, we observed that survival in the dry state in each seed compartment depends on contrasted metabolic and enzymatic apparatus in the embryo and the endosperm, respectively. Thirdly, it was remarkable to identify two different sets of starch biosynthesis enzymes as well as seed storage proteins (glutelins in both embryo and endosperm consistently with the supernumerary embryo hypothesis origin of the endosperm. The presence of a putative new glutelin with a possible embryonic favored abundance is described here for the first time. Finally, we quantified the rate of mRNA translation into proteins. Consistently, the embryonic panel of protein translation initiation factors is much more diverse than that of the endosperm. This work emphasizes the value of tissue-specificity-centered “multi-omics” study in the seed to highlight new features even from well-characterized pathways. It paves the way for future studies of critical genetic determinants of rice seed physiological and nutritional quality.

  7. FUN-LDA: A Latent Dirichlet Allocation Model for Predicting Tissue-Specific Functional Effects of Noncoding Variation: Methods and Applications.

    Science.gov (United States)

    Backenroth, Daniel; He, Zihuai; Kiryluk, Krzysztof; Boeva, Valentina; Pethukova, Lynn; Khurana, Ekta; Christiano, Angela; Buxbaum, Joseph D; Ionita-Laza, Iuliana

    2018-05-03

    We describe a method based on a latent Dirichlet allocation model for predicting functional effects of noncoding genetic variants in a cell-type- and/or tissue-specific way (FUN-LDA). Using this unsupervised approach, we predict tissue-specific functional effects for every position in the human genome in 127 different tissues and cell types. We demonstrate the usefulness of our predictions by using several validation experiments. Using eQTL data from several sources, including the GTEx project, Geuvadis project, and TwinsUK cohort, we show that eQTLs in specific tissues tend to be most enriched among the predicted functional variants in relevant tissues in Roadmap. We further show how these integrated functional scores can be used for (1) deriving the most likely cell or tissue type causally implicated for a complex trait by using summary statistics from genome-wide association studies and (2) estimating a tissue-based correlation matrix of various complex traits. We found large enrichment of heritability in functional components of relevant tissues for various complex traits, and FUN-LDA yielded higher enrichment estimates than existing methods. Finally, using experimentally validated functional variants from the literature and variants possibly implicated in disease by previous studies, we rigorously compare FUN-LDA with state-of-the-art functional annotation methods and show that FUN-LDA has better prediction accuracy and higher resolution than these methods. In particular, our results suggest that tissue- and cell-type-specific functional prediction methods tend to have substantially better prediction accuracy than organism-level prediction methods. Scores for each position in the human genome and for each ENCODE and Roadmap tissue are available online (see Web Resources). Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. The impact of laser ablation on optical soft tissue differentiation for tissue specific laser surgery-an experimental ex vivo study

    Directory of Open Access Journals (Sweden)

    Stelzle Florian

    2012-06-01

    Full Text Available Abstract Background Optical diffuse reflectance can remotely differentiate various bio tissues. To implement this technique in an optical feedback system to guide laser surgery in a tissue-specific way, the alteration of optical tissue properties by laser ablation has to be taken into account. It was the aim of this study to evaluate the general feasibility of optical soft tissue differentiation by diffuse reflectance spectroscopy under the influence of laser ablation, comparing the tissue differentiation results before and after laser intervention. Methods A total of 70 ex vivo tissue samples (5 tissue types were taken from 14 bisected pig heads. Diffuse reflectance spectra were recorded before and after Er:YAG-laser ablation. The spectra were analyzed and differentiated using principal component analysis (PCA, followed by linear discriminant analysis (LDA. To assess the potential of tissue differentiation, area under the curve (AUC, sensitivity and specificity was computed for each pair of tissue types before and after laser ablation, and compared to each other. Results Optical tissue differentiation showed good results before laser exposure (total classification error 13.51%. However, the tissue pair nerve and fat yielded lower AUC results of only 0.75. After laser ablation slightly reduced differentiation results were found with a total classification error of 16.83%. The tissue pair nerve and fat showed enhanced differentiation (AUC: 0.85. Laser ablation reduced the sensitivity in 50% and specificity in 80% of the cases of tissue pair comparison. The sensitivity of nerve–fat differentiation was enhanced by 35%. Conclusions The observed results show the general feasibility of tissue differentiation by diffuse reflectance spectroscopy even under conditions of tissue alteration by laser ablation. The contrast enhancement for the differentiation between nerve and fat tissue after ablation is assumed to be due to laser removal of the

  9. Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

    Directory of Open Access Journals (Sweden)

    Monika Stimac

    Full Text Available Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET (TS plasmid, in comparison to the plasmid with constitutive promoter (CON plasmid, in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

  10. Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

    Science.gov (United States)

    Stimac, Monika; Dolinsek, Tanja; Lampreht, Ursa; Cemazar, Maja; Sersa, Gregor

    2015-01-01

    Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β) co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET) (TS plasmid), in comparison to the plasmid with constitutive promoter (CON plasmid), in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET) of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

  11. Alternative security

    International Nuclear Information System (INIS)

    Weston, B.H.

    1990-01-01

    This book contains the following chapters: The Military and Alternative Security: New Missions for Stable Conventional Security; Technology and Alternative Security: A Cherished Myth Expires; Law and Alternative Security: Toward a Just World Peace; Politics and Alternative Security: Toward a More Democratic, Therefore More Peaceful, World; Economics and Alternative Security: Toward a Peacekeeping International Economy; Psychology and Alternative Security: Needs, Perceptions, and Misperceptions; Religion and Alternative Security: A Prophetic Vision; and Toward Post-Nuclear Global Security: An Overview

  12. Engineering high Zn in tomato shoots through expression of AtHMA4 involves tissue-specific modification of endogenous genes.

    Science.gov (United States)

    Kendziorek, Maria; Klimecka, Maria; Barabasz, Anna; Borg, Sören; Rudzka, Justyna; Szczęsny, Paweł; Antosiewicz, Danuta Maria

    2016-08-12

    To increase the Zn level in shoots, AtHMA4 was ectopically expressed in tomato under the constitutive CaMV 35S promoter. However, the Zn concentration in the shoots of transgenic plants failed to increase at all tested Zn levels in the medium. Modification of Zn root/shoot distribution in tomato expressing 35S::AtHMA4 depended on the concentration of Zn in the medium, thus indicating involvement of unknown endogenous metal-homeostasis mechanisms. To determine these mechanisms, those metal-homeostasis genes that were expressed differently in transgenic and wild-type plants were identified by microarray and RT-qPCR analysis using laser-assisted microdissected RNA isolated from two root sectors: (epidermis + cortex and stele), and leaf sectors (upper epidermis + palisade parenchyma and lower epidermis + spongy parenchyma). Zn-supply-dependent modification of Zn root/shoot distribution in AtHMA4-tomato (increase at 5 μM Zn, no change at 0.5 μM Zn) involved tissue-specific, distinct from that in the wild type, expression of tomato endogenous genes. First, it is suggested that an ethylene-dependent pathway underlies the detected changes in Zn root/shoot partitioning, as it was induced in transgenic plants in a distinct way depending on Zn exposure. Upon exposure to 5 or 0.5 μM Zn, in the epidermis + cortex of the transgenics' roots the expression of the Strategy I Fe-uptake system (ethylene-dependent LeIRT1 and LeFER) was respectively lower or higher than in the wild type and was accompanied by respectively lower or higher expression of the identified ethylene genes (LeNR, LeACO4, LeACO5) and of LeChln. Second, the contribution of LeNRAMP2 expression in the stele is shown to be distinct for wild-type and transgenic plants at both Zn exposures. Ethylene was also suggested as an important factor in a pathway induced in the leaves of transgenic plants by high Zn in the apoplast, which results in the initiation of loading of the excess Zn into the

  13. Alternative additives; Alternative additiver

    Energy Technology Data Exchange (ETDEWEB)

    2007-08-15

    In this project a number of industrial and agricultural waste products have been characterised and evaluated in terms of alkali-getter performance. The intended use is for biomass-fired power stations aiming at reducing corrosion or slagging related problems. The following products have been obtained, characterised and evaluated: 1) Brewery draff 2) Danish de-gassed manure 3) Paper sludge 4) Moulding sand 5) Spent bleaching earth 6) Anorthosite 7) Sand 8) Clay-sludge. Most of the above alternative additive candidates are deemed unsuitable due to insufficient chemical effect and/or expensive requirements for pre-treatment (such as drying and transportation). 3 products were selected for full-scale testing: de-gassed manure, spent bleaching earth and clay slugde. The full scale tests were undertaken at the biomass-fired power stations in Koege, Slagelse and Ensted. Spent bleaching earth (SBE) and clay sludge were the only tested additive candidates that had a proven ability to react with KCl, to thereby reduce Cl-concentrations in deposits, and reduce the deposit flux to superheater tubes. Their performance was shown to nearly as good as commercial additives. De-gassed manure, however, did not evaluate positively due to inhibiting effects of Ca in the manure. Furthermore, de-gassed manure has a high concentration of heavy metals, which imposes a financial burden with regard to proper disposal of the ash by-products. Clay-sludge is a wet clay slurring, and drying and transportation of this product entails substantial costs. Spent bleaching does not require much pre-treatment and is therefore the most promising alternative additive. On the other hand, bleaching earth contains residual plant oil which means that a range of legislation relating to waste combustion comes into play. Not least a waste combustion fee of 330 DKK/tonne. For all alternative (and commercial) additives disposal costs of the increase ash by-products represents a significant cost. This is

  14. Tissue specificity for incorporation of [3H]thymidine by the 10- to 12-somite mouse embryo: alteration by acute exposure to hydroxyurea

    International Nuclear Information System (INIS)

    Miller, S.A.; Runner, M.N.

    1978-01-01

    Radioautograms from 10- to 12-somite mouse embryos labelled for 30 min in vitro with [ 3 H]thymidine were examined for frequency and intensity of incorporation. Results from ten tissues showed that values ranged from 82% of nuclei with a mean of 16.6 grains for visceral yolk sac to 17% of nuclei labelled with a mean of 4.4 grains for epithelium of the anterior gut tube. Labelling in the ten tissues indicated (1) a tissue-specific spectrum of incorporation of [ 3 H]thymidine, (2) close correlation between frequency and intensity of labelling within a tissue and (3) asymmetrical quantities of incorporation between right and left somatopleure. Treatment with hydroxyurea in vitro reduced the frequency of labelled nuclei by 85% to 17% of control values. Mean numbers of grains over treated nuclei, 3.3 to 4.6 grains, were well above background but were clustered below the low end of the control range. Tissues exposed to hydroxyurea showed (1) labelling of significant numbers of nuclei, (2) inhibition of labelling in selected tissues and (3) equalization of bilateral asymmetry in quantity (frequency and intensity) of incorporation in somatopleure. The selective reduction of thymidine incorporation and equalization of asymmetrical rates of proliferation may constitute mechanisms by which hydroxyurea causes abnormal morphogenesis. (author)

  15. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.

    Directory of Open Access Journals (Sweden)

    Louise Madsen

    Full Text Available The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

  16. Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.

    Science.gov (United States)

    Langouet-Astrie, Christophe J; Yang, Zhiyong; Polisetti, Sraavya M; Welsbie, Derek S; Hauswirth, William W; Zack, Donald J; Merbs, Shannath L; Enke, Raymond A

    2016-10-01

    Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Differential accumulation of β-carotene and tissue specific expression of phytoene synthase (MaPsy) gene in banana (Musa sp) cultivars.

    Science.gov (United States)

    Dhandapani, R; Singh, V P; Arora, A; Bhattacharya, R C; Rajendran, Ambika

    2017-12-01

    An experiment was conducted with twelve major Indian banana cultivars to investigate the molecular relationship between the differential accumulation of β-carotene in peel and pulp of the banana fruit and carotenoid biosynthetic pathway genes. The high performance liquid chromatography showed that all banana cultivars accumulated two-three fold more β-carotene in non-edible portion of the banana fruit. However, Nendran , a famous orange fleshed cultivar of South India, had high β-carotene content (1362 µg/100 g) in edible pulp. The gene encoding Musa accuminata phytoene synthase ( MaPsy ) was successfully amplified using a pair of degenerate primers designed from Oncidium orchid. The deduced amino acid sequences shared a high level of identity to phytoene synthase gene from other plants. Gene expression analysis confirmed the presence of two isoforms ( MaPsy1 and MaPsy2 ) of MaPsy gene in banana fruits. Presence of two isoforms of MaPsy gene in peel and one in pulp confirmed the differential accumulation of β-carotene in banana fruits. However, Nendran accumulated more β-carotene in edible pulp due to presence of both the isoforms of MaPsy gene. Thus, carotenoid accumulation is a tissue specific process strongly dependent on differential expression pattern of two isoforms of MaPsy gene in banana.

  18. Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

    Science.gov (United States)

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

    2012-01-01

    We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

  19. Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors

    International Nuclear Information System (INIS)

    Reue, K.; Leff, T.; Breslow, J.L.

    1988-01-01

    Apolipoprotein CIII (apoCIII) is a major protein constituent of triglyceride-rich lipoproteins and is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific apoCIII gene transcription were identified with transient expression assays in the human hepatoma (HepG2) and epithelial carcinoma (HeLa) cell lines. In liver cells, 821 nucleotides of the human apoCIII gene 5'-flanking sequence were required for maximum levels of gene expression, while the proximal 110 nucleotides alone were sufficient. No expression was observed in similar studies with HeLa cells. The level of expression was modulated by a combination of positive and negative cis-acting sequences, which interact with distinct sets of proteins from liver and HeLa cell nuclear extracts. The proximal positive regulatory region shares homology with similarly located sequences of other genes strongly expressed in the liver, including α 1 -antitrypsin and other apolipoprotein genes. The negative regulatory region is striking homologous to the human β-interferon gene regulatory element. The distal positive region shares homology with some viral enhancers and has properties of a tissue-specific enhancer. The regulation of the apoCIII gene is complex but shares features with other genes, suggesting shuffling of regulatory elements as a common mechanism for cell type-specific gene expression

  20. Inheritance of resistance to watermelon mosaic virus in the cucumber line TMG-1: tissue-specific expression and relationship to zucchini yellow mosaic virus resistance.

    Science.gov (United States)

    Wai, T; Grumet, R

    1995-09-01

    The inbred cucumber (Cucumis sativus L.) line TMG-1 is resistant to three potyviruses:zucchini yellow mosaic virus (ZYMV), watermelon mosaic virus (WMV), and the watermelon strain of papaya ringspot virus (PRSV-W). The genetics of resistance to WMV and the relationship of WMV resistance to ZYMV resistance were examined. TMG-1 was crossed with WI-2757, a susceptible inbred line. F1, F2 and backcross progeny populations were screened for resistance to WMV and/or ZYMV. Two independently assorting factors conferred resistance to WMV. One resistance was conferred by a single recessive gene from TMG-1 (wmv-2). The second resistance was conferred by an epistatic interaction between a second recessive gene from TMG-1 (wmv-3) and either a dominant gene from WI-2757 (Wmv-4) or a third recessive gene from TMG-1 (wmv-4) located 20-30 cM from wmv-3. The two resistances exhibited tissue-specific expression. Resistance conferred by wmv-2 was expressed in the cotyledons and throughout the plant. Resistance conferred by wmv-3 + Wmv-4 (or wmv-4) was expressed only in true leaves. The gene conferring resistance to ZYMV appeared to be the same as, or tightly linked to one of the WMV resistance genes, wmv-3.

  1. Quasispecies evolution of the prototypical genotype 1 porcine reproductive and respiratory syndrome virus early during in vivo infection is rapid and tissue specific.

    Science.gov (United States)

    Lu, Zen H; Wang, Xinglong; Wilson, Alison D; Dorey-Robinson, Daniel L W; Archibald, Alan L; Ait-Ali, Tahar; Frossard, Jean-Pierre

    2017-08-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major infectious threat to the pig industry worldwide. Increasing evidence suggests that microevolution within a quasispecies population can give rise to high sequence heterogeneity in PRRSV; potentially impacting the pathogenicity of the virus. Here, we report on micro-evolutionary events taking place within the viral quasispecies population in lung and lymph node 3 days post infection (dpi) following experimental in vivo infection with the prototypical Lelystad PRRSV (LV). Sequence analysis revealed 16 high frequency single nucleotide variants (SNV) or differences from the reference LV genome which are assumed to be representative of the consensus inoculum genome. Additionally, 49 other low frequency SNVs were also found in the inoculum population. At 3 dpi, a total of 9 and 10 SNVs of varying frequencies could already be detected in the LV population infecting the lung and lymph nodes, respectively. Interestingly, of these, three and four novel SNVs emerged independently in the two respective tissues when compared to the inoculum. The remaining variants, though already present at lower frequencies in the inoculum, were positively selected and their frequency increased within the quasispecies population. Hence, we were able to determine directly from tissues infected with PRRSV the repertoire of genetic variants within the viral quasispecies population. Our data also suggest that microevolution of these variants is rapid and some may be tissue-specific.

  2. Persistent Foot-and-Mouth Disease Virus Infection in the Nasopharynx of Cattle; Tissue-Specific Distribution and Local Cytokine Expression.

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    Juan M Pacheco

    Full Text Available Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 steers infected with FMDV serotype A, O or SAT2, had the highest prevalence of overall viral detection in the dorsal nasopharynx (80.95% and dorsal soft palate (71.43%. FMDV was less frequently detected in laryngeal mucosal tissues, oropharyngeal mucosal sites, and lymph nodes draining the pharynx. Immunomicroscopy indicated that within persistently infected mucosal tissues, FMDV antigens were rarely detectable within few epithelial cells in regions of mucosa-associated lymphoid tissue (MALT. Transcriptome analysis of persistently infected pharyngeal tissues by qRT-PCR for 14 cytokine genes indicated a general trend of decreased mRNA levels compared to uninfected control animals. Although, statistically significant differences were not observed, greatest suppression of relative expression (RE was identified for IP-10 (RE = 0.198, IFN-β (RE = 0.269, IL-12 (RE = 0.275, and IL-2 (RE = 0.312. Increased relative expression was detected for IL-6 (RE = 2.065. Overall, this data demonstrates that during the FMDV carrier state in cattle, viral persistence is associated with epithelial cells of the nasopharynx in the upper respiratory tract and decreased levels of mRNA for several immunoregulatory cytokines in the infected tissues.

  3. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins

    DEFF Research Database (Denmark)

    Madsen, Louise; Kriegenburg, Franziska; Lages Lino Vala, Andrea

    2011-01-01

    is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p......The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded...... protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8...

  4. Genome-wide identification and tissue-specific expression analysis of nucleotide binding site-leucine rich repeat gene family in Cicer arietinum (kabuli chickpea).

    Science.gov (United States)

    Sharma, Ranu; Rawat, Vimal; Suresh, C G

    2017-12-01

    The nucleotide binding site-leucine rich repeat (NBS-LRR) proteins play an important role in the defense mechanisms against pathogens. Using bioinformatics approach, we identified and annotated 104 NBS-LRR genes in chickpea. Phylogenetic analysis points to their diversification into two families namely TIR-NBS-LRR and non-TIR-NBS-LRR. Gene architecture revealed intron gain/loss events in this resistance gene family during their independent evolution into two families. Comparative genomics analysis elucidated its evolutionary relationship with other fabaceae species. Around 50% NBS-LRRs reside in macro-syntenic blocks underlining positional conservation along with sequence conservation of NBS-LRR genes in chickpea. Transcriptome sequencing data provided evidence for their transcription and tissue-specific expression. Four cis -regulatory elements namely WBOX, DRE, CBF, and GCC boxes, that commonly occur in resistance genes, were present in the promoter regions of these genes. Further, the findings will provide a strong background to use candidate disease resistance NBS-encoding genes and identify their specific roles in chickpea.

  5. Temporal and tissue specific regulation of RP-associated splicing factor genes PRPF3, PRPF31 and PRPC8--implications in the pathogenesis of RP.

    Directory of Open Access Journals (Sweden)

    Huibi Cao

    2011-01-01

    Full Text Available Genetic mutations in several ubiquitously expressed RNA splicing genes such as PRPF3, PRP31 and PRPC8, have been found to cause retina-specific diseases in humans. To understand this intriguing phenomenon, most studies have been focused on testing two major hypotheses. One hypothesis assumes that these mutations interrupt retina-specific interactions that are important for RNA splicing, implying that there are specific components in the retina interacting with these splicing factors. The second hypothesis suggests that these mutations have only a mild effect on the protein function and thus affect only the metabolically highly active cells such as retinal photoreceptors.We examined the second hypothesis using the PRPF3 gene as an example. We analyzed the spatial and temporal expression of the PRPF3 gene in mice and found that it is highly expressed in retinal cells relative to other tissues and its expression is developmentally regulated. In addition, we also found that PRP31 and PRPC8 as well as snRNAs are highly expressed in retinal cells.Our data suggest that the retina requires a relatively high level of RNA splicing activity for optimal tissue-specific physiological function. Because the RP18 mutation has neither a debilitating nor acute effect on protein function, we suggest that retinal degeneration is the accumulative effect of decades of suboptimal RNA splicing due to the mildly impaired protein.

  6. Alternative promoter usage of the membrane glycoprotein CD36

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    Whatling Carl

    2006-03-01

    Full Text Available Abstract Background CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation. Results We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters. Conclusion Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  7. Genome-wide identification and expression profiling reveal tissue-specific expression and differentially-regulated genes involved in gibberellin metabolism between Williams banana and its dwarf mutant.

    Science.gov (United States)

    Chen, Jingjing; Xie, Jianghui; Duan, Yajie; Hu, Huigang; Hu, Yulin; Li, Weiming

    2016-05-27

    Dwarfism is one of the most valuable traits in banana breeding because semi-dwarf cultivars show good resistance to damage by wind and rain. Moreover, these cultivars present advantages of convenient cultivation, management, and so on. We obtained a dwarf mutant '8818-1' through EMS (ethyl methane sulphonate) mutagenesis of Williams banana 8818 (Musa spp. AAA group). Our research have shown that gibberellins (GAs) content in 8818-1 false stems was significantly lower than that in its parent 8818 and the dwarf type of 8818-1 could be restored by application of exogenous GA3. Although GA exerts important impacts on the 8818-1 dwarf type, our understanding of the regulation of GA metabolism during banana dwarf mutant development remains limited. Genome-wide screening revealed 36 candidate GA metabolism genes were systematically identified for the first time; these genes included 3 MaCPS, 2 MaKS, 1 MaKO, 2 MaKAO, 10 MaGA20ox, 4 MaGA3ox, and 14 MaGA2ox genes. Phylogenetic tree and conserved protein domain analyses showed sequence conservation and divergence. GA metabolism genes exhibited tissue-specific expression patterns. Early GA biosynthesis genes were constitutively expressed but presented differential regulation in different tissues in Williams banana. GA oxidase family genes were mainly transcribed in young fruits, thus suggesting that young fruits were the most active tissue involved in GA metabolism, followed by leaves, bracts, and finally approximately mature fruits. Expression patterns between 8818 and 8818-1 revealed that MaGA20ox4, MaGA20ox5, and MaGA20ox7 of the MaGA20ox gene family and MaGA2ox7, MaGA2ox12, and MaGA2ox14 of the MaGA2ox gene family exhibited significant differential expression and high-expression levels in false stems. These genes are likely to be responsible for the regulation of GAs content in 8818-1 false stems. Overall, phylogenetic evolution, tissue specificity and differential expression analyses of GA metabolism genes can provide a

  8. Tissue-specific differential induction of duplicated fatty acid-binding protein genes by the peroxisome proliferator, clofibrate, in zebrafish (Danio rerio

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    Venkatachalam Ananda B

    2012-07-01

    RNAs for both the duplicated copies of fabp1a/fabp1b.1, and fabp7a/fabp7b, but in different tissues. Clofibrate also increased the steady-state level of fabp10a and fabp11a mRNAs and hnRNAs in liver, but not for fabp10b and fabp11b. Conclusion Some duplicated fabp genes have, most likely, retained PPREs, but induction by clofibrate is over-ridden by an, as yet, unknown tissue-specific mechanism(s. Regardless of the tissue-specific mechanism(s, transcriptional control of duplicated zebrafish fabp genes by clofibrate has markedly diverged since the WGD event.

  9. Tissue-specific expression and regulation by 1,25(OH)2D3 of chick protein kinase inhibitor (PKI) mRNA.

    Science.gov (United States)

    Marchetto, G S; Henry, H L

    1997-02-01

    The heat-stable protein kinase inhibitor (PKI) protein is a specific and potent competitive inhibitor of the catalytic subunit of cAMP-dependent protein kinase (PKA). Previously, it has been shown that vitamin D status affects chick kidney PKI activity: a 5- to 10-fold increase in PKI activity was observed in kidneys of chronically vitamin D-deficient chicks and treatment with 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) in cultured kidney cells resulted in a 95% decrease in PKI activity. The authors have recently cloned the cDNA for chick kidney PKI and have used the coding sequence to study the regulation of PKI mRNA. Northern analysis showed the expression of two PKI messages, which are 2.7 and 3.3 kb in size. These mRNAs are expressed in brain, muscle, testis, and kidney, but not in pancreas, liver, or intestine. PKI mRNA steady-state levels are downregulated by 47% in kidneys from vitamin D-replete chicks as compared to vitamin D-deficient chicks. PKI mRNA levels in brain, muscle, and testis are not affected by vitamin D status. Treatment of primary chick kidney cultures treated with 10(-7) M 1,25(OH)2D3 for 24h resulted in a 20-30% decrease in PKI mRNA. 1,25(OH)2D3 treatment does not affect the stability of PKI mRNA as determined by treatment of cell cultures with actinomycin D. This study shows that 1,25(OH)2D3 directly and tissue-specifically downregulates PKI mRNA in the chick kidney.

  10. A novel rat genomic simple repeat DNA with RNA-homology shows triplex (H-DNA)-like structure and tissue-specific RNA expression

    International Nuclear Information System (INIS)

    Dey, Indranil; Rath, Pramod C.

    2005-01-01

    Mammalian genome contains a wide variety of repetitive DNA sequences of relatively unknown function. We report a novel 227 bp simple repeat DNA (3.3 DNA) with a d {(GA) 7 A (AG) 7 } dinucleotide mirror repeat from the rat (Rattus norvegicus) genome. 3.3 DNA showed 75-85% homology with several eukaryotic mRNAs due to (GA/CU) n dinucleotide repeats by nBlast search and a dispersed distribution in the rat genome by Southern blot hybridization with [ 32 P]3.3 DNA. The d {(GA) 7 A (AG) 7 } mirror repeat formed a triplex (H-DNA)-like structure in vitro. Two large RNAs of 9.1 and 7.5 kb were detected by [ 32 P]3.3 DNA in rat brain by Northern blot hybridization indicating expression of such simple sequence repeats at RNA level in vivo. Further, several cDNAs were isolated from a rat cDNA library by [ 32 P]3.3 DNA probe. Three such cDNAs showed tissue-specific RNA expression in rat. pRT 4.1 cDNA showed strong expression of a 2.39 kb RNA in brain and spleen, pRT 5.5 cDNA showed strong expression of a 2.8 kb RNA in brain and a 3.9 kb RNA in lungs, and pRT 11.4 cDNA showed weak expression of a 2.4 kb RNA in lungs. Thus, genomic simple sequence repeats containing d (GA/CT) n dinucleotides are transcriptionally expressed and regulated in rat tissues. Such d (GA/CT) n dinucleotide repeats may form structural elements (e.g., triplex) which may be sites for functional regulation of genomic coding sequences as well as RNAs. This may be a general function of such transcriptionally active simple sequence repeats widely dispersed in mammalian genome

  11. Transcriptional control of the tissue-specific, developmentally regulated osteocalcin gene requires a binding motif for the Msx family of homeodomain proteins.

    Science.gov (United States)

    Hoffmann, H M; Catron, K M; van Wijnen, A J; McCabe, L R; Lian, J B; Stein, G S; Stein, J L

    1994-12-20

    The OC box of the rat osteocalcin promoter (nt -99 to -76) is the principal proximal regulatory element contributing to both tissue-specific and developmental control of osteocalcin gene expression. The central motif of the OC box includes a perfect consensus DNA binding site for certain homeodomain proteins. Homeodomain proteins are transcription factors that direct proper development by regulating specific temporal and spatial patterns of gene expression. We therefore addressed the role of the homeodomain binding motif in the activity of the OC promoter. In this study, by the combined application of mutagenesis and site-specific protein recognition analysis, we examined interactions of ROS 17/2.8 osteosarcoma cell nuclear proteins and purified Msx-1 homeodomain protein with the OC box. We detected a series of related specific protein-DNA interactions, a subset of which were inhibited by antibodies directed against the Msx-1 homeodomain but which also recognize the Msx-2 homeodomain. Our results show that the sequence requirements for binding the Msx-1 or Msx-2 homeodomain closely parallel those necessary for osteocalcin gene promoter activity in vivo. This functional relationship was demonstrated by transient expression in ROS 17/2.8 osteosarcoma cells of a series of osteocalcin promoter (nt -1097 to +24)-reporter gene constructs containing mutations within and flanking the homeodomain binding site of the OC box. Northern blot analysis of several bone-related cell types showed that all of the cells expressed msx-1, whereas msx-2 expression was restricted to cells transcribing osteocalcin. Taken together, our results suggest a role for Msx-1 and -2 or related homeodomain proteins in transcription of the osteocalcin gene.

  12. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qiongshi Lu

    2017-07-01

    Full Text Available Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD. Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

  13. Bipartite recognition of DNA by TCF/Pangolin is remarkably flexible and contributes to transcriptional responsiveness and tissue specificity of wingless signaling.

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    Hilary C Archbold

    2014-09-01

    Full Text Available The T-cell factor (TCF family of transcription factors are major mediators of Wnt/β-catenin signaling in metazoans. All TCFs contain a High Mobility Group (HMG domain that possesses specific DNA binding activity. In addition, many TCFs contain a second DNA binding domain, the C-clamp, which binds to DNA motifs referred to as Helper sites. While HMG and Helper sites are both important for the activation of several Wnt dependent cis-regulatory modules (W-CRMs, the rules of what constitutes a functional HMG-Helper site pair are unknown. In this report, we employed a combination of in vitro binding, reporter gene analysis and bioinformatics to address this question, using the Drosophila family member TCF/Pangolin (TCF/Pan as a model. We found that while there were constraints for the orientation and spacing of HMG-Helper pairs, the presence of a Helper site near a HMG site in any orientation increased binding and transcriptional response, with some orientations displaying tissue-specific patterns. We found that altering an HMG-Helper site pair from a sub-optimal to optimal orientation/spacing dramatically increased the responsiveness of a W-CRM in several fly tissues. In addition, we used the knowledge gained to bioinformatically identify two novel W-CRMs, one that was activated by Wnt/β-catenin signaling in the prothoracic gland, a tissue not previously connected to this pathway. In sum, this work extends the importance of Helper sites in fly W-CRMs and suggests that the type of HMG-Helper pair is a major factor in setting the threshold for Wnt activation and tissue-responsiveness.

  14. High Quality Unigenes and Microsatellite Markers from Tissue Specific Transcriptome and Development of a Database in Clusterbean (Cyamopsis tetragonoloba, L. Taub

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    Hukam C. Rawal

    2017-11-01

    Full Text Available Clusterbean (Cyamopsis tetragonoloba L. Taub, is an important industrial, vegetable and forage crop. This crop owes its commercial importance to the presence of guar gum (galactomannans in its endosperm which is used as a lubricant in a range of industries. Despite its relevance to agriculture and industry, genomic resources available in this crop are limited. Therefore, the present study was undertaken to generate RNA-Seq based transcriptome from leaf, shoot, and flower tissues. A total of 145 million high quality Illumina reads were assembled using Trinity into 127,706 transcripts and 48,007 non-redundant high quality (HQ unigenes. We annotated 79% unigenes against Plant Genes from the National Center for Biotechnology Information (NCBI, Swiss-Prot, Pfam, gene ontology (GO and KEGG databases. Among the annotated unigenes, 30,020 were assigned with 116,964 GO terms, 9984 with EC and 6111 with 137 KEGG pathways. At different fragments per kilobase of transcript per millions fragments sequenced (FPKM levels, genes were found expressed higher in flower tissue followed by shoot and leaf. Additionally, we identified 8687 potential simple sequence repeats (SSRs with an average frequency of one SSR per 8.75 kb. A total of 28 amplified SSRs in 21 clusterbean genotypes resulted in polymorphism in 13 markers with average polymorphic information content (PIC of 0.21. We also constructed a database named ‘ClustergeneDB’ for easy retrieval of unigenes and the microsatellite markers. The tissue specific genes identified and the molecular marker resources developed in this study is expected to aid in genetic improvement of clusterbean for its end use.

  15. Mammalian transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes and are predicted to act as transcriptional activator hubs.

    Science.gov (United States)

    Joshi, Anagha

    2014-12-30

    Transcriptional hotspots are defined as genomic regions bound by multiple factors. They have been identified recently as cell type specific enhancers regulating developmentally essential genes in many species such as worm, fly and humans. The in-depth analysis of hotspots across multiple cell types in same species still remains to be explored and can bring new biological insights. We therefore collected 108 transcription-related factor (TF) ChIP sequencing data sets in ten murine cell types and classified the peaks in each cell type in three groups according to binding occupancy as singletons (low-occupancy), combinatorials (mid-occupancy) and hotspots (high-occupancy). The peaks in the three groups clustered largely according to the occupancy, suggesting priming of genomic loci for mid occupancy irrespective of cell type. We then characterized hotspots for diverse structural functional properties. The genes neighbouring hotspots had a small overlap with hotspot genes in other cell types and were highly enriched for cell type specific function. Hotspots were enriched for sequence motifs of key TFs in that cell type and more than 90% of hotspots were occupied by pioneering factors. Though we did not find any sequence signature in the three groups, the H3K4me1 binding profile had bimodal peaks at hotspots, distinguishing hotspots from mono-modal H3K4me1 singletons. In ES cells, differentially expressed genes after perturbation of activators were enriched for hotspot genes suggesting hotspots primarily act as transcriptional activator hubs. Finally, we proposed that ES hotspots might be under control of SetDB1 and not DNMT for silencing. Transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes. In ES cells, they are predicted to act as transcriptional activator hubs and might be under SetDB1 control for silencing.

  16. An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis

    Science.gov (United States)

    Lin, Ching-Jung; Smibert, Peter; Zhao, Xiaoyu; Hu, Jennifer F.; Ramroop, Johnny; Kellner, Stefanie M.; Benton, Matthew A.; Govind, Shubha; Dedon, Peter C.; Sternglanz, Rolf; Lai, Eric C.

    2015-01-01

    N6-threonylcarbamoyl-adenosine (t6A) is one of the few RNA modifications that is universally present in life. This modification occurs at high frequency at position 37 of most tRNAs that decode ANN codons, and stabilizes cognate anticodon–codon interactions. Nearly all genetic studies of the t6A pathway have focused on single-celled organisms. In this study, we report the isolation of an extensive allelic series in the Drosophila ortholog of the core t6A biosynthesis factor Kae1. kae1 hemizygous larvae exhibit decreases in t6A that correlate with allele strength; however, we still detect substantial t6A-modified tRNAs even during the extended larval phase of null alleles. Nevertheless, complementation of Drosophila Kae1 and other t6A factors in corresponding yeast null mutants demonstrates that these metazoan genes execute t6A synthesis. Turning to the biological consequences of t6A loss, we characterize prominent kae1 melanotic masses and show that they are associated with lymph gland overgrowth and ectopic generation of lamellocytes. On the other hand, kae1 mutants exhibit other phenotypes that reflect insufficient tissue growth. Interestingly, whole-tissue and clonal analyses show that strongly mitotic tissues such as imaginal discs are exquisitely sensitive to loss of kae1, whereas nonproliferating tissues are less affected. Indeed, despite overt requirements of t6A for growth of many tissues, certain strong kae1 alleles achieve and sustain enlarged body size during their extended larval phase. Our studies highlight tissue-specific requirements of the t6A pathway in a metazoan context and provide insights into the diverse biological roles of this fundamental RNA modification during animal development and disease. PMID:26516084

  17. Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction.

    Science.gov (United States)

    Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J; Liaw, Lucy

    2012-09-28

    We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

  18. The neuropeptides and protein hormones of the agricultural pest fruit fly Bactrocera dorsalis: What do we learn from the genome sequencing and tissue-specific transcriptomes?

    Science.gov (United States)

    Gui, Shun-Hua; Jiang, Hong-Bo; Smagghe, Guy; Wang, Jin-Jun

    2017-12-01

    Neuropeptides and protein hormones are very important signaling molecules, and are involved in the regulation and coordination of various physiological processes in invertebrates and vertebrates. Using a bioinformatics approach, we screened the recently sequenced genome and six tissue-specific transcriptome databases (central nervous system, fat body, ovary, testes, male accessory glands, antennae) of the oriental fruit fly (Bactrocera dorsalis) that is economically one of the most important pest insects of tropical and subtropical fruit. Thirty-nine candidate genes were found to encode neuropeptides or protein hormones. These include most of the known insect neuropeptides and protein hormones, with the exception of adipokinetic hormone-corazonin-related peptide, allatropin, diuretic hormone 34, diuretic hormone 45, IMFamide, inotocin, and sex peptide. Our results showed the neuropeptides and protein hormones of Diptera insects appear to have a reduced repertoire compared to some other insects. Moreover, there are also differences between B. dorsalis and the super-model of Drosophila melanogaster. Interesting features of the oriental fruit fly are the absence of genes coding for sex peptide and the presence of neuroparsin and two genes coding neuropeptide F. The majority of the identified neuropeptides and protein hormones is present in the central nervous system, with only a limited number of these in the other tissues. Moreover, we predicted their physiological functions via comparing with data of FlyBase and FlyAtlas. Taken together, owing to the large number of identified peptides, this study can be used as a reference about structure, tissue distribution and physiological functions for comparative studies in other model and important pest insects. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice.

    Science.gov (United States)

    Welborn, Joshua P; Davis, Matthew G; Ebers, Steven D; Stodden, Genna R; Hayashi, Kanako; Cheatwood, Joseph L; Rao, Manjeet K; MacLean, James A

    2015-07-01

    The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility. © 2015 by the Society for the Study of Reproduction, Inc.

  20. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice1

    Science.gov (United States)

    Welborn, Joshua P.; Davis, Matthew G.; Ebers, Steven D.; Stodden, Genna R.; Hayashi, Kanako; Cheatwood, Joseph L.; Rao, Manjeet K.; MacLean, James A.

    2015-01-01

    The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility. PMID:25972016

  1. Tissue-specific direct microtransfer of nanomaterials into Drosophila embryos as a versatile in vivo test bed for nanomaterial toxicity assessment

    Directory of Open Access Journals (Sweden)

    Vega-Alvarez S

    2014-04-01

    Full Text Available Sasha Vega-Alvarez,1 Adriana Herrera,2 Carlos Rinaldi,2–4 Franklin A Carrero-Martínez1,5 1Department of Biology, 2Department of Chemical Engineering, University of Puerto Rico-Mayagüez, Mayagüez, Puerto Rico; 3J Crayton Pruitt Family Department of Biomedical Engineering, 4Department of Chemical Engineering, University of Florida, Gainesville, FL, USA; 5Department of Anatomy and Neuroscience, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico Abstract: Nanomaterials are the subject of intense research, focused on their synthesis, modification, and biomedical applications. Increased nanomaterial production and their wide range of applications imply a higher risk of human and environmental exposure. Unfortunately, neither environmental effects nor toxicity of nanomaterials to organisms are fully understood. Cost-effective, rapid toxicity assays requiring minimal amounts of materials are needed to establish both their biomedical potential and environmental safety standards. Drosophila exemplifies an efficient and cost-effective model organism with a vast repertoire of in vivo tools and techniques, all with high-throughput scalability and screening feasibility throughout its life cycle. Here we report tissue specific nanomaterial assessment through direct microtransfer into target tissues. We tested several nanomaterials with potential biomedical applications such as single-wall carbon nanotubes, multiwall carbon nanotubes, silver, gold, titanium dioxide, and iron oxide nanoparticles. Assessment of nanomaterial toxicity was conducted by evaluating progression through developmental morphological milestones in Drosophila. This cost-effective assessment method is amenable to high-throughput screening. Keywords: nanotoxicity, Drosophila, microtransfer, nanoparticle, iron oxide, silver, gold, titanium dioxide, carbon nanotube

  2. Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly

    Directory of Open Access Journals (Sweden)

    Quentin eDuriez

    2014-11-01

    Full Text Available We investigated the cross-sectional and longitudinal effects of tobacco smoking on brain atrophy in a large cohort of healthy elderly participants (65 to 80 years. MRI was used for measuring whole brain (WB, gray matter (GM, white matter (WM, and hippocampus (HIP volumes at study entry time (baseline, N=1,451, and the annualized rates of variation of these volumes using a 4-year follow-up MRI in a subpart of the cohort (N=1,111. Effects of smoking status (never, former, or current smoker at study entry and of lifetime tobacco consumption on these brain phenotypes were studied using sex-stratified AN(COVAs, including other health parameters as covariates. At baseline, male current smokers had lower GM, while female current smokers had lower WM. In addition, female former smokers exhibited reduced baseline HIP, the reduction being correlated with lifetime tobacco consumption. Longitudinal analyses demonstrated that current smokers, whether men or women, had larger annualized rates of HIP atrophy, as compared to either current or former smokers, independent of their lifetime consumption of tobacco. There was no effect of smoking on the annualized rate of WM loss. In all cases, measured sizes of these tobacco-smoking effects were of the same order of magnitude than those of age, and larger than effect sizes of any other covariate. These results demonstrate gender- and tissue specific effects of tobacco smoking on brain atrophy. They indicate that tobacco smoking is a major factor of brain aging, with notable effects on the hippocampus annualized-rate of atrophy after the age of 65.

  3. A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.

    Science.gov (United States)

    Smith, Robin P; Riesenfeld, Samantha J; Holloway, Alisha K; Li, Qiang; Murphy, Karl K; Feliciano, Natalie M; Orecchia, Lorenzo; Oksenberg, Nir; Pollard, Katherine S; Ahituv, Nadav

    2013-07-18

    Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

  4. Tissue-specific expression and post-translational modifications of plant- and bacterial-type phosphoenolpyruvate carboxylase isozymes of the castor oil plant, Ricinus communis L.

    Science.gov (United States)

    O’Leary, Brendan; Fedosejevs, Eric T.; Hill, Allyson T.; Bettridge, James; Park, Joonho; Rao, Srinath K.; Leach, Craig A.; Plaxton, William C.

    2011-01-01

    This study employs transcript profiling together with immunoblotting and co-immunopurification to assess the tissue-specific expression, protein:protein interactions, and post-translational modifications (PTMs) of plant- and bacterial-type phosphoenolpyruvate carboxylase (PEPC) isozymes (PTPC and BTPC, respectively) in the castor plant, Ricinus communis. Previous studies established that the Class-1 PEPC (PTPC homotetramer) of castor oil seeds (COS) is activated by phosphorylation at Ser-11 and inhibited by monoubiquitination at Lys-628 during endosperm development and germination, respectively. Elimination of photosynthate supply to developing COS by depodding caused the PTPC of the endosperm and cotyledon to be dephosphorylated, and then subsequently monoubiquitinated in vivo. PTPC monoubiquitination rather than phosphorylation is widespread throughout the castor plant and appears to be the predominant PTM of Class-1 PEPC that occurs in planta. The distinctive developmental patterns of PTPC phosphorylation versus monoubiquitination indicates that these two PTMs are mutually exclusive. By contrast, the BTPC: (i) is abundant in the inner integument, cotyledon, and endosperm of developing COS, but occurs at low levels in roots and cotyledons of germinated COS, (ii) shows a unique developmental pattern in leaves such that it is present in leaf buds and young expanding leaves, but undetectable in fully expanded leaves, and (iii) tightly interacts with co-expressed PTPC to form the novel and allosterically-desensitized Class-2 PEPC heteromeric complex. BTPC and thus Class-2 PEPC up-regulation appears to be a distinctive feature of rapidly growing and/or biosynthetically active tissues that require a large anaplerotic flux from phosphoenolpyruvate to replenish tricarboxylic acid cycle C-skeletons being withdrawn for anabolism. PMID:21841182

  5. Tissue-specific models of spinal muscular atrophy confirm a critical role of SMN in motor neurons from embryonic to adult stages.

    Science.gov (United States)

    Laird, Angela S; Mackovski, Nikolce; Rinkwitz, Silke; Becker, Thomas S; Giacomotto, Jean

    2016-05-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disease linked to survival motor neuron (SMN) protein deficiency. While SMN protein is expressed ubiquitously, its deficiency triggers tissue-specific hallmarks, including motor neuron death and muscle atrophy, leading to impaired motor functions and premature death. Here, using stable miR-mediated knockdown technology in zebrafish, we developed the first vertebrate system allowing transgenic spatio-temporal control of the smn1 gene. Using this new model it is now possible to investigate normal and pathogenic SMN function(s) in specific cell types, independently or in synergy with other cell populations. We took advantage of this new system to first test the effect of motor neuron or muscle-specific smn1 silencing. Anti-smn1 miRNA expression in motor neurons, but not in muscles, reproduced SMA hallmarks, including abnormal motor neuron development, poor motor function and premature death. Interestingly, smn1 knockdown in motor neurons also induced severe late-onset phenotypes including scoliosis-like body deformities, weight loss, muscle atrophy and, seen for the first time in zebrafish, reduction in the number of motor neurons, indicating motor neuron degeneration. Taken together, we have developed a new transgenic system allowing spatio-temporal control of smn1 expression in zebrafish, and using this model, we have demonstrated that smn1 silencing in motor neurons alone is sufficient to reproduce SMA hallmarks in zebrafish. It is noteworthy that this research is going beyond SMA as this versatile gene-silencing transgenic system can be used to knockdown any genes of interest, filling the gap in the zebrafish genetic toolbox and opening new avenues to study gene functions in this organism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Generalized min-max bound-based MRI pulse sequence design framework for wide-range T1 relaxometry: A case study on the tissue specific imaging sequence.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    Full Text Available This paper proposes a new design strategy for optimizing MRI pulse sequences for T1 relaxometry. The design strategy optimizes the pulse sequence parameters to minimize the maximum variance of unbiased T1 estimates over a range of T1 values using the Cramér-Rao bound. In contrast to prior sequences optimized for a single nominal T1 value, the optimized sequence using our bound-based strategy achieves improved precision and accuracy for a broad range of T1 estimates within a clinically feasible scan time. The optimization combines the downhill simplex method with a simulated annealing process. To show the effectiveness of the proposed strategy, we optimize the tissue specific imaging (TSI sequence. Preliminary Monte Carlo simulations demonstrate that the optimized TSI sequence yields improved precision and accuracy over the popular driven-equilibrium single-pulse observation of T1 (DESPOT1 approach for normal brain tissues (estimated T1 700-2000 ms at 3.0T. The relative mean estimation error (MSE for T1 estimation is less than 1.7% using the optimized TSI sequence, as opposed to less than 7.0% using DESPOT1 for normal brain tissues. The optimized TSI sequence achieves good stability by keeping the MSE under 7.0% over larger T1 values corresponding to different lesion tissues and the cerebrospinal fluid (up to 5000 ms. The T1 estimation accuracy using the new pulse sequence also shows improvement, which is more pronounced in low SNR scenarios.

  7. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease.

    Science.gov (United States)

    Lu, Qiongshi; Powles, Ryan L; Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

    2017-07-01

    Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson's disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.

  8. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease

    Science.gov (United States)

    Abdallah, Sarah; Ou, Derek; Wang, Qian; Hu, Yiming; Lu, Yisi; Liu, Wei; Li, Boyang; Mukherjee, Shubhabrata; Crane, Paul K.; Zhao, Hongyu

    2017-01-01

    Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer’s disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson’s disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline. PMID:28742084

  9. Tissue specific expression of potent insecticidal, Allium sativum leaf agglutinin (ASAL) in important pulse crop, chickpea (Cicer arietinum L.) to resist the phloem feeding Aphis craccivora.

    Science.gov (United States)

    Chakraborti, Dipankar; Sarkar, Anindya; Mondal, Hossain Ali; Das, Sampa

    2009-08-01

    The phloem sap-sucking hemipteran insect, Aphis craccivora, commonly known as cowpea aphid, cause major yield loss of important food legume crop chickpea. Among different plant lectins Allium sativum leaf agglutinin (ASAL), a mannose binding lectin was found to be potent antifeedant for sap sucking insect A. craccivora. Present study describes expression of ASAL in chickpea through Agrobacterium-mediated transformation of "single cotyledon with half embryo" explant. ASAL was expressed under the control of CaMV35S promoter for constitutive expression and phloem specific rolC promoter for specifically targeting the toxin at feeding site, using pCAMBIA2301 vector containing plant selection marker nptII. Southern blot analysis demonstrated the integration and copy number of chimeric ASAL gene in chickpea and its inheritance in T(1) and T(2) progeny plants. Expression of ASAL in T(0) and T(1) plants was confirmed through northern and western blot analysis. The segregation pattern of ASAL transgene was observed in T(1) progenies, which followed the 3:1 Mendelian ratio. Enzyme linked immunosorbant assay (ELISA) determined the level of ASAL expression in different transgenic lines in the range of 0.08-0.38% of total soluble protein. The phloem tissue specific expression of ASAL gene driven by rolC promoter has been monitored by immunolocalization analysis of mature stem sections. Survival and fecundity of A. craccivora decreased to 11-26% and 22-42%, respectively when in planta bioassay conducted on T(1) plants compared to untransformed control plant which showed 85% survival. Thus, through unique approach of phloem specific expression of novel insecticidal lectin (ASAL), aphid resistance has been successfully achieved in chickpea.

  10. Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Pradhan, Seema; Kant, Chandra; Verma, Subodh; Bhatia, Sabhyata

    2017-01-01

    The CCCH zinc finger is a group of proteins characterised by a typical motif consisting of three cysteine residues and one histidine residue. These proteins have been reported to play important roles in regulation of plant growth, developmental processes and environmental responses. In the present study, genome wide analysis of the CCCH zinc finger gene family was carried out in the available chickpea genome. Various bioinformatics tools were employed to predict 58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were analysed for their physio-chemical properties. Phylogenetic analysis classified the proteins into 12 groups in which members of a particular group had similar structural organization. Further, the numbers as well as the types of CCCH motifs present in the CarC3H proteins were compared with those from Arabidopsis and Medicago truncatula. Synteny analysis revealed valuable information regarding the evolution of this gene family. Tandem and segmental duplication events were identified and their Ka/Ks values revealed that the CarC3H gene family in chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR expression analysis was performed which helped in identification of several CarC3H members that expressed preferentially in specific chickpea tissues as well as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular characterization of an important member CarC3H45 was carried out. This study provides comprehensive genomic information about the important CCCH zinc finger gene family in chickpea. The identified tissue specific and abiotic stress specific CCCH genes could be potential candidates for further characterization to delineate their functional roles in development and stress.

  11. Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

    Science.gov (United States)

    Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

    2015-01-01

    The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

  12. Alternative Remedies

    Science.gov (United States)

    ... Home › Aging & Health A to Z › Alternative Remedies Font ... medical treatment prescribed by their healthcare provider. Using this type of alternative therapy along with traditional treatments is ...

  13. Alternative Fuels

    Science.gov (United States)

    Alternative fuels include gaseous fuels such as hydrogen, natural gas, and propane; alcohols such as ethanol, methanol, and butanol; vegetable and waste-derived oils; and electricity. Overview of alternative fuels is here.

  14. Alternating Hemiplegia

    Science.gov (United States)

    ... to the symptoms of the disorder. View Full Definition Treatment Drug therapy including verapamil may help to reduce the ... the more serious form of alternating hemiplegia × ... Definition Alternating hemiplegia is a rare neurological disorder that ...

  15. The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

    International Nuclear Information System (INIS)

    Mesarosova, Monika; Valovicova, Zuzana; Srancikova, Annamaria; Krajcovicova, Zdenka; Milcova, Alena; Sokolova, Romana; Schmuczerova, Jana; Topinka, Jan; Gabelova, Alena

    2011-01-01

    The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). A slight but significant level of gene mutations and DNA adducts detected in V79MZh3A4 cells treated with N-MeDBC, only at the highest concentration (30 μM), revealed that this sarcomagenic carcinogen was also metabolized by hCYP3A4. Surprisingly, DBC increased the frequency of 6-thioguanine resistant (6-TG r ) mutations only at the highest concentration (30 μM), while DiMeDBC failed to increase the frequency of these mutations. The resistance to 6-thioguanine is caused by the mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene. The molecular analysis of the coding region of Hprt gene showed a deletion of the entire exon 8 in DiMeDBC-induced 6-TG r mutants, while no changes in the nucleotide sequences were identified in 6-TG r mutants produced by DBC and N-MeDBC. Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism. - Highlights: → DBC activation via CYP3A4 resulted in micronuclei, DNA adduct formation and mutations in V79MZh3A4 cells. → The CYP3A4-mediated DiMeDBC activation caused micronuclei followed by apoptosis in V79MZh3A4 cells. → The genotoxic effects produced by N-MeDBC in V79MZh3A4 cells were negligible. → The hCYP3A4 may play an important role in DBC and DiMeDBC metabolism. → The CYP3A4 might only have a marginal function in N

  16. Tissue-specific in vivo genetic toxicity of nine polycyclic aromatic hydrocarbons assessed using the Muta™Mouse transgenic rodent assay

    Energy Technology Data Exchange (ETDEWEB)

    Long, Alexandra S., E-mail: alexandra.long@hc-sc.gc.ca [Faculty of Graduate and Postdoctoral Studies, Department of Biology, University of Ottawa, Ottawa, ON (Canada); Mechanistic Studies Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON (Canada); Lemieux, Christine L. [Air Health Science Division, Water and Air Quality Bureau, Health Canada, Ottawa, ON (Canada); Arlt, Volker M. [Analytical and Environmental Sciences Division, MRC-PHE Centre for Environment and Health, King' s College London, London (United Kingdom); White, Paul A. [Faculty of Graduate and Postdoctoral Studies, Department of Biology, University of Ottawa, Ottawa, ON (Canada); Mechanistic Studies Division, Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON (Canada)

    2016-01-01

    haematopoietic tissue. • Tissue-specific results are likely related to metabolism, repair, and proliferation. • For oral exposures, it is important to examine effects at the site-of-contact.

  17. Pm55, a developmental-stage and tissue-specific powdery mildew resistance gene introgressed from Dasypyrum villosum into common wheat.

    Science.gov (United States)

    Zhang, Ruiqi; Sun, Bingxiao; Chen, Juan; Cao, Aizhong; Xing, Liping; Feng, Yigao; Lan, Caixia; Chen, Peidu

    2016-10-01

    Powdery mildew resistance gene Pm55 was physically mapped to chromosome arm 5VS FL 0.60-0.80 of Dasypyrum villosum . Pm55 is present in T5VS·5AL and T5VS·5DL translocations, which should be valuable resources for wheat improvement. Powdery mildew caused by Blumeria graminis f. sp. tritici is a major wheat disease worldwide. Exploiting novel genes effective against powdery mildew from wild relatives of wheat is a promising strategy for controlling this disease. To identify novel resistance genes for powdery mildew from Dasypyrum villosum, a wild wheat relative, we evaluated a set of Chinese Spring-D. villosum disomic addition and whole-arm translocation lines for reactions to powdery mildew. Based on the evaluation data, we concluded that the D. villosum chromosome 5V controls post-seedling resistance to powdery mildew. Subsequently, three introgression lines were developed and confirmed by molecular and cytogenetic analysis following ionizing radiation of the pollen of a Chinese Spring-D. villosum 5V disomic addition line. A homozygous T5VS·5AL translocation line (NAU421) with good plant vigor and full fertility was further characterized using sequential genomic in situ hybridization, C-banding, and EST-STS marker analysis. A dominant gene permanently named Pm55 was located in chromosome bin 5VS 0.60-0.80 based on the responses to powdery mildew of all wheat-D. villosum 5V introgression lines evaluated at both seeding and adult stages. This study demonstrated that Pm55 conferred growth-stage and tissue-specific dependent resistance; therefore, it provides a novel resistance type for powdery mildew. The T5VS·5AL translocation line with additional softness loci Dina/Dinb of D. villosum provides a possibility of extending the range of grain textures to a super-soft category. Accordingly, this stock is a new source of resistance to powdery mildew and may be useful in both resistance mechanism studies and soft wheat improvement.

  18. Prolactin receptor, growth hormone receptor, and putative somatolactin receptor in Mozambique tilapia: tissue specific expression and differential regulation by salinity and fasting.

    Science.gov (United States)

    Pierce, A L; Fox, B K; Davis, L K; Visitacion, N; Kitahashi, T; Hirano, T; Grau, E G

    2007-01-01

    , liver levels of GHR1 and GHR2 transcripts, and liver and muscle levels of IGF-I transcripts were unaffected by fasting. These results clearly indicate tissue specific expression and differential physiological regulation of GH family receptors in the tilapia.

  19. A study of alternative splicing in the pig

    Directory of Open Access Journals (Sweden)

    Jørgensen Claus B

    2010-05-01

    Full Text Available Abstract Background Since at least half of the genes in mammalian genomes are subjected to alternative splicing, alternative pre-mRNA splicing plays an important contribution to the complexity of the mammalian proteome. Expressed sequence tags (ESTs provide evidence of a great number of possible alternative isoforms. With the EST resource for the domestic pig now containing more than one million porcine ESTs, it is possible to identify alternative splice forms of the individual transcripts in this species from the EST data with some confidence. Results The pig EST data generated by the Sino-Danish Pig Genome project has been assembled with publicly available ESTs and made available in the PigEST database. Using the Distiller package 2,515 EST clusters with candidate alternative isoforms were identified in the EST data with high confidence. In agreement with general observations in human and mouse, we find putative splice variants in about 30% of the contigs with more than 50 ESTs. Based on the criteria that a minimum of two EST sequences confirmed each splice event, a list of 100 genes with the most distinct tissue-specific alternative splice events was generated from the list of candidates. To confirm the tissue specificity of the splice events, 10 genes with functional annotation were randomly selected from which 16 individual splice events were chosen for experimental verification by quantitative PCR (qPCR. Six genes were shown to have tissue specific alternatively spliced transcripts with expression patterns matching those of the EST data. The remaining four genes had tissue-restricted expression of alternative spliced transcripts. Five out of the 16 splice events that were experimentally verified were found to be putative pig specific. Conclusions In accordance with human and rodent studies we estimate that approximately 30% of the porcine genes undergo alternative splicing. We found a good correlation between EST predicted tissue-specificity

  20. Depolarization-mediated regulation of alternative splicing

    Directory of Open Access Journals (Sweden)

    Alok eSharma

    2011-12-01

    Full Text Available Alternative splicing in eukaryotes plays an important role in regulating gene expression by selectively including alternative exons. A wealth of information has been accumulated that explains how alternative exons are selected in a developmental stage- or tissue-specific fashion. However, our knowledge of how cells respond to environmental changes to alter alternative splicing is very limited. For example, although a number of alternative exons have been shown to be regulated by calcium level alterations, the underlying mechanisms are not well understood. As calcium signaling in neurons plays a crucial role in essential neuronal functions such as learning and memory formation, it is important to understand how this process is regulated at every level in gene expression. The significance of the dynamic control of alternative splicing in response to changes of calcium levels has been largely unappreciated. In this communication, we will summarize the recent advances in calcium signaling-mediated alternative splicing that have provided some insights into the important regulatory mechanisms. In addition to describing the cis-acting RNA elements on the pre-mRNA molecules that respond to changes of intracellular calcium levels, we will summarize how splicing regulators change and affect alternative splicing in this process. We will also discuss a novel mode of calcium-mediated splicing regulation at the level of chromatin structure and transcription.

  1. Alternative wastewatersystems

    DEFF Research Database (Denmark)

    Dyck-Madsen, Søren; Hoffmann, Birgitte; Gabriel, Søren

    1999-01-01

    The report:-  Communicates experiences from Swedish buildings from the establishment and running of alternative wastewater systems. Communicates pictures of alternative buildings and wastewater systems in Sweden. Gives a short evaluation of the performance and the sustainability of the systems....

  2. How alternative are alternative fuels?

    OpenAIRE

    Soffritti, Tiziana; Danielis, Romeo

    1998-01-01

    Could alternative fuel vehicles contribute to a substantial reduction of air pollution? Is there a market for alternative fuel vehicles? Could a market be created via a pollution tax? The article answers these questions on the basis of the available estimates.

  3. Alternative detox.

    Science.gov (United States)

    Ernst, E

    2012-01-01

    The concept that alternative therapies can eliminate toxins and toxicants from the body, i.e. 'alternative detox' (AD) is popular. Selected textbooks and articles on the subject of AD. The principles of AD make no sense from a scientific perspective and there is no clinical evidence to support them. The promotion of AD treatments provides income for some entrepreneurs but has the potential to cause harm to patients and consumers. In alternative medicine, simplistic but incorrect concepts such as AD abound. AREAS TIMELY FOR RESEARCH: All therapeutic claims should be scientifically tested before being advertised-and AD cannot be an exception.

  4. Cosmic alternatives?

    Science.gov (United States)

    Gregory, Ruth

    2009-04-01

    "Cosmologists are often in error but never in doubt." This pithy characterization by the Soviet physicist Lev Landau sums up the raison d'être of Facts and Speculations in Cosmology. Authors Jayant Narlikar and Geoffrey Burbidge are proponents of a "steady state" theory of cosmology, and they argue that the cosmological community has become fixated on a "Big Bang" dogma, suppressing alternative viewpoints. This book very much does what it says on the tin: it sets out what is known in cosmology, and puts forward the authors' point of view on an alternative to the Big Bang.

  5. Growing Alternatives

    DEFF Research Database (Denmark)

    Bagger-Petersen, Mai Corlin

    2014-01-01

    From 2014, Anhui Province will pilot a reform of the residential land market in China, thus integrating rural Anhui in the national housing market. In contrast, artist and activist Ou Ning has proposed the Bishan time money currency, intending to establish an alternative economic circuit in Bishan...

  6. Alternative Veier

    DEFF Research Database (Denmark)

    Kruse, Tove Elisabeth; Salamonsen, Anita

    reflektioner omkring patienters brug af og erfaringer med alternativ behandling. Patientorganisationer, organisatoner for alternative behandlere og organisationer for læger og medicinstuderende har læst bogens patienthistorier og deres perspektiver lægges frem. Til slut i bogen diskuteres betydningen af de...

  7. An Intergenic Region Shared by At4g35985 and At4g35987 in Arabidopsis thaliana Is a Tissue Specific and Stress Inducible Bidirectional Promoter Analyzed in Transgenic Arabidopsis and Tobacco Plants

    Science.gov (United States)

    Banerjee, Joydeep; Sahoo, Dipak Kumar; Dey, Nrisingha; Houtz, Robert L.; Maiti, Indu Bhushan

    2013-01-01

    On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85) showed stronger expression (about 3.5 fold) compared to the At4g35987 promoter (P87). The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold) under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications. PMID:24260266

  8. Tissue-Specific Transcriptome and Hormonal Regulation of Pollinated and Parthenocarpic Fig (Ficus carica L. Fruit Suggest that Fruit Ripening is Coordinated by the Reproductive Part of the Syconium

    Directory of Open Access Journals (Sweden)

    Yogev Rosianski

    2016-11-01

    Full Text Available In the unconventional climacteric fig (Ficus carica fruit, pollinated and parthenocarpic fruit of the same genotype exhibit different ripening characteristics. Integrative comparative analyses of tissue-specific transcript and of hormone levels during fruit repining from pollinated vs. parthenocarpic fig fruit were employed to unravel the similarities and differences in their regulatory processes during fruit repining. Assembling tissue-specific transcripts into 147,000 transcripts with 53,000 annotated genes provided new insights into the spatial distribution of many classes of regulatory and structural genes, including those related to color, taste and aroma, storage, protein degradation, seeds and embryos, chlorophyll, and hormones. Comparison of the pollinated and parthenocarpic tissues during fruit ripening showed differential gene expression, especially in the fruit inflorescence. The distinct physiological green phase II and ripening phase III differed significantly in their gene-transcript patterns in both pulp and inflorescence tissues. Gas chromatographic analysis of whole fruits enabled the first determination of ripening-related hormone levels from pollinated and non-pollinated figs. Ethylene and auxin both increased during fruit ripening, irrespective of pollination, whereas no production of active gibberellins or cytokinins was found in parthenocarpic or pollinated ripening fruit. Tissue-specific transcriptome revealed apparent different metabolic gene patterns for ethylene, auxin and ABA in pollinated vs. parthenocarpic fruit, mostly in the fruit inflorescence. Our results demonstrate that the production of abscisic acid (ABA, non-active ABA–GE conjugate and non-active indoleacetic acid (IAA–Asp conjugate in pollinated fruits is much higher than in parthenocarpic fruits. We suggest that fruit ripening is coordinated by the reproductive part of the syconium and the differences in ABA production between pollinated and

  9. An intergenic region shared by At4g35985 and At4g35987 in Arabidopsis thaliana is a tissue specific and stress inducible bidirectional promoter analyzed in transgenic arabidopsis and tobacco plants.

    Directory of Open Access Journals (Sweden)

    Joydeep Banerjee

    Full Text Available On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985 are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85 showed stronger expression (about 3.5 fold compared to the At4g35987 promoter (P87. The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications.

  10. Energy alternatives

    International Nuclear Information System (INIS)

    Sweet, C.

    1987-01-01

    The designated successor to fossil fuels is nuclear fission/fusion and that turns out to be problematic. Alternative Energy Systems have great potential but political forces seem to be hampering their development and introduction. The technologies are flexible in their use and scale of operation. The learning curve will not be short but neither will it be as long and as costly as nuclear power. It is time that this is recognised and some serious rethinking takes place in what presently passes for energy policies both in the industrialised countries and in the Third World. Alternative energy systems are defined and some of them which are relevant to the United Kingdom are discussed. (author)

  11. Alternative detente

    International Nuclear Information System (INIS)

    Soper, K.; Ryle, M.

    1988-01-01

    The influence of the Chernobyl accident on the disarmament and anti-nuclear movements is discussed. The accident directed attention towards the areas in common rather than the areas of disagreement. It also demonstrated the environmental impact of radioactivity, strengthening the ecological case of the anti-nuclear movement. The issues are discussed for the Western and Eastern bloc countries and the relationship between the two. Sections focus on the Eco-protest, Green politics and economics and on the politics of minority protest and the Green alternative. (U.K.)

  12. Alternative crops

    International Nuclear Information System (INIS)

    Andreasen, L.M.; Boon, A.D.

    1992-01-01

    Surplus cereal production in the EEC and decreasing product prices, mainly for cereals, has prompted considerable interest for new earnings in arable farming. The objective was to examine whether suggested new crops (fibre, oil, medicinal and alternative grains crops) could be considered as real alternatives. Whether a specific crop can compete economically with cereals and whether there is a market demand for the crop is analyzed. The described possibilities will result in ca. 50,000 hectares of new crops. It is expected that they would not immediately provide increased earnings, but in the long run expected price developments are more positive than for cereals. The area for new crops will not solve the current surplus cereal problem as the area used for new crops is only 3% of that used for cereals. Preconditions for many new crops is further research activities and development work as well as the establishment of processing units and organizational initiatives. Presumably, it is stated, there will then be a basis for a profitable production of new crops for some farmers. (AB) (47 refs.)

  13. Energy alternatives

    International Nuclear Information System (INIS)

    1981-01-01

    English. A special committe of the Canadian House of Commons was established on 23 May 1980 to investigate the use of alternative energy sources such as 'gasohol', liquified coal, solar energy, methanol, wind and tidal power, biomass, and propane. In its final report, the committee envisions an energy system for Canada based on hydrogen and electricity, using solar and geothermal energy for low-grade heat. The committe was not able to say which method of generating electricty would dominate in the next century, although it recommends that fossil fuels should not be used. The fission process is not specifically discussed, but the outlook for fusion was investigated, and continued governmental support of fusion research is recommended. The report proposes some improvements in governmental energy organizations and programs

  14. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  15. Tissue-specific and pathogen-inducible expression of a fusion protein containing a Fusarium-specific antibody and a fungal chitinase protects wheat against Fusarium pathogens and mycotoxins.

    Science.gov (United States)

    Cheng, Wei; Li, He-Ping; Zhang, Jing-Bo; Du, Hong-Jie; Wei, Qi-Yong; Huang, Tao; Yang, Peng; Kong, Xian-Wei; Liao, Yu-Cai

    2015-06-01

    Fusarium head blight (FHB) in wheat and other small grain cereals is a globally devastating disease caused by toxigenic Fusarium pathogens. Controlling FHB is a challenge because germplasm that is naturally resistant against these pathogens is inadequate. Current control measures rely on fungicides. Here, an antibody fusion comprised of the Fusarium spp.-specific recombinant antibody gene CWP2 derived from chicken, and the endochitinase gene Ech42 from the biocontrol fungus Trichoderma atroviride was introduced into the elite wheat cultivar Zhengmai9023 by particle bombardment. Expression of this fusion gene was regulated by the lemma/palea-specific promoter Lem2 derived from barley; its expression was confirmed as lemma/palea-specific in transgenic wheat. Single-floret inoculation of independent transgenic wheat lines of the T3 to T6 generations revealed significant resistance (type II) to fungal spreading, and natural infection assays in the field showed significant resistance (type I) to initial infection. Gas chromatography-mass spectrometry analysis revealed marked reduction of mycotoxins in the grains of the transgenic wheat lines. Progenies of crosses between the transgenic lines and the FHB-susceptible cultivar Huamai13 also showed significantly enhanced FHB resistance. Quantitative real-time PCR analysis revealed that the tissue-specific expression of the antibody fusion was induced by salicylic acid drenching and induced to a greater extent by F. graminearum infection. Histochemical analysis showed substantial restriction of mycelial growth in the lemma tissues of the transgenic plants. Thus, the combined tissue-specific and pathogen-inducible expression of this Fusarium-specific antibody fusion can effectively protect wheat against Fusarium pathogens and reduce mycotoxin content in grain. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  16. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    International Nuclear Information System (INIS)

    Kwong, Raymond W.M.; Andres, Jose A.; Niyogi, Som

    2011-01-01

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  17. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    Energy Technology Data Exchange (ETDEWEB)

    Kwong, Raymond W.M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Andres, Jose A. [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada)

    2011-03-15

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  18. Influence of elevated alkalinity and natural organic matter (NOM) on tissue-specific metal accumulation and reproductive performance in fathead minnows during chronic, multi-trophic exposures to a metal mine effluent.

    Science.gov (United States)

    Ouellet, Jacob D; Dubé, Monique G; Niyogi, Som

    2013-09-01

    Metal bioavailability in aquatic organisms is known to be influenced by various water chemistry parameters. The present study examined the influence of alkalinity and natural organic matter (NOM) on tissue-specific metal accumulation and reproductive performance of fathead minnows (Pimephales promelas) during environmentally relevant chronic exposures to a metal mine effluent (MME). Sodium bicarbonate (NaHCO3) or NOM (as commercial humic acid) were added to a Canadian MME [45 percent process water effluent (PWE)] in order to evaluate whether increases in alkalinity (3-4 fold) or NOM (~1.5-3mg/L dissolved organic carbon) would reduce metal accumulation and mitigate reproductive toxicity in fathead minnows during a 21-day multi-trophic exposure. Eleven metals (barium, boron, cobalt, copper, lithium, manganese, molybdenum, nickel, rubidium, selenium, and strontium) were elevated in the 45 percent PWE relative to the reference water. Exposure to the unmodified 45 percent PWE resulted in a decrease of fathead minnow egg production (~300 fewer eggs/pair) relative to the unmodified reference water, over the 21-day exposure period. Water chemistry modifications produced a modest decrease in free ion activity of some metals (as shown by MINTEQ, Version 3) in the 45 percent PWE exposure water, but did not alter the metal burden in the treatment-matched larval Chironomus dilutus (the food source of fish during exposure). The tissue-specific metal accumulation increased in fish exposed to the 45 percent PWE relative to the reference water, irrespective of water chemistry modifications, and the tissue metal concentrations were found to be similar between fish in the unmodified and modified 45 percent PWE (higher alkalinity or NOM) treatments. Interestingly however, increased alkalinity and NOM markedly improved fish egg production both in the reference water (~500 and ~590 additional eggs/pair, respectively) and 45 percent PWE treatments (~570 and ~260 additional eggs

  19. A comparative tissue-specific metabolite analysis and determination of protodioscin content in Asparagus species used in traditional Chinese medicine and Ayurveda by use of laser microdissection, UHPLC-QTOF/MS and LC-MS/MS.

    Science.gov (United States)

    Jaiswal, Yogini; Liang, Zhitao; Ho, Alan; Chen, Hubiao; Zhao, Zhongzhen

    2014-01-01

    Asparagus is esteemed in Traditional Chinese Medicine and Ayurveda, and it is commercially one of the most important drugs in the global herbal market. Comparative metabolite profiling of different species would help in determining the similarities and ascertain their validity for being used as substitutes for each other. Laser microdissection (LMD) facilitates identification of metabolites in specific tissues, and thus it can aid in exploration of metabolic pathways in target tissues. To compare tissue-specific metabolites and protodioscin content of Asparagus cochinchinensis (Lour.) Merr. and Asparagus racemosus Willd. used in China and India. Metabolite analysis of laser-dissected tissues was carried out using UHPLC-QTOF/MS and LC-MS/MS. The protodioscin contents were determined and the method was validated as per the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. Metabolite analysis reveals that the velamen tissue, among other tissues such as cortex, vascular bundles and pith, contained maximum components, specifically those belonging to the steroidal saponin class. Although the metabolite profiles were similar, the content of protodioscin was found to be higher in Chinese than Indian species. The study provided a suitable methodology for metabolite profiling and protodioscin content determination of Asparagus by use of LMD, UHPLC-QTOF/MS and LC-MS/MS. The similarities in metabolite profiles indicate that Asparagus species from India and China can serve as substitute for each other in various therapeutic and pharmaceutical applications. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Alternative Fuel Guidelines for Alternative Transportation Systems.

    Science.gov (United States)

    2011-01-31

    The Volpe Center documented the increased use of alternative fuels on vehicles owned and operated by federal land management agencies. For each alternative fuel type, the Volpe Center documented the availability of vehicles, fueling mechanisms and pr...

  1. Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing.

    Science.gov (United States)

    Castle, John; Garrett-Engele, Phil; Armour, Christopher D; Duenwald, Sven J; Loerch, Patrick M; Meyer, Michael R; Schadt, Eric E; Stoughton, Roland; Parrish, Mark L; Shoemaker, Daniel D; Johnson, Jason M

    2003-01-01

    Microarrays offer a high-resolution means for monitoring pre-mRNA splicing on a genomic scale. We have developed a novel, unbiased amplification protocol that permits labeling of entire transcripts. Also, hybridization conditions, probe characteristics, and analysis algorithms were optimized for detection of exons, exon-intron edges, and exon junctions. These optimized protocols can be used to detect small variations and isoform mixtures, map the tissue specificity of known human alternative isoforms, and provide a robust, scalable platform for high-throughput discovery of alternative splicing.

  2. Targeted Expression of Stromelysin-1 in Mammary Gland Provides Evidence for a Role of Proteinases in Branching Morphogenesis and the Requirement for an Intact Basement Membrane for Tissue-specific Gene Expression

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Talhouk, Rabih S; Alexander, Caroline M; Chin, Jennie R; Cliff, Shirley M; Bissell, Mina J; Werb, Zena

    1994-05-01

    The extracellular matrix (ECM) is an important regulator of the differentiated phenotype of mammary epithelial cells in culture. Despite the fact that ECM-degrading enzymes have been implicated in morphogenesis and tissue remodeling, there is little evidence for a direct role for such regulation in vivo. We generated transgenic mice that express autoactivated isoforms of the matrix metalloproteinase stromelysin-1, under the control of the whey acidic protein gene promoter, to examine the effect of inappropriate expression of this enzyme. Stromelysin-1 is implicated as the primary player in the loss of basement membrane and loss of function in the mammary gland during involution. The transgene was expressed at low levels in mammary glands of virgin female mice, leading to an unexpected phenotype: The primary ducts had supernumerary branches and showed precocious development of alveoli that expressed beta-casein at levels similar to that of an early- to mid-pregnant gland. Lactating glands showed high levels of transgene expression, with accumulation at the basement membrane, and a decrease in laminin and collagen IV, resulting in a loss of basement membrane integrity; this was accompanied by a dramatic alteration of alveolar morphology, with decreased size and shrunken lumina containing little beta-casein. During pregnancy, expression of endogenous whey acidic protein and beta-casein was reduced in transgenic glands, confirming the observed dependence of milk protein transcription of ECM in mammary epithelial cells in culture. These data provide direct evidence that stromelysin-1 activity can be morphogenic for mammary epithelial cells, inducing hyperproliferation and differentiation in virgin animals, and that its lytic activity can, indeed, disrupt membrane integrity and reduce mammary-specific function. We conclude that the balance of ECM-degrading enzymes with their inhibitors, and the associated regulation of ECM structure, is crucial for tissue-specific gene

  3. 3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: A step towards advanced skin tissue engineering.

    Science.gov (United States)

    Kim, Byoung Soo; Kwon, Yang Woo; Kong, Jeong-Sik; Park, Gyu Tae; Gao, Ge; Han, Wonil; Kim, Moon-Bum; Lee, Hyungseok; Kim, Jae Ho; Cho, Dong-Woo

    2018-06-01

    3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment. In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Alternate superior Julia sets

    International Nuclear Information System (INIS)

    Yadav, Anju; Rani, Mamta

    2015-01-01

    Alternate Julia sets have been studied in Picard iterative procedures. The purpose of this paper is to study the quadratic and cubic maps using superior iterates to obtain Julia sets with different alternate structures. Analytically, graphically and computationally it has been shown that alternate superior Julia sets can be connected, disconnected and totally disconnected, and also fattier than the corresponding alternate Julia sets. A few examples have been studied by applying different type of alternate structures

  5. Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner

    International Nuclear Information System (INIS)

    Al-Salman, Fadheela; Plant, Nick

    2012-01-01

    The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation of PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ► Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ► PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ► Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ► Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ► PCB153 is the most potent activator of PXR/CAR target gene in all tissues.

  6. Complementary and Alternative Medicine

    Science.gov (United States)

    ... for Educators Search English Español Complementary and Alternative Medicine KidsHealth / For Teens / Complementary and Alternative Medicine What's ... a replacement. How Is CAM Different From Conventional Medicine? Conventional medicine is based on scientific knowledge of ...

  7. Alternative way of life

    International Nuclear Information System (INIS)

    Fischer, C.

    1980-01-01

    The volume describes the reasons why more and more people seek alternative ways of life, the theoretical background and what alternative life means in practice as well as the sociological significance and history of the alternative movement. It also contains statements of persons who have 'got out' and advice on energy-saving. (HSCH) [de

  8. Depleted uranium management alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Hertzler, T.J.; Nishimoto, D.D.

    1994-08-01

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process.

  9. Depleted uranium management alternatives

    International Nuclear Information System (INIS)

    Hertzler, T.J.; Nishimoto, D.D.

    1994-08-01

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process

  10. Alternative Auditing Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Kandt, Alicen J [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-15

    This presentation for the 2017 Energy Exchange in Tampa, Florida, offers information about advanced auditing technologies and techniques including alternative auditing approaches and considerations and caveats.

  11. Brandmodstandsbidrag for alternative isoleringsmaterialer

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    2001-01-01

    Resume af rapport om alternative isoleringsmaterialers brandmodstandsbidrag, udarbejdet af Dansk Brandteknisk Institut under Energistyrelsens udviklingsprogram "Miljø- og arbejdsmiljøvenlig isolering"......Resume af rapport om alternative isoleringsmaterialers brandmodstandsbidrag, udarbejdet af Dansk Brandteknisk Institut under Energistyrelsens udviklingsprogram "Miljø- og arbejdsmiljøvenlig isolering"...

  12. Anvendelse af alternative isoleringsmaterialer

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place

    2003-01-01

    Resume af By og Byg Anvisning 207 om anvendelse af alternative isoleringsmaterialer, udarbejdet af Statens Byggeforskningsinstitut under udviklingsprogrammet "Miljø- og arbejdsmiljøvenlig isolering"......Resume af By og Byg Anvisning 207 om anvendelse af alternative isoleringsmaterialer, udarbejdet af Statens Byggeforskningsinstitut under udviklingsprogrammet "Miljø- og arbejdsmiljøvenlig isolering"...

  13. Acquisition of Voicing Alternations

    NARCIS (Netherlands)

    Kerkhoff, Annemarie

    "Morpho-phonological alternations are central to phonological theory, but little is known about how they are acquired. Acquiring alternations amounts to dealing with variation in a morpheme’s shape depending on its morphological context. It is generally assumed that children start with an initial

  14. Alternative health insurance schemes

    DEFF Research Database (Denmark)

    Keiding, Hans; Hansen, Bodil O.

    2002-01-01

    In this paper, we present a simple model of health insurance with asymmetric information, where we compare two alternative ways of organizing the insurance market. Either as a competitive insurance market, where some risks remain uninsured, or as a compulsory scheme, where however, the level...... competitive insurance; this situation turns out to be at least as good as either of the alternatives...

  15. Mass spectrometric imaging as a high-spatial resolution tool for functional genomics: Tissue-specific gene expression of TT7 inferred from heterogeneous distribution of metabolites in Arabidopsis flowers

    Energy Technology Data Exchange (ETDEWEB)

    Korte, Andrew R.; Song, Zhihong; Nikolau, Basil J.; Lee, Young Jin

    2011-12-23

    Laser desorption/ionization (LDI) mass spectrometry imaging (MSI) was used to acquire chemical images of flavonoid metabolites on the surface of wild-type and mutant (tt7) Arabidopsis thaliana flowers. Flavonoids were localized to the petals and carpels of flowers, with tissue heterogeneity in the petals. Specifically, kaempferol and/or its glycosides were abundant in the distal region of petals and quercetin and its downstream flavonoids were highly enriched in the more proximal region of petals. As a result of a mutation in the TT7 gene which blocks the conversion of dihydrokaempferol to dihydroquercetin, the downstream metabolites, quercetin, isohamnetin, and their glycosides, were not observed in the mutant flowers. Instead, the metabolites in an alternative pathway, kaempferol and/or its glycosides, were as highly abundant on the proximal region of the petals as in the distal region. In addition, the combined flavonoid amounts on the proximal region of petals in the wild-type are almost equivalent to the amounts of kaempferol and/or its glycosides in the mutant. This strongly suggests that the expression of the TT7 gene is localized on the proximal part of the petal while the other genes in the upper stream pathway are evenly expressed throughout the petal. Most importantly, this work demonstrates MSI of metabolites can be utilized for the localization of gene expression.

  16. HL-LHC alternatives

    CERN Document Server

    Tomás, R; White, S

    2014-01-01

    The HL-LHC parameters assume unexplored regimes for hadron colliders in various aspects of accelerator beam dynamics and technology. This paper reviews three alternatives that could potentially improve the LHC performance: (i) the alternative filling scheme 8b+4e, (ii) the use of a 200 MHz RF system in the LHC and (iii) the use of proton cooling methods to reduce the beam emittance (at top energy and at injection). The alternatives are assessed in terms of feasibility, pros and cons, risks versus benefits and the impact on beam availability.

  17. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  18. Alternative gravity theories

    International Nuclear Information System (INIS)

    Francaviglia, M.

    1990-01-01

    Although general relativity is a well-established discipline the theory deserves efforts aimed at producing alternative or more general frameworks for investigating the classical properties of gravity. These are either devoted to producing alternative viewpoints or interpretations of standard general relativity, or at constructing, discussing and proposing experimental tests for alternative descriptions of the dynamics of the gravitational field and its interaction (or unification) with external matter fields. Classical alternative theories of gravitation can roughly classified as follows; theories based on a still 4-dimensional picture, under the assumption that the dynamics of the gravitational field is more complicated than Einstein's and theories based on higher-dimensional pictures. This leads to supergravity and strings which are not included here. Theories based on higher-dimensional pictures on the assumption that space-time is replaced by a higher-dimensional manifold. Papers on these classifications are reviewed. (author)

  19. Complementary and Alternative Medicine

    Science.gov (United States)

    ... therapies are often lacking; therefore, the safety and effectiveness of many CAM therapies are uncertain. The National Center for Complementary and Alternative Medicine (NCCAM) is sponsoring research designed to fill this ...

  20. Alternative Menopause Treatments

    Science.gov (United States)

    ... menopausal symptoms. These include estrogen—still the most effective treatment for many menopausal symptoms—non-estrogen prescription drugs, and complementary and alternative medicine (CAM). What is CAM? CAM refers to practices ...

  1. Seal design alternatives study

    International Nuclear Information System (INIS)

    Van Sambeek, L.L.; Luo, D.D.; Lin, M.S.; Ostrowski, W.; Oyenuga, D.

    1993-06-01

    This report presents the results from a study of various sealing alternatives for the WIPP sealing system. Overall, the sealing system has the purpose of reducing to the extent possible the potential for fluids (either gas or liquid) from entering or leaving the repository. The sealing system is divided into three subsystems: drift and panel seals within the repository horizon, shaft seals in each of the four shafts, and borehole seals. Alternatives to the baseline configuration for the WIPP seal system design included evaluating different geometries and schedules for seal component installations and the use of different materials for seal components. Order-of-magnitude costs for the various alternatives were prepared as part of the study. Firm recommendations are not presented, but the advantages and disadvantages of the alternatives are discussed. Technical information deficiencies are identified and studies are outlined which can provide required information

  2. Bone Graft Alternatives

    Science.gov (United States)

    ... Spine Treatment Spondylolisthesis BLOG FIND A SPECIALIST Treatments Bone Graft Alternatives Patient Education Committee Patient Education Committee ... procedure such as spinal fusion. What Types of Bone Grafts are There? Bone grafts that are transplanted ...

  3. Alternative Assessment Techniques.

    Science.gov (United States)

    Lowenthal, Barbara

    1988-01-01

    Maintaining the precision necessary for administering norm referenced tests can be a problem for the special education teacher who is trained to assist the student. Criterion-referenced tests, observations, and interviews are presented as effective alternative assessment techniques. (JDD)

  4. Evaluation of Expenditure Alternates

    Science.gov (United States)

    Poehlein, Gary W.; And Others

    1973-01-01

    Illustrates a system of calculating dollar expenditures over periods of time in terms of present value. The system enables planners, school boards, and administrators to compare expenditure alternatives as a decisionmaking factor. (Author)

  5. Alternative fuel cycles

    International Nuclear Information System (INIS)

    Penn, W.J.

    1979-05-01

    Uranium resource utilization and economic considerations provide incentives to study alternative fuel cycles as future options to the PHWR natural uranium cycle. Preliminary studies to define the most favourable alternatives and their possible introduction dates are discussed. The important and uncertain components which influence option selection are reviewed, including nuclear capacity growth, uranium availability and demand, economic potential, and required technological developments. Finally, a summary of Ontario Hydro's program to further assess cycle selection and define development needs is given. (auth)

  6. The alternative library

    OpenAIRE

    Collinson, Timothy; Williams, A.

    2004-01-01

    Much time and effort has been devoted to designing and developing library Web sites that are easy to navigate by both new students and experienced researchers. In a review of the Southampton Institute Library it was decided that in addition to updating the existing homepage an alternative would be offered. Drawing on theory relating to user interface design, learning styles and creative thinking, an Alternative Library navigation system was added to the more traditional library homepage. The ...

  7. Alternative drugs of abuse.

    Science.gov (United States)

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  8. Alternative Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    West, M.; Duckers, L.; Lockett, P.; Loughridge, B.; Peatfield, T.; White, P.

    1984-01-01

    The Coventry (Lanchester) Polytechnic Wave Energy Group has been involved in the United Kingdom wave energy research programme since its inception in 1975. Whilst the work of the group is mainly concerned with wave energy, and currently is directed towards the design of a wave energy device tailored to the needs of isolated/island communities, it has some involvement with other aspects of the alternatives. This conference, dealing with alternative energy systems and their electrical integration and utilisation was engendered by the general interest which the Polytechnic group members have in the alternatives and their use. The scope for electrical integration and utilisation is very broad. Energy for family groups may be provided in a relatively unsophisticated way which is acceptable to them. Small population centres, for example island communities relying upon diesel equipment, can reap the benefits of the alternatives through their ability to accept novel integration schemes and a flexible approach to the use of the energy available. Consumers already enjoying the benefits of a 'firm' electricity grid supply can use energy from a variety of alternative systems, via the grid, without having to modify their energy consumption habits. In addition to the domestic and industrial applications and coastal possibilities, specialist applications in isolated environments have also emerged. The Proceedings detail practical, technical and economic aspects of the alternatives and their electrical integration and utilisation.

  9. A novel CDX2 isoform regulates alternative splicing.

    Directory of Open Access Journals (Sweden)

    Matthew E Witek

    Full Text Available Gene expression is a dynamic and coordinated process coupling transcription with pre-mRNA processing. This regulation enables tissue-specific transcription factors to induce expression of specific transcripts that are subsequently amplified by alternative splicing allowing for increased proteome complexity and functional diversity. The intestine-specific transcription factor CDX2 regulates development and maintenance of the intestinal epithelium by inducing expression of genes characteristic of the mature enterocyte phenotype. Here, sequence analysis of CDX2 mRNA from colonic mucosa-derived tissues revealed an alternatively spliced transcript (CDX2/AS that encodes a protein with a truncated homeodomain and a novel carboxy-terminal domain enriched in serine and arginine residues (RS domain. CDX2 and CDX2/AS exhibited distinct nuclear expression patterns with minimal areas of co-localization. CDX2/AS did not activate the CDX2-dependent promoter of guanylyl cyclase C nor inhibit transcriptional activity of CDX2. Unlike CDX2, CDX2/AS co-localized with the putative splicing factors ASF/SF2 and SC35. CDX2/AS altered splicing patterns of CD44v5 and Tra2-β1 minigenes in Lovo colon cancer cells independent of CDX2 expression. These data demonstrate unique dual functions of the CDX2 gene enabling it to regulate gene expression through both transcription (CDX2 and pre-mRNA processing (CDX2/AS.

  10. Alternative fuels for vehicles; Alternative drivmidler

    Energy Technology Data Exchange (ETDEWEB)

    2012-02-15

    Up until 2020 and onwards the analysis indicates that especially electricity, biogas and natural gas as propellants is economically attractive compared to conventional gasoline and diesel while other fuels have the same or higher costs for petrol and diesel. Especially biogas and electricity will also offer significant reductions in CO{sub 2} emissions, but also hydrogen, methanol, DME and to a lesser extent the second generation bioethanol and most of the other alternative fuels reduce CO{sub 2} emissions. Use of the traditional food-based first generation biofuels involves, at best, only modest climate benefits if land use changes are counted, and at worst, significant negative climate effects. Natural gas as a propellant involves a moderate climate gain, but may play a role for building infrastructure and market for gaseous fuels in large fleets, thereby contributing to the phasing in of biogas for transport. The electric-based automotive fuels are the most effective due to a high efficiency of the engine and an increasing proportion of wind energy in the electricity supply. The methanol track also has a relatively high efficiency. Among the others, the track based on diesel engines (biodiesel) is more effective than the track based on gasoline/Otto engines (gas and ethanol) as a result of the diesel engine's better efficiency. For the heavy vehicles all the selected alternative fuels to varying degrees reduce emissions of CO{sub 2}, particularly DME based on wood. The only exception to this is - as for passenger cars - the propellant synthetic diesel based on coal. (LN).

  11. on some properties of the alternating sylvester series and alternating

    African Journals Online (AJOL)

    DJFLEX

    . (iii) above is known in literature as the alternating Sylvester series while (iv) is known as the alternating Engel expansion (Kalpazidou and Ganatsiou (1991)). We are interested in studying the properties of these alternating series. Theorem 2: ...

  12. Catalysis for alternative energy generation

    CERN Document Server

    2012-01-01

    Summarizes recent problems in using catalysts in alternative energy generation and proposes novel solutions  Reconsiders the role of catalysis in alternative energy generation  Contributors include catalysis and alternative energy experts from across the globe

  13. Alternative pricing methodologies

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    With the increased interest in competitive market forces and growing recognition of the deficiencies in current practices, FERC and others are exploring alternatives to embedded cost pricing. A number of these alternatives are discussed in this chapter. Marketplace pricing, discussed briefly here, is the subject of the next chapter. Obviously, the pricing formula may combine several of these methodologies. One utility of which the authors are aware is seeking a price equal to the sum of embedded costs, opportunity costs, line losses, value of service, FERC's percentage adder formula and a contract service charge

  14. Flued head replacement alternatives

    International Nuclear Information System (INIS)

    Smetters, J.L.

    1987-01-01

    This paper discusses flued head replacement options. Section 2 discusses complete flued head replacement with a design that eliminates the inaccessible welds. Section 3 discusses alternate flued head support designs that can drastically reduce flued head installation costs. Section 4 describes partial flued head replacement designs. Finally, Section 5 discusses flued head analysis methods. (orig./GL)

  15. Alternative inerting agents

    CSIR Research Space (South Africa)

    Du

    1997-08-01

    Full Text Available Final Project Report ALTERNATIVE INERTING AGENTS Author/s: J J L DU PLESSIS Research Agency: OSIR MINING TECHNOLOGY Project No: Date: 3 2 7 2 COL 443 APRIL 1999 N’ ) ( G~6~ I Title: 9 / The results show...

  16. Alternate energy sources

    International Nuclear Information System (INIS)

    Stevens-Guille, P.D.

    1975-01-01

    The author highlights the interesting points made by the speeches during the conference on Energy and its Future in Southern Africa. He also draws attention to potential alternate energy sources such as power from tides, ocean waves, ocean temperature differences and geothermal power

  17. Phrasal alternation in Kerinci

    NARCIS (Netherlands)

    Ernanda, N.

    2017-01-01

    This dissertation is a descriptive study of a linguistic phenomenon known as phrasal alternation, focusing on the Pondok Tinggi (PT) dialect of Kerinci, spoken in Indonesia. In essence, almost every Kerinci word displays two forms, labeled absolute and oblique. These forms differ in the shape of

  18. Alternative Energy Busing

    Science.gov (United States)

    LaFee, Scott

    2012-01-01

    In recent years, school districts have converted portions of their bus fleets to cleaner-burning, sometimes cheaper, alternative fossil fuels, such as compressed natural gas or propane. Others have adopted biodiesel, which combines regular diesel with fuel derived from organic sources, usually vegetable oils or animal fats. The number of biodiesel…

  19. Energy conversion alternatives study

    Science.gov (United States)

    Shure, L. T.

    1979-01-01

    Comparison of coal based energy systems is given. Study identifies and compares various advanced energy conversion systems using coal or coal derived fuels for baselaoad electric power generation. Energy Conversion Alternatives Study (ECAS) reports provede government, industry, and general public with technically consistent basis for comparison of system's options of interest for fossilfired electric-utility application.

  20. Alternatives in solar energy

    Science.gov (United States)

    Schueler, D. G.

    1978-01-01

    Although solar energy has the potential of providing a significant source of clean and renewable energy for a variety of applications, it is expected to penetrate the nation's energy economy very slowly. The alternative solar energy technologies which employ direct collection and conversion of solar radiation as briefly described.

  1. Alternative Work Schedules: Definitions

    Science.gov (United States)

    Journal of the College and University Personnel Association, 1977

    1977-01-01

    The term "alternative work schedules" encompasses any variation of the requirement that all permanent employees in an organization or one shift of employees adhere to the same five-day, seven-to-eight-hour schedule. This article defines staggered hours, flexible working hours (flexitour and gliding time), compressed work week, the task system, and…

  2. Alternatives to Traditional Notation.

    Science.gov (United States)

    Gaare, Mark

    1997-01-01

    Provides a introduction and overview to alternative music notation systems. Describes guitar tablature, accordion tablature, klavarskribo (a keyboard notational system developed by Cornelius Pot, a Dutch engineer), and the digital piano roll. Briefly discusses the history of notation reform and current efforts. Includes examples from scores. (MJP)

  3. Compensated pulsed alternator

    International Nuclear Information System (INIS)

    Weldon, W.F.; Driga, M.D.; Woodson, H.H.

    1980-01-01

    This invention relates to an electromechanical energy converter with inertial energy storage. The device, a single phase, two or multi-pole alternator with stationary field coils, and a rotating armature is provided. The rotor itself may be of laminated steel for slower pulses or for faster pulses should be nonmagnetic and electrically nonconductive in order to allow rapid penetration of the field as the armature coil rotates. The armature coil comprises a plurality of power generating conductors mounted on the rotor. The alternator may also include a stationary or counterrotating compensating coil to increase the output voltage thereof and to reduce the internal impedance of the alternator at the moment of peak output. As the machine voltage rises sinusoidally, an external trigger switch is adapted to be closed at the appropriate time to create the desired output current from said alternator to an external load circuit, and as the output current passes through zero a self-commutating effect is provided to allow the switch to disconnect the generator from the external circuit

  4. TWTF design alternates

    International Nuclear Information System (INIS)

    Ayers, A.L. Sr.

    1982-03-01

    The Transuranic Waste Treatment Facility (TWTF) will process transuranic (TRU) waste in retrievable storage at the Idaho National Engineering Laboratory (INEL). The costs for a TWTF concept using a slagging pyrolysis incinerator were excessive. Alternate concepts using a slow speed shredder, a rotary kiln incinerator, and concrete immobilization should result in significant cost reductions. These will be included in future TWTF considerations

  5. Alternatives to Violence.

    Science.gov (United States)

    Children Today, 1994

    1994-01-01

    Notes that our capacity to diffuse conflict rests in our ability to recognize and verbalize feelings, develop empathy, and think of alternatives to violence. Explores the influence of role models and culture on violence and how the media can use violent images effectively in helping us confront a culture of violence. (HTH)

  6. Publishing: Alternatives and Economics.

    Science.gov (United States)

    Penchansky, Mimi; And Others

    The Library Association of the City University of New York presents an annotated bibliography on the subject of small and alternative publishing. In the first section directories, indexes, catalogs, and reviews are briefly described. Book distributors for small publishers are listed next. The major portion of the bibliography is a listing of books…

  7. The Alternative to Occupy

    DEFF Research Database (Denmark)

    Husted, Emil; Hansen, Allan Dreyer

    2017-01-01

    the institutionalization of radical politics (as carried out by The Alternative) entails a move from universality towards particularity. This move, however, comes with the risk of cutting-off supporters who no longer feel represented by the project. We refer to this problem as ‘the problem of particularization...

  8. Alternative Fuels Data Center: Biodiesel

    Science.gov (United States)

    Biodiesel Printable Version Share this resource Send a link to Alternative Fuels Data Center : Biodiesel to someone by E-mail Share Alternative Fuels Data Center: Biodiesel on Facebook Tweet about Alternative Fuels Data Center: Biodiesel on Twitter Bookmark Alternative Fuels Data Center: Biodiesel on

  9. The role of alternative Polyadenylation in regulation of rhythmic gene expression.

    Science.gov (United States)

    Ptitsyna, Natalia; Boughorbel, Sabri; El Anbari, Mohammed; Ptitsyn, Andrey

    2017-08-04

    Alternative transcription is common in eukaryotic cells and plays important role in regulation of cellular processes. Alternative polyadenylation results from ambiguous PolyA signals in 3' untranslated region (UTR) of a gene. Such alternative transcripts share the same coding part, but differ by a stretch of UTR that may contain important functional sites. The methodoogy of this study is based on mathematical modeling, analytical solution, and subsequent validation by datamining in multiple independent experimental data from previously published studies. In this study we propose a mathematical model that describes the population dynamics of alternatively polyadenylated transcripts in conjunction with rhythmic expression such as transcription oscillation driven by circadian or metabolic oscillators. Analysis of the model shows that alternative transcripts with different turnover rates acquire a phase shift if the transcript decay rate is different. Difference in decay rate is one of the consequences of alternative polyadenylation. Phase shift can reach values equal to half the period of oscillation, which makes alternative transcripts oscillate in abundance in counter-phase to each other. Since counter-phased transcripts share the coding part, the rate of translation becomes constant. We have analyzed a few data sets collected in circadian timeline for the occurrence of transcript behavior that fits the mathematical model. Alternative transcripts with different turnover rate create the effect of rectifier. This "molecular diode" moderates or completely eliminates oscillation of individual transcripts and stabilizes overall protein production rate. In our observation this phenomenon is very common in different tissues in plants, mice, and humans. The occurrence of counter-phased alternative transcripts is also tissue-specific and affects functions of multiple biological pathways. Accounting for this mechanism is important for understanding the natural and engineering

  10. Alternative propulsion for automobiles

    CERN Document Server

    Stan, Cornel

    2017-01-01

    The book presents – based on the most recent research and development results worldwide - the perspectives of new propulsion concepts such as electric cars with batteries and fuel cells, and furthermore plug in hybrids with conventional and alternative fuels. The propulsion concepts are evaluated based on specific power, torque characteristic, acceleration behaviour, specific fuel consumption and pollutant emissions. The alternative fuels are discussed in terms of availability, production, technical complexity of the storage on board, costs, safety and infrastructure. The book presents summarized data about vehicles with electric and hybrid propulsion. The propulsion of future cars will be marked by diversity – from compact electric city cars and range extender vehicles for suburban and rural areas up to hybrid or plug in SUV´s, Pick up´s and luxury class automobiles.

  11. Alternative international currencies

    Directory of Open Access Journals (Sweden)

    Rozhentsova Vladimirovna Elena

    2012-01-01

    Full Text Available The modern international monetary system has a number of flaws and therefore needs cardinal change. Hence, economists from all over the world are suggesting alternative international currencies that would make the international monetary system more efficient. However, it is essential when approaching the creation of a new international currency to analyze and take into account the experience of all the past international currencies. Therefore this paper begins with an exploration of the drawbacks of each of the past and present international currencies. Drawing on this analysis a justification will be made for the necessity of introducing a new international currency, pointing to the requirements it should meet. Further on, this paper proposes an alternative theoretically possible variant of the international currency, with a fixed value relative to a commodity basket. An abstract example is used to demonstrate its composition and circulation mechanism.

  12. Radioactive waste management alternatives

    International Nuclear Information System (INIS)

    Baranowski, F.P.

    1976-01-01

    The information in the US ERDA ''Technical Alternatives Document'' is summarized. The first two points show that waste treatment, interim storage and transportation technologies for all wastes are currently available. Third, an assessment of integrated waste management systems is needed. One such assessment will be provided in our expanded waste management environmental statement currently planned for release in about one year. Fourth, geologies expected to be suitable for final geologic storage are known. Fifth, repository system assessment methods, that is a means to determine and assess the acceptability of a terminal storage facility for nonretrievable storage, must and will be prepared. Sixth, alternatives to geologic storage are not now available. Seventh, waste quantities and characteristics are sensitive to technologies and fuel-cycle modes, and therefore an assessment of these technologies and modes is important. Eighth, and most important, it is felt that the LWR fuel cycle can be closed with current technologies

  13. Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    Luis Fernando Cadavid Gutierrez

    2011-09-01

    Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

  14. [Alternatives to animal testing].

    Science.gov (United States)

    Fabre, Isabelle

    2009-11-01

    The use of alternative methods to animal testing are an integral part of the 3Rs concept (refine, reduce, replace) defined by Russel & Burch in 1959. These approaches include in silico methods (databases and computer models), in vitro physicochemical analysis, biological methods using bacteria or isolated cells, reconstructed enzyme systems, and reconstructed tissues. Emerging "omic" methods used in integrated approaches further help to reduce animal use, while stem cells offer promising approaches to toxicologic and pathophysiologic studies, along with organotypic cultures and bio-artificial organs. Only a few alternative methods can so far be used in stand-alone tests as substitutes for animal testing. The best way to use these methods is to integrate them in tiered testing strategies (ITS), in which animals are only used as a last resort.

  15. Alternative nuclear fuel cycles

    International Nuclear Information System (INIS)

    Till, C.E.

    1979-01-01

    This diffuse subject involves value judgments that are political as well as technical, and is best understood in that context. The four questions raised here, however, are mostly from the technical viewpoints: (1) what are alternative nuclear fuel cycles; (2) what generalizations are possible about their characteristics; (3) what are the major practical considerations; and (4) what is the present situation and what can be said about the outlook for the future

  16. Alternative REST Splicing Underappreciated

    OpenAIRE

    Chen, Guo-Lin; Miller, Gregory

    2017-01-01

    As a major orchestrator of the cellular epigenome, the repressor element-1 silencing transcription factor (REST) can either repress or activate thousands of genes depending on cellular context, suggesting a highly context-dependent REST function tuned by environmental cues. While REST shows cell-type non-selective active transcription, an N-terminal REST4 isoform caused by alternative splicing - inclusion of an extra exon (N3c) which introduces a pre-mature stop codon - has been implicated in...

  17. The renewable alternative

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This chapter discusses renewable energy sources as an alternative to a fossil fuel based economy. The topics discussed in the chapter include the historic aspects and current status of use of renewable energy, status of the renewable energy industry, market barriers to renewable energy, research and development and commercialization of renewable energy, the environmental and social costs associated with renewable energy, valuing future costs and benefits of energy use, and the potential market of renewable energy

  18. Metamaterials critique and alternatives

    CERN Document Server

    Munk, Ben A

    2009-01-01

    A Convincing and Controversial Alternative Explanation of Metamaterials with a Negative Index of Refraction In a book that will generate both support and controversy, one of the world's foremost authorities on periodic structures addresses several of the current fashions in antenna design-most specifically, the popular subject of double negative metamaterials. Professor Munk provides a comprehensive theoretical electromagnetic investigation of the issues and concludes that many of the phenomena claimed by researchers may be impossible. While denying the existence of negative refractio

  19. ALTERNATIVE DISPUTE RESOLUTION

    Directory of Open Access Journals (Sweden)

    Mihaela Irina IONESCU

    2016-05-01

    Full Text Available Alternative dispute resolution (ADR includes dispute resolution processes and techniques that act as a means for disagreeing parties to come to an agreement short of litigation. It is a collective term for the ways that parties can settle disputes, with (or without the help of a third party. Despite historic resistance to ADR by many popular parties and their advocates, ADR has gained widespread acceptance among both the general public and the legal profession in recent years. In fact, some courts now require some parties to resort to ADR of some type, before permitting the parties' cases to be tried. The rising popularity of ADR can be explained by the increasing caseload of traditional courts, the perception that ADR imposes fewer costs than litigation, a preference for confidentiality, and the desire of some parties to have greater control over the selection of the individual or individuals who will decide their dispute. Directive 2013/11/EU of the European Parliament and of the Council on alternative dispute resolution for consumer disputes and amending Regulation (EC No 2006/2004 and Directive 2009/22/EC (hereinafter „Directive 2013/11/EU” aims to ensure a high level of consumer protection and the proper functioning of the internal market by ensuring that complaints against traders can be submitted by consumers on a voluntary basis, to entities of alternative disputes which are independent, impartial, transparent, effective, simple,quick and fair. Directive 2013/11/EU establishes harmonized quality requirements for entities applying alternative dispute resolution procedure (hereinafter "ADR entity" to provide the same protection and the same rights of consumers in all Member States. Besides this, the present study is trying to present broadly how are all this trasposed in the romanian legislation.

  20. Alternative Energy Sources

    CERN Document Server

    Michaelides, Efstathios E (Stathis)

    2012-01-01

    Alternative Energy Sources is designed to give the reader, a clear view of the role each form of alternative energy may play in supplying the energy needs of the human society in the near and intermediate future (20-50 years).   The two first chapters on energy demand and supply and environmental effects, set the tone as to why the widespread use of alternative energy is essential for the future of human society. The third chapter exposes the reader to the laws of energy conversion processes, as well as the limitations of converting one energy form to another. The sections on exergy give a succinct, quantitative background on the capability/potential of each energy source to produce power on a global scale. The fourth, fifth and sixth chapters are expositions of fission and fusion nuclear energy. The following five chapters (seventh to eleventh) include detailed descriptions of the most common renewable energy sources – wind, solar, geothermal, biomass, hydroelectric – and some of the less common sources...

  1. Alternative energy review

    International Nuclear Information System (INIS)

    1991-09-01

    A review is presented of electricity generation technologies which are considered to be alternatives to more conventional technologies. The review is limited to those technologies which have application in Ontario, and provides descriptions, technical and economic assessments, environmental information, and forecasts of potential use of solar energy, wind energy, fuel cells, biomass energy, peat, and municipal solid wastes. Of these technologies, only municipal solid waste combustion is economically viable under current conditions, but government policies prohibit the implementation of new facilities. Certain photovoltaic and wind energy technologies are being found viable for remote sites unconnected to the power grid. Wood waste combustion is viable in the forest products industry. The total potential contribution of these six alternative technologies to Ontario's energy production is forecast at under 190 MW to a range of 685-1,465 MW by the year 2005, according to three different scenarios. The technologies showing the greatest future promise are fuel cells, photovoltaics, and biomass. Except for municipal waste combustion, cost continues to be a significant barrier to utility-scale application of alternative generation technologies in Ontario. However, private individuals and corporations (non-utility generators) may adopt some of these technologies in the absence of access to the power grid, in cogeneration applications, or for demonstration purposes. 120 refs., 79 figs., 93 tabs

  2. State alternative route designations

    International Nuclear Information System (INIS)

    1989-07-01

    Pursuant to the Hazardous Materials Transportation Act (HMTA), the Department of Transportation (DOT) has promulgated a comprehensive set of regulations regarding the highway transportation of high-level radioactive materials. These regulations, under HM-164 and HM-164A, establish interstate highways as the preferred routes for the transportation of radioactive materials within and through the states. The regulations also provide a methodology by which a state may select alternative routes. First,the state must establish a ''state routing agency,'' defined as an entity authorized to use the state legal process to impose routing requirements on carriers of radioactive material (49 CFR 171.8). Once identified, the state routing agency must select routes in accordance with Large Quantity Shipments of Radioactive Materials or an equivalent routing analysis. Adjoining states and localities should be consulted on the impact of proposed alternative routes as a prerequisite of final route selection. Lastly, the states must provide written notice of DOT of any alternative route designation before the routes are deemed effective

  3. Tissue-specific designs of stem cell hierarchies

    NARCIS (Netherlands)

    Visvader, Jane E.; Clevers, Hans

    2016-01-01

    Recent work in the field of stem cell biology suggests that there is no single design for an adult tissue stem cell hierarchy, and that different tissues employ distinct strategies to meet their self-renewal and repair requirements. Stem cells may be multipotent or unipotent, and can exist in

  4. Tissue-specific designs of stem cell hierarchies

    NARCIS (Netherlands)

    Visvader, Jane E; Clevers, Hans

    Recent work in the field of stem cell biology suggests that there is no single design for an adult tissue stem cell hierarchy, and that different tissues employ distinct strategies to meet their self-renewal and repair requirements. Stem cells may be multipotent or unipotent, and can exist in

  5. Description of electrophoretic loci and tissue specific gene ...

    African Journals Online (AJOL)

    1994-02-09

    Feb 9, 1994 ... alligators (Dessauer & Densmore 1983), lizards of the Xan- tusiidae (Bezy ..... expressed in red blood cells, and Esa-5 in brain (Harris &. Hopkinson ... catalyses the conversion of glucose to gluconic acid (Harris &. Hopkinson ...

  6. Host- and tissue-specific pathogenic traits of Staphylococcus aureus.

    NARCIS (Netherlands)

    W.B. van Leeuwen (Willem); D.C. Melles (Damian); A. Alaidan (Alwaleed); M. Al-Ahdal (Mohammed); H.A.M. Boelens (Hélène); S.V. Snijders (Susan); H.F.L. Wertheim (Heiman); E. van Duijkeren (Engeline); J.K. Peeters (Justine); P.J. van der Spek (Peter); R.F.J. Gorkink (Raymond); G. Simons (Guus); H.A. Verbrugh (Henri); A.F. van Belkum (Alex)

    2005-01-01

    textabstractComparative genomics were used to assess genetic differences between Staphylococcus aureus strains derived from infected animals versus colonized or infected humans. A total of 77 veterinary isolates were genetically characterized by high-throughput amplified fragment length polymorphism

  7. Combinatorial regulation of tissue specification by GATA and FOG factors

    Science.gov (United States)

    Chlon, Timothy M.; Crispino, John D.

    2012-01-01

    The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

  8. Tissue-specific histochemical localization of iron and ferritin gene ...

    Indian Academy of Sciences (India)

    ficient and inappropriate diet is a severe nutritional problem. (Goto et al. 2001) that affects ... Ferritin is an iron storage protein which stores 4500 iron atoms in its central ... content in a high-economic-value indica rice variety (Oryza sativa L. cv.

  9. Description of electrophoretic loci and tissue specific gene ...

    African Journals Online (AJOL)

    1994-02-09

    Ieucyl-glycyl-glycine (Pep-B» Peptidase-C. (substrate: leucyl-tyrosine-I (Pep-C» and Peptidase-D (sub- strate: phenylalanyl-proline (Pep-D)). Alleles encoding allo-. Lymes were designated as with mobilities relative to the most.

  10. Tissue specific heterogeneity in effector immune cell response

    Directory of Open Access Journals (Sweden)

    Saba eTufail

    2013-08-01

    Full Text Available Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A and sunlight (vitamin D3 prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells.

  11. Alternatives to nuclear energy

    International Nuclear Information System (INIS)

    Terrado, E.N.

    1981-01-01

    This article discusses several possibilities as alternatives to nuclear energy and their relevance to the Philippine case. The major present and future fuel alternatives to petroleum and nuclear energy are coal, geothermal heat, solar energy and hydrogen, the first two of which are being used. Different conversion technologies are also discussed for large scale electricity production namely solar thermal electric conversion (STC), photovoltaic electric power system (PEPS) and ocean thermal energy conversion (OTEC). Major environmental considerations affect the choice of energy sources and technologies. We have the problem of long term accumulation of radioactive waste in the case of nuclear energy; in geothermal and fossil-fuels carbon dioxide uranium and accumulation may cause disastrous consequences. With regard to Philippine option, the greatest considerations in selecting alternative energy options would be resources availability - both energy and financial and technology status. For the country's energy plan, coal and geothermal energy are expected to play a significant role. The country's coal resources are 1.4 billion metric tons. For geothermal energy, 25 volcanic centers were identified and has a potential equivalent to 2.5 x 10 6 million barrels of oil. Solar energy if harnessed, being in the sunbelt, averaging some 2000 hours a year could be an energy source. The present dilemma of the policy maker is whether national resources are better spent on large scale urban-based energy projects or whether those should be focused on small scale, rural oriented installations which produced benefits to the more numerous and poorer members of the population. (RTD)

  12. Energy and power alternatives

    International Nuclear Information System (INIS)

    Messerle, H.K.

    1992-01-01

    Taking into consideration the need for a safe energy supply, rising demand for energy worldwide and limited oil reserves, alternative energy resources for bulk power are discussed. They are nuclear fuel, fluidized bed combustion of coal, coal gasification with combined cycle process, coal-oil mixture combustion and MHD power generation process. It is pointed out that the major environmental impact of fossil fuels is in accumulation of greenhouse gases in the atmosphere and air pollution due to sulphur emission. (M.G.B.)

  13. Alternate fusion fuels workshop

    International Nuclear Information System (INIS)

    1981-06-01

    The workshop was organized to focus on a specific confinement scheme: the tokamak. The workshop was divided into two parts: systems and physics. The topics discussed in the systems session were narrowly focused on systems and engineering considerations in the tokamak geometry. The workshop participants reviewed the status of system studies, trade-offs between d-t and d-d based reactors and engineering problems associated with the design of a high-temperature, high-field reactor utilizing advanced fuels. In the physics session issues were discussed dealing with high-beta stability, synchrotron losses and transport in alternate fuel systems. The agenda for the workshop is attached

  14. Alternate fuels; Combustibles alternos

    Energy Technology Data Exchange (ETDEWEB)

    Romero Paredes R, Hernando; Ambriz G, Juan Jose [Universidad Autonoma Metropolitana. Iztapalapa (Mexico)

    2003-07-01

    In the definition and description of alternate fuels we must center ourselves in those technological alternatives that allow to obtain compounds that differ from the traditional ones, in their forms to be obtained. In this article it is tried to give an overview of alternate fuels to the conventional derivatives of petroleum and that allow to have a clear idea on the tendencies of modern investigation and the technological developments that can be implemented in the short term. It is not pretended to include all the tendencies and developments of the present world, but those that can hit in a relatively short term, in accordance with agreed with the average life of conventional fuels. Nevertheless, most of the conversion principles are applicable to the spectrum of carbonaceous or cellulosic materials which are in nature, are cultivated or wastes of organic origin. Thus one will approach them in a successive way, the physical, chemical and biological conversions that can take place in a production process of an alternate fuel or the same direct use of the fuel such as burning the sweepings derived from the forests. [Spanish] En la definicion y descripcion de combustibles alternos nos debemos centrar en aquellas alternativas tecnologicas que permitan obtener compuestos que difieren de los tradicionales, al menos en sus formas de ser obtenidos. En este articulo se pretende dar un panorama de los combustibles alternos a los convencionales derivados del petroleo y que permita tener una idea clara sobre las tendencias de la investigacion moderna y los desarrollos tecnologicos que puedan ser implementados en el corto plazo. No se pretende abarcar todas las tendencias y desarrollos del mundo actual, sino aquellas que pueden impactar en un plazo relativamente corto, acordes con la vida media de los combustibles convencionales. Sin embargo, la mayor parte de los principios de conversion son aplicables al espectro de materiales carbonaceos o celulosicos los cuales se

  15. Alternatives to Seesaw

    International Nuclear Information System (INIS)

    Murayama, Hitoshi

    2004-01-01

    The seesaw mechanism is attractive not only because it 'explains' small neutrino mass, but also because of its packaging with the SUSY-GUT, leptogenesis, Dark Matter, and electroweak symmetry breaking. However, this package has the flavor, CP, and gravitino problems. I discuss two alternatives to the seesaw mechanism. In one of them, the anomaly-mediated supersymmetry breaking solves these problems, while predicts naturally light Dirac neutrinos. In the other, the light Majorana neutrinos arise from supersymmetry breaking with right-handed neutrinos below TeV, and the Dark Matter and collider phenomenology are significantly different.

  16. Alternatives to OPEC oil

    International Nuclear Information System (INIS)

    Johnson, C.

    1981-01-01

    This paper starts from the assumption that, for various reasons, the supply of OPEC oil required to meet a rising world energy demand will continue to be limited. Its purpose is to present a synoptic look at the various sources of energy which are alternatives to OPEC oil, with an economic commentary on the prospects for each source. A wide variety of projects are going forward for the development of non-OPEC oil, gas, coal, and nuclear power, as well as renewable energy resources. Special attention is devoted to questions of energy pricing, investment costs, and sources of finance. (author)

  17. Alternative energy options

    International Nuclear Information System (INIS)

    Bennett, K.F.

    1983-01-01

    It is accepted that coal will continue to play the major role in the supply of energy to the country for the remainder of the century. In this paper, however, emphasis has been directed to those options which could supplement coal in an economic and technically sound manner. The general conclusion is that certain forms of solar energy hold the most promise and it is in this direction that research, development and implementation programmes should be directed. Tidal energy, fusion energy, geothermal energy, hydrogen energy and fuel cells are also discussed as alternative energy options

  18. Niobium technological alternatives

    International Nuclear Information System (INIS)

    Pinatti, D.G.; Dainesi, C.R.

    1981-01-01

    The process-product matrix of Niobium is presented, through which the technological alternatives for Niobium are identified. It is shown that the three axes of Niobium application, steels, superalloys and metallic Niobium have a tendency to be economical by equivalent. The critical points where technological development of Niobium is needed are analyzed and results are presented on the following products: Nb 2 O 5 by volatilization, metalic Niobium, Niobium powder, bars and sheets, NbTi alloy, corrosion resistent Niobium alloys and superconductor cable and wires. (Author) [pt

  19. Alternative energy sources

    International Nuclear Information System (INIS)

    Chapman, P.

    1978-01-01

    It is suggested that the development of alternative energy sources has made them more attractive than nuclear power, due to their characteristics, such as small scale and short lead times, moderate costs and minimal environmental impact. The objectives of energy policy are discussed in relation to forecasts of energy demand. Tables show (a) projected useful energy demands UK; (b) patterns of end-use of energy; (c) costs of heating fuels; (d) net present value of gas purchases; (e) useful-energy by end-use analysis; and (f) primary fuel summary 2025. The contributions of hydro, nuclear, waves, solar, oil, gas and coal are estimated to 2025. (U.K.)

  20. Dounreay: an alternative development

    International Nuclear Information System (INIS)

    Low, K.

    1990-01-01

    With the Government decision to phase out the Fast Reactor at Dounreay there is a need to find alternative employment in the area. Traditionally Caithness is an area of farming, fishing and tourism which could be damaged if Dounreay were to be made a nuclear waste repository. The suggestion is that Dounreay should become a centre for research, development and subsequent manufacture of renewable energy sources and devices to harness renewable energy. The Scottish coastline has potential for wind and wave power developments and this could lead to a whole industry in the future. (UK)

  1. Alternate cover materials

    International Nuclear Information System (INIS)

    1988-09-01

    As an effort to enhance compliance with the proposed US Environmental Protection Agency (EPA) groundwater standards, several special studies are being performed by the Technical Assistance Contractor (TAC) to identify and evaluate various design features that may reduce groundwater-related releases from tailings piles. The objective of this special study is to assess the suitability of using alternate cover materials (other than geomembranes) as infiltration barriers in Uranium Mill Tailings Remedial Action (UMTRA) Project piles to minimize leachate generation. The materials evaluated in this study include various types of asphalts, concretes, and a sodium bentonite clay/polypropylene liner system

  2. Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer's disease and progressive supranuclear palsy brains.

    Science.gov (United States)

    Huin, Vincent; Buée, Luc; Behal, Hélène; Labreuche, Julien; Sablonnière, Bernard; Dhaenens, Claire-Marie

    2017-10-03

    Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.

  3. Alternative Therapies for PKU

    Directory of Open Access Journals (Sweden)

    Norma Spécola MD

    2017-01-01

    Full Text Available The phenylalanine (PHE-restricted diet has improved in quality and diversity over time and has proven to be effective in all patients. Nevertheless, this treatment imposes a heavy social and economic burden to patient and family and impacts quality of life. Sustained adherence to PHE restriction is difficult to maintain. Moreover, even patients with phenylketonuria (PKU with normal intelligence quotient (IQ have lower IQ than matched individuals without PKU and can have deficits in multiple other aspects of neuropsychological function, including cognitive and executive function, working memory. They can also have behavior problems, depression, and low self-esteem. In recent years, alternative treatments for PKU have been developed and their use has been indicated for some patients who are candidates for options besides traditional treatment. Sapropterindihydrochloride, large neutral amino acids, and glycomacropeptide are alternative treatment options in use for selected patients. The aim of this article is to review the current knowledge of these new approaches to PKU treatment.

  4. Ignition experiment - alternatives

    International Nuclear Information System (INIS)

    Knobloch, A.F.

    1979-10-01

    This report comprises three short papers on cost estimates, integral burn time and alternative versions of Tokamak ignition experiments. These papers were discussed at the ZEPHYR workshop with participants from IPP Garching, MIT Cambridge and PPPL Princeton (Garching July 30 - August 2 1979) (Chapters A, B, C). It is shown, that starting from a practical parameter independent minimum integral burn time of Tokamak ignition experiments (some 10 3 s) by adding a shield for protection of the magnet insulation (permitted neutron dose 10 9 rad) an integral burn time of some 10 4 s can be achieved for only about 30% more outlay. For a substantially longer integral burn time the outlay approaches rather quickly that for a Tokamak reactor. Some examples for alternatives to ZEPHYR are being given, including some with low or no compression. In a further chapter D some early results of evaluating an ignition experiment on the basis of the energy confinement scaling put forward by Coppi and Mazzucato are presented. As opposed to the case of the Alcator scaling used in chapters A through C the minimum integral burn time of Tokamak ignition experiments here depends on the plasma current. Provided neutral injectors up to about 160 keV are available compression boosting is not required with this scaling. The results presented have been obtained neglecting the effects of the toroidal field ripple. (orig.) 891 HT/orig. 892 RKD [de

  5. Herbs, Supplements and Alternative Medicines

    Science.gov (United States)

    ... A A Listen En Español Herbs, Supplements and Alternative Medicines It is best to get vitamins and minerals ... this section Medication Other Treatments Herbs, Supplements, and Alternative Medicines Types of Dietary Supplements Side Effects and Drug ...

  6. ALTERNATIVE FUELS FOR DIESEL ENGINES

    Directory of Open Access Journals (Sweden)

    Jacek Caban

    2013-12-01

    Full Text Available This paper presents the development and genesis of the use of alternative fuels in internal combustion ignition engines. Based on the analysis of the literature, this article shows various alternative fuels used in Poland and all over the world. Furthermore, this article describes the research directions for alternative fuels use in road transport powered by diesel engines.

  7. Comparing solar energy alternatives

    Energy Technology Data Exchange (ETDEWEB)

    White, J R

    1984-01-01

    The paper outlines a computational procedure for comparing the merits of alternative processes to convert solar radiation to heat, electrical power, or chemical energy. The procedure uses the ratio of equipment investment to useful work as an index. Comparisons with conversion counterparts based on conventional fuels are also facilitated by examining this index. The procedure is illustrated by comparisons of (1) photovoltaic converters of differing efficiencies; (2) photovoltaic converters with and without focusing concentrators; (3) photovoltaic conversion plus electrolysis vs photocatalysis for the production of hydrogen; (4) photovoltaic conversion plus plasma arcs vs photocatalysis for nitrogen fixation. Estimates for conventionally-fuelled processes are included for comparison. The reasons why solar-based concepts fare poorly in such comparisons are traced to the low energy density of solar radiation and its low stream time factor resulting from the limited number of daylight hours available and clouds obscuring the sun.

  8. Comparing solar energy alternatives

    Energy Technology Data Exchange (ETDEWEB)

    White, J R

    1984-01-01

    This paper outlines a computational procedure for comparing the merits of alternative processes to convert solar radiation to heat, electrical power, or chemical energy. The procedure uses the ratio of equipment investment to useful work as an index. Comparisons with conversion counterparts based on conventional fuels are also facilitated by examining this index. The procedure is illustrated by comparisons of (1) photovoltaic converters of differing efficiencies; (2) photovoltaic converters with and without focusing concentrators; (3) photovoltaic conversion plus electrolysis vs photocatalysis for the production of hydrogen; (4) photovoltaic conversion plus plasma arcs vs photocatalysis for nitrogen fixation. Estimates for conventionally-fuelled processes are included for comparison. The reasons why solar-based concepts fare poorly in such comparisons are traced to the low energy density of solar radiation and its low stream time factor resulting from the limited number of daylight hours available and clouds obscuring the sun. 11 references.

  9. Alternative to BGO

    International Nuclear Information System (INIS)

    Anderson, D.F.

    1982-01-01

    For some applications, the scintillating crystal RaF 2 may be preferable to BGO. When coupled to a liquid TMAE photocathode and wire chamber, RaF 2 offers the possibility of an order of magnitude better timing resolution, ease of operating in strong magnetic fields, greater flexibility of design, and more information. For BGO its main advantage is its radiation length and its disadvantages are cost, timing, and difficulty of use in a magnetic field. The main advantages of RaF 2 are its timing, the ease of working in a magnetic field with a wire chamber, the flexibility of design, and greater information out. Its disadvantages are cost and its radiation length. Although BaF 2 has its own shortcomings, coupled to a LPC it has some unique strengths that make it a viable alternative to BGO in some applications of calorimetry in high energy physics

  10. Alternatives to neoliberalism?

    DEFF Research Database (Denmark)

    Warring, Niels; Ahrenkiel, Annegrethe; Nielsen, Birger Steen

    This paper will discuss the consequences of neoliberal governance in Danish day care centres, the social educators’ response, and the possible development of alternatives based on collective participation of social educators and union representatives. We will show how important and unnoticed...... professional competencies come under pressure, and how collective interest representation is challenged. We will discuss how concepts of “gestural knowledge”, “coherence” and “rhythm” open for a new understanding of professional competence. And we will conclude that the social educators and their unions have...... the possibility to contribute to the development of a new welfare paradigm. The paper is based on material from two research projects (Ahrenkiel et al. 2009, 2011) involving social educators and union representatives in day care institutions. We have observed everyday work activities in day care centres...

  11. Alternate laser fusion drivers

    International Nuclear Information System (INIS)

    Pleasance, L.D.

    1979-11-01

    One objective of research on inertial confinement fusion is the development of a power generating system based on this concept. Realization of this goal will depend on the availability of a suitable laser or other system to drive the power plant. The primary laser systems used for laser fusion research, Nd 3+ : Glass and CO 2 , have characteristics which may preclude their use for this application. Glass lasers are presently perceived to be incapable of sufficiently high average power operation and the CO 2 laser may be limited by and issues associated with target coupling. These general perceptions have encouraged a search for alternatives to the present systems. The search for new lasers has been directed generally towards shorter wavelengths; most of the new lasers discovered in the past few years have been in the visible and ultraviolet region of the spectrum. Virtually all of them have been advocated as the most promising candidate for a fusion driver at one time or another

  12. The alternative energy future

    International Nuclear Information System (INIS)

    Spitzley, H.

    1989-02-01

    The alternative energy future can be achieved only by making energy conservation programmes successful, and by fully committing to the utilization of soft energy sources. This is the perspective drawn by the author who in this book investigates the fundamentals of an ecologically and socially sound energy policy for the future. Looking at California, USA, where completely near concepts have been put to work in the energy sector since the mid-seventies, the author shows how it can be done, by rewarding energy conserving activities, using available energy sources more efficiently, developing the means for renewable energy exploitation wherever appropriate. A turn in energy policy is feasible also in West Germany, both in technical and political terms. Starting from the experience gained in the USA, the author presents an outline of options and potentials of a new energy strategy for the Federal Republic of Germany. (orig./HP) [de

  13. Ordering alternatives in MCDM problems

    International Nuclear Information System (INIS)

    De Baets, B.

    1994-01-01

    A new approach to the study of a set of alternatives in a multi-criteria decision making problem is presented. Alternatives are described by means of fuzzy sets in the set of criteria, expressing the degrees to which they fulfill the different criteria. The concept of a fuzzy inclusion is introduced and is discussed from an axiomatic point of view. To each implication operator corresponds a fuzzy inclusion. The fuzzy inclusion corresponding to the Goedel operator is used to measure the degree to which the scores of one alternative are contained in the scores of another one. Repeating this for all couples of alternatives yields a fuzzy quasi-order relation in a set of alternatives. The cuts of this fuzzy relation are then classical quasi-order relations: they express orderings of the alternatives, allowing alternatives to be indifferent or incomparable, corresponding to different degrees of confidence

  14. The nuclear power alternative

    International Nuclear Information System (INIS)

    Blix, H.

    1989-04-01

    The Director General of the IAEA stressed the need for energy policies and other measures which would help to slow and eventually halt the present build-up of carbon dioxide, methane and other so-called greenhouse gases, which are held to cause global warming. He urged that nuclear power and various other sources of energy, none of which contribute to global warming, should not be seen as alternatives, but should all be used to counteract the greenhouse effect. He pointed out that the commercially used renewable energies, apart from hydropower, currently represent only 0.3% of the world's energy consumption and, by contrast, the 5% of the world's energy consumption coming from nuclear power is not insignificant. Dr. Blix noted that opposition for nuclear power stems from fear of accidents and concern about the nuclear wastes. But no generation of electricity, whether by coal, hydro, gas or nuclear power, is without some risk. He emphasized that safety can never be a static concept, and that many new measures are being taken by governments and by the IAEA to further strengthen the safety of nuclear power

  15. Lightweight superconducting alternators

    International Nuclear Information System (INIS)

    Keim, T.A.

    1988-01-01

    One of the most efficient and most lightweight means of converting high-temperature heat energy to electricity is a turboalternator set. Turboalternators are potentially important components of burst-mode power systems, either chemical or nuclear powered. Also, they are probable key components in future electric propulsion systems. Existing examples of multimegawatt turbomachines have been optimized for a variety of aerospace uses, ranging from aircraft propulsion to rocket engine fuel pump drives. There is no corresponding history of multimegawatt alternators built to aerospace standards of mass, performance, and reliability. This paper discusses one of the few such development efforts presently in progress, and gives an indication of possible future potential. In large power ratings, superconducting generators offer substantial power density, specific weight, and efficiency advantages over competing technologies. A program at GE has led to the construction of a lightweight high-voltage 20-MW generator with a superconducting field winding. The first part of this paper describes the design of the generator. The second projects the capabilities of the generator to other ratings

  16. Alternative energy sources

    Energy Technology Data Exchange (ETDEWEB)

    Ruiter, J P [N. V. Kema te Arnhem, NL

    1975-01-01

    A review of alternative energy sources is presented. Solar energy may be used by collecting the heat for direct use or by converting it to electricity. Flat-plate and concentrating collectors are described. Wind energy is an indirect form of solar energy, and has been used for many years in the Netherlands. Calculations of the efficiency of windmills, and of the useful available wind energy along the Netherlands' coastline, are provided. The conversion of organic waste to useable energy is described, including techniques of pyrolysis, combustion, and biological conversion. Tidal energy and ocean-thermal-gradient power plants are briefly described. Geothermal energy is a particularly attractive resource. The average temperature gradient is about 30/sup 0/C/km, ranging from 10/sup 0/C/km in South Africa to 150/sup 0/C/km in Italy. In the Netherlands it ranges from 20-50/sup 0/C/km. The various types of geothermal systems (steam, water, geopressured) are reviewed, and presently operating geothermal power plants are described. A comparison is made of the costs of various energy sources, and 27 references are provided.

  17. Alternative cover design

    International Nuclear Information System (INIS)

    1988-11-01

    The special study on Alternative Cover Designs is one of several studies initiated by the US Department of Energy (DOE) in response to the proposed US Environmental Protection Agency (EPA) groundwater standards. The objective of this study is to investigate the possibility of minimizing the infiltration of precipitation through stabilized tailings piles by altering the standard design of covers currently used on the Uranium Mill Tailings Remedial Action (UMTRA) Project. Prior. to the issuance of the proposed standards, UMTRA Project piles had common design elements to meet the required criteria, the most important of which were for radon diffusion, long-term stability, erosion protection, and groundwater protection. The standard pile covers consisted of three distinct layers. From top to bottom they were: rock for erosion protection; a sand bedding layer; and the radon barrier, usually consisting of a clayey sand material, which also functioned to limit infiltration into the tailings. The piles generally had topslopes from 2 to 4 percent and sideslopes of 20 percent

  18. Enhanced Design Alternative IV

    International Nuclear Information System (INIS)

    Kramer, N.E.

    1999-01-01

    This report evaluates Enhanced Design Alternative (EDA) IV as part of the second phase of the License Application Design Selection (LADS) effort. The EDA IV concept was compared to the VA reference design using criteria from the Design Input Request for LADS Phase II EDA Evaluations (CRWMS M and O 1999b) and (CRWMS M and O 1999f). Briefly, the EDA IV concept arranges the waste packages close together in an emplacement configuration known as line load. Continuous pre-closure ventilation keeps the waste packages from exceeding their 350 C cladding and 200 C (4.3.6) drift wall temperature limits. This EDA concept keeps relatively high, uniform emplacement drift temperatures (post-closure) to drive water away from the repository and thus dry out the pillars between emplacement drifts. The waste package is shielded to permit human access to emplacement drifts and includes an integral filler inside the package to reduce the amount of water that can contact the waste form. Closure of the repository is desired 50 years after first waste is emplaced. Both backfill and drip shields will be emplaced at closure to improve post-closure performance. The EDA IV concept includes more defense-in-depth layers than the VA reference design because of its backfill, drip shield, waste package shielding, and integral filler features. These features contribute to the low dose-rate to the public achieved during the first 10,000 years of repository life as shown in Figure 3. Investigation of the EDA IV concept has led to the following general conclusions: (1) The total life cycle cost for EDA IV is about $21.7 billion which equates to a $11.3 billion net present value (both figures rounded up). (2) The incidence of design basis events for EDA IV is similar to the VA reference design. (3) The emplacement of the waste packages in drifts will be similar to the VA reference design. However, heavier equipment may be required because the shielded waste package will be heavier. (4) The heavier

  19. Differential HFE gene expression is regulated by alternative splicing in human tissues.

    Science.gov (United States)

    Martins, Rute; Silva, Bruno; Proença, Daniela; Faustino, Paula

    2011-03-03

    The pathophysiology of HFE-derived Hereditary Hemochromatosis and the function of HFE protein in iron homeostasis remain uncertain. Also, the role of alternative splicing in HFE gene expression regulation and the possible function of the corresponding protein isoforms are still unknown. The aim of this study was to gain insights into the physiological significance of these alternative HFE variants. Alternatively spliced HFE transcripts in diverse human tissues were identified by RT-PCR, cloning and sequencing. Total HFE transcripts, as well as two alternative splicing transcripts were quantified using a real-time PCR methodology. Intracellular localization, trafficking and protein association of GFP-tagged HFE protein variants were analysed in transiently transfected HepG2 cells by immunoprecipitation and immunofluorescence assays. Alternatively spliced HFE transcripts present both level- and tissue-specificity. Concerning the exon 2 skipping and intron 4 inclusion transcripts, the liver presents the lowest relative level, while duodenum presents one of the highest amounts. The protein resulting from exon 2 skipping transcript is unable to associate with β2M and TfR1 and reveals an ER retention. Conversely, the intron 4 inclusion transcript gives rise to a truncated, soluble protein (sHFE) that is mostly secreted by cells to the medium in association with β2M. HFE gene post-transcriptional regulation is clearly affected by a tissue-dependent alternative splicing mechanism. Among the corresponding proteins, a sHFE isoform stands out, which upon being secreted into the bloodstream, may act in remote tissues. It could be either an agonist or antagonist of the full length HFE, through hepcidin expression regulation in the liver or by controlling dietary iron absorption in the duodenum.

  20. Differential HFE gene expression is regulated by alternative splicing in human tissues.

    Directory of Open Access Journals (Sweden)

    Rute Martins

    Full Text Available BACKGROUND: The pathophysiology of HFE-derived Hereditary Hemochromatosis and the function of HFE protein in iron homeostasis remain uncertain. Also, the role of alternative splicing in HFE gene expression regulation and the possible function of the corresponding protein isoforms are still unknown. The aim of this study was to gain insights into the physiological significance of these alternative HFE variants. METHODOLOGY/PRINCIPAL FINDINGS: Alternatively spliced HFE transcripts in diverse human tissues were identified by RT-PCR, cloning and sequencing. Total HFE transcripts, as well as two alternative splicing transcripts were quantified using a real-time PCR methodology. Intracellular localization, trafficking and protein association of GFP-tagged HFE protein variants were analysed in transiently transfected HepG2 cells by immunoprecipitation and immunofluorescence assays. Alternatively spliced HFE transcripts present both level- and tissue-specificity. Concerning the exon 2 skipping and intron 4 inclusion transcripts, the liver presents the lowest relative level, while duodenum presents one of the highest amounts. The protein resulting from exon 2 skipping transcript is unable to associate with β2M and TfR1 and reveals an ER retention. Conversely, the intron 4 inclusion transcript gives rise to a truncated, soluble protein (sHFE that is mostly secreted by cells to the medium in association with β2M. CONCLUSIONS/SIGNIFICANCE: HFE gene post-transcriptional regulation is clearly affected by a tissue-dependent alternative splicing mechanism. Among the corresponding proteins, a sHFE isoform stands out, which upon being secreted into the bloodstream, may act in remote tissues. It could be either an agonist or antagonist of the full length HFE, through hepcidin expression regulation in the liver or by controlling dietary iron absorption in the duodenum.

  1. Prospects for alternative Fusion Fuels

    International Nuclear Information System (INIS)

    Glancy, J.

    1986-01-01

    The author has worked on three different magnetic confinement concepts for alternate fusion fueled reactors: tokamaks; tanden mirrors, and reversed field pinches. The focus of this article is on prospects for alternate fusion fuels as the author sees them relative to the other choices: increased numbers of coal plants, fission reactors, renewables, and D-T fusion. Discussion is limited on the consideration of alternate fusion fuels to the catalyzed deuterium-deuterium fuel cycle. Reasons for seeking an alternate energy source are cost, a more secure fuel supply, environmental impact and safety. The technical risks associated with development of fusion are examined briefly

  2. Alternative fuelds in urban fleets

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, T.

    1994-12-31

    In this presentation the author addresses four main objectives. They are to: discuss programs that are driving the introduction of alternative fuels into fleet operations in urban areas around the country; define alternative fuels; quantify the present use and future projections on alternative fuel vehicles (AVFs) in the Chicago metropolitan statistical area; and discuss benefits of increased use of alternative fuels in urban areas. Factors which touch on these points include: present domestic dependence on petroleum for autos, with usage exceeding production; the large populations in urban areas which do not meet Clean Air Standards; recent legislative initiatives which give guidance and aid in the adoption of such strategies.

  3. Alternative fuelds in urban fleets

    International Nuclear Information System (INIS)

    Lindsay, T.

    1994-01-01

    In this presentation the author addresses four main objectives. They are to: discuss programs that are driving the introduction of alternative fuels into fleet operations in urban areas around the country; define alternative fuels; quantify the present use and future projections on alternative fuel vehicles (AVFs) in the Chicago metropolitan statistical area; and discuss benefits of increased use of alternative fuels in urban areas. Factors which touch on these points include: present domestic dependence on petroleum for autos, with usage exceeding production; the large populations in urban areas which do not meet Clean Air Standards; recent legislative initiatives which give guidance and aid in the adoption of such strategies

  4. Alternative RNA splicing and cancer

    Science.gov (United States)

    Liu, Sali; Cheng, Chonghui

    2015-01-01

    Alternative splicing of pre-messenger RNA (mRNA) is a fundamental mechanism by which a gene can give rise to multiple distinct mRNA transcripts, yielding protein isoforms with different, even opposing, functions. With the recognition that alternative splicing occurs in nearly all human genes, its relationship with cancer-associated pathways has emerged as a rapidly growing field. In this review, we summarize recent findings that have implicated the critical role of alternative splicing in cancer and discuss current understandings of the mechanisms underlying dysregulated alternative splicing in cancer cells. PMID:23765697

  5. Alternative Fuels Data Center: Indiana Transportation Data for Alternative

    Science.gov (United States)

    (nameplate, MW) 1,430 Source: BioFuels Atlas from the National Renewable Energy Laboratory Case Studies Video Alternative Fuels Save Money in Indy April 1, 2012 More Case Studies Videos Text Version More Indiana Videos on YouTube Video thumbnail for Indiana Beverage Company Invests in Alternative Fuels Indiana Beverage

  6. Alternative energy in Nepal

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, H.B.; Bhandari, K.P.

    2011-05-15

    Renewable energy Technology (RET) becomes the mainstream option for rural Nepal to access modern source of energy. It focuses on the trend of RET applications consisting of biogas technology, solar thermal, micro and Pico hydropower, biomass technology bio fuel technology, wind power technology etc. The RET's which provide both electricity based as well as non electricity based services, have been shown to most immediately meet the needs of a cleaner indoor environment, better quality lightning for education and income generating, activities, alternative cooking fuels and agro processing as well as rural industries. Improved cooking stoves and much more beneficial than other technologies. Wind energy utilization is still not popular. Solar thermal to generate thermal energy to cook, warm and dry, biogas for lighting and cooking services. Micro hydropower for electric as well as mechanical use and solar PV mainly for domestic lighting may become choice. The most important Renewable Energy Technology (RET's) in Nepal are related to Pico hydropower and micro-hydropower, biomass energy (biogas, briquettes, gasifies, improved cooking stoves, bio-fuels etc.) solar photovoltaic energy, solar PV water pumping, solar thermal energy (solar heater, solar dryers, solar cookers etc.) and wind energy (such as wind generators, wind mills etc.). One renowned Non-governmental organization has been established in the Jhapa and Mornag Bhutanese refugee camp. Two families from all the seven camps in Nepal received one solar cooker, one hay box and two cooking posts to each family. Under this programme, a total of 6,850 solar cookers, 12600 hay boxes and 25,200 cooking pots have been distributed 2009. The number of beneficiaries from this program has reached 85,000. Before the distribution of the cookers and the utensils, the instruction and orientation training for the maintenance and repair and operation method was improved. The refugees were divided in 315 groups of 40

  7. Normetex Pump Alternatives Study

    International Nuclear Information System (INIS)

    Clark, Elliot A.

    2013-01-01

    A mainstay pump for tritium systems, the Normetex scroll pump, is currently unavailable because the Normetex company went out of business. This pump was an all-metal scroll pump that served tritium processing facilities very well. Current tritium system operators are evaluating replacement pumps for the Normetex pump and for general used in tritium service. An all-metal equivalent alternative to the Normetex pump has not yet been identified. 1. The ideal replacement tritium pump would be hermetically sealed and contain no polymer components or oils. Polymers and oils degrade over time when they contact ionizing radiation. 2. Halogenated polymers (containing fluorine, chlorine, or both) and oils are commonly found in pumps. These materials have many properties that surpass those of hydrocarbon-based polymers and oils, including thermal stability (higher operating temperature) and better chemical resistance. Unfortunately, they are less resistant to degradation from ionizing radiation than hydrocarbon-based materials (in general). 3. Polymers and oils can form gaseous, condensable (HF, TF), liquid, and solid species when exposed to ionizing radiation. For example, halogenated polymers form HF and HCl, which are extremely corrosive upon reaction with water. If a pump containing polymers or oils must be used in a tritium system, the system must be designed to be able to process the unwanted by-products. Design features to mitigate degradation products include filters and chemical or physical traps (eg. cold traps, oil traps). 4. Polymer components can work in tritium systems, but must be replaced regularly. Polymer components performance should be monitored or be regularly tested, and regular replacement of components should be viewed as an expected normal event. A radioactive waste stream must be established to dispose of used polymer components and oil with an approved disposal plan developed based on the facility location and its regulators. Polymers have varying

  8. Alternative Fuels Data Center: Publications

    Science.gov (United States)

    Windstars; 14) and the use of alternative fuel vehicles at the Olympics. Alternative Fuels In Trucking, Vol and their economic and environmental benefits. This report is designed to share the experiences and National Academy of Engineering suggested that 'DOE might have its greatest impact by leading the private

  9. Catching lightning for alternative energy

    Energy Technology Data Exchange (ETDEWEB)

    Helman, D.S. [California State University, Long Beach, 1250 Bellflower Blvd., Long Beach, CA 90840 (United States)

    2011-05-15

    The article reviews the current literature related to lightning and makes a case for using lightning as an alternative source of energy. Objections to using lightning as an alternative source of energy are listed. Current literature is reviewed and articles are suggested as useful for building a tower, or using rockets or lasers to target a strike, or for quantifying a lightning strike. (author)

  10. Difficulties of Alternatively Certified Teachers

    Science.gov (United States)

    Schonfeld, Irvin Sam; Feinman, Samantha J.

    2012-01-01

    This daily diary study followed, over a 2-week period, 252 beginning New York City public school teachers. Seventy percent were alternatively certified (New York City Teaching Fellows) and the rest, traditionally certified teachers. Alternatively certified teachers were more likely to experience stressors such as violent incidents and classroom…

  11. [Alternative approaches in thyroid surgery].

    Science.gov (United States)

    Maurer, E; Wächter, S; Bartsch, D K

    2017-08-01

    In thyroid surgery multiple different cervical minimally invasive (partly endoscopically assisted) and extracervical endoscopic (partly robot-assisted) approaches have been developed in the last 20 years. The aim of all these alternative approaches to the thyroid gland is optimization of the cosmetic result. The indications for the use of alternative and conventional approaches are principally the same. Important requirements for the use of alternative methods are nevertheless a broad experience in conventional thyroid operations of the thyroid and adequate patient selection under consideration of the size of the thyroid and the underlying pathology. Contraindications for the use of alternative approaches are a large size of the thyroid gland including local symptoms, advanced carcinomas, reoperations and previous radiations of the anterior neck. The current article gives an overview of the clinically implemented alternative approaches for thyroid surgery. Of those the majority must still be considered as experimental. The alternative approaches to the thyroid gland can be divided in cervical minimally invasive, extracervical endosopic (robot-assisted) and transoral operations (natural orifice transluminal endoscopic surgery, NOTES). Since conventional thyroid operations are standardized procedures with low complication rates, alternative approaches to the thyroid gland are considered critically in Germany. The request for a perfect cosmetic result should not overweigh patients' safety. Only a few alternative approaches (e. g. MIVAT, RAT) can yet be considered as a safe addition in experienced hands in highly selected patients.

  12. Marital Alternatives and Marital Disruption.

    Science.gov (United States)

    Udry, J. Richard

    1981-01-01

    Explores the usefulness of "marital alternatives" as a dimension in explaining marital stability, using longitudinal data from a panel of married, White, urban couples from 16 urban areas. Results indicated the dimension of marital alternatives appeared to be a better predictor of marital disruption than marital satisfaction. (Author/RC)

  13. Alternative Genres of IS Research

    DEFF Research Database (Denmark)

    Avital, Michel; Mathiassen, Lars; Crowston, Kevin

    2012-01-01

    The potential value of alternative genres in IS research is the core question that drives this panel discussion. The term “Alternative Genres” refers to unconventional forms of thinking, doing, and communicating scholarship and practice. It relates to innovation with respect to epistemological pe...

  14. Alternative Fuels in Cement Production

    DEFF Research Database (Denmark)

    Larsen, Morten Boberg

    The substitution of alternative for fossil fuels in cement production has increased significantly in the last decade. Of these new alternative fuels, solid state fuels presently account for the largest part, and in particular, meat and bone meal, plastics and tyre derived fuels (TDF) accounted...... for the most significant alternative fuel energy contributors in the German cement industry. Solid alternative fuels are typically high in volatile content and they may differ significantly in physical and chemical properties compared to traditional solid fossil fuels. From the process point of view......, considering a modern kiln system for cement production, the use of alternative fuels mainly influences 1) kiln process stability (may accelerate build up of blockages preventing gas and/or solids flow), 2) cement clinker quality, 3) emissions, and 4) decreased production capacity. Kiln process stability...

  15. Verb aspect, alternations and quantification

    Directory of Open Access Journals (Sweden)

    Svetla Koeva

    2015-11-01

    Full Text Available Verb aspect, alternations and quantification In this paper we are briefly discuss the nature of Bulgarian verb aspect and argue that the verb aspect pairs are different lexical units with different (although related meaning, different argument structure (reflecting categories, explicitness and referential status of arguments and different sets of semantic and syntactic alternations. The verb prefixes resulting in perfective verbs derivation in some cases can be interpreted as lexical quantifiers as well. Thus the Bulgarian verb aspect is related (in different way both with the potential for the generation of alternations and with the prefixal lexical quantification. It is shown that the scope of the lexical quantification by means of verbal prefixes is the quantified verb phrase and the scope remains constant in all derived alternations. The paper concerns the basic issues of these complex problems, while the detailed description of the conditions satisfying particular alternation or particular lexical quantification are subject of a more detailed study.

  16. Commentary on "tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl) nitrosamine as the basis for urothelial cell carcinogenesis." He Z, Kosinska W, Zhao ZL, Wu XR, Guttenplan JB, Department of Basic Science, New York University Dental College, NY, USA.: Mutat Res 2012;742(1-2):92-5 [Epub 2011 Dec 4].

    Science.gov (United States)

    Scherr, Douglas S

    2014-02-01

    Bladder cancer is one of the few cancers that have been linked to carcinogens in the environment and tobacco smoke. Of the carcinogens tested in mouse chemical carcinogenesis models, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is one that reproducibly causes high-grade, invasive cancers in the urinary bladder, but not in any other tissues. However, the basis for such a high-level tissue-specificity has not been explored. Using mutagenesis in lacI (Big Blue™) mice, we show here that BBN is a potent mutagen and it causes high-level of mutagenesis specifically in the epithelial cells (urothelial) of the urinary bladder. After a 2-6-week treatment of 0.05% BBN in the drinking water, mutagenesis in urothelial cells of male and female mice was about two orders of magnitude greater than the spontaneous mutation background. In contrast, mutagenesis in smooth muscle cells of the urinary bladder was about five times lower than in urothelial tissue. No appreciable increase in mutagenesis was observed in kidney, ureter, liver or forestomach. In lacI (Big Blue™) rats, BBN mutagenesis was also elevated in urothelial cells, albeit not nearly as profoundly as in mice. This provides a potential explanation as to why rats are less prone than mice to the formation of aggressive form of bladder cancer induced by BBN. Our results suggest that the propensity to BBN-triggered mutagenesis of urothelial cells underlies its heightened susceptibility to this carcinogen and that mutagenesis induced by BBN represents a novel model for initiation of bladder carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Pheromone based alternative route planning

    Directory of Open Access Journals (Sweden)

    Liangbing Feng

    2016-08-01

    Full Text Available In this work, we propose an improved alternative route calculation based on alternative figures, which is suitable for practical environments. The improvement is based on the fact that the main traffic route is the road network skeleton in a city. Our approach using nodes may generate a higher possibility of overlapping. We employ a bidirectional Dijkstra algorithm to search the route. To measure the quality of an Alternative Figures (AG, three quotas are proposed. The experiment results indicate that the improved algorithm proposed in this paper is more effective than others.

  18. Alternative trading systems in Poland

    Directory of Open Access Journals (Sweden)

    Magdalena Mosionek-Schweda

    2009-12-01

    Full Text Available The first Polish alternative trading system – called NewConnect – was opened on 30 August 2007. It has the status of an organized market, but it is operated by the Warsaw Stock Exchange outside the regulated market. Two years later, on 30 September 2009, the WSE launched another market – Catalyst – which consists of four segments including: two regular markets and two alternative trading platforms. The present paper aims to describe fundamental rules of the Polish alternative trading platforms as well as to depict a short overview of their trading indicators and basic statistics.

  19. Disturbance maintains alternative biome states.

    Science.gov (United States)

    Dantas, Vinícius de L; Hirota, Marina; Oliveira, Rafael S; Pausas, Juli G

    2016-01-01

    Understanding the mechanisms controlling the distribution of biomes remains a challenge. Although tropical biome distribution has traditionally been explained by climate and soil, contrasting vegetation types often occur as mosaics with sharp boundaries under very similar environmental conditions. While evidence suggests that these biomes are alternative states, empirical broad-scale support to this hypothesis is still lacking. Using community-level field data and a novel resource-niche overlap approach, we show that, for a wide range of environmental conditions, fire feedbacks maintain savannas and forests as alternative biome states in both the Neotropics and the Afrotropics. In addition, wooded grasslands and savannas occurred as alternative grassy states in the Afrotropics, depending on the relative importance of fire and herbivory feedbacks. These results are consistent with landscape scale evidence and suggest that disturbance is a general factor driving and maintaining alternative biome states and vegetation mosaics in the tropics. © 2015 John Wiley & Sons Ltd/CNRS.

  20. Alternative food safety intervention technologies

    Science.gov (United States)

    Alternative nonthermal and thermal food safety interventions are gaining acceptance by the food processing industry and consumers. These technologies include high pressure processing, ultraviolet and pulsed light, ionizing radiation, pulsed and radiofrequency electric fields, cold atmospheric plasm...

  1. Alternative Hamiltonian representation for gravity

    Energy Technology Data Exchange (ETDEWEB)

    Rosas-RodrIguez, R [Instituto de Fisica, Universidad Autonoma de Puebla, Apdo. Postal J-48, 72570, Puebla, Pue. (Mexico)

    2007-11-15

    By using a Hamiltonian formalism for fields wider than the canonical one, we write the Einstein vacuum field equations in terms of alternative variables. This variables emerge from the Ashtekar's formalism for gravity.

  2. Alternative Hamiltonian representation for gravity

    International Nuclear Information System (INIS)

    Rosas-RodrIguez, R

    2007-01-01

    By using a Hamiltonian formalism for fields wider than the canonical one, we write the Einstein vacuum field equations in terms of alternative variables. This variables emerge from the Ashtekar's formalism for gravity

  3. Alternative energies updates on progress

    CERN Document Server

    Ferreira, Germán

    2013-01-01

    This book examines the key pillars of alternative energy, including biomass, hydrogen, solar and geothermal. It features life cycle assessment and thermoeconomic analysis as tools for evaluating and optimising environmental and cost subjects.

  4. Alternatives for radioactive waste management

    International Nuclear Information System (INIS)

    Bartlett, J.W.

    1975-10-01

    The safety aspects of waste management alternatives are emphasized. The options for waste management, their safety characteristics, and the methods that might be used to evaluate the options and their safety are outlined

  5. Alternative Medicine and Your Child

    Science.gov (United States)

    ... Spirituality Affect Your Family's Health? Talking to Your Child's Doctor Medications: Using Them Safely Talking to the Pharmacist Complementary and Alternative Medicine View more About Us Contact Us Partners Editorial ...

  6. Commercial aviation alternative fuels initiative

    Science.gov (United States)

    2010-04-22

    This presentation looks at alternative fuels to enhance environmental stability, reduction of greenhouse gas emissions, air quality benefits (e.g., SOx and PM), fuel supply stability, and fuel price stability.

  7. An alternative plutonium disposition method

    International Nuclear Information System (INIS)

    Kueppers, C.

    2002-01-01

    This paper provides a feasibility study on vitrification of plutonium with high active waste concentrate, and fabrication of MOX fuel rods for direct final disposal. These are potential alternatives to the direct use of MOX fuel in a reactor. (author)

  8. The neurogenetics of alternative splicing.

    Science.gov (United States)

    Vuong, Celine K; Black, Douglas L; Zheng, Sika

    2016-05-01

    Alternative precursor-mRNA splicing is a key mechanism for regulating gene expression in mammals and is controlled by specialized RNA-binding proteins. The misregulation of splicing is implicated in multiple neurological disorders. We describe recent mouse genetic studies of alternative splicing that reveal its critical role in both neuronal development and the function of mature neurons. We discuss the challenges in understanding the extensive genetic programmes controlled by proteins that regulate splicing, both during development and in the adult brain.

  9. Spent-fuel-storage alternatives

    International Nuclear Information System (INIS)

    1980-01-01

    The Spent Fuel Storage Alternatives meeting was a technical forum in which 37 experts from 12 states discussed storage alternatives that are available or are under development. The subject matter was divided into the following five areas: techniques for increasing fuel storage density; dry storage of spent fuel; fuel characterization and conditioning; fuel storage operating experience; and storage and transport economics. Nineteen of the 21 papers which were presented at this meeting are included in this Proceedings. These have been abstracted and indexed

  10. Genomic organization and the tissue distribution of alternatively spliced isoforms of the mouse Spatial gene

    Directory of Open Access Journals (Sweden)

    Mattei Marie-Geneviève

    2004-07-01

    Full Text Available Abstract Background The stromal component of the thymic microenvironment is critical for T lymphocyte generation. Thymocyte differentiation involves a cascade of coordinated stromal genes controlling thymocyte survival, lineage commitment and selection. The "Stromal Protein Associated with Thymii And Lymph-node" (Spatial gene encodes a putative transcription factor which may be involved in T-cell development. In the testis, the Spatial gene is also expressed by round spermatids during spermatogenesis. Results The Spatial gene maps to the B3-B4 region of murine chromosome 10 corresponding to the human syntenic region 10q22.1. The mouse Spatial genomic DNA is organised into 10 exons and is alternatively spliced to generate two short isoforms (Spatial-α and -γ and two other long isoforms (Spatial-δ and -ε comprising 5 additional exons on the 3' site. Here, we report the cloning of a new short isoform, Spatial-β, which differs from other isoforms by an additional alternative exon of 69 bases. This new exon encodes an interesting proline-rich signature that could confer to the 34 kDa Spatial-β protein a particular function. By quantitative TaqMan RT-PCR, we have shown that the short isoforms are highly expressed in the thymus while the long isoforms are highly expressed in the testis. We further examined the inter-species conservation of Spatial between several mammals and identified that the protein which is rich in proline and positive amino acids, is highly conserved. Conclusions The Spatial gene generates at least five alternative spliced variants: three short isoforms (Spatial-α, -β and -γ highly expressed in the thymus and two long isoforms (Spatial-δ and -ε highly expressed in the testis. These alternative spliced variants could have a tissue specific function.

  11. ALTERNATIVE

    Directory of Open Access Journals (Sweden)

    HUMBERTO ESCALANTE H.

    2014-01-01

    Full Text Available En Colombia, el procesamiento agroindustrial de fique genera aproximadamente 20 800 kg de residuos/ha sembrada que corresponden a. jugo y bagazo. Estos residuos son descartados al ambiente generando problemas de contaminación. El bagazo de fique tiene un valor calorífico de 3 297.91 kcal/kg, altas concentraciones de celulosa, hemicelulosa y una relación C/N favorable para tratar este residuo mediante conversión anaerobia. Sin embargo, la presencia de lignina en el bagazo hace que se requiera un consorcio microbiano específico para llevar a cabo la degradación. En este trabajo se estudio la producción de biogás a partir del bagazo de fique, empleando como inóculo una mezcla de líquido ruminal y lodo estiércol de cerdo. Se alcanzó una producción de metano de 0.35 m3CH4/kg Sólidos Volátiles (SV adicionados durante quince días de digestión, equivalente a 1.38 kWh/kg SV adicionado, indicando que el bagazo de fique es un residuo atractivo para ser usado como fuente de energía renovable.

  12. Advances in alternative cementitious binders

    International Nuclear Information System (INIS)

    Juenger, M.C.G.; Winnefeld, F.; Provis, J.L.; Ideker, J.H.

    2011-01-01

    There is a burgeoning interest in the development, characterization, and implementation of alternatives to Portland cement as a binder in concrete. The construction materials industry is under increasing pressure to reduce the energy used in production of Portland cement clinker and the associated greenhouse gas emissions. Further, Portland cement is not the ideal binder for all construction applications, as it suffers from durability problems in particularly aggressive environments. Several alternative binders have been available for almost as long as Portland cement, yet have not been extensively used, and new ones are being developed. In this paper, four promising binders available as alternatives to Portland cement are discussed, namely calcium aluminate cement, calcium sulfoaluminate cement, alkali-activated binders, and supersulfated cements. The history of the binders, their compositions and reaction mechanisms, benefits and drawbacks, unanswered questions, and primary challenges are described.

  13. DESIGN OF ALTERNATIVE ENERGY SOURCES

    Directory of Open Access Journals (Sweden)

    Popa Stefania

    2013-11-01

    Full Text Available By energy sources we understand technologies and materials used to obtain various forms of energy necessary for the development of society. These sources must be in adequate quantities and be conveniently exploited in terms of technical, economic and sustainable perspective. Alternative energy uses the inherent power of natural sources like wind, tides, the sun. Alternative energy is a term used for some energy sources and energy storage technologies. Generally it indicates energies that are nontraditional and have low impact to the environment. The alternative energy term is used in contrast with the term fossil fuel according to some sources, while other sources use it with the meaning of renewable energy purposes.

  14. [Alternative treatment methods in ENT].

    Science.gov (United States)

    Friese, K H

    1997-08-01

    In this review, the most important complementary und alternative therapies are discussed, focusing particularly on their use in otorhinolaryngology. These therapies include balneology, Kneipp therapy, microbiological therapy, fasting, excretion therapy, different oxygen therapies, hydro-colon therapy, urine therapy, own-blood therapy, Bach therapy, orthomolecular therapy, order therapy, environmental medicine, phytotherapy, homeopathy, complex homeopathy, anthroposophy, neural therapy, electroaccupuncture according to Voll and similar therapies, nasal reflex therapy, reflex-zone massage, manual therapy, massage, lymph drainage, aroma therapy, thermotherapy, bioresonance, kinesiology, hopi candles, and dietetics. Some of these methods and regimens can be recommended, but others should be rejected. In universities, these methods are only represented to a minor extend, but are more accepted by otorhinolaryngologists in practice. This paper provides a guide to which alternative therapies are sensible and possible in otorhinolaryngology. The aim is to stimulate interest in these methods. It is necessary to discuss these alternative methods reasonably and credibly with patients.

  15. Revisiting the solar hydrogen alternative

    Energy Technology Data Exchange (ETDEWEB)

    Tomkiewicz, M. [Brooklyn College of CUNY, NY (United States)

    1996-09-01

    Research aimed at the development of technology to advance the solar-hydrogen alternative is per definition mission oriented. The priority that society puts on such research rise and fall with the priorities that we associate with the mission. The mission that we associate with the hydrogen economy is to provide a technological option for an indefinitely sustainable energy and material economies in which society is in equilibrium with its environment. In this paper we try to examine some global aspects of the hydrogen alternative and recommend formulation of a {open_quotes}rational{close_quotes} tax and regulatory system that is based on efforts needed to restore the ecological balance. Such a system, once entered into the price structure of the alternative energy schemes, will be used as a standard to compare energy systems that in turn will serve as a base for prioritization of publicly supported research and development.

  16. [Alternative medicine: faith or science?].

    Science.gov (United States)

    Pletscher, A

    1990-04-21

    For the success of both alternative and scientific (conventional) medicine, factors such as the psychological influence of the doctor, loving care, human affection, the patient's belief in the treatment, the suggestive power of attractive (even unproven) theories, dogmas and chance events (e.g. spontaneous remissions) etc. play a major role. Some practices of alternative medicine have a particularly strong appeal to the non-rational side of the human being. Conventional medicine includes a component which is based on scientific and statistical methods. The possibility that in alternative medicine principles and effects exist which are not (yet) known to scientific medicine, but which match up to scientific criteria, cannot be excluded. However, up to now this has not been convincingly proven. The difficulties which arise in the elucidation of this problem are discussed in the light of examples from the literature and some experiments of our own.

  17. Alternatives to the Dirac equation

    International Nuclear Information System (INIS)

    Girvin, S.M.; Brownstein, K.R.

    1975-01-01

    Recent work by Biedenharn, Han, and van Dam (BHvD) has questioned the uniqueness of the Dirac equation. BHvD have obtained a two-component equation as an alternate to the Dirac equation. Although they later show their alternative to be unitarily equivalent to the Dirac equation, certain physical differences were claimed. BHvD attribute the existence of this alternate equation to the fact that their factorizing matrices were position-dependent. To investigate this, we factor the Klein-Gordon equation in spherical coordinates allowing the factorizing matrices to depend arbitrarily upon theta and phi. It is shown that despite this additional freedom, and without involving any relativistic covariance, the conventional four-component Dirac equation is the only possibility

  18. Experiences in mainstreaming alternative energy

    Energy Technology Data Exchange (ETDEWEB)

    Cabraal, A.

    1997-12-01

    The author discusses efforts by the Asia Alternative Energy Unit (ASTAE) of the World Bank in supporting alternative energy source projects in Asia. Energy growth rates have been as high as 18% per year, with power capacity doubling each decade in the 1960`s, 70`s and 80`s. Much of this has come from fossil fuel projects coupled with major hydroelectric projects. One consequence is developing air pollution loads originating in Asia. ASTAE has been supporting pilot programs in applying alternative energy sources. The goal has been to mainstream renewable energy sources in World Bank operations, by working with managers from different countries to: include renewable energy in country assistance strategies and sectorial development plans; provide assistance to renewable energy initiatives; expand initiatives to new countries, sectors and technologies.

  19. FMDP reactor alternative summary report: Volume 4, Evolutionary LWR alternative

    International Nuclear Information System (INIS)

    1996-09-01

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] have become surplus to national defense needs both in the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES ampersand H) consequences if surplus fissile materials are not properly managed. The purpose of this report is to provide schedule, cost, and technical information that will be used to support the Record of Process (ROD). Following the screening process, DOE/MD via its national laboratories initiated a more detailed analysis activity to further evaluate each of the ten plutonium disposition alternatives that survived the screening process. Three ''Alternative Teams,'' chartered by DOE and comprised of technical experts from across the DOE national laboratory complex, conducted these analyses. One team was chartered for each of the major disposition classes (borehole, immobilization, and reactors). During the last year and a half, the Fissile Materials Disposition Program (FMDP) Reactor Alternative Team (RxAT) has conducted extensive analyses of the cost, schedule, technical maturity, S ampersand S, and other characteristics of reactor-based plutonium disposition. The results of the RxAT's analyses of the existing LWR, CANDU, and partially complete LWR alternatives are documented in Volumes 1-3 of this report. This document (Volume 4) summarizes the results of these analyses for the ELWR-based plutonium disposition option

  20. FMDP reactor alternative summary report: Volume 4, Evolutionary LWR alternative

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-01

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] have become surplus to national defense needs both in the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES&H) consequences if surplus fissile materials are not properly managed. The purpose of this report is to provide schedule, cost, and technical information that will be used to support the Record of Process (ROD). Following the screening process, DOE/MD via its national laboratories initiated a more detailed analysis activity to further evaluate each of the ten plutonium disposition alternatives that survived the screening process. Three ``Alternative Teams,`` chartered by DOE and comprised of technical experts from across the DOE national laboratory complex, conducted these analyses. One team was chartered for each of the major disposition classes (borehole, immobilization, and reactors). During the last year and a half, the Fissile Materials Disposition Program (FMDP) Reactor Alternative Team (RxAT) has conducted extensive analyses of the cost, schedule, technical maturity, S&S, and other characteristics of reactor-based plutonium disposition. The results of the RxAT`s analyses of the existing LWR, CANDU, and partially complete LWR alternatives are documented in Volumes 1-3 of this report. This document (Volume 4) summarizes the results of these analyses for the ELWR-based plutonium disposition option.

  1. Alternative Fuels Data Center: Vermont Transportation Data for Alternative

    Science.gov (United States)

    alternative fuels Fuel Public Private Biodiesel (B20 and above) 3 0 Compressed Natural Gas (CNG) 1 2 Electric Recycled Cooking Oil Powers Biodiesel Vehicles in Vermont Recycled Cooking Oil Powers Biodiesel Vehicles in sold per GGE Biodiesel (B20) $2.79/gallon $2.54/GGE $2.84/gallon $2.58/GGE Biodiesel (B99-B100) $2.47

  2. Alternative Fuels Data Center: Virginia Transportation Data for Alternative

    Science.gov (United States)

    /2018 Biodiesel and Green Diesel Definitions updated 4/9/2018 Data Download Fueling Stations 706 stations in Virginia with alternative fuels Fuel Public Private Biodiesel (B20 and above) 1 9 Compressed unit sold per GGE per unit sold per GGE Biodiesel (B20) $2.47/gallon $2.25/GGE $2.84/gallon $2.58/GGE

  3. Alternative Fuels Data Center: Missouri Transportation Data for Alternative

    Science.gov (United States)

    stations in Missouri with alternative fuels Fuel Public Private Biodiesel (B20 and above) 1 2 Compressed Students Get Hands-On Training With Biodiesel Missouri High School Students Get Hands-On Training With Biodiesel Feb. 5, 2016 https://youtube.com/embed/p4pVRgoWyZw Video thumbnail for AT&T Fleet Reaches

  4. Alternative Fuels Data Center: Maine Transportation Data for Alternative

    Science.gov (United States)

    Biodiesel-Blended Diesel Documentation Requirement Data Download Fueling Stations 149 stations in Maine with alternative fuels Fuel Public Private Biodiesel (B20 and above) 2 1 Compressed Natural Gas (CNG) 0 2 Electric ://www.youtube.com/embed/jHftlruFR40 Video thumbnail for Maine's Only Biodiesel Manufacturer Powers Fleets in the

  5. Alternative Fuels Data Center: James Madison University Teaches Alternative

    Science.gov (United States)

    Alternative Fuels Sept. 16, 2017 Photo of a truck Phoenix Utility Fleet Drives Smarter with Biodiesel Aug. 26 Cooking Oil Powers Biodiesel Vehicles in Rhode Island July 14, 2017 Photo of a truck Idaho Transports Mail Home Runs on Biodiesel in North Carolina June 9, 2017 Photo of a bus New Hampshire Cleans up with

  6. Alternative transportation fuels: Financing issues

    International Nuclear Information System (INIS)

    Squadron, W.F.; Ward, C.O.; Brown, M.H.

    1992-06-01

    A multitude of alternative fuels could reduce air pollution and the impact of oil price shocks. Only a few of these fuels are readily available and inexpensive enough to merit serious consideration over the coming five years. In New York City, safety regulations narrow the field still further by eliminating propane. As a result, this study focuses on the three alternative fuels readily available in New York City: compressed natural gas, methanol, and electricity. Each has significant environmental benefits and each has different cost characteristics. With the Clean Air Act and the National Energy Strategy highlighting the country's need to improve urban air quality and move away from dependence on imported fuels, fleets may soon have little choice but to convert to altemative fuels. Given the potential for large infrastructure and vehicle costs, these fleets may have difficulty finding the capital to make that conversion. Ultimately, then, it will be the involvement of the private sector that will determine the success of alternative fuels. Whether it be utilities, fuel distributors or suppliers, private financing partners or others, it is critical that altemative fuels programs be structured and planned to attract their involvement. This report examines financing methods that do not involve government subsidies. It also explores financing methods that are specific to alternative fuels. Bond issues and other mechanisms that are used for conventional vehicles are not touched upon in this report. This report explores ways to spread the high cost of alternative fuels among a number of parties within the private sector. The emphasis is on structuring partnerships that suit methanol, electric, or natural gas vehicle fleets. Through these partnerships, alternative fuels may ultimately compete effectively against conventional vehicle fuels

  7. Alternative Cancer Treatments: 10 Options to Consider

    Science.gov (United States)

    Alternative cancer treatments: 10 options to consider Alternative cancer treatments can't cure your cancer, but they may provide some ... that may help them, including complementary and alternative cancer treatments. If cancer makes you feel as if you ...

  8. Alternative Fuel News, Vol. 6, No. 4

    Energy Technology Data Exchange (ETDEWEB)

    2003-03-01

    Quarterly magazine with articles on Alternate Fuel Vehicles (AFVs) in India, alternative fuels for emergency preparedness, and testing of propane vehicles by UPS. Also an interview of author Jeremy Rifkin on how alternative fuels provide pathways to hydrogen.

  9. A remedial alternative prioritization method

    International Nuclear Information System (INIS)

    Richter, S.A.; Travis, C.C.

    1987-01-01

    This study develops and tests a technique for evaluating and prioritizing alternative remedial actions for hazardous waste sites. The method is based on criteria involving risk, benefit and cost, and identifies the most cost-effective solution to a given remedial problem. Four sites on the Department of Energy's Oak Ridge National Laboratory (ORNL) property in Oak Ridge, Tennessee, were used in a case study to develop and test the method. Results of the case study indicate that even if the cap providing in situ containment must be replaced every 10 years, it is a superior alternative to total excavation of the waste sites

  10. GLOBAL TRENDS OF ALTERNATIVE INVESTMENTS

    Directory of Open Access Journals (Sweden)

    Ivan LUCHIAN

    2016-08-01

    Full Text Available An alternative investment is an investment product other than the traditional investments of stocks, bonds, cash, or property. The term is a relatively loose one and includes tangible assets such as art, wine, antiques, coins, or stamps and some financial assets such as commodities, hedge funds, venture capital,and others. At the moment it was created a global industry opportunities for making investments in nontraditional form. The aim of this paper consists in demonstrating the possibilities of these investments. For this have been studied related main international markets, a fter then deducted world dominant trends. This article is concerned to present some details of alternative investments global market.

  11. Multipebble Simulations for Alternating Automata

    Science.gov (United States)

    Clemente, Lorenzo; Mayr, Richard

    We study generalized simulation relations for alternating Büchi automata (ABA), as well as alternating finite automata. Having multiple pebbles allows the Duplicator to "hedge her bets" and delay decisions in the simulation game, thus yielding a coarser simulation relation. We define (k 1,k 2)-simulations, with k 1/k 2 pebbles on the left/right, respectively. This generalizes previous work on ordinary simulation (i.e., (1,1)-simulation) for nondeterministic Büchi automata (NBA)[4] in and ABA in [5], and (1,k)-simulation for NBA in [3].

  12. Bell's inequality without alternative settings

    International Nuclear Information System (INIS)

    Cabello, Adan

    2003-01-01

    A suitable generalized measurement described by a 4-element positive operator-valued measure (POVM) on each particle of a two-qubit system in the singlet state is, from the point of view of Einstein, Podolsky, and Rosen's (EPR's) criterion of elements of reality, equivalent to a random selection between two alternative projective measurements. It is shown that an EPR-experiment with a fixed POVM on each particle provides a violation of Bell's inequality without requiring local observers to choose between the alternatives. This approach could be useful for designing a loophole-free test of Bell's inequality

  13. Alternative general-aircraft engines

    Science.gov (United States)

    Tomazic, W. A.

    1976-01-01

    The most promising alternative engine (or engines) for application to general aircraft in the post-1985 time period was defined, and the level of technology was cited to the point where confident development of a new engine can begin early in the 1980's. Low emissions, multifuel capability, and fuel economy were emphasized. Six alternative propulsion concepts were considered to be viable candidates for future general-aircraft application: the advanced spark-ignition piston, rotary combustion, two- and four-stroke diesel, Stirling, and gas turbine engines.

  14. Spent-fuel-storage alternatives

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    The Spent Fuel Storage Alternatives meeting was a technical forum in which 37 experts from 12 states discussed storage alternatives that are available or are under development. The subject matter was divided into the following five areas: techniques for increasing fuel storage density; dry storage of spent fuel; fuel characterization and conditioning; fuel storage operating experience; and storage and transport economics. Nineteen of the 21 papers which were presented at this meeting are included in this Proceedings. These have been abstracted and indexed. (ATT)

  15. Special Issue: Aviation Alternative Fuels

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2014-12-01

    Full Text Available The investigation of aviation alternative fuels has increased significantly in recent years in an effort to reduce the environment and climate impact by aviation industry. Special requirements have to be met for qualifying as a suitable aviation fuel. The fuel has to be high in energy content per unit of mass and volume, thermally stable and avoiding freezing at low temperatures. There are also many other special requirements on viscosity, ignition properties and compatibility with the typical aviation materials. There are quite a few contending alternative fuels which can be derived from coal, natural gas and biomass.[...

  16. Alternative Medicine on the Internet

    Science.gov (United States)

    Muret, Marc

    2000-01-01

    If you go to a bookstore to look for information on a particular health problem you will have a choice between the "medicine" corner with scientific manuals for professionals and the "health" corner with all kinds of books about acupuncture, ayurveda, natural healing, homeopathy, nutrition, massage, and so on! How is it on the Net? Even a short tour will bring you a lot of "medical" information, but when you look for alternative approaches in the "health" corner you will be rather disappointed. Interesting sites are rare and the amount of information very sparse. In many cases the lists of therapists are seriously incomplete; professional therapists with long experience do not appear in them. Recommendations for alternative treatments are superficial and encourage the user to buy some specialties or some book. Many sites are inflated by just quoting other sites so that, in the end, the basic information is rather poor. As we know, "health" information is becoming increasingly important since patients want to take more responsibility for themselves. They look for alternative methods. Doctors too, as 46% of Swiss doctors use alternative methods in one way or another (Médecine et Hygiène, 1996). That is why we should not leave this part of the Internet in the hands of unqualified people. To some doctors, alternative medicine may seem a chaotic maelstrom of superstition and odd techniques. That is not so. Nearly every alternative therapy has a long tradition with its own rules and principles. All reliable therapists have undergone years of training and expect the same from their colleagues. Why should this search for quality not be present online? What is needed? Good quality information. The identity of the author must be clear (education, tradition, professional experience, training). As many schools claim to be "the only one", the user should be informed about the differences and conflicts between all the approaches. Ethical behavior must be encouraged: respect

  17. 77 FR 31756 - Energy Conservation Program: Alternative Efficiency Determination Methods and Alternative Rating...

    Science.gov (United States)

    2012-05-30

    ...-AC46 Energy Conservation Program: Alternative Efficiency Determination Methods and Alternative Rating... regulations authorizing the use of alternative methods of determining energy efficiency or energy consumption... alternative methods of determining energy efficiency or energy consumption of various consumer products and...

  18. An Alternative to Ability Grouping

    Science.gov (United States)

    Tomlinson, Carol Ann

    2006-01-01

    Ability grouping is a common approach to dealing with student variance in learning. In general, findings suggest that such an approach to dealing with student differences is disadvantageous to students who struggle in school and advantageous to advanced learners. The concept of differentiation suggests that there is another alternative to…

  19. "Partial Vision" in Alternative Education.

    Science.gov (United States)

    Miller, Ron

    1997-01-01

    A comparison of the philosophies and pedagogies of Waldorf and Montessori schools points out that no single educational perspective can encompass all possibilities of human growth. Educators should attend to the "seed qualities" of alternative educational philosophies rather than their dogmas. A caring relationship between teachers and students is…

  20. DESIGN ALTERNATIVES ON THE LAMINATES

    Directory of Open Access Journals (Sweden)

    Gökay Nemli

    2004-04-01

    Full Text Available Wood based panel manufacturers use increasing volumes of laminates. Laminates are resistant to the water, humidity, scratch, abrasion, burning and chemicals. These products consist of printed decor papers that have been saturated with thermosetting resin. In this study, laminate types, composition form and design alternatives were investigated.

  1. A Technique: Generating Alternative Thoughts

    Directory of Open Access Journals (Sweden)

    Serkan AKKOYUNLU

    2013-04-01

    Conclusion: Generating alternative explanations and balanced thoughts are the end point and important part of therapy work on automatic thoughts. When applied properly and rehearsed as homework between sessions, these methods may lead to improvement in many mental disorders. [JCBPR 2013; 2(1.000: 53-59

  2. Wire chambers: Trends and alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Regler, Meinhard

    1992-05-15

    The subtitle of this year's Vienna Wire Chamber Conference - 'Recent Trends and Alternative Techniques' - signalled that it covered a wide range of science and technology. While an opening Vienna talk by wire chamber pioneer Georges Charpak many years ago began 'Les funerailles des chambres a fils (the burial of wire chambers)', the contrary feeling this year was that wire chambers are very much alive!.

  3. Alternative instruments for the CAP?

    NARCIS (Netherlands)

    Silvis, H.J.; Rijswick, van C.W.J.; Bont, de C.J.A.M.

    2001-01-01

    With parallel negotiations taking place on enlargement of the EU and a new WTO agreement, EU's Common Agricultural Policy is facing further reforms. This report addresses the issue of whether any alternatives can be found for the instruments of this policy, and looks at decoupled payments, a net

  4. Alternative energies. Updates on progress

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, German (ed.) [CIRCE - Centre of Research for Energy Resources and Consumption, Zaragoza (Spain)

    2013-07-01

    Presents fundamental and applied research of alternative energies. Address key pillars in the alternative energy field, such as: biomass energy, hydrogen energy, solar energy, wind energy, hydroelectric power, geothermal energy and their environmental implications, with the most updated progress. Includes the life cycle assessment and thermoeconomic analysis as tools for evaluating and optimising environmental and cost subjects. This book presents nine chapters based on fundamental and applied research of alternative energies. At the present time, the challenge is that technology has to come up with solutions that can provide environmentally friendly energy supply options that are able to cover the current world energy demand. Experts around the world are working on these issues for providing new solutions that will break the existing technological barriers. This book aims to address key pillars in the alternative energy field, such as: biomass energy, hydrogen energy, solar energy, wind energy, hydroelectric power, geothermal energy and their environmental implications, with the most updated progress for each pillar. It also includes the life cycle assessment (LCA) and thermoeconomic analysis (TA) as tools for evaluating and optimising environmental and cost subjects. Chapters are organized into fundamental research, applied research and future trends; and written for engineers, academic researches and scientists.

  5. Evaluating Alternatives to Exclusive "He."

    Science.gov (United States)

    Todd-Mancillas, William R.

    A study was conducted to determine the effects on reading comprehension of the use of the exclusive pronoun "he" and more or less contrived alternatives. Subjects, 358 students enrolled in an introduction to human communication at a large northeastern university, read three different forms of the same essay. One essay form exclusively used "he,"…

  6. Alternatives to allogeneic platelet transfusion.

    Science.gov (United States)

    Desborough, Michael J R; Smethurst, Peter A; Estcourt, Lise J; Stanworth, Simon J

    2016-11-01

    Allogeneic platelet transfusions are widely used for the prevention and treatment of bleeding in thrombocytopenia. Recent evidence suggests platelet transfusions have limited efficacy and are associated with uncertain immunomodulatory risks and concerns about viral or bacterial transmission. Alternatives to transfusion are a well-recognised tenet of Patient Blood Management, but there has been less focus on different strategies to reduce bleeding risk by comparison to platelet transfusion. Direct alternatives to platelet transfusion include agents to stimulate endogenous platelet production (thrombopoietin mimetics), optimising platelet adhesion to endothelium by treating anaemia or increasing von Willebrand factor levels (desmopressin), increasing formation of cross-linked fibrinogen (activated recombinant factor VII, fibrinogen concentrate or recombinant factor XIII), decreasing fibrinolysis (tranexamic acid or epsilon aminocaproic acid) or using artificial or modified platelets (cryopreserved platelets, lyophilised platelets, haemostatic particles, liposomes, engineered nanoparticles or infusible platelet membranes). The evidence base to support the use of these alternatives is variable, but an area of active research. Much of the current randomised controlled trial focus is on evaluation of the use of thrombopoietin mimetics and anti-fibrinolytics. It is also recognised that one alternative strategy to platelet transfusion is choosing not to transfuse at all. © 2016 John Wiley & Sons Ltd.

  7. Alternative energy sources: ECC report

    International Nuclear Information System (INIS)

    Renwick, Lord; Stoddart, Lord; Lauderdale, Earl of

    1988-01-01

    The European Communities Committee Report on Alternative Energy Resources was debated. Six alternative energy sources were first described - wind power, biomass, geothermal energy, solar energy, wave and tidal power. Combined heat and power was also mentioned. General questions concerning alternative energy sources were then considered. In particular, their potential contribution to the energy demand was assessed. The evidence presented to the committee suggested that they would only make a small contribution in the near future and could not be considered as a substitute for coal and nuclear power. However, by the year 2030 it would be possible for 18% of the national electricity demand to be met by alternative energy sources. The economic and environmental issues were assessed briefly and the report's conclusions were summarized. An independent review of wave power was called for in view of conflicting evidence presented to the committee. The debate which followed lasted three hours and is reported verbatim. Other issues raised included energy conservation, public attitudes to energy, the environment, government and private funding of research and development of nuclear power, including fusion. (U.K.)

  8. Not Just Another Alternative School

    Science.gov (United States)

    Gulson, Kalervo N.; Webb, P. Taylor

    2016-01-01

    In this article, we problematize the establishment of an Africentric Alternative School in Toronto, Canada. We argue that policy, and race and racializations cannot be understood outside of, or immune to, neoliberalism. We contend that policy is a form of racial biopolitics, and race is now produced through neoliberal markets, in conjunction with…

  9. Europe 2020: an alternative proposal

    International Nuclear Information System (INIS)

    Stagnaro, Carlo

    2008-01-01

    In order to achieve its greenhouse gas emissions reduction targets, the European Union is pursuing a strengthening of the EU Emissions Trading Scheme. However, serious doubts hold as far as this instrument's effectiveness and efficiency are concerned. It is urgent to consider alternative solutions, such as an EU-wide carbon tax [it

  10. Alternate Theory Formation by Students.

    Science.gov (United States)

    Hanson, R. Keith

    Video tapes of student teachers micro-teaching in a high school biology class were analyzed. Attention was focussed on students' interpretations of data and the teacher's responses to these interpretations. Examples are given of student explanations which teachers find unsatisfactory but which are valid alternatives based on the data available to…

  11. Alternative materials for sustainable transportation.

    Science.gov (United States)

    2012-08-01

    A shortage of asphalt and polymers is creating opportunities for engineers to utilize alternative pavement materials. Three types of bio oil, untreated bio oil (UTB), treated bio oil (TB) and polymer-modified bio oil (PMB) were studied in this resear...

  12. Alternative Fuel for Marine Application

    Science.gov (United States)

    2012-02-29

    The U.S. Maritime Administration (MARAD) is participating in the U.S. Navy's ongoing efforts to test alternative fuels for marine use by demonstrating their applicability on commercial vessels. In support of this effort, the Navy provided neat hydrot...

  13. Praktiske erfaringer med alternative isoleringsmaterialer

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn; Hansen, Klavs Feilberg

    Borup Seniorby er et demonstrationsbyggeri hvori der både er anvendt alternative isoleringsmaterialer og mineraluld. Denne rapport introducerer byggeriet og redegør for byggeprocessen samt håndteringen af de valgte isoleringsprodukter. Ni forskellige produkter, enten i form af løsfyld eller...

  14. Language Alternation in University Classrooms

    Science.gov (United States)

    Taha, T. A.

    2008-01-01

    This paper examines the alternate use of Arabic and English in the context of a university classroom, where a policy to use the former language in place of the latter was being implemented. Analysis of a sample of recorded university lectures of English and Arabic medium classes in sciences and humanities reveals that teachers use code switching,…

  15. Evaluation of alternatives in EIA

    Energy Technology Data Exchange (ETDEWEB)

    Ikonen, A. [Posiva Oy, Helsinki (Finland)

    2000-07-01

    According to the Finnish law, a 'Decision in Principle' is required for the final disposal facility for spent nuclear fuel. The decision is made by the government and it needs to be approved by the Parliament. Before the decision can be made an EIA report must be produced for the facility. Alternatives in the management of spent fuel were already described in EIA programme which was drafted in the scoping stage. In the programme arguments for the so-called 'base alternative' were presented. However, a more extensive evaluation of the alternatives was required by the contact authority based on the first hearing. This presentation shows how alternatives were evaluated in assessment phase and how people reacted to them during the second hearing. The presentation is based on the general summary of EIA report and the statements given on the report. In Finland the environmental impact assessment procedure has been finished and the Decision in Principle is expected to be taken in the near future. (author)

  16. Looking for alternative energy sources.

    Science.gov (United States)

    Gross, Michael

    2012-02-21

    With unrest in oil-exporting countries, backlashes against biofuels and photovoltaics, and a nuclear incident in Japan, the year 2011 rattled confidence in future energy supplies. The search for alternatives is all the more urgent, but some of the solutions investigated hark back to fossil fuels that we can't afford to burn.

  17. A two-matrix alternative

    Czech Academy of Sciences Publication Activity Database

    Rohn, Jiří

    2013-01-01

    Roč. 26, 15 December (2013), s. 836-841 ISSN 1537-9582 Institutional support: RVO:67985807 Keywords : two-matrix alternative * solution * algorithm Subject RIV: BA - General Mathematics Impact factor: 0.514, year: 2013 http://www.math.technion.ac.il/iic/ ela / ela -articles/articles/vol26_pp836-841.pdf

  18. Biotherapeutics as alternatives to antibiotics

    Science.gov (United States)

    Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

  19. Assessment of alternative disposal concepts

    Energy Technology Data Exchange (ETDEWEB)

    Autio, J.; Saanio, T.; Tolppanen, P. [Saanio and Riekkola Consulting Engineers, Helsinki (Finland); Raiko, H.; Vieno, T. [VTT Energy, Espoo (Finland); Salo, J.P. [Posiva Oy, Helsinki (Finland)

    1996-12-01

    Four alternative repository designs for the disposal of spent nuclear in the Finnish crystalline bedrock were assessed in the study. The alternatives were: (1) the basic KBS-3 design in which copper canisters are emplaced in vertical deposition holes bored in the floors of horizontal tunnels, (2) the KBS-3-2C design with two canisters in a deposition hole, (3) Short Horizontal Holes (SHH) in the side walls of the tunnels, and (4) the Medium Long Holes (MLH) concept in which approximately 25 canisters are emplaced in a horizontal deposition hole about 200 metres in length bored between central and side tunnels. In all the alternatives considered, the thickness of the layer of compacted bentonite between copper canister and bedrock is 35 cm. Two different copper canister designs were also assessed. Technical feasibility and flexibility, post-closure safety and repository cost were assessed for each of the alternative canister and repository designs. On the basis of this assessment it is recommended that further development and studies should focus on the vacuum- or inert gas-filled cast insert type copper canister and the basic KBS-3 type repository design with a single canister in a vertical deposition hole. The KBS-3 design is robust and flexible and provides excellent post-closure safety. The transfer, emplacement and sealing operations are technically uncomplicated. The alternative options assessed do not offer any significant benefits in safety or cost over the basic design, but they are technically more complex and also in some respects more vulnerable to malfunction during the emplacement of canisters and buffer, as well as common mode failures. (60 refs.).

  20. Assessment of alternative disposal concepts

    International Nuclear Information System (INIS)

    Autio, J.; Saanio, T.; Tolppanen, P.; Raiko, H.; Vieno, T.; Salo, J.P.

    1996-12-01

    Four alternative repository designs for the disposal of spent nuclear in the Finnish crystalline bedrock were assessed in the study. The alternatives were: (1) the basic KBS-3 design in which copper canisters are emplaced in vertical deposition holes bored in the floors of horizontal tunnels, (2) the KBS-3-2C design with two canisters in a deposition hole, (3) Short Horizontal Holes (SHH) in the side walls of the tunnels, and (4) the Medium Long Holes (MLH) concept in which approximately 25 canisters are emplaced in a horizontal deposition hole about 200 metres in length bored between central and side tunnels. In all the alternatives considered, the thickness of the layer of compacted bentonite between copper canister and bedrock is 35 cm. Two different copper canister designs were also assessed. Technical feasibility and flexibility, post-closure safety and repository cost were assessed for each of the alternative canister and repository designs. On the basis of this assessment it is recommended that further development and studies should focus on the vacuum- or inert gas-filled cast insert type copper canister and the basic KBS-3 type repository design with a single canister in a vertical deposition hole. The KBS-3 design is robust and flexible and provides excellent post-closure safety. The transfer, emplacement and sealing operations are technically uncomplicated. The alternative options assessed do not offer any significant benefits in safety or cost over the basic design, but they are technically more complex and also in some respects more vulnerable to malfunction during the emplacement of canisters and buffer, as well as common mode failures. (60 refs.)

  1. Alternating Copolymers and Alternative Device Geometries for Organic Photovoltaics

    OpenAIRE

    Inganäs, Olle; Zhang, Fengling; Andersson, Mats R.

    2012-01-01

    The efficiency of conversion of light to electrical energy with the help of conjugated polymers and molecules is rapidly improving. The optical absorption properties of these materials can be designed, and implemented via molecular engineering. Full coverage of the solar spectrum is thus feasible. Narrow absorption spectra allow construction of tandem solar cells. The poor transport properties of these materials require thin devices, which limits optical absorption. Alternative device geometr...

  2. Alternative Fuels Data Center: Biodiesel Equipment Options

    Science.gov (United States)

    Equipment Options to someone by E-mail Share Alternative Fuels Data Center: Biodiesel Equipment Options on Facebook Tweet about Alternative Fuels Data Center: Biodiesel Equipment Options on Twitter Bookmark Alternative Fuels Data Center: Biodiesel Equipment Options on Google Bookmark Alternative Fuels

  3. Alternative Fuels Data Center: Natural Gas Vehicles

    Science.gov (United States)

    Natural Gas Printable Version Share this resource Send a link to Alternative Fuels Data Center : Natural Gas Vehicles to someone by E-mail Share Alternative Fuels Data Center: Natural Gas Vehicles on Facebook Tweet about Alternative Fuels Data Center: Natural Gas Vehicles on Twitter Bookmark Alternative

  4. Alternative Fuels Data Center: Natural Gas

    Science.gov (United States)

    Natural Gas Printable Version Share this resource Send a link to Alternative Fuels Data Center : Natural Gas to someone by E-mail Share Alternative Fuels Data Center: Natural Gas on Facebook Tweet about Alternative Fuels Data Center: Natural Gas on Twitter Bookmark Alternative Fuels Data Center: Natural Gas on

  5. Alternative Fuels Data Center: Natural Gas Benefits

    Science.gov (United States)

    Benefits to someone by E-mail Share Alternative Fuels Data Center: Natural Gas Benefits on Facebook Tweet about Alternative Fuels Data Center: Natural Gas Benefits on Twitter Bookmark Alternative Fuels Data Center: Natural Gas Benefits on Google Bookmark Alternative Fuels Data Center: Natural Gas

  6. Muscle-specific splicing factors ASD-2 and SUP-12 cooperatively switch alternative pre-mRNA processing patterns of the ADF/cofilin gene in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Genta Ohno

    Full Text Available Pre-mRNAs are often processed in complex patterns in tissue-specific manners to produce a variety of protein isoforms from single genes. However, mechanisms orchestrating the processing of the entire transcript are not well understood. Muscle-specific alternative pre-mRNA processing of the unc-60 gene in Caenorhabditis elegans, encoding two tissue-specific isoforms of ADF/cofilin with distinct biochemical properties in regulating actin organization, provides an excellent in vivo model of complex and tissue-specific pre-mRNA processing; it consists of a single first exon and two separate series of downstream exons. Here we visualize the complex muscle-specific processing pattern of the unc-60 pre-mRNA with asymmetric fluorescence reporter minigenes. By disrupting juxtaposed CUAAC repeats and UGUGUG stretch in intron 1A, we demonstrate that these elements are required for retaining intron 1A, as well as for switching the processing patterns of the entire pre-mRNA from non-muscle-type to muscle-type. Mutations in genes encoding muscle-specific RNA-binding proteins ASD-2 and SUP-12 turned the colour of the unc-60 reporter worms. ASD-2 and SUP-12 proteins specifically and cooperatively bind to CUAAC repeats and UGUGUG stretch in intron 1A, respectively, to form a ternary complex in vitro. Immunohistochemical staining and RT-PCR analyses demonstrate that ASD-2 and SUP-12 are also required for switching the processing patterns of the endogenous unc-60 pre-mRNA from UNC-60A to UNC-60B in muscles. Furthermore, systematic analyses of partially spliced RNAs reveal the actual orders of intron removal for distinct mRNA isoforms. Taken together, our results demonstrate that muscle-specific splicing factors ASD-2 and SUP-12 cooperatively promote muscle-specific processing of the unc-60 gene, and provide insight into the mechanisms of complex pre-mRNA processing; combinatorial regulation of a single splice site by two tissue-specific splicing regulators

  7. Alternatives to shallow land burial

    International Nuclear Information System (INIS)

    Kuck, P.H.; Wacks, M.E.

    1980-01-01

    The paper discusses disposal alternatives that suggest there is a great diversity of man-made and natural spaces that should be considered as alternative sites for LLW disposal. Dry caverns outside of karst regions with integrated subsurface drainage might be given further consideration. The excavation of new space in tectonically and chemically stable rock formations also shows considerable promise. The principal problems in using either existing or new space involve hydrology, rock mechanics, chemical stability of the wall-rock minerals, and socio-political interactions. The chemical, physical and radiological properties of the wastes will also enter into the evaluation. All seven of these aspects will have to be examined in detail before a solution to the problem of minimizing radionuclide transport into the biosphere can be outlined

  8. An alternative dimensional reduction prescription

    International Nuclear Information System (INIS)

    Edelstein, J.D.; Giambiagi, J.J.; Nunez, C.; Schaposnik, F.A.

    1995-08-01

    We propose an alternative dimensional reduction prescription which in respect with Green functions corresponds to drop the extra spatial coordinate. From this, we construct the dimensionally reduced Lagrangians both for scalars and fermions, discussing bosonization and supersymmetry in the particular 2-dimensional case. We argue that our proposal is in some situations more physical in the sense that it maintains the form of the interactions between particles thus preserving the dynamics corresponding to the higher dimensional space. (author). 12 refs

  9. Implications of alternative fuel cycles

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The United States is re-examining alternative fuel cycles and nuclear power strategies, and doubtful attempts are being made to justify the economics of the 'throw-away' fuel cycle. At an international forum on 'An acceptable nuclear energy future for the world' at Fort Lauderdale, Karl Cohen of General Electric and a leading authority on this topic put the implications into perspective. Extracts from his address are presented

  10. Wire chambers: Trends and alternatives

    International Nuclear Information System (INIS)

    Regler, Meinhard

    1992-01-01

    The subtitle of this year's Vienna Wire Chamber Conference - 'Recent Trends and Alternative Techniques' - signalled that it covered a wide range of science and technology. While an opening Vienna talk by wire chamber pioneer Georges Charpak many years ago began 'Les funerailles des chambres a fils (the burial of wire chambers)', the contrary feeling this year was that wire chambers are very much alive!

  11. Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Kessel, Kurt R.

    2016-01-01

    Corrosion is an extensive problem that affects the National Aeronautics and Space Administration (NASA) and European Space Agency (ESA). The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys.

  12. Alternative right ventricular pacing sites.

    Science.gov (United States)

    Łuciuk, Dariusz; Łuciuk, Marek; Gajek, Jacek

    2015-01-01

    The main adverse effect of chronic stimulation is stimulation-induced heart failure in case of ventricular contraction dyssynchrony. Because of this fact, new techniques of stimulation should be considered to optimize electrotherapy. One of these methods is pacing from alternative right ventricular sites. The purpose of this article is to review currently accumulated data about alternative sites of cardiac pacing. Medline and PubMed bases were used to search English and Polish reports published recently. Recent studies report a deleterious effect of long term apical pacing. It is suggested that permanent apical stimulation, by omitting physiological conduction pattern with His-Purkinie network, may lead to electrical and mechanical dyssynchrony of heart muscle contraction. In the long term this pathological situation can lead to severe heart failure and death. Because of this, scientists began to search for some alternative sites of cardiac pacing to reduce the deleterious effect of stimulation. Based on current accumulated data, it is suggested that the right ventricular outflow tract, right ventricular septum, direct His-bundle or biventricular pacing are better alternatives due to more physiological electrical impulse propagation within the heart and the reduction of the dyssynchrony effect. These methods should preserve a better left ventricular function and prevent the development of heart failure in permanent paced patients. As there is still not enough, long-term, randomized, prospective, cross-over and multicenter studies, further research is required to validate the benefits of using this kind of therapy. The article should pay attention to new sites of cardiac stimulation as a better and safer method of treatment.

  13. Alternatives to the atomic state

    International Nuclear Information System (INIS)

    Peters, J.

    1979-01-01

    The booklet gives in many original articles a general view at the opinions in the total alternative movement. For example, it describes the points of view of the Ecology Movement and compiles the arguments against nuclear power plants. It does not intend to give uniform ideological guiding lines for the practical work but is rather meant as a contribution to improve the communication and connection among the initiatives. (HSCH) [de

  14. Alternative Medicine on the Internet

    OpenAIRE

    Muret, Marc

    2000-01-01

    If you go to a bookstore to look for information on a particular health problem you will have a choice between the "medicine" corner with scientific manuals for professionals and the "health" corner with all kinds of books about acupuncture, ayurveda, natural healing, homeopathy, nutrition, massage, and so on! How is it on the Net? Even a short tour will bring you a lot of "medical" information, but when you look for alternative approaches in the "health" corner you will be rather disappointe...

  15. Alternative bufferlayers for CIGS solarcells

    Energy Technology Data Exchange (ETDEWEB)

    Beleanu, A.; Gruhn, T.; Blum, C.G.F.; Balke, B.; Felser, C. [Institute of Inorganic and Analytical Chemistry, Johannes Gutenberg - University, Mainz (Germany)

    2010-07-01

    Cadmium sulfide is a highly efficient buffer layer material in Cu(In,Ga)(S,Se2)[CIGS] solar devices, but for environmental reasons and possible gains in efficiency there is a great interest in replacing CdS by a cadmium-free alternative buffer layer. Using standard density functional theory (DFT) methods possible candidates like LiZnP and LiCuS have been proposed as alternative buffer layers. The experimental verification of the DFT results was quite challenging due to the fact that LiCuS was an unknow and completely new material. In a first step, we tried to synthesize LiCuS through solid state reactions in a corund crucible. After optimizing the parameters and successfully synthesizing the material its properties were investigated. In a second step, huge amounts of LiCuS and LiZnP were synthesized and pressed using Spark Plasma Sintering as 3 inch targets. LiCuS and LiZnP films were grown by radio-frequency magnetron sputtering from these target and their properties as an alternative buffer layer in CIGS solar cells were investigated. The 1:1:1 stoichiometry of the films was delivered from in-situ XPS measurements. Absorption measurements show a band gap of {approx}2.0 eV which is in good agreement with the theoretical estimates.

  16. ALTERNATIVE FUNDING THECNIQUES. COMPARATIVE ANALYSIS

    Directory of Open Access Journals (Sweden)

    Elena Mihaela ILIESCU

    2018-05-01

    Full Text Available The main objective of this paper isto highlight the dynamics, diversity and especially the availability of an alternative financial market, developed outside of the traditional banking system, on online trading platforms, a market that can constitute an efficient solution, at the expense of entities open to fast funding, wide raging, with limited guaranties and minimum procedural and legislative formalities. For this purpose, we shall analyze briefly the main alternative financing methods, both empirically and qualitatively, in terms of similarities and differences between the two of them, inclusively of the amount that can be employed in this process through different methods. The current paper aims to be a practical guide meant to support those facing difficulties in obtaining financing for start-ups, implementing or/and developing business and entrepreneurship initiatives, and also a guide for those who want to be informed regarding the latest funding techniques. Another aspect to be considered is the legal framework in which this process takes place, because the regulation for these levers remains constantly behind the development process of new methods. The classic financiers should also consider reviewing the lending policy as the amounts attracted and accessed through these alternative methods increase exponentially from one year to the other, the volume of sums involved surpassing each time the forecasts, making thus possible the transformations of these paradigms from the financial sector into preponderant financial funding’s.

  17. Alternative Aviation Fuel Experiment (AAFEX)

    Science.gov (United States)

    Anderson, B. E.; Beyersdorf, A. J.; Hudgins, C. H.; Plant, J. V.; Thornhill, K. L.; Winstead, E. L.; Ziemba, L. D.; Howard, R.; Corporan, E.; Miake-Lye, R. C.; hide

    2011-01-01

    The rising cost of oil coupled with the need to reduce pollution and dependence on foreign suppliers has spurred great interest and activity in developing alternative aviation fuels. Although a variety of fuels have been produced that have similar properties to standard Jet A, detailed studies are required to ascertain the exact impacts of the fuels on engine operation and exhaust composition. In response to this need, NASA acquired and burned a variety of alternative aviation fuel mixtures in the Dryden Flight Research Center DC-8 to assess changes in the aircraft s CFM-56 engine performance and emission parameters relative to operation with standard JP-8. This Alternative Aviation Fuel Experiment, or AAFEX, was conducted at NASA Dryden s Aircraft Operations Facility (DAOF) in Palmdale, California, from January 19 to February 3, 2009 and specifically sought to establish fuel matrix effects on: 1) engine and exhaust gas temperatures and compressor speeds; 2) engine and auxiliary power unit (APU) gas phase and particle emissions and characteristics; and 3) volatile aerosol formation in aging exhaust plumes

  18. Alternating copolymers and alternative device geometries for organic photovoltaics.

    Science.gov (United States)

    Inganäs, Olle; Zhang, Fengling; Andersson, Mats R

    2012-01-01

    The efficiency of conversion of light to electrical energy with the help of conjugated polymers and molecules is rapidly improving. The optical absorption properties of these materials can be designed, and implemented via molecular engineering. Full coverage of the solar spectrum is thus feasible. Narrow absorption spectra allow construction of tandem solar cells. The poor transport properties of these materials require thin devices, which limits optical absorption. Alternative device geometries for these flexible materials compensate for the optical absorption by light trapping, and allow tandem cells.

  19. FMDP reactor alternative summary report. Volume 1 - existing LWR alternative

    International Nuclear Information System (INIS)

    Greene, S.R.; Bevard, B.B.

    1996-01-01

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] are becoming surplus to national defense needs in both the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES ampersand H) consequences if surplus fissile materials are not properly managed. This document summarizes the results of analysis concerned with existing light water reactor plutonium disposition alternatives

  20. FMDP reactor alternative summary report. Volume 1 - existing LWR alternative

    Energy Technology Data Exchange (ETDEWEB)

    Greene, S.R.; Bevard, B.B. [and others

    1996-10-07

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] are becoming surplus to national defense needs in both the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES&H) consequences if surplus fissile materials are not properly managed. This document summarizes the results of analysis concerned with existing light water reactor plutonium disposition alternatives.

  1. Thyroid Disease and Complementary and Alternative Medicine (CAM)

    Science.gov (United States)

    ... Alternative Medicine in Thyroid Disease Complementary and Alternative Medicine in Thyroid Disease (CAM) WHAT IS COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM)? Complementary and Alternative Medicine (CAM) is defined ...

  2. [Alternative medicine: really an alternative to academic medicine?].

    Science.gov (United States)

    Happle, R

    2000-06-01

    Numerous courses on alternative medicine are regularly advertised in Deutsches Arzteblatt, the organ of the German Medical Association. The present German legislation likewise supports this form of medicine, and this explains why Iscador, an extract of the mistletoe, is found in the Rote Liste, a directory of commercially available medical drugs, under the heading "cytostatic and antimetastatic drugs" although such beneficial effect is unproven. To give another example, a German health insurance fund was sentenced to pay for acupuncture as a treatment for hepatic failure. This judgement is characteristic of the present German judicial system and represents a victory of "oracling irrationalism" (Popper). The astonishing popularity of alternative medicine can be explained by a revival of romanticism. An intellectually fair opposite position has been delineated by Karl Popper in the form of critical rationalism. It is important to realize, however, that our decision to adhere to rational thinking is made in the innermost depth of our heart but not on the basis of rational arguing. Rather, the decision in favor of reason has a moral dimension.

  3. Analysis of the Reliability of the "Alternator- Alternator Belt" System

    Directory of Open Access Journals (Sweden)

    Ivan Mavrin

    2012-10-01

    Full Text Available Before starting and also during the exploitation of va1ioussystems, it is vety imp011ant to know how the system and itsparts will behave during operation regarding breakdowns, i.e.failures. It is possible to predict the service behaviour of a systemby determining the functions of reliability, as well as frequencyand intensity of failures.The paper considers the theoretical basics of the functionsof reliability, frequency and intensity of failures for the twomain approaches. One includes 6 equal intetvals and the other13 unequal intetvals for the concrete case taken from practice.The reliability of the "alternator- alternator belt" system installedin the buses, has been analysed, according to the empiricaldata on failures.The empitical data on failures provide empirical functionsof reliability and frequency and intensity of failures, that arepresented in tables and graphically. The first analysis perfO!med by dividing the mean time between failures into 6 equaltime intervals has given the forms of empirical functions of fa ilurefrequency and intensity that approximately cotTespond totypical functions. By dividing the failure phase into 13 unequalintetvals with two failures in each interval, these functions indicateexplicit transitions from early failure inte1val into the randomfailure interval, i.e. into the ageing intetval. Functions thusobtained are more accurate and represent a better solution forthe given case.In order to estimate reliability of these systems with greateraccuracy, a greater number of failures needs to be analysed.

  4. Alternative energy and environmental concerns

    International Nuclear Information System (INIS)

    2002-01-01

    The New Brunswick Market Design Committee will address environmental concerns within the context of the new energy policy and market rules for the newly restructured electric power industry. The new rules that come with power restructuring will in some ways facilitate environmental protection but they can also complicate it. With open access markets, it will be possible to coordinate evolving energy frameworks with current environmental objectives. Restructuring provides an opportunity to create incentives and guidelines to operate in an environmentally sustainable manner, as suggested in the New Brunswick Energy Policy, White Paper which outlines green pricing, the development of a provincial Climate Change Action Plan, and promotion of alternative energy. The Market Design Committee examined the environmental concerns listed within the White Paper that pertain to the generation and transmission of electricity. These include the integration of energy and environmental policy. Other issues addressed in this report were trans-boundary and global air emissions, the development of a provincial climate change action plan, and a federal-provincial climate change framework agreement. New Brunswick will encourage the development of pilot studies that demonstrate the benefits of renewable and alternative technologies and that help promote the market to manufacture, sell and maintain renewable and alternative technologies in small-scale on-site power generation. This report also discussed the 4 key air pollutants for which specific treatment has been defined, including sulphur dioxide, nitrogen oxides, mercury and carbon dioxide. Recommendations for reducing these emissions include the use of renewable energy sources, the use of lower carbon fuels, increased efficiency of power transmission/generation/distribution systems, reducing power demand by the industrial sector, and promoting energy efficient building codes. 34 refs., 1 tab

  5. Alternatives to quintessence model building

    International Nuclear Information System (INIS)

    Avelino, P.P.; Beca, L.M.G.; Pinto, P.; Carvalho, J.P.M. de; Martins, C.J.A.P.

    2003-01-01

    We discuss the issue of toy model building for the dark energy component of the universe. Specifically, we consider two generic toy models recently proposed as alternatives to quintessence models, respectively known as Cardassian expansion and the Chaplygin gas. We show that the former is entirely equivalent to a class of quintessence models. We determine the observational constraints on the latter, coming from recent supernovae results and from the shape of the matter power spectrum. As expected, these restrict the model to a behavior that closely matches that of a standard cosmological constant Λ

  6. The Development of Nonstructural Alternatives.

    Science.gov (United States)

    1979-05-01

    particular appeal and benefits for those concerned with environmental issues. However, on reflection it is clear that, almost by definition, easily...peculiar to nonstructural alternatives (that is, the social costs are borne primaqrilv by th,, )ent ficiaries) makes them appealing from the national...Costs Of prId-nt ! loo41p l jotve iopment lie basically in the costs of elevated 111’Z ’’l’i. Pie 1land reqat reti c,- snob dovelIopmeot is loss

  7. Alternative dipole magnets for ISABELLE

    Science.gov (United States)

    Taylor, C.; Althaus, R.; Caspi, S.; Gilbert, W.; Hassenzahl, W. V.; Meuser, R.; Rechen, J.; Warren, R.

    1982-05-01

    A dipole magnet, intended as a possible alternative for the ISABELLE main ring magnet, was designed. Three layers of FNAL Doubler/Saver conductor were used. Two 1.3-m-long models were built and tested, both with and without an iron core, and in both helium I and helium II. The training behavior, cyclic energy loss, point of quench initiation, and quench velocity were determined. A central field of 6.5 tesla was obtained in He I (4.4 K), and 7.6 tesla in He II (1.8K).

  8. Erythrocytes in alternating electric fields

    International Nuclear Information System (INIS)

    Morariu, V.V.; Chifu, A.; Simplaceanu, T.; Frangopol, P.T.

    1983-02-01

    The elastic and inelastic deformation of erythrocytes induced by alternating fields and the suggestion that moderate field intensities (1.2 kV/cm) when continuously applied can cause lysis by a different mechanism compared to the action of short intense field pulses is presented. The different experimental conditions can be used to approach various properties of the membrane such as those related to the dielectric polarization of the membrane or to the interfacial polarization, leading to the inelastic deformation of the cells. (authors)

  9. Alternating current for the West

    International Nuclear Information System (INIS)

    2006-01-01

    In the framework of the reactor EPR construction in the Manche, the authors wonder on the pertinence of this energy choice for the economy and the environment of the West France. They show that there is an alternative to this choice. In a first part a state of the situation concerning the electricity supply and demand in the region is detailed. Then from the local potential of renewable electric power production and the electricity conservation, they propose many concrete actions. (A.L.B.)

  10. The difference between alternative averages

    Directory of Open Access Journals (Sweden)

    James Vaupel

    2012-09-01

    Full Text Available BACKGROUND Demographers have long been interested in how compositional change, e.g., change in age structure, affects population averages. OBJECTIVE We want to deepen understanding of how compositional change affects population averages. RESULTS The difference between two averages of a variable, calculated using alternative weighting functions, equals the covariance between the variable and the ratio of the weighting functions, divided by the average of the ratio. We compare weighted and unweighted averages and also provide examples of use of the relationship in analyses of fertility and mortality. COMMENTS Other uses of covariances in formal demography are worth exploring.

  11. Bayesian Alternation During Tactile Augmentation

    Directory of Open Access Journals (Sweden)

    Caspar Mathias Goeke

    2016-10-01

    Full Text Available A large number of studies suggest that the integration of multisensory signals by humans is well described by Bayesian principles. However, there are very few reports about cue combination between a native and an augmented sense. In particular, we asked the question whether adult participants are able to integrate an augmented sensory cue with existing native sensory information. Hence for the purpose of this study we build a tactile augmentation device. Consequently, we compared different hypotheses of how untrained adult participants combine information from a native and an augmented sense. In a two-interval forced choice (2 IFC task, while subjects were blindfolded and seated on a rotating platform, our sensory augmentation device translated information on whole body yaw rotation to tactile stimulation. Three conditions were realized: tactile stimulation only (augmented condition, rotation only (native condition, and both augmented and native information (bimodal condition. Participants had to choose one out of two consecutive rotations with higher angular rotation. For the analysis, we fitted the participants’ responses with a probit model and calculated the just notable difference (JND. Then we compared several models for predicting bimodal from unimodal responses. An objective Bayesian alternation model yielded a better prediction (χred2 = 1.67 than the Bayesian integration model (χred2= 4.34. Slightly higher accuracy showed a non-Bayesian winner takes all model (χred2= 1.64, which either used only native or only augmented values per subject for prediction. However the performance of the Bayesian alternation model could be substantially improved (χred2= 1.09 utilizing subjective weights obtained by a questionnaire. As a result, the subjective Bayesian alternation model predicted bimodal performance most accurately among all tested models. These results suggest that information from augmented and existing sensory modalities in

  12. MR pelvimetry - a practical alternative

    International Nuclear Information System (INIS)

    Wright, A.R.; English, P.T.; Cameron, H.M.; Wilsdon, J.B.

    1992-01-01

    Pelvimetry remains a useful technique as part of the assessment of the term breech pregnancy where vaginal delivery is planned. MR pelvimetry is accurate, well tolerated and shows soft-tissue structures as well as bone. It avoids the potentially carcinogenic effects of ionising radiation and is thought to be completely safe for mother and fetus. A technique of MR pelvimetry is described which uses gradient-echo sequences. This quick, practical method makes minimal in roads into valuable scanning time, and may therefore be considered a potentially cost-effective alternative to conventional pelvimetry. (orig.)

  13. Alternate Energy for National Security.

    Science.gov (United States)

    Rath, Bhakta

    2010-02-01

    Recent price fluctuations at the gas pump have brought our attention to the phenomenal increase of global energy consumption in recent years. It is now evident that we have almost reached a peak in global oil production. Several projections indicate that total world consumption of oil will rise by nearly 60 per cent between 1999 and 2020. In 1999 consumption was equivalent to 86 million barrels of oil per day, which has reached a peak of production extracted from most known oil reserves. These projections, if accurate, will present an unprecedented crisis to the global economy and industry. As an example, in the US, nearly 40 per cent of energy usage is provided by petroleum, of which nearly a third is used in transportation. The US Department of Defense (DOD) is the single largest buyer of fuel, amounting to, on the average, 13 million gallons per day. Additionally, these fuels have to meet different requirements that prevent use of ethanol additives and biodiesel. An aggressive search for alternate energy sources, both renewable and nonrenewable, is vital. The presentation will review national and DOD perspectives on the exploration of alternate energy with a focus on energy derivable from the ocean. )

  14. Alternate approaches to nuclear safety

    International Nuclear Information System (INIS)

    Crane, A.T.

    1985-01-01

    For the US nuclear power industry to expand, a greatly increased portion of the public must come to share the industry's confidence in reactor safety. Major obstacles to establishing this confidence are frequent incidents with potential safety implications and a lack of incontrovertible proof that the risk of a major accident is very low. The most important step toward overcoming these obstacles would be for each utility to operate, maintain, and evaluate its reactors according to far higher standards. With improvements in reliability and safety margins, existing plants would be a stimulus for building new ones rather than an impediment. If changes to the operation of existing plants and improvements to the design of future ones were inadequate, the only hope for a revival of the nuclear industry would be an alternative reactor so obviously safe that risk would no longer be an issue. Three possible concepts are the modular high-temperature gas reactor, the process inherent ultimate safety reactor, and the liquid-metal fast reactor. All three have inherent safety features that should make a meltdown essentially impossible. They cannot know just how great the advantage of these alternate reactors would be, but the benefits of developing one or more of the concepts appear great

  15. [Alternative nutrition and glutathione levels].

    Science.gov (United States)

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Brtková, A; Magálová, T; Barteková, S

    1999-08-30

    Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P vegan diet also in adult age.

  16. Alternative fuels: a Brazilian outlook

    International Nuclear Information System (INIS)

    Moreira, J.R.; Serra, G.E.

    1990-01-01

    This paper focuses on studies and information related to the use of alternative fuels in Brazil. The first part of this paper deals with the economics of different biomass technologies. The analysis consists of a careful costing of all operations involved. The study deals with wood, sugar cane and cassava, since these crops are exploited for commercial purposes in Brazil. Corn, although a useful raw material for producing ethanol in the United States, is not used for this purpose in Brazil. The second part deals with the industrial technologies used to convert biomass into energy. We consider several forms of energy derived from biomass and evaluate the economics of the processes. When opportune, we compare costs with those of the North American market. Market analysis and displacement of conventional energy are the subject of the third part of the paper. While the cost of each product is evaluated in most cases; in others the current market price is used. Finally, we raise the issues of institutional problems and planning and offer some conclusions on the future of biomass as an alternative energy source. The technological discussion in this paper is based on the Brazilian experience in producing ethanol and other fuels from biomass. It is possible to extrapolate the Brazilian experience to other developing countries. The observations made in this chapter are based on the conditions prevalent in the Brazilian south-central agricultural region, specifically the state of Sao Paulo. (author). 91 refs., 16 figs., 11 tabs

  17. Alternate Double Single Track Lines

    Energy Technology Data Exchange (ETDEWEB)

    Moraga Contreras, P.; Grande Andrade, Z.; Castillo Ron, E.

    2016-07-01

    The paper discusses the advantages and shortcomings of alternate double single track (ADST) lines with respect to double track lines for high speed lines. ADST lines consists of sequences of double and single track segments optimally selected in order to reduce the construction and maintenance costs of railway lines and to optimize the timetables used to satisfy a given demand. The single tracks are selected to coincide with expensive segments (tunnels and viaducts) and the double tracks are chosen to coincide with flat areas and only where they are necessary. At the same time, departure times are adjusted for trains to cross at the cheap double track segments. This alternative can be used for new lines and also for existing conventional lines where some new tracks are to be constructed to reduce travel time (increase speed). The ADST proposal is illustrated with some examples of both types (new lines and where conventional lines exist), including the Palencia-Santander, the Santiago-Valparaíso-Viña del Mar and the Dublin-Belfast lines, where very important reductions (90 %) are obtained, especially where a railway infrastructure already exist. (Author)

  18. Alternatives for nuclear fuel disposal

    International Nuclear Information System (INIS)

    Ramirez S, J. R.; Badillo A, V.; Palacios H, J.; Celis del Angel, L.

    2010-10-01

    The spent fuel is one of the most important issues in the nuclear industry, currently spent fuel management is been cause of great amount of research, investments in the construction of repositories or constructing the necessary facilities to reprocess the fuel, and later to recycle the plutonium recovered in thermal reactors. What is the best solution? or, What is the best technology for a specific solution? Many countries have deferred the decision on selecting an option, while other works actively constructing repositories and others implementing the reprocessing facilities to recycle the plutonium obtained from nuclear spent fuel. In Mexico the nuclear power is limited to two reactors BWR type and medium size. So the nuclear spent fuel discharged has been accommodated at reactor's spent fuel pools. Originally these pools have enough capacity to accommodate spent fuel for the 40 years of designed plant operation. However, currently is under process an extended power up rate to 20% of their original power and also there are plans to extend operational life for 20 more years. Under these conditions there will not be enough room for spent fuel in the pools. So this work describes some different alternatives that have been studied in Mexico to define which will be the best alternative to follow. (Author)

  19. Advanced Technology and Alternative Fuel Vehicles

    International Nuclear Information System (INIS)

    Tuttle, J.

    2001-01-01

    This fact sheet provides a basic overview of today's alternative fuel choices--including biofuels, biodiesel, electricity, and hydrogen--alternative fuel vehicles, and advanced vehicle technology, such as hybrid electric vehicles, fuel cells and advanced drive trains

  20. Alternative Fuel News, Volume 4, Number 3

    Energy Technology Data Exchange (ETDEWEB)

    Ficker, C.

    2000-11-14

    This issue of Alternative Fuel News focuses on transit buses and refuse haulers. Many transit agencies and waste management companies are investigating alternatives to traditional diesel buses and refuse haulers.