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Sample records for class ii-related endogenous

  1. Evolution and Distribution of Class II-Related Endogenous Retroviruses†

    PubMed Central

    Gifford, Robert; Kabat, Peter; Martin, Joanne; Lynch, Clare; Tristem, Michael

    2005-01-01

    Endogenous retroviruses (ERVs) are widespread in vertebrate genomes and have been loosely grouped into “classes” on the basis of their phylogenetic relatedness to the established genera of exogenous retroviruses. Four of these genera—the lentiviruses, alpharetroviruses, betaretroviruses, and deltaretroviruses—form a well-supported clade in retroviral phylogenies, and ERVs that group with these genera have been termed class II ERVs. We used PCR amplification and sequencing of retroviral fragments from more than 130 vertebrate taxa to investigate the evolution of the class II retroviruses in detail. We confirm that class II retroviruses are largely confined to mammalian and avian hosts and provide evidence for a major novel group of avian retroviruses, and we identify additional members of both the alpha- and the betaretrovirus genera. Phylogenetic analyses demonstrated that the avian and mammalian viruses form distinct monophyletic groups, implying that interclass transmission has occurred only rarely during the evolution of the class II retroviruses. In contrast to previous reports, the lentiviruses clustered as sister taxa to several endogenous retroviruses derived from rodents and insectivores. This topology was further supported by the shared loss of both the class II PR-Pol frameshift site and the class II retrovirus G-patch domain. PMID:15858031

  2. Endogenous Antigen Presentation of MHC Class II Epitopes through Non-Autophagic Pathways

    PubMed Central

    Leung, Carol S. K.

    2015-01-01

    Antigenic peptides presented by major histocompatibility complex (MHC) class II molecules are generally derived from exogenous proteins acquired by antigen presenting cells. However, in some circumstances, MHC class II molecules can present intracellular proteins expressed within the antigen-presenting cells. There are several described pathways by which endogenous antigens are degraded and gain access to MHC class II molecules. These include autophagy and other non-autophagic pathways; the latter category includes the MHC class I-like pathways, heat shock protein 90-mediated pathways, and internalization from the plasma membrane. This review will summarize and discuss the non-autophagic pathways. PMID:26441969

  3. Macroautophagy in Endogenous Processing of Self- and Pathogen-Derived Antigens for MHC Class II Presentation

    PubMed Central

    Duraes, Fernanda V.; Niven, Jennifer; Dubrot, Juan; Hugues, Stéphanie; Gannagé, Monique

    2015-01-01

    Although autophagy is a process that has been studied for several years its link with antigen presentation and T cell immunity has only recently emerged. Autophagy, which means “self-eating,” is important to maintain cell homeostasis and refers to a collection of mechanisms that delivers intracellular material for degradation into lysosomes. Among them, macroautophagy pathway has many implications in different biological processes, including innate and adaptive immunity. In particular, macroautophagy can provide a substantial source of intracellular antigens for loading onto MHC class II molecules using the alternative MHC class II pathway. Through autophagosomes, endogenous self-antigens as well as antigens derived from intracellular pathogens can be delivered to MHC class II compartment and presented to CD4+ T cells. The pathway will, therefore, impact both peripheral T cell tolerance and the pathogen specific immune response. This review will describe the contribution of autophagy to intracellular presentation of endogenous self- or pathogen-derived antigens via MHC class II and its consequences on CD4+ T cell responses. PMID:26441964

  4. Response Patterns in Health State Valuation Using Endogenous Attribute Attendance and Latent Class Analysis.

    PubMed

    Hole, Arne Risa; Norman, Richard; Viney, Rosalie

    2016-02-01

    Not accounting for simplifying decision-making heuristics when modelling data from discrete choice experiments has been shown potentially to lead to biased inferences. This study considers two ways of exploring the presence of attribute non-attendance (that is, respondents considering only a subset of the attributes that define the choice options) in a health state valuation discrete choice experiment. The methods used include the latent class (LC) and endogenous attribute attendance (EAA) models, which both required adjustment to reflect the structure of the quality-adjusted life year (QALY) framework for valuing health outcomes. We find that explicit consideration of attendance patterns substantially improves model fit. The impact of allowing for non-attendance on the estimated QALY weights is dependent on the assumed source of non-attendance. If non-attendance is interpreted as a form of preference heterogeneity, then the inferences from the LC and EAA models are similar to those from standard models, while if respondents ignore attributes to simplify the choice task, the QALY weights differ from those using the standard approach. Because the cause of non-attendance is unknown in the absence of additional data, a policymaker may use the range of weights implied by the two approaches to conduct a sensitivity analysis. PMID:25521533

  5. HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen.

    PubMed Central

    Bertoletti, A; Ferrari, C; Fiaccadori, F; Penna, A; Margolskee, R; Schlicht, H J; Fowler, P; Guilhot, S; Chisari, F V

    1991-01-01

    Knowledge of the immune effector mechanisms responsible for clearance of hepatitis B virus (HBV)-infected cells has been severely limited by the absence of reproducible systems to selectively expand and to characterize HBV-specific cytotoxic T lymphocytes (CTLs) in the peripheral blood of patients with viral hepatitis. By using a strategy involving sequential stimulation with HBV nucleocapsid synthetic peptides followed by autologous, or HLA class I-matched, HBV nucleocapsid transfectants, we now report the existence of CTLs able to lyse target cells that express endogenously synthesized HBV nucleocapsid antigen in the peripheral blood of patients with acute viral hepatitis B. The CTL response is HLA-A2 restricted, mediated by CD8-positive T cells, and specific for a single epitope, located between amino acid residues 11 and 27 of HBV core protein; these residues are shared with the secretable precore-derived hepatitis B e antigen. Equivalent lysis of target cells that express each of these proteins suggests that their intracellular trafficking pathways may intersect. The current report provides definitive evidence that HLA class I-restricted, CD8-positive CTLs that recognize endogenously synthesized HBV nucleocapsid antigen are induced during acute HBV infection in humans and establishes a strategy that should permit a detailed analysis of the role played by HBV-specific CTLs in the immunopathogenesis of viral hepatitis. PMID:1660137

  6. Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule.

    PubMed

    Wynne, James W; Woon, Amanda P; Dudek, Nadine L; Croft, Nathan P; Ng, Justin H J; Baker, Michelle L; Wang, Lin-Fa; Purcell, Anthony W

    2016-06-01

    Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome-like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes. In this study, we used an affinity purification/mass spectrometry approach to demonstrate that a bat MHC class I molecule, Ptal-N*01:01, binds antigenic peptides and associates with peptide-loading complex components. We identified several bat MHC class I-binding partners, including calnexin, calreticulin, protein disulfide isomerase A3, tapasin, TAP1, and TAP2. Additionally, endogenous peptide ligands isolated from Ptal-N*01:01 displayed a relatively broad length distribution and an unusual preference for a C-terminal proline residue. Finally, we demonstrate that this preference for C-terminal proline residues was observed in Hendra virus-derived peptides presented by Ptal-N*01:01 on the surface of infected cells. To our knowledge, this is the first study to identify endogenous and viral MHC class I ligands for any bat species and, as such, provides an important avenue for monitoring and development of vaccines against major bat-borne viruses both in the reservoir and spillover hosts. Additionally, it will provide a foundation to understand the role of adaptive immunity in bat antiviral responses. PMID:27183594

  7. Virus infection triggers widespread silencing of host genes by a distinct class of endogenous siRNAs in Arabidopsis

    PubMed Central

    Cao, Mengji; Du, Peng; Wang, Xianbing; Yu, Yun-Qi; Qiu, Yan-Hong; Li, Wanxiang; Gal-On, Amit; Zhou, Changyong; Li, Yi; Ding, Shou-Wei

    2014-01-01

    Antiviral immunity controlled by RNA interference (RNAi) in plants and animals is thought to specifically target only viral RNAs by the virus-derived small interfering RNAs (siRNAs). Here we show that activation of antiviral RNAi in Arabidopsis plants is accompanied by the production of an abundant class of endogenous siRNAs mapped to the exon regions of more than 1,000 host genes and rRNA. These virus-activated siRNAs (vasiRNAs) are predominantly 21 nucleotides long with an approximately equal ratio of sense and antisense strands. Genetically, vasiRNAs are distinct from the known plant endogenous siRNAs characterized to date and instead resemble viral siRNAs by requiring Dicer-like 4 and RNA-dependent RNA polymerase 1 (RDR1) for biogenesis. However, loss of EXORIBONUCLEASE4/THYLENE-INSENSITIVE5 enhances vasiRNA biogenesis and virus resistance without altering the biogenesis of viral siRNAs. We show that vasiRNAs are active in directing widespread silencing of the target host genes and that Argonaute-2 binds to and is essential for the silencing activity of vasiRNAs. Production of vasiRNAs is readily detectable in Arabidopsis after infection by viruses from two distinct supergroups of plant RNA virus families and is targeted for inhibition by the silencing suppressor protein 2b of Cucumber mosaic virus. These findings reveal RDR1 production of Arabidopsis endogenous siRNAs and identify production of vasiRNAs to direct widespread silencing of host genes as a conserved response of plants to infection by diverse viruses. A possible function for vasiRNAs to confer broad-spectrum antiviral activity distinct to the virus-specific antiviral RNAi by viral siRNAs is discussed. PMID:25201959

  8. Dendritic cell preactivation impairs MHC class II presentation of vaccines and endogenous viral antigens

    PubMed Central

    Young, Louise J.; Wilson, Nicholas S.; Schnorrer, Petra; Mount, Adele; Lundie, Rachel J.; La Gruta, Nicole L.; Crabb, Brendan S.; Belz, Gabrielle T.; Heath, William R.; Villadangos, Jose A.

    2007-01-01

    When dendritic cells (DCs) encounter signals associated with infection or inflammation, they become activated and undergo maturation. Mature DCs are very efficient at presenting antigens captured in association with their activating signal but fail to present subsequently encountered antigens, at least in vitro. Such impairment of MHC class II (MHC II) antigen presentation has generally been thought to be a consequence of down-regulation of endocytosis, so it might be expected that antigens synthesized by the DCs themselves (for instance, viral antigens) would still be presented by mature DCs. Here, we show that DCs matured in vivo could still capture and process soluble antigens, but were unable to present peptides derived from these antigens. Furthermore, presentation of viral antigens synthesized by the DCs themselves was also severely impaired. Indeed, i.v. injection of pathogen mimics, which caused systemic DC activation in vivo, impaired the induction of CD4 T cell responses against subsequently encountered protein antigens. This immunosuppressed state could be reversed by adoptive transfer of DCs loaded exogenously with antigens, demonstrating that impairment of CD4 T cell responses was due to lack of antigen presentation rather than to overt suppression of T cell activation. The biochemical mechanism underlying this phenomenon was the down-regulation of MHC II–peptide complex formation that accompanied DC maturation. These observations have important implications for the design of prophylactic and therapeutic DC vaccines and contribute to the understanding of the mechanisms causing immunosuppression during systemic blood infections. PMID:17978177

  9. HIV-Infected Dendritic Cells Present Endogenous MHC Class II-Restricted Antigens to HIV-Specific CD4+ T Cells.

    PubMed

    Coulon, Pierre-Grégoire; Richetta, Clémence; Rouers, Angéline; Blanchet, Fabien P; Urrutia, Alejandra; Guerbois, Mathilde; Piguet, Vincent; Theodorou, Ioannis; Bet, Anne; Schwartz, Olivier; Tangy, Frédéric; Graff-Dubois, Stéphanie; Cardinaud, Sylvain; Moris, Arnaud

    2016-07-15

    It is widely assumed that CD4(+) T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)-restricted Ags have been described, in particular epitopes derived from newly synthesized proteins (so-called endogenous). In this study, we show that HIV-infected dendritic cells (DC) present MHC-II-restricted endogenous viral Ags to HIV-specific (HS) CD4(+) T cells. This endogenous pathway functions independently of the exogenous route for HIV Ag presentation and offers a distinct possibility for the immune system to activate HS CD4(+) T cells. We examined the implication of autophagy, which plays a crucial role in endogenous viral Ag presentation and thymic selection of CD4(+) T cells, in HIV endogenous presentation. We show that infected DC do not use autophagy to process MHC-II-restricted HIV Ags. This is unlikely to correspond to a viral escape from autophagic degradation, as infecting DC with Nef- or Env-deficient HIV strains did not impact HS T cell activation. However, we demonstrate that, in DC, specific targeting of HIV Ags to autophagosomes using a microtubule-associated protein L chain 3 (LC3) fusion protein effectively enhances and broadens HS CD4(+) T cell responses, thus favoring an endogenous MHC-II-restricted presentation. In summary, in DC, multiple endogenous presentation pathways lead to the activation of HS CD4(+) T cell responses. These findings will help in designing novel strategies to activate HS CD4(+) T cells that are required for CTL activation/maintenance and B cell maturation. PMID:27288536

  10. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects

    PubMed Central

    Yore, Mark M.; Syed, Ismail; Moraes-Vieira, Pedro M.; Zhang, Tejia; Herman, Mark A.; Homan, Edwin; Patel, Rajesh T.; Lee, Jennifer; Chen, Shili; Peroni, Odile D.; Dhaneshwar, Abha; Hammarstedt, Ann; Smith, Ulf; McGraw, Timothy E.; Saghatelian, Alan; Kahn, Barbara B.

    2014-01-01

    Summary Increased adipose tissue lipogenesis is associated with enhanced insulin sensitivity. Mice overexpressing the Glut4 glucose transporter in adipocytes have elevated lipogenesis and increased glucose tolerance despite being obese with elevated circulating fatty acids. Lipidomic analysis of adipose tissue revealed the existence of branched fatty acid esters of hydroxy fatty acids (FAHFAs) that were elevated 16–18-fold in these mice. FAHFA isomers differ by the branched ester position on the hydroxy fatty acid (e.g. palmitic-acid-9-hydroxy-stearic acid, 9-PAHSA). PAHSAs are synthesized in vivo and regulated by fasting and high fat feeding. PAHSA levels correlate highly with insulin sensitivity and are reduced in adipose tissue and serum of insulin-resistant humans. PAHSA administration in mice lowers ambient glycemia and improves glucose tolerance while stimulating GLP-1 and insulin secretion. PAHSAs also reduce adipose tissue inflammation. In adipocytes, PAHSAs signal through GPR-120 to enhance insulin-stimulated glucose uptake. Thus, FAHFAs are endogenous lipids with the potential to treat type 2 diabetes. PMID:25303528

  11. Genetic and biochemical characterization of TRU-1, the endogenous class C beta-lactamase from Aeromonas enteropelogenes.

    PubMed

    De Luca, Filomena; Giraud-Morin, Chantal; Rossolini, Gian Maria; Docquier, Jean-Denis; Fosse, Thierry

    2010-04-01

    Aeromonas enteropelogenes (formerly A. tructi) was described to be an ampicillin-susceptible and cephalothin-resistant Aeromonas species, which suggests the production of a cephalosporinase. Strain ATCC 49803 was susceptible to amoxicillin, cefotaxime, and imipenem but resistant to cefazolin (MICs of 2, 0.032, 0.125, and >256 microg/ml, respectively) and produced an inducible beta-lactamase. Cefotaxime-resistant mutants (MIC, 32 microg/ml) that showed constitutive beta-lactamase production could be selected in vitro. The gene coding for the cephalosporinase of A. enteropelogenes ATCC 49803 was cloned, and its biochemical properties were investigated. Escherichia coli transformants showing resistance to various beta-lactams carried a 3.5-kb plasmid insert whose sequence revealed a 1,146-bp open reading frame (ORF) encoding a class C beta-lactamase, named TRU-1, showing the highest identity scores with A. punctata CAV-1 (75%), A. salmonicida AmpC (75%), and A. hydrophila CepH (71%). The bla(TRU-1) locus includes open reading frames (ORFs) showing significant homology with genes found in the genomes of other Aeromonas species, although it exhibits a different organization, as reflected by the presence of additional ORFs located downstream of the beta-lactamase gene in the A. hydrophila and A. salmonicida genomes. Specific PCR assays were negative for cphA-like and bla(OXA-12)-like genes in three A. enteropelogenes ATCC strains. Purified TRU-1 showed a broad substrate profile, efficiently hydrolyzing benzylpenicillin, cephalothin, cefoxitin, and, although with significantly lower turnover rates, oxyiminocephalosporins. Cephaloridine and cefepime were poorly recognized by the enzyme, as reflected by the high K(m) values observed with these substrates. Thus far, A. enteropelogenes represents the only known example of an Aeromonas species that produces only one beta-lactamase belonging to molecular class C. PMID:20124004

  12. Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens.

    PubMed Central

    Penna, A; Fowler, P; Bertoletti, A; Guilhot, S; Moss, B; Margolskee, R F; Cavalli, A; Valli, A; Fiaccadori, F; Chisari, F V

    1992-01-01

    In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B. PMID:1731098

  13. Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4+ T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways

    PubMed Central

    Thiele, Frank; Tao, Sha; Zhang, Yi; Muschaweckh, Andreas; Zollmann, Tina; Protzer, Ulrike; Abele, Rubert

    2014-01-01

    ABSTRACT CD4+ T lymphocytes play a central role in the immune system and mediate their function after recognition of their respective antigens presented on major histocompatibility complex II (MHCII) molecules on antigen-presenting cells (APCs). Conventionally, phagocytosed antigens are loaded on MHCII for stimulation of CD4+ T cells. Certain epitopes, however, can be processed directly from intracellular antigens and are presented on MHCII (endogenous MHCII presentation). Here we characterized the MHCII antigen presentation pathways that are possibly involved in the immune response upon vaccination with modified vaccinia virus Ankara (MVA), a promising live viral vaccine vector. We established CD4+ T-cell lines specific for MVA-derived epitopes as tools for in vitro analysis of MHCII antigen processing and presentation in MVA-infected APCs. We provide evidence that infected APCs are able to directly transfer endogenous viral proteins into the MHCII pathway to efficiently activate CD4+ T cells. By using knockout mice and chemical inhibitory compounds, we further elucidated the molecular basis, showing that among the various subcellular pathways investigated, proteasomes and autophagy are key players in the endogenous MHCII presentation during MVA infection. Interestingly, although proteasomal processing plays an important role, neither TAP nor LAMP-2 was found to be involved in the peptide transport. Defining the molecular mechanism of MHCII presentation during MVA infection provides a basis for improving MVA-based vaccination strategies by aiming for enhanced CD4+ T-cell activation by directing antigens into the responsible pathways. IMPORTANCE This work contributes significantly to our understanding of the immunogenic properties of pathogens by deciphering antigen processing pathways contributing to efficient activation of antigen-specific CD4+ T cells. We identified autophagosome formation, proteasomal activity, and lysosomal integrity as being crucial for

  14. Endogenous ochronosis.

    PubMed

    Turgay, E; Canat, D; Gurel, M S; Yuksel, T; Baran, M F; Demirkesen, C

    2009-12-01

    Endogenous ochronosis or alkaptonuria is a rare, autosomal recessive disease of tyrosine metabolism that is caused by a deficiency of the enzyme homogentisic acid oxidase. The disease results in the accumulation and deposition of homogentisic acid in the cartilage, eyelids, forehead, cheeks, axillae, genital region, buccal mucosa, larynx, tympanic membranes, and tendons. The disease generally presents in adults with arthritis and skin abnormalities; occasionally, involvement of other organs may be seen. A 49-year-old man was referred to our clinic with verrucous lesions on his hands. On physical examination, caviar-like ochronotic papules were found around his eyes and the helix cartilage of his ears, and on the dorsa of both hands. There were brown macules on the sclera (Osler's sign). The patient had arthritis and nephrolithiasis, and a sample of his urine darkened upon standing. Histopathological examination showed deposition of ochronotic pigment. High-dose ascorbic acid was given, and the patient showed improvement on follow-up examination 6 months later. PMID:20055850

  15. DC-expressed MHC class I single-chain trimer-based vaccines prime cytotoxic T lymphocytes against exogenous but not endogenous antigens.

    PubMed

    Ordaz, Maria L; Larmonier, Nicolas; Lybarger, Lonnie

    2010-01-01

    The poor immunogenicity of many tumors can be partly explained by the inefficiency of the MHC class I peptide presentation pathway. MHC-I-based single-chain trimers (SCT) represent a new class of molecules with the potential to overcome this limitation. We here evaluated the ability of SCT presenting a melanoma antigen peptide (TRP-2) to prime cytotoxic T lymphocyte (CTL) responses in mice when given as DNA vaccines via Gene Gun or when expressed by dendritic cells. The SCT was unable to induce detectable priming or significant anti-tumor activity of CTL using either vaccination strategy, whereas control SCT (with an exogenous peptide) primed strong responses. This study thus provides the first data related to the use of SCT in combination with DC and their application toward self antigens and suggest this potent technology, alone, is insufficient to overcome self tolerance. PMID:20199770

  16. Cloning and characterization of the endogenous cephalosporinase gene, cepA, from Bacteroides fragilis reveals a new subgroup of Ambler class A beta-lactamases.

    PubMed Central

    Rogers, M B; Parker, A C; Smith, C J

    1993-01-01

    Bacteroides fragilis CS30 is a clinical isolate resistant to high concentrations of benzylpenicillin and cephaloridine but not to cephamycin or penem antibiotics. beta-Lactam resistance is mediated by a chromosomally encoded cephalosporinase produced at a high level. The gene encoding this beta-lactamase was cloned from genomic libraries constructed in Escherichia coli and then mated with B. fragilis 638 for identification of ampicillin-resistant (Apr) strains. Apr transconjugants contained a nitrocefin-reactive protein with the physical and enzymatic properties of the original CS30 isolate. The beta-lactamase gene (cepA) was localized by deletion analysis and subcloned, and its nucleotide sequence was determined. The 903-bp cepA open reading frame encoded a 300-amino-acid precursor protein (predicted molecular mass, 34,070 Da). A beta-lactamase-deficient mutant strain of B. fragilis 638 was constructed by insertional inactivation with the cepA gene of CS30, demonstrating strict functional homology between these chromosomal beta-lactamase genes. An extensive comparison of the CepA protein sequence by alignment with other beta-lactamases revealed the strict conservation of at least four elements common to Ambler class A. A further comparison of the CepA protein sequence with protein sequences of beta-lactamases from two other Bacteroides species indicated that they constitute their own distinct subgroup of class A beta-lactamases. Images PMID:8285623

  17. Inhibition by chloroquine of the class II major histocompatibility complex-restricted presentation of endogenous antigens varies according to the cellular origin of the antigen-presenting cells, the nature of the T-cell epitope, and the responding T cell.

    PubMed Central

    Lombard-Platlet, S; Bertolino, P; Deng, H; Gerlier, D; Rabourdin-Combe, C

    1993-01-01

    Chloroquine treatment of antigen-presenting cells (APC) was explored as a tool to investigate the processing pathway for major histocompatibility complex (MHC) class II-restricted presentation of the endogenous secreted hen egg lysozyme (HEL) and transmembrane measles virus haemagglutinin (HA). A 72-hr pretreatment of the APC with 25 microM chloroquine blocked the presentation of the HEL(52-61) T-cell epitope generated from endogenous HEL to the I-Ak-restricted 3A9 T-cell hybridoma by MHC class II-transfected L cells expressing the invariant chain (Ii). The presentation of exogenously added HEL peptides was not affected. Under the same conditions, no inhibition of the presentation of HEL(106-116) to the I-Ed-restricted G28 high-avidity T-cell hybridoma, nor of HA when synthesized by L cells, was observed. When B-lymphoid APC were used, inhibition was observed in every case with a low number of B APC pretreated for 48 hr with chloroquine prior to the T-cell stimulation test. Moreover, addition of chloroquine to untreated B APC during the T-cell stimulation assay was sufficient to inhibit completely the presentation of HEL(106-116) to the B10.D24.42 low avidity T-cell hybridoma. Altogether these studies suggest that an apparent resistance of endogenous Ag presentation to chloroquine inhibition may not necessarily indicate the existence of a non-endosomal pathway but may be due to the nature of the T-cell epitope, to the use of 'non-professional' APC such as L cells, to the use of T cells of high avidity, and to high amounts of pre-existing MHC class II-peptide complexes expressed by the APC. We demonstrate here that, at least in conventional APC such as B cells, class II-restricted presentation of both endogenous secreted HEL and transmembrane HA involves an endosomal pathway. PMID:7508420

  18. Endogenous Pyrogen Physiology.

    ERIC Educational Resources Information Center

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  19. Bacillus cereus endogenous panophthalmitis.

    PubMed

    Bouza, E; Grant, S; Jordan, C; Yook, R H; Sulit, H L

    1979-03-01

    A case of severe suppurative endogenous panophthalmitis caused by Bacillus cereus resulted from intravenously administered medications. This is the first, to our knowledge, well-documented case of endogenous endophthalmitis associated with this organism. It is recommended that if on Gram's stain of the anterior chamber fluid, Gram-positive rods are seen, chloramphenicol should be administered in addition to penicillin because of the possibility of B cereus infection. PMID:105693

  20. The Endogenous Exposome

    PubMed Central

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  1. Endogenous opioids and reward.

    PubMed

    Van Ree, J M; Niesink, R J; Van Wolfswinkel, L; Ramsey, N F; Kornet, M M; Van Furth, W R; Vanderschuren, L J; Gerrits, M A; Van den Berg, C L

    2000-09-29

    The discovery of endogenous opioids has markedly influenced the research on the biology of addiction and reward brain processes. Evidence has been presented that these brain substances modulate brain stimulation reward, self-administration of different drugs of abuse, sexual behaviour and social behaviour. There appears to be two different domains in which endogenous opioids, present in separate and distinct brain regions, are involved. One is related to the modulation of incentive motivational processes and the other to the performance of certain behaviours. It is concluded that endogenous opioids may play a role in the vulnerability to certain diseases, such as addiction and autism, but also when the disease is present, such as alcoholism. PMID:11033317

  2. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  3. Mammalian Endogenous Retroviruses.

    PubMed

    Mager, Dixie L; Stoye, Jonathan P

    2015-02-01

    Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles. PMID:26104559

  4. Endogenous pulmonary antibiotics.

    PubMed

    Gibbons, M A; Bowdish, D M; Davidson, D J; Sallenave, J M; Simpson, A J

    2006-05-01

    The human lung produces a variety of peptides and proteins which have intrinsic antimicrobial activity. In general these molecules have broad spectra of antimicrobial activity, kill micro-organisms rapidly, and evade resistance generated by pathogens. In recent years it has become increasingly apparent that the antimicrobial peptides (AMPs) simultaneously possess immunomodulatory functions, suggesting complex roles for these molecules in regulating the clearance of, and immune response to, invading pathogens. These collective properties have stimulated considerable interest in the potential clinical application of endogenous AMPs. This article outlines the biology of AMPs, their pattern of expression in the lung, and their functions, with reference to both antimicrobial and immunomodulatory activity. We then consider the biological importance of AMPs, before concentrating on the potential to use AMPs to therapeutic effect. The principles discussed in the article apply to innate immune defence throughout the body, but particular emphasis is placed on AMPs in the lung and the potential application to pulmonary infection. PMID:16722137

  5. [Endogenous bacterial endophthalmitis].

    PubMed

    Cornut, P-L; Chiquet, C

    2011-01-01

    Endogenous bacterial endophthalmitis, also called metastatic bacterial endophthalmitis, remains a diagnostic and therapeutic challenge. It is a rare and potentially sight-threatening ocular infection that occurs when bacteria reach the eye via the bloodstream, cross the blood-ocular barrier, and multiply within the eye. It usually affects immunocompromised patients and those suffering from diabetes mellitus, malignancy, or cardiac disease, but has also been reported after invasive procedures or in previously healthy people. In most cases, the ocular symptoms occur after the diagnosis of septicemia or systemic infection. Ocular symptoms include decreased vision, redness, discharge, pain, and floaters. The ocular inflammatory signs may be anterior and/or posterior. Bilateral involvement occurs in nearly 25% of cases. A wide range of microorganisms are involved, with differences in their frequency according to geography as well as the patient's age and past medical history, because of variations in the predisposing conditions and the source of the sepsis. The majority of patients are initially misdiagnosed, and ophthalmologists should be aware of this because prompt local and general management is required to save the eye and/or the patient's life. PMID:21145128

  6. Endogenous strategy in exploration.

    PubMed

    Solman, Grayden J F; Kingstone, Alan

    2015-12-01

    We examined the characteristics of endogenous exploratory behaviors in a generalized search task in which guidance signals (e.g., landmarks, semantics, visual saliency, layout) were limited or precluded. Individuals looked for the highest valued cell in an array and were scored on the quality of the best value they could find. Exploration was guided only by the cells that had been previously examined, and the value of this guidance was manipulated by adjusting spatial autocorrelation to produce relatively smooth and rough landscapes-that is, arrays in which nearby cells had unrelated values (low correlation = rough) or similar values (high correlation = smooth). For search in increasingly rough as compared with smooth arrays, we found reduced performance despite increased sampling and increased time spent searching after revelation of a searcher's best cell. Spatially, sampling strategies tended toward more excursive, branching, and space-filling patterns as correlation decreased. Using a novel generalized-recurrence analysis, we report that these patterns reflect an increase in systematic search paths, characterized by regularized sweeps with localized infilling. These tendencies were likewise enhanced for high-performance as compared with low-performance participants. The results suggest a trade-off between guidance (in smooth arrays) and systematicity (in rough arrays), and they provide insight into the particular strategic approaches adopted by searchers when exogenous guiding information is minimized. PMID:26214501

  7. Endogenous rhythms influence interpersonal synchrony.

    PubMed

    Zamm, Anna; Wellman, Chelsea; Palmer, Caroline

    2016-05-01

    Interpersonal synchrony, the temporal coordination of actions between individuals, is fundamental to social behaviors from conversational speech to dance and music-making. Animal models indicate constraints on synchrony that arise from endogenous rhythms: Intrinsic periodic behaviors or processes that continue in the absence of change in external stimulus conditions. We report evidence for a direct causal link between endogenous rhythms and interpersonal synchrony in a music performance task, which places high demands on temporal coordination. We first establish that endogenous rhythms, measured by spontaneous rates of individual performance, are stable within individuals across stimulus materials, limb movements, and time points. We then test a causal link between endogenous rhythms and interpersonal synchrony by pairing each musician with a partner who is either matched or mismatched in spontaneous rate and by measuring their joint behavior up to 1 year later. Partners performed melodies together, using either the same or different hands. Partners who were matched for spontaneous rate showed greater interpersonal synchrony in joint performance than mismatched partners, regardless of hand used. Endogenous rhythms offer potential to predict optimal group membership in joint behaviors that require temporal coordination. (PsycINFO Database Record PMID:26820249

  8. Nematode endogenous small RNA pathways

    PubMed Central

    Hoogstrate, Suzanne W; Volkers, Rita JM; Sterken, Mark G; Kammenga, Jan E; Snoek, L Basten

    2014-01-01

    The discovery of small RNA silencing pathways has greatly extended our knowledge of gene regulation. Small RNAs have been presumed to play a role in every field of biology because they affect many biological processes via regulation of gene expression and chromatin remodeling. Most well-known examples of affected processes are development, fertility, and maintenance of genome stability. Here we review the role of the three main endogenous small RNA silencing pathways in Caenorhabditis elegans: microRNAs, endogenous small interfering RNAs, and PIWI-interacting RNAs. After providing an entry-level overview on how these pathways function, we discuss research on other nematode species providing insight into the evolution of these small RNA pathways. In understanding the differences between the endogenous small RNA pathways and their evolution, a more comprehensive picture is formed of the functions and effects of small RNAs. PMID:25340013

  9. Quantitative analysis of endogenous compounds.

    PubMed

    Thakare, Rhishikesh; Chhonker, Yashpal S; Gautam, Nagsen; Alamoudi, Jawaher Abdullah; Alnouti, Yazen

    2016-09-01

    Accurate quantitative analysis of endogenous analytes is essential for several clinical and non-clinical applications. LC-MS/MS is the technique of choice for quantitative analyses. Absolute quantification by LC/MS requires preparing standard curves in the same matrix as the study samples so that the matrix effect and the extraction efficiency for analytes are the same in both the standard and study samples. However, by definition, analyte-free biological matrices do not exist for endogenous compounds. To address the lack of blank matrices for the quantification of endogenous compounds by LC-MS/MS, four approaches are used including the standard addition, the background subtraction, the surrogate matrix, and the surrogate analyte methods. This review article presents an overview these approaches, cite and summarize their applications, and compare their advantages and disadvantages. In addition, we discuss in details, validation requirements and compatibility with FDA guidelines to ensure method reliability in quantifying endogenous compounds. The standard addition, background subtraction, and the surrogate analyte approaches allow the use of the same matrix for the calibration curve as the one to be analyzed in the test samples. However, in the surrogate matrix approach, various matrices such as artificial, stripped, and neat matrices are used as surrogate matrices for the actual matrix of study samples. For the surrogate analyte approach, it is required to demonstrate similarity in matrix effect and recovery between surrogate and authentic endogenous analytes. Similarly, for the surrogate matrix approach, it is required to demonstrate similar matrix effect and extraction recovery in both the surrogate and original matrices. All these methods represent indirect approaches to quantify endogenous compounds and regardless of what approach is followed, it has to be shown that none of the validation criteria have been compromised due to the indirect analyses. PMID

  10. Endogenized viral sequences in mammals.

    PubMed

    Parrish, Nicholas F; Tomonaga, Keizo

    2016-06-01

    Reverse-transcribed RNA molecules compose a significant portion of the human genome. Many of these RNA molecules were retrovirus genomes either infecting germline cells or having done so in a previous generation but retaining transcriptional activity. This mechanism itself accounts for a quarter of the genomic sequence information of mammals for which there is data. We understand relatively little about the causes and consequences of retroviral endogenization. This review highlights functions ascribed to sequences of viral origin endogenized into mammalian genomes and suggests some of the most pressing questions raised by these observations. PMID:27128186

  11. [Endogenous hyperlactatemia and insulin secretion].

    PubMed

    Ribes, G; Valette, G; Lignon, F; Loubatières-Mariani, M M

    1978-01-01

    In the normal anesthetized dog, the endogenous hyperlactatemia induced either by intense muscular work or by a high dose of phenformin (20 mg/kg subtucaneously) is followed by an increase in the pancreaticoduodenal insulin output. A previous perfusion of sodium dichloroacetate (50 mg/kg. h) opposes the hyperlactatemia, and reduces or suppresses the increase in insulin output. PMID:150887

  12. Endogenous opiates and behavior: 2014.

    PubMed

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  13. Endogenous respiration of Polyporus sulphureus

    SciTech Connect

    Li, S.M.W.; Siehr, D.J.

    1980-01-01

    Thirty percent of the dry weight of the basidiomycete Polyporus sulphureus is triterpenoid acid. The endogenous respiratory quotient of this organism is 0.8 indicating that the triterpenoid is being used as an endogenous storage material. Monosaccharides did not seem to be utilized as exogenous substrates but Krebs-cycle intermediates stimulated oxygen uptake. Pyruvic acid inhibited oxygen uptake. Studies with /sup 14/C-labeled glucose indicated that 27% of the glucose was metabolized by way of glycolysis. The hexose-monophosphate pathway was the major metabolic path for the utilization of glucose. Despite the fact that P. sulphureus is associated with brown rot, its carbon metabolism suggests that it utilizes substances associated with the degradation of lignin more readily than it does glucose.

  14. Endogenous Mechanisms of Cardiac Regeneration.

    PubMed

    Xiang, M S W; Kikuchi, K

    2016-01-01

    Zebrafish possess a remarkable capacity for cardiac regeneration throughout their lifetime, providing a model for investigating endogenous cellular and molecular mechanisms regulating myocardial regeneration. By contrast, adult mammals have an extremely limited capacity for cardiac regeneration, contributing to mortality and morbidity from cardiac diseases such as myocardial infarction and heart failure. However, the viewpoint of the mammalian heart as a postmitotic organ was recently revised based on findings that the mammalian heart contains multiple undifferentiated cell types with cardiogenic potential as well as a robust regenerative capacity during a short period early in life. Although it occurs at an extremely low level, continuous cardiomyocyte turnover has been detected in adult mouse and human hearts, which could potentially be enhanced to restore lost myocardium in damaged human hearts. This review summarizes and discusses recent advances in the understanding of endogenous mechanisms of cardiac regeneration. PMID:27572127

  15. Endogenous opiates and behavior: 2004.

    PubMed

    Bodnar, Richard J; Klein, Gad E

    2005-12-01

    This paper is the 27th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over 30 years of research. It summarizes papers published during 2004 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses. PMID:16039752

  16. Endogenous opiates and behavior: 2013.

    PubMed

    Bodnar, Richard J

    2014-12-01

    This paper is the thirty-sixth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2013 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses. PMID:25263178

  17. Endogenous opiates and behavior: 2007.

    PubMed

    Bodnar, Richard J

    2008-12-01

    This paper is the thirtieth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2007 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses. PMID:18851999

  18. Regulation of Tumor Angiogenesis and Choroidal Neovascularization by Endogenous Angioinhibitors

    PubMed Central

    Gunda, Venugopal; Sudhakar, Yakkanti A

    2014-01-01

    Angiogenesis is the process of neovascularization from parent blood vessels, which is a prerequisite for many physiological and pathological conditions and is regulated by a balance between endogenous angioinhibitors and angioactivators or angiogenic factors. Imbalance between angioinhibitors and angioactivators is associated with neovascularization capacity during progression of tumor development and Choroidal Neovascularization (CNV). Normalization of pathological angiogenesis is considered as an alternative strategy to prevent the tumor growth in cancer progression or retinal damage in CNV. Various angioinhibitors are being identified and evaluated for their pathological angiogenesis regulation, of which endogenous angioinhibitors are one class derived either from extra cellular matrix or from non-extra cellular matrix of human origin. Endogenous angioinhibitors are gaining much significance as they interact with proliferating endothelial cells by binding to distinct integrins and non-integrin receptors, regulating different intracellular signaling mechanisms leading to inhibition of choroidal neovascularization and tumor growth. This review will focus on endogenous angioinhibitors and their receptor(s) mediated angioinhibitory signaling, which are of major concern in angiogenesis and their clinical and pharmaceutical implications. PMID:25258675

  19. "Racializing" Class

    ERIC Educational Resources Information Center

    Hatt-Echeverria, Beth; Urrieta, Luis, Jr.

    2003-01-01

    In an effort to explore how racial and class oppressions intersect, the authors use their autobiographical narratives to depict cultural and experiential continuity and discontinuity in growing up white working class versus Chicano working class. They specifically focus on "racializing class" due to the ways class is often used as a copout by…

  20. Endogenous endostatin inhibits choroidal neovascularization.

    PubMed

    Marneros, Alexander G; She, Haicheng; Zambarakji, Hadi; Hashizume, Hiroya; Connolly, Edward J; Kim, Ivana; Gragoudas, Evangelos S; Miller, Joan W; Olsen, Bjorn R

    2007-12-01

    Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age-related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin and in control mice. CNV lesions in mutant mice were approximately 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age-related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions. PMID:17526870

  1. Endogenous Opiates and Behavior: 2006

    PubMed Central

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  2. Endogenous opiates and behavior: 2012.

    PubMed

    Bodnar, Richard J

    2013-12-01

    This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:24126281

  3. Endogenous opiates and behavior: 2009.

    PubMed

    Bodnar, Richard J

    2010-12-01

    This paper is the 32nd consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2009 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:20875476

  4. Endogenous opiates and behavior: 2005.

    PubMed

    Bodnar, Richard J; Klein, Gad E

    2006-12-01

    This paper is the 28th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2005 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity, neurophysiology and transmitter release (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); immunological responses (Section 17). PMID:16973239

  5. Endogenous opiates and behavior: 2008.

    PubMed

    Bodnar, Richard J

    2009-12-01

    This paper is the 31st consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2008 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:19793543

  6. Endogenous opiates and behavior: 2010.

    PubMed

    Bodnar, Richard J

    2011-12-01

    This paper is the thirty-third consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2010 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration (Section 16); and immunological responses (Section 17). PMID:21983105

  7. Endogenous opiates and behavior: 2006.

    PubMed

    Bodnar, Richard J

    2007-12-01

    This paper is the 29th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning 30 years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  8. Endogenous opiates and behavior: 2011.

    PubMed

    Bodnar, Richard J

    2012-12-01

    This paper is the thirty-fourth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2011 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration (Section 16); and immunological responses (Section 17). PMID:23041439

  9. Endogenous opiates and behavior: 2002.

    PubMed

    Bodnar, Richard J; Hadjimarkou, Maria M

    2003-08-01

    This paper is the twenty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2002 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:14612197

  10. Endogenous opiates and behavior: 2003.

    PubMed

    Bodnar, Richard J; Klein, Gad E

    2004-12-01

    This paper is the 26th consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning over a quarter-century of research. It summarizes papers published during 2003 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:15572211

  11. Generation of BAC transgenic tadpoles enabling live imaging of motoneurons by using the urotensin II-related peptide (ust2b) gene as a driver.

    PubMed

    Bougerol, Marion; Auradé, Frédéric; Lambert, François M; Le Ray, Didier; Combes, Denis; Thoby-Brisson, Muriel; Relaix, Frédéric; Pollet, Nicolas; Tostivint, Hervé

    2015-01-01

    Xenopus is an excellent tetrapod model for studying normal and pathological motoneuron ontogeny due to its developmental morpho-physiological advantages. In mammals, the urotensin II-related peptide (UTS2B) gene is primarily expressed in motoneurons of the brainstem and the spinal cord. Here, we show that this expression pattern was conserved in Xenopus and established during the early embryonic development, starting at the early tailbud stage. In late tadpole stage, uts2b mRNA was detected both in the hindbrain and in the spinal cord. Spinal uts2b+ cells were identified as axial motoneurons. In adult, however, the uts2b expression was only detected in the hindbrain. We assessed the ability of the uts2b promoter to drive the expression of a fluorescent reporter in motoneurons by recombineering a green fluorescent protein (GFP) into a bacterial artificial chromosome (BAC) clone containing the entire X. tropicalis uts2b locus. After injection of this construction in one-cell stage embryos, a transient GFP expression was observed in the spinal cord of about a quarter of the resulting animals from the early tailbud stage and up to juveniles. The GFP expression pattern was globally consistent with that of the endogenous uts2b in the spinal cord but no fluorescence was observed in the brainstem. A combination of histological and electrophysiological approaches was employed to further characterize the GFP+ cells in the larvae. More than 98% of the GFP+ cells expressed choline acetyltransferase, while their projections were co-localized with α-bungarotoxin labeling. When tail myotomes were injected with rhodamine dextran amine crystals, numerous double-stained GFP+ cells were observed. In addition, intracellular electrophysiological recordings of GFP+ neurons revealed locomotion-related rhythmic discharge patterns during fictive swimming. Taken together our results provide evidence that uts2b is an appropriate driver to express reporter genes in larval motoneurons of the

  12. Endogenous Retroviruses and Human Evolution

    PubMed Central

    Lebedev, Yuri; Sverdlov, Eugene

    2002-01-01

    Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus, the differences between these species are unlikely to be in gene content but could be caused by inherited changes in regulatory systems. Endogenous retroviruses (ERVs) comprise ∼ 5% of the human genome. The LTRs of ERVs contain many regulatory sequences, such as promoters, enhancers, polyadenylation signals and factor-binding sites. Thus, they can influence the expression of nearby human genes. All known human-specific LTRs belong to the HERV-K (human ERV) family, the most active family in the human genome. It is likely that some of these ERVs could have integrated into regulatory regions of the human genome, and therefore could have had an impact on the expression of adjacent genes, which have consequently contributed to human evolution. This review discusses possible functional consequences of ERV integration in active coding regions. PMID:18629260

  13. Endogenous opiates and behavior: 2001.

    PubMed

    Bodnar, Richard J; Hadjimarkou, Maria M

    2002-12-01

    This paper is the twenty-fourth installment of the annual review of research concerning the opiate system. It summarizes papers published during 2001 that studied the behavioral effects of the opiate peptides and antagonists. The particular topics covered this year include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology(Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:12535711

  14. Endogenous Peer Effects: Fact or Fiction?

    ERIC Educational Resources Information Center

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  15. Endogenous timing factors in bird migration

    NASA Technical Reports Server (NTRS)

    Gwinner, E. G.

    1972-01-01

    Several species of warbler birds were observed in an effort to determine what initiates and terminates migration. Environmental and endogenous timing mechanisms were analyzed. The results indicate that endogenous stimuli are dominant factors for bird migration especially for long distances. It was concluded that environmental factors act as an assist mechanism.

  16. A Linkage Map of Endogenous Murine Leukemia Proviruses

    PubMed Central

    Frankel, W. N.; Stoye, J. P.; Taylor, B. A.; Coffin, J. M.

    1990-01-01

    Thirty endogenous proviruses belonging to the modified polytropic (Mpmv) class of murine leukemia virus (MLV) were identified by proviral-cellular DNA junction fragment segregation in several sets of recombinant inbred mice. Twenty-six Mpmv loci were mapped to chromosomal regions by matching proviral strain distribution patterns to those of previously assigned genes. Like other endogenous nonecotropic MLVs, Mpmv loci were present on several chromosomes in all strains examined. We pooled recombinant inbred strain linkage data from 110 MLV loci and selected marker genes in order to construct a chromosomal linkage map. Every mouse chromosome was found to harbor at least one proviral insertion, and several regions contained multiple integrations. However, the overall distribution of the 110 mapped proviruses did not deviate significantly from a random distribution. Because of their polymorphism in inbred strains of mice, and the ability to score as many as 57 proviruses per strain using only three hybridization probes, the nonecotropic MLVs mapped in common strains of mice offer a significant advantage over older methods (e.g., biochemical or individual restriction fragment polymorphisms) as genetic markers. These endogenous insertion elements should also be useful for assessing strain purity, and for studying the relatedness of common and not-so-common inbred strains. PMID:2155154

  17. Gravity effects on endogenous movements

    NASA Astrophysics Data System (ADS)

    Johnsson, Anders; Antonsen, Frank

    Gravity effects on endogenous movements A. Johnsson * and F. Antonsen *+ * Department of Physics, Norwegian University of Science and Technology,NO-7491, Trond-heim, Norway, E-mail: anders.johnsson@ntnu.no + Present address: Statoil Research Center Trondheim, NO-7005, Trondheim, Norway Circumnutations in stems/shoots exist in many plants and often consists of more or less regular helical movements around the plumb line under Earth conditions. Recent results on circumnu-tations of Arabidopsis in space (Johnsson et al. 2009) showed that minute amplitude oscilla-tions exist in weightlessness, but that centripetal acceleration (mimicking the gravity) amplified and/or created large amplitude oscillations. Fundamental mechanisms underlying these results will be discussed by modeling the plant tissue as a cylinder of cells coupled together. As a starting point we have modeled (Antonsen 1998) standing waves on a ring of biological cells, as first discussed in a classical paper (Turing 1952). If the coupled cells can change their water content, an `extension' wave could move around the ring. We have studied several, stacked rings of cells coupled into a cylinder that together represent a cylindrical plant tissue. Waves of extensions travelling around the cylinder could then represent the observable circumnutations. The coupling between cells can be due to cell-to-cell diffusion, or to transport via channels, and the coupling can be modeled to vary in both longitudinal and transversal direction of the cylinder. The results from ISS experiments indicate that this cylindrical model of coupled cells should be able to 1) show self-sustained oscillations without the impact of gravity (being en-dogenous) and 2) show how an environmental factor like gravity can amplify or generate the oscillatory movements. Gravity has been introduced in the model by a negative, time-delayed feed-back transport across the cylinder. This represents the physiological reactions to acceler

  18. Class Size.

    ERIC Educational Resources Information Center

    Johnston, Holly R.

    Exploring the class-size issue, this paper focuses on the primary grades and asks questions such as "does a reduction in class size promote an increase in academic achievement?" and "how substantial does the reduction in numbers have to be in order for a significant increase to occur?" The paper surveys debates on class size and the social factors…

  19. Class Size.

    ERIC Educational Resources Information Center

    Underwood, Siobhan; Lumsden, Linda S.

    1994-01-01

    The items featured in this annotated bibliography touch on several aspects of the multifaceted class-size debate. Allen Odden reviews the literature and contends that class-size reduction should be used "sparingly and strategically." C. M. Achilles and colleagues examines two different class-size situations and find student test performance in the…

  20. Class Matters

    ERIC Educational Resources Information Center

    Valdata, Patricia

    2005-01-01

    Ever since George Washington opted for the title of president rather than king, Americans have been uncomfortable with the idea of class distinctions. This article presents an interview with Dr. Janet Galligani Casey regarding the idea of class distinctions. Galligani Casey, who grew up in a working-class neighborhood in Somerville, Massachusetts,…

  1. Engineered cardiac micromodules for the in vitro fabrication of 3D endogenous macro-tissues.

    PubMed

    Totaro, A; Urciuolo, F; Imparato, G; Netti, P A

    2016-01-01

    The in vitro fabrication of an endogenous cardiac muscle would have a high impact for both in vitro studies concerning cardiac tissue physiology and pathology, as well as in vivo application to potentially repair infarcted myocardium. To reach this aim, we engineered a new class of cardiac tissue precursor (CTP), specifically conceived in order to promote the synthesis and the assembly of a cardiac extracellular matrix (ECM). The CTPs were obtained by culturing a mixed cardiac cell population, composed of myocyte and non-myocyte cells, into porous gelatin microspheres in a dynamic bioreactor. By engineering the culture conditions, the CTP developed both beating properties and an endogenous immature cardiac ECM. By following a bottom-up approach, a macrotissue was fabricated by molding and packing the engineered tissue precursor in a maturation chamber. During the macrotissue formation, the tissue precursors acted as cardiac tissue depots by promoting the formation of an endogenous and interconnected cardiac network embedding the cells and the microbeads. The myocytes cell fraction pulled on ECM network and induced its compaction against the internal posts represented by the initial porous microbeads. This reciprocal interplay induced ECM consolidation without the use of external biophysical stimuli by leading to the formation of a beating and endogenous macrotissue. We have thus engineered a new class of cardiac micromodules and show its potential for the fabrication of endogenous cardiac tissue models useful for in vitro studies that involve the cardiac tissue remodeling. PMID:27213995

  2. Endogenous pacemaker activity of rat tumour somatotrophs

    PubMed Central

    Kwiecien, Renata; Robert, Christophe; Cannon, Robert; Vigues, Stephan; Arnoux, Annie; Kordon, Claude; Hammond, Constance

    1998-01-01

    Cells derived from a rat pituitary tumour (GC cell line) that continuously release growth hormone behave as endogenous pacemakers. In simultaneous patch clamp recordings and cytosolic Ca2+ concentration ([Ca2+]i) imaging, they displayed rhythmic action potentials (44.7 ± 2.7 mV, 178 ± 40 ms, 0.30 ± 0.04 Hz) and concomitant [Ca2+]i transients (374 ± 57 nM, 1.0 ± 0.2 s, 0.27 ± 0.03 Hz). Action potentials and [Ca2+]i transients were reversibly blocked by removal of external Ca2+, addition of nifedipine (1 μM) or Ni2+ (40 μM), but were insensitive to TTX (1 μM). An L-type Ca2+ current activated at -33.6 ± 0.4 mV (holding potential (Vh), −40 mV), peaked at -1.8 ± 1.3 mV, was reduced by nifedipine and enhanced by S-(+)-SDZ 202 791. A T/R-type Ca2+ current activated at -41.7 ± 2.7 mV (Vh, -80 or -60 mV), peaked at -9.2 ± 3.0 mV, was reduced by low concentrations of Ni2+ (40 μM) or Cd2+ (10 μM) and was toxin resistant. Parallel experiments revealed the expression of the class E calcium channel α1-subunit mRNA. The K+ channel blockers TEA (25 mM) and charybdotoxin (10–100 nM) enhanced spike amplitude and/or duration. Apamin (100 nM) also strongly reduced the after-spike hyperpolarization. The outward K+ tail current evoked by a depolarizing step that mimicked an action potential reversed at −69.8 ± 0.3 mV, presented two components, lasted 2–3 s and was totally blocked by Cd2+ (400 μM). The slow pacemaker depolarization (3.5 ± 0.4 s) that separated consecutive spikes corresponded to a 2- to 3-fold increase in membrane resistance, was strongly Na+ sensitive but TTX insensitive. Computer simulations showed that pacemaker activity can be reproduced by a minimum of six currents: an L-type Ca2+ current underlies the rising phase of action potentials that are repolarized by a delayed rectifier and Ca2+-activated K+ currents. In between spikes, the decay of Ca2+-activated K+ currents and a persistent inward cationic current depolarize the membrane

  3. Tobacco/Nicotine and Endogenous Brain Opioids

    PubMed Central

    Xue, Yue; Domino, Edward F.

    2008-01-01

    Smoking is a major public health problem with devastating health consequences. Although many cigarette smokers are able to quit, equal numbers of others cannot! Standard medications to assist in smoking cessation, such as nicotine replacement therapies and bupropion, are ineffective in many remaining smokers. Recent developments in the neurobiology of nicotine dependence have identified several neurotransmitter systems that may contribute to the process of smoking maintenance and relapse. These include: especially dopamine, but also norepinephrine, 5-hydroxytryptamine, acetylcholine, endogenous opioids, gamma-aminobutyric acid (GABA), glutamate, and endocannabinoids. The present review examines the limited contribution of the endogenous opioid system to the complex effects of nicotine/tobacco smoking. PMID:18215788

  4. An endogenous model of the credit network

    NASA Astrophysics Data System (ADS)

    He, Jianmin; Sui, Xin; Li, Shouwei

    2016-01-01

    In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.

  5. Animal spirits, competitive markets, and endogenous growth

    NASA Astrophysics Data System (ADS)

    Miyazaki, Kenji

    2013-10-01

    This paper uses a simple model with an endogenous discount rate and linear technology to investigate whether a competitive equilibrium has a higher balanced growth path (BGP) than the social planning solution and whether the BGP is determinate or indeterminate. The implications are as follows. To start with, people with an instinct to compare themselves with others possess an endogenous discount rate. In turn, this instinct affects the economic growth rate in a competitive market economy. The competitive market economy also sometimes achieves higher economic growth than a social planning economy. However, the outcomes of market economy occasionally fluctuate because of the presence of the self-fulfilling prophecy or animal spirits.

  6. Effect of different organic and inorganic blockers of calcium entry on the release of endogenous dopamine from tuberoinfundibular neurones.

    PubMed

    Annunziato, L; Amoroso, S; Taglialatela, M; De Natale, G; Di Renzo, G F

    1986-05-01

    In the present study the effect of different blockers of calcium entry belonging to different chemical classes on basal and K+-elicited release of endogenous dopamine (DA) from tuberoinfundibular dopaminergic neurones was studied in vitro. For this purpose fragments of hypothalamus containing arcuate-periventricular nuclei and median eminence were incubated in vitro and endogenous DA released into the medium was assayed by radioenzymatic assay. The organic blockers of calcium entry, nitrendipine, nimodipine, nifedipine, diltiazem and flunarizine did not modify basal or K+-evoked release of endogenous DA, unless very large concentrations (100 microM) of nifedipine or diltiazem were used. The phenylalkylamine methoxyverapamil (D-600) consistently inhibited K+-stimulated release of endogenous DA in concentrations of 50 and 100 microM. Cobalt and lanthanum, two ions with an ionic radius similar to that of calcium and which are known to inhibit calcium fluxes through nerve membranes, significantly blocked release of endogenous DA elicited by 35 mM K+. In summary, the results of the present study showed that calcium channels in the tuberoinfundibular dopaminergic system displayed a different sensitivity to various classes of blockers of calcium entry. Inorganic blockers of calcium entry, like lanthanum and cobalt, appeared to be the most effective in blocking Ca2+-dependent release of endogenous DA, whereas, among the organic calcium antagonists, phenylalkylamines seemed to possess a certain degree of effectiveness. PMID:3736788

  7. Endogenous CD8+ T cell expansion during regression of monoclonal EBV-associated posttransplant lymphoproliferative disorder.

    PubMed

    Khatri, V P; Baiocchi, R A; Peng, R; Oberkircher, A R; Dolce, J M; Ward, P M; Herzig, G P; Caligiuri, M A

    1999-07-01

    There are experimental data which suggest that the primary immune effector cell responsible for maintaining immune surveillance against the outgrowth of EBV-transformed B cells in humans is the CTL, but in vivo proof of this is lacking. In this study we perform a series of cellular and molecular assays to characterize an autologous, endogenous immune response against a transplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferative disorder (PTLD). Following allogeneic bone marrow transplantation, a patient developed a monoclonal PTLD of donor B cell origin. With a decrease in immune suppression, we document the emergence of endogenous, donor-derived CD3+CD8+ CTLs, followed by regression of the PTLD. The TCR Vbeta repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vbeta pattern during the outgrowth and regression of PTLD. Donor-derived CD3+CD8+ T lymphocytes displayed MHC class I-restricted cytolytic activity against the autologous EBV+ B cells ex vivo without additional in vitro sensitization. The striking temporal relationship between the endogenous expansion of a TCR Vbeta-restricted, CD3+CD8+ population of MHC class I-restricted CTL, and the regression of an autologous monoclonal PTLD, provides direct evidence in humans that endogenous CD3+CD8+ CTLs can be responsible for effective immune surveillance against malignant transformation of EBV+ B cells. PMID:10384154

  8. Essays on Policy Evaluation with Endogenous Adoption

    ERIC Educational Resources Information Center

    Gentile, Elisabetta

    2011-01-01

    Over the last decade, experimental and quasi-experimental methods have been favored by researchers in empirical economics, as they provide unbiased causal estimates. However, when implementing a program, it is often not possible to randomly assign subjects to treatment, leading to a possible endogeneity bias. This dissertation consists of two…

  9. Endogenous opioids and excessive alcohol consumption.

    PubMed Central

    Gianoulakis, C

    1993-01-01

    Alcohol is one of the most popular drugs of abuse in our society, and alcoholism is an important cause of absenteeism at work and a major health and social problem. Ethanol induces a number of effects, such as disinhibition, a feeling of general well-being, tolerance and physical dependence. Since there are no specific receptors with which ethanol interacts, it has been proposed that ethanol exerts its effects by altering the activity of a number of neuronal and neuroendocrine systems. Studies have indicated that alcohol influences the activity of the dopaminergic, serotonergic and opioidergic systems. The implication of the endogenous opioid system in mediating some of the effects of ethanol is indicated by the observations that some of the behavioral and pharmacological effects of ethanol are similar to those of the opiates. Indeed, injections of small amounts of morphine increased ethanol consumption, while the administration of naltrexone decreased ethanol consumption among rats and other experimental animals, in a number of experimental paradigms, suggesting that endogenous opioids may play an important role in controlling voluntary ethanol consumption. This paper reviews studies of the effects of ethanol on the activity of the endogenous opioid system and on the importance of endogenous opioids in controlling alcohol consumption. PMID:7690585

  10. Project CLASS.

    ERIC Educational Resources Information Center

    McBain, Susan L.; And Others

    Project CLASS (Competency-Based Live-Ability Skills) uses a series of 60 modules to teach life survival skills to adults with low-level reading ability--especially Adult Basic Education/English as a Second Language students. Two versions of the modules have been developed: one for use with teacher-directed instruction and another for independent…

  11. Class Trash.

    ERIC Educational Resources Information Center

    Chemecology, 1992

    1992-01-01

    Presents a classroom activity in which students calculate the amount and types of trash thrown out by their class at school to investigate how much trash is generated, where it goes, and speculate about alternatives. Students need to be familiar with the concepts of weight, volume, and numbers. (MCO)

  12. Endogenous Nuclear RNAi Mediates Behavioral Adaptation to Odor

    PubMed Central

    Juang, Bi-Tzen; Gu, Chen; Starnes, Linda; Palladino, Francesca; Goga, Andrei; Kennedy, Scott; L'Etoile, Noelle D.

    2014-01-01

    Summary Most eukaryotic cells express small regulatory RNAs. The purpose of one class, the somatic endogenous siRNAs (endo-siRNAs) remains unclear. Here we show the endo-siRNA pathway promotes odor adaptation in C. elegans AWC olfactory neurons. In adaptation, the nuclear Argonaute NRDE-3, which acts in AWC, is loaded with siRNAs targeting odr-1, a gene who's down regulation is required for adaptation. Concomitant with increased odr-1 siRNA in AWC, we observe increased binding of the HP1 homolog HPL-2 at the odr-1 locus in AWC and reduced odr-1 mRNA in adapted animals. Phosphorylation of HPL-2, an in vitro substrate of the EGL-4 kinase that promotes adaption, is necessary and sufficient for behavioral adaptation. Thus, environmental stimulation amplifies an endo-siRNA negative feedback loop to dynamically repress cognate gene expression and shape behavior. This class of siRNA may act broadly as a rheostat allowing prolonged stimulation to dampen gene expression and promote cellular memory formation. PMID:23993094

  13. The Cannabinoid Acids, Analogs and Endogenous Counterparts

    PubMed Central

    Burstein, Sumner H.

    2015-01-01

    The cannabinoid acids are a structurally heterogeneous group of compounds some of which are endogenous molecules and others that are metabolites of phytocannabinoids. The prototypic endogenous substance is N-arachidonoyl glycine (NAgly) that is closely related in structure to the cannabinoid agonist anandamide. The most studied phytocannabinoid is Δ9–THC-11-oic acid, the principal metabolite of Δ9–THC. Both types of acids have in common several biological actions such as low affinity for CB1, anti-inflammatory activity and analgesic properties. This suggests that there may be similarities in their mechanism of action, a point that is discussed in this review. Also presented are reports on analogs of the acids that provide opportunities for the development of novel therapeutic agents, such as ajulemic acid. PMID:24731541

  14. Induction of Neurorestoration From Endogenous Stem Cells.

    PubMed

    Yu, Ji Hea; Seo, Jung-Hwa; Lee, Ji Yong; Lee, Min-Young; Cho, Sung-Rae

    2016-01-01

    Neural stem cells (NSCs) persist in the subventricular zone lining the ventricles of the adult brain. The resident stem/progenitor cells can be stimulated in vivo by neurotrophic factors, hematopoietic growth factors, magnetic stimulation, and/or physical exercise. In both animals and humans, the differentiation and survival of neurons arising from the subventricular zone may also be regulated by the trophic factors. Since stem/progenitor cells present in the adult brain and the production of new neurons occurs at specific sites, there is a possibility for the treatment of incurable neurological diseases. It might be feasible to induce neurogenesis, which would be particularly efficacious in the treatment of striatal neurodegenerative conditions such as Huntington's disease, as well as cerebrovascular diseases such as ischemic stroke and cerebral palsy, conditions that are widely seen in the clinics. Understanding of the molecular control of endogenous NSC activation and progenitor cell mobilization will likely provide many new opportunities as therapeutic strategies. In this review, we focus on endogenous stem/progenitor cell activation that occurs in response to exogenous factors including neurotrophic factors, hematopoietic growth factors, magnetic stimulation, and an enriched environment. Taken together, these findings suggest the possibility that functional brain repair through induced neurorestoration from endogenous stem cells may soon be a clinical reality. PMID:26787093

  15. Contemporary perspective on endogenous myocardial regeneration

    PubMed Central

    Milasinovic, Dejan; Mohl, Werner

    2015-01-01

    Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaining limitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells (i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis “embryonic recall”, we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes. PMID:26131310

  16. Endogenous Viral Elements in Animal Genomes

    PubMed Central

    Katzourakis, Aris; Gifford, Robert J.

    2010-01-01

    Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs) derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized. PMID:21124940

  17. Endogenous cholecystokinin regulates growth of human cholangiocarcinoma.

    PubMed Central

    Evers, B M; Gomez, G; Townsend, C M; Rajaraman, S; Thompson, J C

    1989-01-01

    Exogenous administration of cholecystokinin (CCK) or caerulein inhibits growth of SLU-132, a human cholangiocarcinoma that we have shown to possess receptors for CCK. Chronic administration of cholestyramine, a resin that binds bile salts, increases release of CCK and growth of the pancreas in guinea pigs. Feeding the bile salt, taurocholate, inhibits meal-stimulated release of CCK. The purpose of this study was to determine whether endogenous CCK affects growth of the human cholangiocarcinoma, SLU-132. We implanted SLU-132 subcutaneously into athymic nude mice. The bile salt pool was depleted by feeding 4% cholestyramine for 40 days, either alone or enriched with 0.5% taurocholate for 32 days. When the mice were killed, tumors and pancreas were removed. Cholestyramine significantly inhibited the growth of SLU-132 and stimulated growth of the normal pancreas. Feeding of taurocholate acted to stimulate tumor growth. These results demonstrate that endogenous levels of CCK regulate growth of this human cholangiocarcinoma. Our findings suggest that manipulation of levels of endogenous gut hormones may, in the future, play a role in management of patients with certain gastrointestinal cancers. Images Fig. 1. PMID:2476084

  18. Induced pluripotency with endogenous and inducible genes

    SciTech Connect

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-10-15

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER{sup TAM}) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols.

  19. Presence of endogenous prednisolone in human urine.

    PubMed

    Fidani, Marco; Gamberini, Maria C; Pompa, Giuseppe; Mungiguerra, Francesca; Casati, Alessio; Arioli, Francesco

    2013-02-01

    The possibility of an endogenous presence of the glucocorticoid prednisolone has already been demonstrated in bovine and horse urine, with the aim of clarifying its origin in this matrix, which is used by official agencies for the control of illicit treatments. From this point of view, the endogenous nature of prednisolone could be a major topic in doping control of both amateur and professional human athletes. A study was therefore made on 34 human volunteers (13 males and 21 females; aged 22-62) to detect the presence of prednisolone in their urine by HPLC-MS(3). One of the volunteers underwent vernal allergy treatment with betamethasone for two subsequent years. An investigation was carried out with the aim of verifying if the suppression, and the circadian rhythm, of cortisol urinary levels could also apply to prednisolone. The results of the study show that prednisolone was present in the urine of all 34 volunteers, with a concentration very close to 100-times lower that of cortisol, with no dependence on gender. The same ratio (1/100) was observed in the prednisolone and cortisol levels detected during the 24h together with the suppression of prednisolone by betamethasone treatment. These data demonstrate the endogenous nature of low concentrations of prednisolone in human urine, and motivate further studies about the biosynthetic pathways of this corticosteroid and its relationship with stress in humans, as already described in cows. PMID:23182764

  20. Opportunistic activation of TRP receptors by endogenous lipids: Exploiting lipidomics to understand TRP receptor cellular communication

    PubMed Central

    Bradshaw, Heather B.; Raboune, Siham; Hollis, Jennifer L.

    2012-01-01

    Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining “orphans”. That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are “promiscuous” in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically “opportunistic” in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an “orphan” lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors. PMID:23178153

  1. Prevalent Class I-Restricted T-Cell Response to the Theiler’s Virus Epitope Db:VP2121–130 in the Absence of Endogenous CD4 Help, Tumor Necrosis Factor Alpha, Gamma Interferon, Perforin, or Costimulation through CD28

    PubMed Central

    Johnson, Aaron J.; Njenga, M. Kariuki; Hansen, Michael J.; Kuhns, Scott T.; Chen, Lieping; Rodriguez, Moses; Pease, Larry R.

    1999-01-01

    C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel’s strain of Theiler’s murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syndrome similar to multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121–130 sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially. Db:VP2121–130 peptide tetramers were used to stain CD8+ CNS-ILs, revealing that 50 to 63% of these cells bear receptors specific for VP2121–130 presented in the context of Db. No T cells bearing this specificity were found in the cervical lymph nodes or spleens of TMEV-infected mice. H-2b mice lacking CD4, class II, gamma interferon, or CD28 expression are susceptible to persistent virus infection but surprisingly still generate high frequencies of CD8+, Db:VP2121–130-specific T cells. However, CD4-negative mice generate a lower frequency of Db:VP2121–130-specific T cells than do class II negative or normal H-2b animals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8+ CNS-ILs specific for Db:VP2121–130. Furthermore, normally susceptible FVB mice that express a Db transgene generate Db:VP2121–130-specific CD8+ CNS-ILs at a frequency similar to that of C57BL/6 mice. These results demonstrate that VP2121–130 presented in the context of Db is an immunodominant epitope in TMEV infection and that the frequency of the VP2121–130-specific CTLs appears to be independent of several key inflammatory mediators and genetic background but is regulated in part by the expression of CD4. PMID:10196262

  2. Host Control of Insect Endogenous Retroviruses: Small RNA Silencing and Immune Response

    PubMed Central

    Fablet, Marie

    2014-01-01

    Endogenous retroviruses are relics of ancient infections from retroviruses that managed to integrate into the genome of germline cells and remained vertically transmitted from parent to progeny. Subsequent to the endogenization process, these sequences can move and multiply in the host genome, which can have deleterious consequences and disturb genomic stability. Natural selection favored the establishment of silencing pathways that protect host genomes from the activity of endogenous retroviruses. RNA silencing mechanisms are involved, which utilize piRNAs. The response to exogenous viral infections uses siRNAs, a class of small RNAs that are generated via a distinct biogenesis pathway from piRNAs. However, interplay between both pathways has been identified, and interactions with anti-bacterial and anti-fungal immune responses are also suspected. This review focuses on Diptera (Arthropods) and intends to compile pieces of evidence showing that the RNA silencing pathway of endogenous retrovirus regulation is not independent from immunity and the response to infections. This review will consider the mechanisms that allow the lasting coexistence of viral sequences and host genomes from an evolutionary perspective. PMID:25412365

  3. Class distinction

    NASA Astrophysics Data System (ADS)

    White, M. Catherine

    Typical 101 courses discourage many students from pursuing higher level science and math courses. Introductory classes in science and math serve largely as a filter, screening out all but the most promising students, and leaving the majority of college graduates—including most prospective teachers—with little understanding of how science works, according to a study conducted for the National Science Foundation. Because few teachers, particularly at the elementary level, experience any collegiate science teaching that stresses skills of inquiry and investigation, they simply never learn to use those methods in their teaching, the report states.

  4. Distribution of Endogenous Retroviruses in Crocodilians▿

    PubMed Central

    Jaratlerdsiri, Weerachai; Rodríguez-Zárate, Clara J.; Isberg, Sally R.; Damayanti, Chandramaya Siska; Miles, Lee G.; Chansue, Nantarika; Moran, Chris; Melville, Lorna; Gongora, Jaime

    2009-01-01

    Knowledge of endogenous retroviruses (ERVs) in crocodilians (Crocodylia) is limited, and their distribution among extant species is unclear. Here we analyzed the phylogenetic relationships of these retroelements in 20 species of crocodilians by studying the pro-pol gene. The results showed that crocodilian ERVs (CERVs) cluster into two major clades (CERV 1 and CERV 2). CERV 1 clustered as a sister group of the genus Gammaretrovirus, while CERV 2 clustered distantly with respect to all known ERVs. Interestingly, CERV 1 was found only in crocodiles (Crocodylidae). The data generated here could assist future studies aimed at identifying orthologous and paralogous ERVs among crocodilians. PMID:19605486

  5. Insertional Polymorphisms of Endogenous Feline Leukemia Viruses

    PubMed Central

    Roca, Alfred L.; Nash, William G.; Menninger, Joan C.; Murphy, William J.; O'Brien, Stephen J.

    2005-01-01

    The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats. PMID:15767400

  6. Endogenous Technology Adoption and Medical Costs.

    PubMed

    Lamiraud, Karine; Lhuillery, Stephane

    2016-09-01

    Despite the claim that technology has been one of the most important drivers of healthcare spending growth over the past decades, technology variables are rarely introduced explicitly in cost equations. Furthermore, technology is often considered exogenous. Using 1996-2007 panel data on Swiss geographical areas, we assessed the impact of technology availability on per capita healthcare spending covered by basic health insurance whilst controlling for the endogeneity of health technology availability variables. Our results suggest that medical research, patent intensity and the density of employees working in the medical device industry are influential factors for the adoption of technology and can be used as instruments for technology availability variables in the cost equation. These results are similar to previous findings: CT and PET scanner adoption is associated with increased healthcare spending, whilst increased availability of percutaneous transluminal coronary angioplasty facilities is associated with reductions in per capita spending. However, our results suggest that the magnitude of these relationships is much greater in absolute value than that suggested by previous studies that did not control for the possible endogeneity of the availability of technologies. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27492052

  7. Human endogenous retroviruses in neurologic disease.

    PubMed

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. PMID:26818266

  8. Live Imaging of Endogenous PSD-95 Using ENABLED: A Conditional Strategy to Fluorescently Label Endogenous Proteins

    PubMed Central

    Fortin, Dale A.; Tillo, Shane E.; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B.; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V.; Guo, Caiying

    2014-01-01

    Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. PMID:25505322

  9. Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

    PubMed Central

    Thompson, Georgina L.; Canals, Meritxell; Poole, Daniel P.

    2014-01-01

    This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals. PMID:25506328

  10. Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches.

    PubMed

    Izquierdo-Serra, Mercè; Bautista-Barrufet, Antoni; Trapero, Ana; Garrido-Charles, Aida; Díaz-Tahoces, Ariadna; Camarero, Nuria; Pittolo, Silvia; Valbuena, Sergio; Pérez-Jiménez, Ariadna; Gay, Marina; García-Moll, Alejandro; Rodríguez-Escrich, Carles; Lerma, Juan; de la Villa, Pedro; Fernández, Eduardo; Pericàs, Miquel À; Llebaria, Amadeu; Gorostiza, Pau

    2016-01-01

    Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities. PMID:27436051

  11. Endogenous retrovirus and radiation-induced leukemia in the RMF mouse

    SciTech Connect

    Tennant, R.W.; Boone, L.R.; Lalley, P.; Yang, W.K.

    1982-01-01

    The induction of myeloid leukemia in irradiated RFM/Un mice has been associated with retrovirus infection. However, two characteristics of this strain complicate efforts to define the role of the virus. This strain possesses only one inducible host range class of endogenous virus and a unique gene, in addition to the Fv-1/sup n/ locus, which specifically restricts exogenous infection by endogenous viruses. These characteristics possibly account for absence of recombinant viruses in this strain, even though virus is amply expressed during most of the animal's life span. We have examined further the distribution of retrovirus sequences and the chromosomal locus of the inducible virus in this strain. This report describes evidence for additional viral sequences in cells of a radiation-induced myeloid leukemia line and discusses the possible origin of these added copies.

  12. Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches

    PubMed Central

    Izquierdo-Serra, Mercè; Bautista-Barrufet, Antoni; Trapero, Ana; Garrido-Charles, Aida; Díaz-Tahoces, Ariadna; Camarero, Nuria; Pittolo, Silvia; Valbuena, Sergio; Pérez-Jiménez, Ariadna; Gay, Marina; García-Moll, Alejandro; Rodríguez-Escrich, Carles; Lerma, Juan; de la Villa, Pedro; Fernández, Eduardo; Pericàs, Miquel À; Llebaria, Amadeu; Gorostiza, Pau

    2016-01-01

    Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities. PMID:27436051

  13. Endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1.

    PubMed

    Hui, Chee-Kin

    2013-03-01

    Endogenous lipoid pneumonia is an uncommon condition. This is a report of a 29-year-old woman diagnosed with endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1 infection. The patient's endogenous lipoid pneumonia resolved completely after treatment for Legionella pneumophila infection. This suggests that early diagnosis and aggressive treatment of the underlying infection may prevent any long-term sequelae of lipoid pneumonia. PMID:23546039

  14. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    PubMed

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR. PMID:26895065

  15. [Endogenous retroviruses are associated with autoimmune diseases].

    PubMed

    Nexø, Bjørn A; Jensen, Sara B; Hansen, Bettina; Laska, Magdalena J

    2016-06-13

    Retroviruses can be transmitted in two fundamentally different ways: 1) They can be horizontally transmitted as infectious virus, or 2) they can integrate in the germ line and be transmitted to offspring and the offsprings' offspring as DNA. The latter is called endogenous viruses. The mode of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus grows and this contributes to disease, one should be able to alleviate disease with antiretroviral drugs. We call for clinical trials to elucidate this issue. PMID:27292833

  16. Endogenous cannabinoids revisited: a biochemistry perspective.

    PubMed

    Fonseca, B M; Costa, M A; Almada, M; Correia-da-Silva, G; Teixeira, N A

    2013-01-01

    Marijuana is the most commonly used illegal drug, particularly in Western societies. The discovery of an endogenous cannabinoid system (ECS) highlighted new molecules in various physiological processes. The ECS consists of G-protein-coupled cannabinoid receptors that can be activated by small lipid mediators, termed endocannabinoids (eCBs) and cannabis-derived drugs, plus the associated biochemical machinery (precursors, synthesis and degradative enzymes, and transporters). Several biochemical, pharmacological and physiological studies have shown that endocannabinoid system elements are widely distributed throughout the body, with regional variations and organ-specific actions. This review portrays the endocannabinoid "family" on new studies concerning eCB storage, release and functional roles and on the growing importance of its bioactive metabolites. Those findings reinforce and confirm the importance of ECS. Strategies for manipulating the system for the treatment of human disease will require a thorough understanding of the roles of the different eCBs and their sources. PMID:23474290

  17. Endogenous Group Formation via Unproductive Costs

    PubMed Central

    Aimone, Jason A.; Iannaccone, Laurence R.; Makowsky, Michael D.; Rubin, Jared

    2013-01-01

    Sacrifice is widely believed to enhance cooperation in churches, communes, gangs, clans, military units, and many other groups. We find that sacrifice can also work in the lab, apart from special ideologies, identities, or interactions. Our subjects play a modified VCM game—one in which they can voluntarily join groups that provide reduced rates of return on private investment. This leads to both endogenous sorting (because free-riders tend to reject the reduced-rate option) and substitution (because reduced private productivity favours increased club involvement). Seemingly unproductive costs thus serve to screen out free-riders, attract conditional cooperators, boost club production, and increase member welfare. The sacrifice mechanism is simple and particularly useful where monitoring difficulties impede punishment, exclusion, fees, and other more standard solutions. PMID:24808623

  18. Endogenous retroviruses and the development of cancer

    PubMed Central

    Kassiotis, George

    2013-01-01

    Mammalian genomes include a considerable number of endogenous retroviruses (ERVs), relics of ancestral infectious retroviruses, whose proviruses have invaded the germ-line. The documented ability of infectious retroviruses to cause cancer has greatly contributed to the discovery of ERVs. It also reinforced the concept that ERVs are causative agents of many cancers, a notion that historically has not always stood up to experimental scrutiny. The recent greater appreciation of the complexity of ERV biology and the identification of dedicated host mechanisms controlling ERV activity have revealed novel interactions between ERVs and their hosts with the potential to cause or contribute to disease. In this review, the involvement of ERVs in cancer initiation and progression is discussed, as well as their contribution to our understanding of the process of transformation and to the invention of innovative preventive and therapeutic cancer treatments. PMID:24511094

  19. Chitin is endogenously produced in vertebrates

    PubMed Central

    Sohn, Joel J.; Amemiya, Chris T.

    2015-01-01

    Chitin, a biopolymer of N-acetylglucosamine, is abundant in invertebrates and fungi, and is an important structural molecule. There has been a longstanding belief that vertebrates do not produce chitin, however, we have obtained compelling evidence to the contrary. Chitin synthase genes are present in numerous fishes and amphibians, and chitin is localized in situ to the lumen of the developing zebrafish gut, in epithelial cells of fish scales, and in at least three different cell types in larval salamander appendages. Chitin synthase gene knockdowns and various histochemical experiments in zebrafish further authenticated our results. Finally, a polysaccharide was extracted from scales of salmon that exhibited all the chemical hallmarks of chitin. Our data and analyses demonstrate the existence of endogenous chitin in vertebrates and suggest that it serves multiple roles in vertebrate biology. PMID:25772447

  20. Parental representations of neurotic and endogenous depressives.

    PubMed

    Parker, G; Kiloh, L; Hayward, L

    1987-01-01

    Low parental care and parental overprotection have been incriminated as risk factors to depression in adult life. The relevance of these parental characteristics to broad depressive 'types' with their varying imputed aetiologies was assessed by having 26 patients with endogenous depression (ED) and 40 with neurotic depression (ND) complete the Parental Bonding Instrument (PBI) self-report measure. In comparison to their controls, the EDs did not differ on the parental care and overprotection scales. The NDs, by contrast, were more likely than their controls to report their parents as uncaring and overprotective. A PBI care scale score of less than 10 was particularly discriminating, being reported by 3.8% of the EDs and 37.5% of the NDs. While findings support the binary view of depression in terms of broad imputed aetiological factors, several response biases which might influence the findings are considered. PMID:2959703

  1. Endogenous fluorescence emission of the ovary

    NASA Astrophysics Data System (ADS)

    Utzinger, Urs; Kirkpatrick, Nathaniel D.; Drezek, Rebekah A.; Brewer, Molly A.

    2005-03-01

    Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers. Early detection would significantly improve survival and quality of life of women at increased risk to develop ovarian cancer. We have constructed a device to investigate endogenous signals of the ovarian tissue surface in the UV C to visible range and describe our initial investigation of the use of optical spectroscopy to characterize the condition of the ovary. We have acquired data from more than 33 patients. A table top spectroscopy system was used to collect endogenous fluorescence with a fiberoptic probe that is compatible with endoscopic techniques. Samples were broken into five groups: Normal-Low Risk (for developing ovarian cancer) Normal-High Risk, Benign, and Cancer. Rigorous statistical analysis was applied to the data using variance tests for direct intensity versus diagnostic group comparisons and principal component analysis (PCA) to study the variance of the whole data set. We conclude that the diagnostically most useful excitation wavelengths are located in the UV. Furthermore, our results indicate that UV B and C are most useful. A safety analysis indicates that UV-C imaging can be conducted at exposure levels below safety thresholds. We found that fluorescence excited in the UV-C and UV-B range increases from benign to normal to cancerous tissues. This is in contrast to the emission created with UV-A excitation which decreased in the same order. We hypothesize that an increase of protein production and a decrease of fluorescence contributions of the extracellular matrix could explain this behavior. Variance analysis also identified fluctuation of fluorescence at 320/380 which is associated with collagen cross link residues. Small differences were observed between the group at high risk and normal risk for ovarian cancer. High risk samples deviated towards the cancer group and low risk samples towards benign group.

  2. How Active Are Porcine Endogenous Retroviruses (PERVs)?

    PubMed Central

    Denner, Joachim

    2016-01-01

    Porcine endogenous retroviruses (PERVs) represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs), which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (CRISPR/Cas) technology. PMID:27527207

  3. Endogenous Methanol Regulates Mammalian Gene Activity

    PubMed Central

    Komarova, Tatiana V.; Petrunia, Igor V.; Shindyapina, Anastasia V.; Silachev, Denis N.; Sheshukova, Ekaterina V.; Kiryanov, Gleb I.; Dorokhov, Yuri L.

    2014-01-01

    We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis. PMID:24587296

  4. Dynamic option pricing with endogenous stochastic arbitrage

    NASA Astrophysics Data System (ADS)

    Contreras, Mauricio; Montalva, Rodrigo; Pellicer, Rely; Villena, Marcelo

    2010-09-01

    Only few efforts have been made in order to relax one of the key assumptions of the Black-Scholes model: the no-arbitrage assumption. This is despite the fact that arbitrage processes usually exist in the real world, even though they tend to be short-lived. The purpose of this paper is to develop an option pricing model with endogenous stochastic arbitrage, capable of modelling in a general fashion any future and underlying asset that deviate itself from its market equilibrium. Thus, this investigation calibrates empirically the arbitrage on the futures on the S&P 500 index using transaction data from September 1997 to June 2009, from here a specific type of arbitrage called “arbitrage bubble”, based on a t-step function, is identified and hence used in our model. The theoretical results obtained for Binary and European call options, for this kind of arbitrage, show that an investment strategy that takes advantage of the identified arbitrage possibility can be defined, whenever it is possible to anticipate in relative terms the amplitude and timespan of the process. Finally, the new trajectory of the stock price is analytically estimated for a specific case of arbitrage and some numerical illustrations are developed. We find that the consequences of a finite and small endogenous arbitrage not only change the trajectory of the asset price during the period when it started, but also after the arbitrage bubble has already gone. In this context, our model will allow us to calibrate the B-S model to that new trajectory even when the arbitrage already started.

  5. Parkinson's disease, L-DOPA, and endogenous morphine: a revisit.

    PubMed

    Stefano, George B; Mantione, Kirk J; Králíčková, Milena; Ptacek, Radek; Kuzelova, Hana; Esch, Tobias; Kream, Richard M

    2012-08-01

    Clinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson's Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review. PMID:22847214

  6. Crosstalk between endogenous and synthetic components--synthetic signaling meets endogenous components.

    PubMed

    Morey, Kevin J; Antunes, Mauricio S; Barrow, Matt J; Solorzano, Fernando A; Havens, Keira L; Smith, J Jeff; Medford, June

    2012-07-01

    Synthetic biology uses biological components to engineer new functionality in living organisms. We have used the tools of synthetic biology to engineer detector plants that can sense man-made chemicals, such as the explosive trinitrotoluene, and induce a response detectable by eye or instrumentation. A goal of this type of work is to make the designed system orthogonal, that is, able to function independently of systems in the host. In this review, the design and function of two partially synthetic signaling pathways for use in plants is discussed. We describe observed interactions (crosstalk) with endogenous signaling components. This crosstalk can be beneficial, allowing the creation of hybrid synthetic/endogenous signaling pathways, or detrimental, resulting in system noise and/or false positives. Current approaches in the field of synthetic biology applicable to the design of orthogonal signaling systems, including the design of synthetic components, partially synthetic systems that utilize crosstalk to signal through endogenous components, computational redesign of proteins, and the use of heterologous components, are discussed. PMID:22649041

  7. Endogenous Sensory Discrimination and Selection by a Fast Brain Switch for a High Transfer Rate Brain-Computer Interface.

    PubMed

    Xu, Ren; Jiang, Ning; Dosen, Strahinja; Lin, Chuang; Mrachacz-Kersting, Natalie; Dremstrup, Kim; Farina, Dario

    2016-08-01

    In this study, we present a novel multi-class brain-computer interface (BCI) for communication and control. In this system, the information processing is shared by the algorithm (computer) and the user (human). Specifically, an electro-tactile cycle was presented to the user, providing the choice (class) by delivering timely sensory input. The user discriminated these choices by his/her endogenous sensory ability and selected the desired choice with an intuitive motor task. This selection was detected by a fast brain switch based on real-time detection of movement-related cortical potentials from scalp EEG. We demonstrated the feasibility of such a system with a four-class BCI, yielding a true positive rate of  ∼ 80% and  ∼ 70%, and an information transfer rate of  ∼ 7 bits/min and  ∼ 5 bits/min, for the movement and imagination selection command, respectively. Furthermore, when the system was extended to eight classes, the throughput of the system was improved, demonstrating the capability of accommodating a large number of classes. Combining the endogenous sensory discrimination with the fast brain switch, the proposed system could be an effective, multi-class, gaze-independent BCI system for communication and control applications. PMID:26849869

  8. Do Endogenous and Exogenous Action Control Compete for Perception?

    ERIC Educational Resources Information Center

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-01-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

  9. [Clinical and psychopathological aspects of endogenous apathetic depressions].

    PubMed

    Sorokin, S A

    2011-01-01

    The study included 45 patients with endogenous apathetic depressions differing in clinical picture and psychopathological structure. Typological classification of these depressions into 3 variants dominated by decreased interests, initiative or will is proposed. The problem of nosological identification of apathetic depressions is discussed. Dynamics of these conditions in the structure of endogenous affective diseases and paroxysmal progredient schizophrenia is described. PMID:21674919

  10. INTESTINAL EXCRETION OF ENDOGENOUS ZINC IN GUATEMALAN SCHOOL CHILDREN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The intestine is the major route of excretion of endogenous zinc and has a key role in maintaining zinc homeostasis. Phytate has been reported to increase these losses. Objective: To determine the rate of excretion of endogenous zinc in school-aged children in a poor rural community for ...

  11. Social Interactions with Endogenous Associations. NBER Working Paper No. 13038

    ERIC Educational Resources Information Center

    Weinberg, Bruce A.

    2007-01-01

    This paper develops a model of social interactions with endogenous association. People are assumed to invest in relationships to maximize their utility. Even in a linear-in-means model, when associations are endogenous, the effect of macro-group composition on behavior is non-linear and varies across individuals. We also show that larger groups…

  12. Identifying Class Size Effects in Developing Countries: Evidence from Rural Schools in Bolivia.

    ERIC Educational Resources Information Center

    Urquiola, Miguel

    Although great interest surrounds class size as a policy instrument, inferences on its effects are controversial. Recent work highlights a particular way to consider the endogeneity issues that affect this variable: class size is often correlated with enrollment, which in turn may be related to socioeconomic status (SES). This paper shows why such…

  13. Endovanilloids. Putative endogenous ligands of transient receptor potential vanilloid 1 channels.

    PubMed

    Van Der Stelt, Mario; Di Marzo, Vincenzo

    2004-05-01

    Endovanilloids are defined as endogenous ligands of the transient receptor potential vanilloid type 1 (TRPV1) protein, a nonselective cation channel that belongs to the large family of TRP ion channels, and is activated by the pungent ingredient of hot chilli peppers, capsaicin. TRPV1 is expressed in some nociceptor efferent neurons, where it acts as a molecular sensor of noxious heat and low pH. However, the presence of these channels in various regions of the central nervous system, where they are not likely to be targeted by these noxious stimuli, suggests the existence of endovanilloids. Three different classes of endogenous lipids have been found recently that can activate TRPV1, i.e. unsaturated N-acyldopamines, lipoxygenase products of arachidonic acid and the endocannabinoid anandamide with some of its congeners. To classify a molecule as an endovanilloid, the compound should be formed or released in an activity-dependent manner in sufficient amounts to evoke a TRPV1-mediated response by direct activation of the channel. To control TRPV1 signaling, endovanilloids should be inactivated within a short time-span. In this review, we will discuss, for each of the proposed endogenous ligands of TRPV1, their ability to act as endovanilloids in light of the criteria mentioned above. PMID:15128293

  14. Are endogenous cardenolides controlled by atrial natriuretic peptide.

    PubMed

    Brar, Kanwarjeet S; Gao, Yonglin; El-Mallakh, Rif S

    2016-07-01

    Endogenous cardenolides are digoxin-like substances and ouabain-like substances that have been implicated in the pathogenesis of hypertension and mood disorders in clinical and pre-clinical studies. Regulatory signals for endogenous cardenolides are still unknown. These endogenous compounds are believed to be produced by the adrenal gland in the periphery and the hypothalamus in the central nervous system, and constitute part of an hormonal axis that may regulate the catalytic activity of the α subunit of Na(+)/K(+)-ATPase. A review of literature suggests that there is great overlap in physiological environments that are associated with either elevations or reductions in the levels of atrial natriuretic peptide (ANP) and endogenous cardenolides. This suggests that these two factors may share a common regulatory signal or perhaps that ANP may be involved in the regulation of endogenous cardenolides. PMID:27241248

  15. An Endogenous Mammalian Retinoid X Receptor Ligand, At Last!

    PubMed

    de Lera, Ángel R; Krezel, Wojciech; Rühl, Ralph

    2016-05-19

    9-cis-Retinoic acid was identified and claimed to be the endogenous ligand of the retinoid X receptors (RXRs) in 1992. Since then, the endogenous presence of this compound has never been rigorously confirmed. Instead, concerns have been raised by other groups that have reported that 9-cis-retinoic acid is undetectable or that its presence occurs at very low levels. Furthermore, these low levels could not satisfactorily explain the physiological activation of RXR. Alternative ligands, among them various lipids, have also been identified, but also did not fulfill criteria for rigorous endogenous relevance, and their consideration as bona fide endogenous mammalian RXR ligand has likewise been questioned. Recently, novel studies claim that the saturated analogue 9-cis-13,14-dihydroretinoic acid functions as an endogenous physiologically relevant mammalian RXR ligand. PMID:27151148

  16. Endogenous polyamine function—the RNA perspective

    PubMed Central

    Lightfoot, Helen L.; Hall, Jonathan

    2014-01-01

    Recent progress with techniques for monitoring RNA structure in cells such as ‘DMS-Seq’ and ‘Structure-Seq’ suggests that a new era of RNA structure-function exploration is on the horizon. This will also include systematic investigation of the factors required for the structural integrity of RNA. In this context, much evidence accumulated over 50 years suggests that polyamines play important roles as modulators of RNA structure. Here, we summarize and discuss recent literature relating to the roles of these small endogenous molecules in RNA function. We have included studies directed at understanding the binding interactions of polyamines with polynucleotides, tRNA, rRNA, mRNA and ribozymes using chemical, biochemical and spectroscopic tools. In brief, polyamines bind RNA in a sequence-selective fashion and induce changes in RNA structure in context-dependent manners. In some cases the functional consequences of these interactions have been observed in cells. Most notably, polyamine-mediated effects on RNA are frequently distinct from those of divalent cations (i.e. Mg2+) confirming their roles as independent molecular entities which help drive RNA-mediated processes. PMID:25232095

  17. Endogenous opioids: opposing stress with a cost

    PubMed Central

    Van Bockstaele, Elisabeth

    2015-01-01

    The stress response is characterized by the coordinated engagement of central and peripheral neural systems in response to life-threatening challenges. It has been conserved through evolution and is essential for survival. However, the frequent or continual elicitation of the stress response by repeated or chronic stress, respectively, results in the dysfunction of stress response circuits, ultimately leading to stress-related pathology. In an effort to best respond to stressors, yet at the same time maintain homeostasis and avoid dysfunction, stress response systems are finely balanced and co-regulated by neuromodulators that exert opposing effects. These opposing systems serve to restrain certain stress response systems and promote recovery. However, the engagement of opposing systems comes with the cost of alternate dysfunctions. This review describes, as an example of this dynamic, how endogenous opioids function to oppose the effects of the major stress neuromediator, corticotropin-releasing hormone, and promote recovery from a stress response and how these actions can both protect and be hazardous to health. PMID:26097731

  18. Endogenous prostaglandin in guinea pig taenia coli.

    PubMed

    Yamaguchi, T; Hitzig, B; Coburn, R F

    1976-01-01

    Prostaglandin (PGE) is synthesized in the guinea pig taenia coli. A low threshold concentration for an effect of exogenous PGE1 or PGE2 on spontaneous mechanical activity was demonstrated. The PG synthetase inhibitors aspirin, indomethacin, and 5,8,11,14-eicosatetraynoic acid, at concentrations that inhibited PGE efflux, had effects on spontaneous mechanical activity, membrane potential, membrane resistance, and evoked and spontaneous action potentials (single and double sucrose-gap methods) that were consistent with an action due to inhibition of membrane PGE concentration. The threshold concentration of indomethacin, which inhibited PGE efflux, was the same as the concentration that inhibited spontaneous mechanical activity. Pretreatment with ouabain (10(-6)-10(-5) g/ml) or elevated extracellular K+ (29 and 126 mM) made the guinea pig taenia coli entirely refractory to exogenous PGE1 or PGE2; the mechanical effects of the three prostaglandin synthetase inhibitors also were absent in the presence of elevated K+ or ouabain. The data are consistent with a hypothesis that, under conditions of our experiments, endogenous PGE has an effect on resting tension and spontaneous mechanical activity and on properties of the surface membrane of the guinea pig taenia coli. PMID:1251900

  19. Stem Cell Stimulation of Endogenous Myocyte Regeneration

    PubMed Central

    Weil, Brian R.; Canty, John M.

    2015-01-01

    Cell-based therapy has emerged as a promising approach to combat the myocyte loss and cardiac remodeling that characterize the progression of left ventricular dysfunction to heart failure. Several clinical trials conducted during the past decade have shown that a variety of autologous bone marrow- and peripheral blood-derived stem and progenitor cell populations can be safely administered to patients with ischemic heart disease and yield modest improvements in cardiac function. Concurrently, rapid progress has been made at the preclinical level to identify novel therapeutic cell populations, delineate the mechanisms underlying cell-mediated cardiac repair, and optimize cell-based approaches for clinical use. The following review summarizes the progress that has been made in this rapidly evolving field over the past decade and examines how our current understanding of the mechanisms involved in successful cardiac regeneration should direct future investigation in this area. Particular emphasis is placed on discussion of the general hypothesis that the benefits of cell therapy primarily result from stimulation of endogenous cardiac repair processes that have only recently been identified in the adult mammalian heart, rather than direct differentiation of exogenous cells. Continued scientific investigation in this area will guide the optimization of cell-based approaches for myocardial regeneration, with the ultimate goal of clinical implementation and substantial improvement in our ability to restore cardiac function in ischemic heart disease patients. PMID:23577634

  20. Identification of receptors for pig endogenous retrovirus

    PubMed Central

    Ericsson, Thomas A.; Takeuchi, Yasuhiro; Templin, Christian; Quinn, Gary; Farhadian, Shelli F.; Wood, James C.; Oldmixon, Beth A.; Suling, Kristen M.; Ishii, Jennifer K.; Kitagawa, Yoshinori; Miyazawa, Takayuki; Salomon, Daniel R.; Weiss, Robin A.; Patience, Clive

    2003-01-01

    Xenotransplantation of porcine tissues has the potential to treat a wide variety of major health problems including organ failure and diabetes. Balanced against the potential benefits of xenotransplantation, however, is the risk of human infection with a porcine microorganism. In particular, the transmission of porcine endogenous retrovirus (PERV) is a major concern [Chapman, L. E. & Bloom, E. T. (2001) J. Am. Med. Assoc. 285, 2304–2306]. Here we report the identification of two, sequence-related, human proteins that act as receptors for PERV-A, encoded by genes located on chromosomes 8 and 17. We also describe homologs from baboon and porcine cells that also are active as receptors. Conversely, activity could not be demonstrated with a syntenic murine receptor homolog. Sequence analysis indicates that PERV-A receptors [human PERV-A receptor (HuPAR)-1, HuPAR-2, baboon PERV-A receptor 2, and porcine PERV-A receptor] are multiple membrane-spanning proteins similar to receptors for other gammaretroviruses. Expression is widespread in human tissues including peripheral blood mononuclear cells, but their biological functions are unknown. The identification of the PERV-A receptors opens avenues of research necessary for a more complete assessment of the retroviral risks of pig to human xenotransplantation. PMID:12740431

  1. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes.

    PubMed

    Gilbert, C; Meik, J M; Dashevsky, D; Card, D C; Castoe, T A; Schaack, S

    2014-09-22

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. PMID:25080342

  2. Endogenous Candida endophthalmitis after induced abortion.

    PubMed

    Chen, S J; Chung, Y M; Liu, J H

    1998-06-01

    Reported, in this article, are the cases of two young women who developed endogenous Candida endophthalmitis after induced abortion. Both women experienced transient fever, chills, and abdominal pain after the abortion and were given antibiotics. The diagnosis of endophthalmitis was established on the basis of typical fundus appearance, positive vaginal culture, and (in one case) positive vitreous culture. In the first woman, who received vitrectomy and intravitreal amphotericin B injection, the affected eye had a best corrected visual acuity of 20/200. In the second woman, who was given systemic corticosteroid treatment before the correct diagnosis was reached, recurrent retinal detachment developed and the best corrected visual acuity was counting fingers. It appears that Candida organisms harbored in the genital tract are directly inoculated into the venous system during induced abortion. Once in the blood, if sufficient fungal load is present, Candida albicans tends to localize in the choroid and to spread toward the retina and vitreous cavity. The immunosuppressive effect of corticosteroids further increases the risk of endophthalmitis. PMID:9645729

  3. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

    PubMed Central

    Gilbert, C.; Meik, J. M.; Dashevsky, D.; Card, D. C.; Castoe, T. A.; Schaack, S.

    2014-01-01

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. PMID:25080342

  4. Teachers in Class

    ERIC Educational Resources Information Center

    Van Galen, Jane

    2008-01-01

    In this article, I argue for a closer read of the daily "class work" of teachers, as posited by Reay, 1998. In developing exploratory class portraits of four teachers who occupy distinctive social positions (two from working-class homes now teaching upper-middle-class children and two from upper-middle-class homes now teaching poor children), I…

  5. [Spectral characteristics of soluble metabolites during endogenous respiration].

    PubMed

    Li, Zhi-hua; Zhang, Qin; Bai, Xu-li; Liu, Yi

    2014-09-01

    Endogenous respiration phase plays an important role in the sewage treatment process. In order to clearly understand the endogenous respiration process of the activated sludge process, three-dimensional fluorescence spectroscopy, ultraviolet spectroscopy and respirogram were employed for the analysis of endogenous respiration process. Results showed that the three-dimensional fluorescence spectroscopy and UV spectroscopy could identify all stages significantly. The following conclusions could be drawn: (1) Rapid decline phase of endogenous respiration:the excitation wavelength (EX) and emission wavelength (Em) of humic peak showed blue shift of 5 nm and 6 nm, respectively, the fluorescence index f450/500 and HIX (humification index) were reduced by 9. 3% and 0.2%, respectively, UV253/203 and UV254 increased by 37.5% and 200%, respectively. These results indicated the presence of bioavailable organics; (2)Slow decline phase of endogenous respiration: f450/500 was increased by 0. 5% , HIX was reduced by 0. 2% , UV253/203 was reduced by 20% , UV254 was increased by 16. 7%. These results indicated that hydrolysis or autolysis of cells might occur; (3)Stable phase of endogenous respiration: humic acid peak remained unchanged, indicating the adaption of microorganisms to starving environment. The analysis of the endogenous respiration process from the perspective of metabolites provides a new way for control of microbial wastewater treatment process. PMID:25518670

  6. Minority Aging and Endogenous Pain Facilitatory Processes

    PubMed Central

    Bulls, Hailey W.; Goodin, Burel R.; McNew, Myriah; Gossett, Ethan W.; Bradley, Laurence A.

    2016-01-01

    Objective The aim of the current study was to examine the relationships among age, ethnicity, and endogenous pain facilitation using temporal summation (TS) responses to mechanical and heat stimuli. Design The present study assessed hyperalgesia and pain facilitation to thermal and mechanical stimuli at the knee and distal sites in 98 pain-free men and women. Participants were drawn from two ethnic (African-Americans, AA; and non-Hispanic whites, NHW) and age groups (19-35 and 45-85). Results Significant main effects of ethnicity were demonstrated for both mechanical and heat modalities (all p’s≤0.05), suggesting that AA participants, relative to NHW counterparts, demonstrated enhanced hyperalgesia. Age differences (older > younger) in hyperalgesia were found in mechanical pain ratings only. Results indicated that mechanical pain ratings significantly increased from first to maximal pain as a function of both age group and ethnicity (all p’s≤0.05), and a significant ethnicity by age interaction for TS of mechanical pain was found at the forearm (p<0.05) and trended towards significance at the knee (p=0.071). Post-hoc tests suggested that results were primarily driven by the older AA participants, who demonstrated the greatest mechanical TS. Additionally, evidence of differences in heat TS due to both ethnicity alone (all p’s≤0.05) and minority aging was also found. Conclusions This study provides evidence suggesting that older AAs demonstrate enhanced pain facilitatory processes, which is important because this group may be at increased risk for development of chronic pain. These results underscore the necessity of testing pain modulatory mechanisms when addressing questions related to pain perception and minority aging. PMID:26814250

  7. Endogenous angiogenesis inhibitors and their therapeutic implications.

    PubMed

    Cao, Y

    2001-04-01

    A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to act specifically on the proliferating endothelial cell compartment of the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but may also provide an important therapeutic strategy for the treatment of cancer and other angiogenesis dependent diseases, including diabetic retinopathy and chronic inflammations. Systemic administration of these angiogenesis inhibitors in animals significantly suppresses the growth of a variety of tumors and their metastases. However, their production as functional recombinant proteins has been proven to be difficult. In addition, high dosages of these inhibitors are required to suppress tumor growth in animal studies. Other disadvantages of the antiangiogenic protein therapy include repeated injections, prolonged treatment, transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative strategies need to be developed in order to improve the clinical settings of antiangiogenic therapy. Developments of these strategies are ongoing and they include identification of more potent inhibitors, antiangiogenic gene therapy, improvement of protein/compound half-lives in the circulation, increase of their concentrations at the disease location, and combinatorial therapies with approaches including chemotherapy, radiotherapy, and immunotherapy. Despite the above-mentioned disadvantages, a few inhibitors have entered into the early stages of clinical trials and

  8. Endogenous opioids: The downside of opposing stress

    PubMed Central

    Valentino, Rita J.; Van Bockstaele, Elisabeth

    2014-01-01

    Our dynamic environment regularly exposes us to potentially life-threatening challenges or stressors. To answer these challenges and maintain homeostasis, the stress response, an innate coordinated engagement of central and peripheral neural systems is initiated. Although essential for survival, the inappropriate initiation of the stress response or its continuation after the stressor is terminated has pathological consequences that have been linked to diverse neuropsychiatric and medical diseases. Substantial individual variability exists in the pathological consequences of stressors. A theme of this Special Issue is that elucidating the basis of individual differences in resilience or its flipside, vulnerability, will greatly advance our ability to prevent and treat stress-related diseases. This can be approached by studying individual differences in “pro-stress” mediators such as corticosteroids or the hypothalamic orchestrator of the stress response, corticotropin-releasing factor. More recently, the recognition of endogenous neuromodulators with “anti-stress” activity that have opposing actions or that restrain stress-response systems suggests additional bases for individual differences in stress pathology. These “anti-stress” neuromodulators offer alternative strategies for manipulating the stress response and its pathological consequences. This review uses the major brain norepinephrine system as a model stress-response system to demonstrate how co-regulation by opposing pro-stress (corticotropin-releasing factor) and anti-stress (enkephalin) neuromodulators must be fine-tuned to produce an adaptive response to stress. The clinical consequences of tipping this fine-tuned balance in the direction of either the pro- or anti-stress systems are emphasized. Finally, that each system provides multiple points at which individual differences could confer stress vulnerability or resilience is discussed. PMID:25506603

  9. Strand-asymmetric endogenous Tetrahymena small RNA production requires a previously uncharacterized uridylyltransferase protein partner

    PubMed Central

    Talsky, Kristin Benjamin; Collins, Kathleen

    2012-01-01

    Many eukaryotes initiate pathways of Argonaute-bound small RNA (sRNA) production with a step that specifically targets sets of aberrant and/or otherwise deleterious transcripts for recognition by an RNA-dependent RNA polymerase complex (RDRC). The biogenesis of 23- to 24-nt sRNAs in growing Tetrahymena occurs by physical and functional coupling of the growth-expressed Dicer, Dcr2, with one of three RDRCs each containing the single genome-encoded RNA-dependent RNA polymerase, Rdr1. Tetrahymena RDRCs contain an active uridylyltransferase, either Rdn1 or Rdn2, and Rdn1 RDRCs also contain the Rdf1 and Rdf2 proteins. Although Rdn2 is nonessential and RDRC-specific, Rdn1 is genetically essential and interacts with a non-RDRC protein of 124 kDa. Here we characterize this 124-kDa protein, designated RNA silencing protein 1 (Rsp1), using endogenous locus tagging, affinity purification, and functional assays, as well as gene-knockout studies. We find that Rsp1 associates with Rdn1-Rdf1 or Rdn1-Rdf2 subcomplexes as an alternative to Rdr1, creating Rsp1 complexes (RSPCs) that are physically separate from RDRCs. The uridylyltransferase activity of Rdn1 is greatly reduced in RSPCs compared with RDRCs, suggesting enzyme regulation by the alternative partners. Surprisingly, despite the loss of all known RDRC-generated classes of endogenous sRNAs, RSP1 gene knockout was tolerated in growing cells. A minority class of Dcr2-dependent sRNAs persists in cells lacking Rsp1 with increased size heterogeneity. These findings bring new insights about the essential and nonessential functions of RNA silencing in Tetrahymena, about mechanisms of endogenous small interfering RNA production, and about the roles of cellular uridylyltransferases. PMID:22706992

  10. Does Class Size Matter?

    ERIC Educational Resources Information Center

    Ehrenberg, Ronald G.; Brewer, Dominic J.; Gamoran, Adam; Willms, J. Douglas

    2001-01-01

    Reports on the significance of class size to student learning. Includes an overview of class size in various countries, the importance of teacher adaptability, and the Asian paradox of large classes allied to high test scores. (MM)

  11. [The placebo effect: classes of explanation].

    PubMed

    Gybels, J

    1999-01-01

    The placebo effect is a frequent phenomenon in medicine, but very little is known about its mechanisms. An overview is given of the different classes of explanation of the placebo effect in analgesia and in particular the role of endogenous opioids, classical conditioning and expectations. Then the question is raised which are the properties of placebo for which a theory has to provide answers in order to be coherent. These properties are, between others, the efficacy of placebo in a variety of conditions, in individuals with different personality characteristics, etc. Finally, the difficulty of observing individual placebo is emphasized and problems concerning the diagnostic and therapeutic use of placebo are mentioned. PMID:10379195

  12. tirant, a newly discovered active endogenous retrovirus in Drosophila simulans.

    PubMed

    Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina; Fablet, Marie

    2012-04-01

    Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species. PMID:22278247

  13. tirant, a Newly Discovered Active Endogenous Retrovirus in Drosophila simulans

    PubMed Central

    Akkouche, Abdou; Rebollo, Rita; Burlet, Nelly; Esnault, Caroline; Martinez, Sonia; Viginier, Barbara; Terzian, Christophe; Vieira, Cristina

    2012-01-01

    Endogenous retroviruses have the ability to become permanently integrated into the genomes of their host, and they are generally transmitted vertically from parent to progeny. With the exception of gypsy, few endogenous retroviruses have been identified in insects. In this study, we describe the tirant endogenous retrovirus in a subset of Drosophila simulans natural populations. By focusing on the envelope gene, we show that the entire retroviral cycle (transcription, translation, and retrotransposition) can be completed for tirant within one population of this species. PMID:22278247

  14. Divergent patterns of endogenous small RNA populations from seed and vegetative tissues of Glycine max

    PubMed Central

    2012-01-01

    Background Small non-coding RNAs (smRNAs) are known to have major roles in gene regulation in eukaryotes. In plants, knowledge of the biogenesis and mechanisms of action of smRNA classes including microRNAs (miRNAs), short interfering RNAs (siRNAs), and trans-acting siRNAs (tasiRNAs) has been gained mostly through studies with Arabidopsis. In recent years, high throughput sequencing of smRNA populations has enabled extension of knowledge from model systems to plants with larger, more complex genomes. Soybean (Glycine max) now has many genomics resources available including a complete genome sequence and predicted gene models. Relatively little is known, however, about the full complement of its endogenous smRNAs populations and the silenced genes. Results Using Illumina sequencing and computational analysis, we characterized eight smRNA populations from multiple tissues and organs of soybean including developing seed and vegetative tissues. A total of 41 million raw sequence reads collapsed into 135,055 unique reads were mapped to the soybean genome and its predicted cDNA gene models. Bioinformatic analyses were used to distinguish miRNAs and siRNAs and to determine their genomic origins and potential target genes. In addition, we identified two soybean TAS3 gene homologs, the miRNAs that putatively guide cleavage of their transcripts, and the derived tasiRNAs that could target soybean genes annotated as auxin response factors. Tissue-differential expression based on the flux of normalized miRNA and siRNA abundances in the eight smRNA libraries was evident, some of which was confirmed by smRNA blotting. Our global view of these smRNA populations also revealed that the size classes of smRNAs varied amongst different tissues, with the developing seed and seed coat having greater numbers of unique smRNAs of the 24-nt class compared to the vegetative tissues of germinating seedlings. The 24-nt class is known to be derived from repetitive elements including transposons

  15. Therapeutic Implications of Modifying Endogenous Serotonergic Analgesic Systems

    PubMed Central

    Frier, James W.

    1985-01-01

    Basic research strongly implicates the neurotransmitter serotonin as a modulator of endogenous analgesic systems. Recently, clinical strategies have been developed to activate endogenous serotonergic systems as a therapeutic approach to pain control. This paper reviews the biochemistry, anatomical distribution, and physiologic functions of serotonin. The evidence reviewed suggests that precursor loading to increase brain serotonin levels and administration of serotonin receptor inhibitors and serotonin receptor agonists may lead to novel methods of pain control and the development of useful analgesic drugs. PMID:2986489

  16. Method for the Purification of Endogenous Unanchored Polyubiquitin Chains.

    PubMed

    Scott, Daniel; Strachan, Jo; Krishna, Varun Gopala; Shaw, Barry; Tooth, David J; Searle, Mark S; Oldham, Neil J; Layfield, Rob

    2016-01-01

    Unanchored polyubiquitin chains are endogenous non-substrate linked ubiquitin polymers which have emerging roles in the control of cellular physiology. We describe an affinity purification method based on an isolated ubiquitin-binding domain, the ZnF_UBP domain of the deubiquitinating enzyme USP5, which permits the selective purification of mixtures of endogenous unanchored polyubiquitin chains that are amenable to downstream molecular analyses. Further, we present methods for detection of unanchored polyubiquitin chains in purified fractions. PMID:27613037

  17. Remarkable Diversity of Endogenous Viruses in a Crustacean Genome

    PubMed Central

    Thézé, Julien; Leclercq, Sébastien; Moumen, Bouziane; Cordaux, Richard; Gilbert, Clément

    2014-01-01

    Recent studies in paleovirology have uncovered myriads of endogenous viral elements (EVEs) integrated in the genome of their eukaryotic hosts. These fragments result from endogenization, that is, integration of the viral genome into the host germline genome followed by vertical inheritance. So far, most studies have used a virus-centered approach, whereby endogenous copies of a particular group of viruses were searched in all available sequenced genomes. Here, we follow a host-centered approach whereby the genome of a given species is comprehensively screened for the presence of EVEs using all available complete viral genomes as queries. Our analyses revealed that 54 EVEs corresponding to 10 different viral lineages belonging to 5 viral families (Bunyaviridae, Circoviridae, Parvoviridae, and Totiviridae) and one viral order (Mononegavirales) became endogenized in the genome of the isopod crustacean Armadillidium vulgare. We show that viral endogenization occurred recurrently during the evolution of isopods and that A. vulgare viral lineages were involved in multiple host switches that took place between widely divergent taxa. Furthermore, 30 A. vulgare EVEs have uninterrupted open reading frames, suggesting they result from recent endogenization of viruses likely to be currently infecting isopod populations. Overall, our work shows that isopods have been and are still infected by a large variety of viruses. It also extends the host range of several families of viruses and brings new insights into their evolution. More generally, our results underline the power of paleovirology in characterizing the viral diversity currently infecting eukaryotic taxa. PMID:25084787

  18. Remarkable diversity of endogenous viruses in a crustacean genome.

    PubMed

    Thézé, Julien; Leclercq, Sébastien; Moumen, Bouziane; Cordaux, Richard; Gilbert, Clément

    2014-08-01

    Recent studies in paleovirology have uncovered myriads of endogenous viral elements (EVEs) integrated in the genome of their eukaryotic hosts. These fragments result from endogenization, that is, integration of the viral genome into the host germline genome followed by vertical inheritance. So far, most studies have used a virus-centered approach, whereby endogenous copies of a particular group of viruses were searched in all available sequenced genomes. Here, we follow a host-centered approach whereby the genome of a given species is comprehensively screened for the presence of EVEs using all available complete viral genomes as queries. Our analyses revealed that 54 EVEs corresponding to 10 different viral lineages belonging to 5 viral families (Bunyaviridae, Circoviridae, Parvoviridae, and Totiviridae) and one viral order (Mononegavirales) became endogenized in the genome of the isopod crustacean Armadillidium vulgare. We show that viral endogenization occurred recurrently during the evolution of isopods and that A. vulgare viral lineages were involved in multiple host switches that took place between widely divergent taxa. Furthermore, 30 A. vulgare EVEs have uninterrupted open reading frames, suggesting they result from recent endogenization of viruses likely to be currently infecting isopod populations. Overall, our work shows that isopods have been and are still infected by a large variety of viruses. It also extends the host range of several families of viruses and brings new insights into their evolution. More generally, our results underline the power of paleovirology in characterizing the viral diversity currently infecting eukaryotic taxa. PMID:25084787

  19. In Situ Tissue Regeneration: Chemoattractants for Endogenous Stem Cell Recruitment

    PubMed Central

    2014-01-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration PMID:23678952

  20. Endogenous control genes in complex vascular tissue samples

    PubMed Central

    2009-01-01

    Background Gene expression microarrays and real-time PCR are common methods used to measure mRNA levels. Each method has a fundamentally different approach of normalization between samples. Relative quantification of gene expression using real-time PCR is often done using the 2^(-ΔΔCt) method, in which the normalization is performed using one or more endogenous control genes. The choice of endogenous control gene is often arbitrary or bound by tradition. We here present an analysis of the differences in expression results obtained with microarray and real-time PCR, dependent on different choices of endogenous control genes. Results In complex tissue, microarray data and real-time PCR data show the best correlation when endogenous control genes are omitted and the normalization is done relative to total RNA mass, as measured before reverse transcription. Conclusion We have found that for real-time PCR in heterogeneous tissue samples, it may be a better choice to normalize real-time PCR Ct values to the carefully measured mass of total RNA than to use endogenous control genes. We base this conclusion on the fact that total RNA mass normalization of real-time PCR data shows better correlation to microarray data. Because microarray data use a different normalization approach based on a larger part of the transcriptome, we conclude that omitting endogenous control genes will give measurements more in accordance with actual concentrations. PMID:19900295

  1. Tectonic conditionality endogenic geoecological processes on a shelf

    NASA Astrophysics Data System (ADS)

    Kholmiansky, Mikhail; Anokhin, Vladimir; Kholmianskaia, Galina

    2014-05-01

    Influence on a sea ecosystem of deep tectonic structures and processes is considered. From the point of view of studying endogenic geoecological processes and the phenomena ensuring origin of «endogenic» ecological dangers, us the following interests, first of all: a structurally-tectonic structure, a lithologic-stratigraphic section, hydro- and lithodynamic, a hydrology, seismic activity, endogenic ingress of heavy metals, a structure cryolithozone The map of endogenic dangers to water area Barents and Karasky seas is made. In the list of the endogenic dangers which have been taken out on the map, have entered: - Areas of heavy metals endogenic origins; - Zones of hyperactivity of corrosion processes; - Zones of the raised seismological activity; - Areas active roiling at seismological influences; - Zones of negative influence on biogene communities, - Characteristics of influence of natural electric field on lithodynamic processes. The most part flooded at the bottom of technogenic objects is located within the tectonic zones characterised by raised intensity of corrosion processes. The tectonic reasons, in the big degree, cause dynamics of the deep hydro-geological processes providing receipt in hydrosphere of the sea highly mineralized waters, negatively influencing on a biogenic component of an ecosystem. The most vulnerable are the biogenic forms living in deeper sites of the sea. On the map are allocated and ranked some zones endogenic hydro-geological dangers to biogenic communities. At displays of seismological activity endogenic tectonic nature process roiling the ground deposits, menacing to normal dwelling biota, leading to death ground invertebral organisms, to sharp pauperisation of a forage reserve benthos feeder will have fishes, to sharp reduction of population nectobentofages and predators. At last, infringement of a hydrochemical mode in aggregate with endogenic receipts can strengthen aforementioned negative processes. The geoecological map of

  2. Endogenous Cortical Oscillations Constrain Neuromodulation by Weak Electric Fields

    PubMed Central

    Schmidt, Stephen L.; Iyengar, Apoorva K.; Foulser, A. Alban; Boyle, Michael R.; Fröhlich, Flavio

    2014-01-01

    Background Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations with the application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. Objective We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that the structure of the response to stimulation depended on matching the stimulation frequency to the endogenous cortical oscillation. Methods We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. Results Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing but not overriding of intrinsic network dynamics. Conclusion Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms. PMID:25129402

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

    PubMed Central

    Koles, Kate; Yeh, Anna R.; Rodal, Avital A.

    2016-01-01

    ABSTRACT 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. PMID:26700726

  4. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    PubMed

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair. PMID:26559963

  5. Class Notes for "Class-Y-News."

    ERIC Educational Resources Information Center

    Stuart, Judy L.

    1991-01-01

    A self-contained class of students with mild to moderate disabilities published a monthly newsletter which was distributed to students' families. Students became involved in writing, typing, drawing, folding, basic editing, and disseminating. (JDD)

  6. Endogenous cardiac stem cells for the treatment of heart failure

    PubMed Central

    Fuentes, Tania; Kearns-Jonker, Mary

    2013-01-01

    Stem cell-based therapies hold promise for regenerating the myocardium after injury. Recent data obtained from phase I clinical trials using endogenous cardiovascular progenitors isolated directly from the heart suggest that cell-based treatment for heart patients using stem cells that reside in the heart provides significant functional benefit and an improvement in patient outcome. Methods to achieve improved engraftment and regeneration may extend this therapeutic benefit. Endogenous cardiovascular progenitors have been tested extensively in small animals to identify cells that improve cardiac function after myocardial infarction. However, the relative lack of large animal models impedes translation into clinical practice. This review will exclusively focus on the latest research pertaining to humans and large animals, including both endogenous and induced sources of cardiovascular progenitors. PMID:24426784

  7. Purification and analysis of endogenous human RNA exosome complexes

    PubMed Central

    Domanski, Michal; Upla, Paula; Rice, William J.; Molloy, Kelly R.; Ketaren, Natalia E.; Stokes, David L.; Jensen, Torben Heick; Rout, Michael P.

    2016-01-01

    As a result of its importance in key RNA metabolic processes, the ribonucleolytic RNA exosome complex has been the focus of intense study for almost two decades. Research on exosome subunit assembly, cofactor and substrate interaction, enzymatic catalysis and structure have largely been conducted using complexes produced in the yeast Saccharomyces cerevisiae or in bacteria. Here, we examine different populations of endogenous exosomes from human embryonic kidney (HEK) 293 cells and test their enzymatic activity and structural integrity. We describe methods to prepare EXOSC10-containing, enzymatically active endogenous human exosomes at suitable yield and purity for in vitro biochemistry and negative stain transmission electron microscopy. This opens the door for assays designed to test the in vitro effects of putative cofactors on human exosome activity and will enable structural studies of preparations from endogenous sources. PMID:27402899

  8. Body position differentially influences responses to exogenous and endogenous cues.

    PubMed

    McAuliffe, Jim; Johnson, Michel J; Weaver, Bruce; Deller-Quinn, Miranda; Hansen, Steve

    2013-10-01

    The influence of vestibular inputs on exogenous (Exp. 1) and endogenous (Exp. 2) orienting of visual attention was examined. The vestibular system was manipulated through a change in static body position. Participants engaged in an exogenous or endogenous response task while in a seated position, while lying in a prone position, and while in a prone position with their head down and neck flexed (HDNF). An attenuation of inhibition and facilitation effects during the exogenous task was observed in the HDNF position. However, responses to the cues remained similar in the endogenous task, irrespective of body position. The results reveal a potential dissociation between reflexive and volitional orienting of visual attention that is dependent on vestibular inputs. PMID:24092358

  9. Purification and analysis of endogenous human RNA exosome complexes.

    PubMed

    Domanski, Michal; Upla, Paula; Rice, William J; Molloy, Kelly R; Ketaren, Natalia E; Stokes, David L; Jensen, Torben Heick; Rout, Michael P; LaCava, John

    2016-09-01

    As a result of its importance in key RNA metabolic processes, the ribonucleolytic RNA exosome complex has been the focus of intense study for almost two decades. Research on exosome subunit assembly, cofactor and substrate interaction, enzymatic catalysis and structure have largely been conducted using complexes produced in the yeast Saccharomyces cerevisiae or in bacteria. Here, we examine different populations of endogenous exosomes from human embryonic kidney (HEK) 293 cells and test their enzymatic activity and structural integrity. We describe methods to prepare EXOSC10-containing, enzymatically active endogenous human exosomes at suitable yield and purity for in vitro biochemistry and negative stain transmission electron microscopy. This opens the door for assays designed to test the in vitro effects of putative cofactors on human exosome activity and will enable structural studies of preparations from endogenous sources. PMID:27402899

  10. Residential water demand with endogenous pricing: The Canadian Case

    NASA Astrophysics Data System (ADS)

    Reynaud, Arnaud; Renzetti, Steven; Villeneuve, Michel

    2005-11-01

    In this paper, we show that the rate structure endogeneity may result in a misspecification of the residential water demand function. We propose to solve this endogeneity problem by estimating a probabilistic model describing how water rates are chosen by local communities. This model is estimated on a sample of Canadian local communities. We first show that the pricing structure choice reflects efficiency considerations, equity concerns, and, in some cases, a strategy of price discrimination across consumers by Canadian communities. Hence estimating the residential water demand without taking into account the pricing structures' endogeneity leads to a biased estimation of price and income elasticities. We also demonstrate that the pricing structure per se plays a significant role in influencing price responsiveness of Canadian residential consumers.

  11. Ordered Nanostructured Amphiphile Self-Assembly Materials from Endogenous Nonionic Unsaturated Monoethanolamide Lipids in Water

    SciTech Connect

    Sagnella, Sharon M.; Conn, Charlotte E.; Krodkiewska, Irena; Moghaddam, Minoo; Seddon, John M.; Drummond, Calum J.

    2010-08-23

    The self-assembly, solid state and lyotropic liquid crystalline phase behavior of a series of endogenous n-acylethanolamides (NAEs) with differing degrees of unsaturation, viz., oleoyl monoethanolamide, linoleoyl monoethanolamide, and linolenoyl monoethanolamide, have been examined. The studied molecules are known to possess inherent biological function. Both the monoethanolamide headgroup and the unsaturated hydrophobe are found to be important in dictating the self-assembly behavior of these molecules. In addition, all three molecules form lyotropic liquid crystalline phases in water, including the inverse bicontinuous cubic diamond (Q{sub II}{sup D}) and gyroid (Q{sub II}{sup G}) phases. The ability of the NAE's to form inverse cubic phases and to be dispersed into ordered nanostructured colloidal particles, cubosomes, in excess water, combined with their endogenous nature and natural medicinal properties, makes this new class of soft mesoporous amphiphile self-assembly materials suitable candidates for investigation in a variety of advanced multifunctional applications, including encapsulation and controlled release of therapeutic agents and incorporation of medical imaging agents.

  12. First-Class Inquiry

    ERIC Educational Resources Information Center

    Hesser, Kathi; Buck, Gayle; Dopp, Sandra

    2005-01-01

    In the activity described in this article, students will explore how variables in a first-class lever, specifically arm length, position of the fulcrum, and placement of the load, affect the effort needed to lift the load. To begin the lesson, demonstrate to the class how a first-class lever works and review what is meant by the terms fulcrum,…

  13. Girls' Class, Infinite Possibilities.

    ERIC Educational Resources Information Center

    Ost, Nancy

    1999-01-01

    The co-director of a small independent school describes Girls' Class, which she created in order to have a special time together with the girls in grades 6 through 8. The class provides guidance and celebrates spirituality and the beginning of menses for the young women. To end the class, each person says a positive self-affirmation and gives…

  14. Assessing the bioequivalence of analogues of endogenous substances (‘endogenous drugs’): considerations to optimize study design

    PubMed Central

    Dissanayake, Sanjeeva

    2010-01-01

    BACKGROUND Assessment of the bioequivalence of generic versions of certain reference drugs is complicated by the presence of endogenous levels of said compounds which cannot be distinguished from externally derived compound levels following drug administration. If unaccounted for, the presence of endogenous compound biases towards equivalence in bioequivalence studies of these drugs. Bioequivalence assessments may be complicated further as disposition of the exogenous analogue can be subject to various endogenous processes resulting in nonlinear pharmacokinetics. To overcome these inherent biases a number of different strategies have been employed. AIMS To critically review methods used to overcome confounding biases in bioequivalence studies of ‘endogenous’ drugs. METHODS A literature search of the EMBASE and PubMed databases was performed. RESULTS The following strategies were identified: ablation/modulation of baseline endogenous substance levels; recruitment of ‘substance-deficient’ populations; restriction of dietary intake of the relevant substance; standardization of conditions with the potential to affect relevant homeostatic mechanisms; correction for baseline substance levels; and administration of supra-therapeutic drug doses. CONCLUSIONS On the basis of this review key study design concepts, intended to optimize the design of future bioequivalence studies of these so-called ‘endogenous drugs’, are described. The dual stable isotope method, which could be used in a specific context, is also discussed. PMID:20233194

  15. Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins

    PubMed Central

    Li, Yingxue; Lefever, Mark R; Muthu, Dhanasekaran; Bidlack, Jean M; Bilsky, Edward J; Polt, Robin

    2012-01-01

    Over the past two decades, potent and selective analgesics have been developed from endogenous opioid peptides. Glycosylation provides an important means of modulating interaction with biological membranes, which greatly affects the pharmacodynamics and pharmacokinetics of the resulting glycopeptide analogues. Furthermore, manipulation of the membrane affinity allows penetration of cellular barriers that block efficient drug distribution, including the blood–brain barrier. Extremely potent and selective opiate agonists have been developed from endogenous peptides, some of which show great promise as drug candidates. PMID:22300099

  16. Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.

    PubMed

    Mercer, Andrew C; Gaj, Thomas; Sirk, Shannon J; Lamb, Brian M; Barbas, Carlos F

    2014-10-17

    The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks. PMID:24251925

  17. Detection and characterization of endogenous retroviruses in the horse genome by in silico analysis.

    PubMed

    Garcia-Etxebarria, Koldo; Jugo, Begoña M

    2012-12-01

    Endogenous retroviruses (ERVs) are proviral phases of exogenous retroviruses that have become incorporated into the host genome. Little is known about ERVs in the horse genome. By combining 3 bioinformatic approaches, we detected 1947 putative ERVs in the horse genome. These equine ERVs are not scattered randomly across the genome and are especially abundant in the X chromosome. Based on phylogenetic relationships, some of these equine ERVs were classified into 15 previously uncharacterized families of Classes I, II and III. Compared with the cow and other species, the horse genome appears to container fewer ERVs. Although this could be due to limitations of the detection process, it could also stem from characteristics of the horse genome or the effect of the domestication process. PMID:23026066

  18. Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.

    PubMed

    Elsässer, Simon J; Noh, Kyung-Min; Diaz, Nichole; Allis, C David; Banaszynski, Laura A

    2015-06-11

    Transposable elements comprise roughly 40% of mammalian genomes. They have an active role in genetic variation, adaptation and evolution through the duplication or deletion of genes or their regulatory elements, and transposable elements themselves can act as alternative promoters for nearby genes, resulting in non-canonical regulation of transcription. However, transposable element activity can lead to detrimental genome instability, and hosts have evolved mechanisms to silence transposable element mobility appropriately. Recent studies have demonstrated that a subset of transposable elements, endogenous retroviral elements (ERVs) containing long terminal repeats (LTRs), are silenced through trimethylation of histone H3 on lysine 9 (H3K9me3) by ESET (also known as SETDB1 or KMT1E) and a co-repressor complex containing KRAB-associated protein 1 (KAP1; also known as TRIM28) in mouse embryonic stem cells. Here we show that the replacement histone variant H3.3 is enriched at class I and class II ERVs, notably those of the early transposon (ETn)/MusD family and intracisternal A-type particles (IAPs). Deposition at a subset of these elements is dependent upon the H3.3 chaperone complex containing α-thalassaemia/mental retardation syndrome X-linked (ATRX) and death-domain-associated protein (DAXX). We demonstrate that recruitment of DAXX, H3.3 and KAP1 to ERVs is co-dependent and occurs upstream of ESET, linking H3.3 to ERV-associated H3K9me3. Importantly, H3K9me3 is reduced at ERVs upon H3.3 deletion, resulting in derepression and dysregulation of adjacent, endogenous genes, along with increased retrotransposition of IAPs. Our study identifies a unique heterochromatin state marked by the presence of both H3.3 and H3K9me3, and establishes an important role for H3.3 in control of ERV retrotransposition in embryonic stem cells. PMID:25938714

  19. International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function.

    PubMed

    Vaudry, Hubert; Leprince, Jérôme; Chatenet, David; Fournier, Alain; Lambert, David G; Le Mével, Jean-Claude; Ohlstein, Eliot H; Schwertani, Adel; Tostivint, Hervé; Vaudry, David

    2015-01-01

    Urotensin II (UII) is a cyclic neuropeptide that was first isolated from the urophysis of teleost fish on the basis of its ability to contract the hindgut. Subsequently, UII was characterized in tetrapods including humans. Phylogenetic studies and synteny analysis indicate that UII and its paralogous peptide urotensin II-related peptide (URP) belong to the somatostatin/cortistatin superfamily. In mammals, the UII and URP genes are primarily expressed in cholinergic neurons of the brainstem and spinal cord. UII and URP mRNAs are also present in various organs notably in the cardiovascular, renal, and endocrine systems. UII and URP activate a common G protein-coupled receptor, called UT, that exhibits relatively high sequence identity with somatostatin, opioid, and galanin receptors. The UT gene is widely expressed in the central nervous system (CNS) and in peripheral tissues including the retina, heart, vascular bed, lung, kidney, adrenal medulla, and skeletal muscle. Structure-activity relationship studies and NMR conformational analysis have led to the rational design of a number of peptidic and nonpeptidic UT agonists and antagonists. Consistent with the wide distribution of UT, UII has now been shown to exert a large array of biologic activities, in particular in the CNS, the cardiovascular system, and the kidney. Here, we review the current knowledge concerning the pleiotropic actions of UII and discusses the possible use of antagonists for future therapeutic applications. PMID:25535277

  20. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    SciTech Connect

    Neumaier, J.F.

    1989-01-01

    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced ({sup 3}H)-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of ({sup 3}H)-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand ({sup 3}H)-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity.

  1. Optical Control of Mammalian Endogenous Transcription and Epigenetic States

    PubMed Central

    Trevino, Alexandro; Hsu, Patrick D.; Heidenreich, Matthias; Cong, Le; Platt, Randall J.; Scott, David A.; Church, George M.; Zhang, Feng

    2013-01-01

    The dynamic nature of gene expression enables cellular programming, homeostasis, and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high precision spatiotemporal control of many cellular functions1-11. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here, we describe the development of Light-Inducible Transcriptional Effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain12-14 with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical co-factors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility3,4,6,7,15. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of awake mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states. PMID:23877069

  2. Endogenous mitigation of H2S inside of the landfills.

    PubMed

    Fang, Yuan; Zhong, Zhong; Shen, Dongsheng; Du, Yao; Xu, Jing; Long, Yuyang

    2016-02-01

    Vast quantities of hydrogen sulfide (H2S) emitted from landfill sites require urgent disposal. The current study focused on source control and examined the migration and conversion behavior of sulfur compounds in two lab-scale simulated landfills with different operation modes. It aimed to explore the possible strategies and mechanisms for H2S endogenous mitigation inside of landfills during decomposition. It was found that the strength of H2S emissions from the landfill sites was dependent on the municipal solid waste (MSW) degradation speed and vertical distribution of sulfide. Leachate recirculation can shorten both the H2S influence period and pollution risk to the surrounding environment. H2S endogenous mitigation may be achieved by chemical oxidation, biological oxidation, adsorption, and/or precipitation in different stages. Migration and conversion mainly affected H2S release behavior during the initial stabilization phase in the landfill. Microbial activities related to sulfur, nitrogen, and iron can further promote H2S endogenous mitigation during the high reducing phase. Thus, H2S endogenous mitigation can be effectively enhanced via control of the aforementioned processes. PMID:26423286

  3. Proteomics investigation of endogenous S-nitrosylation in Arabidopsis

    SciTech Connect

    Fares, Abasse; Rossignol, Michel; Peltier, Jean-Benoit

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Identification and quantification of nitrosothiols. Black-Right-Pointing-Pointer A first dataset of endogenously nitrosylated cysteines in Arabidopsis cells. Black-Right-Pointing-Pointer Nitrosothiols display apolar motifs not located in close vicinity of cysteines. Black-Right-Pointing-Pointer Salt stress alters the endogenous nitrosylation of specific cysteines in Arabidopsis. -- Abstract: S-Nitrosylation emerges as an important protein modification in many processes. However, most data were obtained at the protein level after addition of a NO donor, particularly in plants where information about the cysteines nitrosylated in these proteins is scarce. An adapted work-flow, combining the classical biotin switch method and labeling with isotope-coded affinity tags (ICAT), is proposed. Without addition of NO donor, a total of 53 endogenous nitrosocysteines was identified in Arabidopsis cells, in proteins belonging to all cell territories, including membranes, and covering a large panel of functions. This first repertoire of nitrosothiols in plants enabled also preliminary structural description. Three apolar motifs, not located in close vicinity of cysteines and accounting for half the dataset, were detected and are proposed to complement nitrosylation prediction algorithms, poorly trained with plant data to date. Analysis of changes induced by a brief salt stress showed that NaCl modified the nitrosylation level of a small proportion of endogenously nitrosylated proteins and did not concern all nitrosothiols in these proteins. The possible role of some NO targets in the response to salt stress was discussed.

  4. Purification of the endogenous glucocorticoid receptor stabilizing factor

    SciTech Connect

    Meshinchi, S.; Stancato, L.F.; Pratt, W.B. ); Gordon, B.M.; Jones, K.W. )

    1991-09-03

    A ubiquitous, low molecular weight, heat-stable component of cytosol stabilizes the glucocorticoid receptor in its untransformed state in association with hsp90. This heat-stable factor mimics molybdate in its effects on receptor function, and it has the heat stability, charge, and chelation properties of a metal oxyanion. In this paper, the authors describe the further purification of the endogenous factor from rat liver cytosol by anion-exchange HPCL (Ion-110) after prepurification by molecular sieving, cation absorption, and charcoal absorption. Elution of the factor with an isocratic gradient of ammonium bicarbonate results in recovery of all of the bioactivity in a single peak which coelutes with inorganic phosphate and contains all of the endogenous molybdenum. The bioactivity can be separated from inorganic phosphate by chromatography of the partially purified endogenous factor on a metal-chelating column of Chelex-100. The chelating procedure results in complete loss of bioactivity with recovery of 98% of the inorganic phosphate in both the column drop-through and a subsequent 1 M NaCl wash. These observations support the proposal that an endogenous metal can stabilize the binding of hsp90 to the receptor but it is likely that other cytosolic components that are not present in the immunopurified complex must contribute to the stability of the soluble protein-protein complex in cytosol.

  5. RXR function requires binding to an endogenous terpenoid ligand

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The issue of whether the nuclear receptor RXR must bind to an endogenous, nanomolar affinity ligand in order to perform its natural function is still unsettled (1). On the basis of our previous studies establishing that the Drosophilamelanogaster ortholog of the retinoid X receptor ("ultraspiracle,"...

  6. Evolutionary Systems Theory, Universities, and Endogenous Regional Economic Development

    ERIC Educational Resources Information Center

    Bowen, William M.

    2007-01-01

    Universities today are increasingly being viewed in terms of serving the purpose of economic development. This paper postulates that their chief purpose is to advance knowledge and that in doing so they effectuate regional economic growth and development through processes specified in the endogenous economic growth model. To achieve this purpose…

  7. RELIABLE ASSAYS FOR DETERMINING ENDOGENOUS COMPONENTS OF HUMAN MILK

    EPA Science Inventory

    Healthy women from 18-38 years old (N=25) fasted for several hours and twice donated blood and milk (postpartum 2-7 weeks and 3-4 months) for the EPA's Methods Advancement for Milk Analysis study, a pilot for the National Children's Study (NCS). Endogenous components were chosen...

  8. Novel endogenous angiogenesis inhibitors and their therapeutic potential

    PubMed Central

    Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

    2015-01-01

    Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application. PMID:26364800

  9. Endogenous protease activity in byproducts of pink salmon (Oncorhynchus gorbuscha)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrolysate production is a low-cost method of preservation that could be employed to decrease the amount of fish byproducts discarded by Alaska’s salmon industry. However, endogenous enzymes within salmon vary with spawning maturity, and must be controlled in the raw material to ensure a consistent...

  10. Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System?

    ERIC Educational Resources Information Center

    Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk

    2010-01-01

    The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids…

  11. Conceptual Understanding of Multiplicative Properties through Endogenous Digital Game Play

    ERIC Educational Resources Information Center

    Denham, Andre

    2012-01-01

    This study purposed to determine the effect of an endogenously designed instructional game on conceptual understanding of the associative and distributive properties of multiplication. Additional this study sought to investigate if performance on measures of conceptual understanding taken prior to and after game play could serve as predictors of…

  12. Isolating Exogenous and Endogenous Modes of Temporal Attention

    ERIC Educational Resources Information Center

    Lawrence, Michael A.; Klein, Raymond M.

    2013-01-01

    The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current report seeks to ameliorate this…

  13. English walnuts (Juglans regia L.) protect endogenous antioxidants in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ellagic acid monomers, polymeric tannins and related phenolic compounds isolated from English walnuts (Juglans regia L.) have been reported to inhibit LDL oxidation ex vivo and decrease biomarkers of oxidative stress in animal models. To determine whether dietary and endogenous antioxidants are pres...

  14. Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.

    PubMed

    Jacob, Michael S; Presti, David E

    2005-01-01

    The presence of the potent hallucinogenic psychoactive chemical N,N-dimethyltryptamine (DMT) in the human body has puzzled scientists for decades. Endogenous DMT was investigated in the 1960s and 1970s and it was proposed that DMT was involved in psychosis and schizophrenia. This hypothesis developed from comparisons of the blood and urine of schizophrenic and control subjects. However, much of this research proved inconclusive and conventional thinking has since held that trace levels of DMT, and other endogenous psychoactive tryptamines, are insignificant metabolic byproducts. The recent discovery of a G-protein-coupled, human trace amine receptor has triggered a reappraisal of the role of compounds present in limited concentrations in biological systems. Interestingly enough, DMT and other psychoactive tryptamine hallucinogens elicit a robust response at the trace amine receptor. While it is currently accepted that serotonin 5-HT(2A) receptors play a pivotal role in the activity of hallucinogenic/psychedelic compounds, we propose that the effects induced by exogenous DMT administration, especially at low doses, are due in part to activity at the trace amine receptor. Furthermore, we suggest that endogenous DMT interacts with the TA receptor to produce a calm and relaxed mental state, which may suppress, rather than promote, symptoms of psychosis. This hypothesis may help explain the inconsistency in the early analysis of endogenous DMT in humans. Finally, we propose that amphetamine action at the TA receptor may contribute to the calming effects of amphetamine and related drugs, especially at low doses. PMID:15780487

  15. [Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

    PubMed

    Fan, Xin-rong; Tang, Nong; Ji, Yun-xi; Zhang, Yao-zhong; Jiang, Li; Huang, Gui-hua; Xie, Sheng; Li, Liu-mei; Song, Chun-hui; Ling, Jiang-hong

    2015-08-01

    The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases. PMID:26485920

  16. Investigation of insoluble endogenous fractions of gastrointestinal tract by SRXRF

    NASA Astrophysics Data System (ADS)

    Trunova, V. A.; Zvereva, V. V.

    2005-05-01

    For the determination of the elemental composition of insoluble endogenous fractions from gastrointestinal tract by SRXRF (XRF experimental beam line, VEPP-3, INP SU RAS, Novosibirsk), an analytical method was developed for producing epithelial tissue in vivo. The metrological characteristics were determined using a number of international biological standards.

  17. Endogenous morphine: up-to-date review 2011.

    PubMed

    Stefano, G B; Ptáček, R; Kuželová, H; Kream, R M

    2012-01-01

    Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. Despite the establishment of a progressively rigorous and mechanistically focused historical literature extending from the mid 1970s to the mid 1980s that supported the expression of chemically authentic morphine by animal cellular and organ systems, prejudicial scepticism and early dismissal by scientists and clinicians most often obscured widespread acceptance of the biological importance and medical implications of endogenous morphine. The current critical paper presents and evaluates key recent coordinated studies in endogenous morphine research, highlighting those that have advanced our understanding of the functional roles of cognate alkaloid-selective μ(3) and μ(4) opiate receptors. We propose that the expression of endogenous morphine by animal and human cells is designed to mediate homeopathic regulation of metabolic activity via activation of cognate μ(3) and μ(4) receptors that serve as transductive conduits for shortcircuit Ca(++) fluxes. The implications of endogenous morphine coupling to nitric oxide regulation of mitochondrial function, with special reference to the cardiovascular system, are now formulated after many years of neglect. PMID:22578954

  18. Competition Between Endogenous and Exogenous Orienting of Visual Attention

    ERIC Educational Resources Information Center

    Berger, Andrea; Henik, Avishai; Rafal, Robert

    2005-01-01

    The relation between reflexive and voluntary orienting of visual attention was investigated with 4 experiments: a simple detection task, a localization task, a saccade toward the target task, and a target identification task in which discrimination difficulty was manipulated. Endogenous and exogenous orienting cues were presented in each trial and…

  19. Quantitative Live Imaging of Endogenous DNA Replication in Mammalian Cells

    PubMed Central

    Burgess, Andrew; Lorca, Thierry; Castro, Anna

    2012-01-01

    Historically, the analysis of DNA replication in mammalian tissue culture cells has been limited to static time points, and the use of nucleoside analogues to pulse-label replicating DNA. Here we characterize for the first time a novel Chromobody cell line that specifically labels endogenous PCNA. By combining this with high-resolution confocal time-lapse microscopy, and with a simplified analysis workflow, we were able to produce highly detailed, reproducible, quantitative 4D data on endogenous DNA replication. The increased resolution allowed accurate classification and segregation of S phase into early-, mid-, and late-stages based on the unique subcellular localization of endogenous PCNA. Surprisingly, this localization was slightly but significantly different from previous studies, which utilized over-expressed GFP tagged forms of PCNA. Finally, low dose exposure to Hydroxyurea caused the loss of mid- and late-S phase localization patterns of endogenous PCNA, despite cells eventually completing S phase. Taken together, these results indicate that this simplified method can be used to accurately identify and quantify DNA replication under multiple and various experimental conditions. PMID:23029203

  20. Health and Wages: Panel Data Estimates Considering Selection and Endogeneity

    ERIC Educational Resources Information Center

    Jackle, Robert; Himmler, Oliver

    2010-01-01

    This paper complements previous studies on the effects of health on wages by addressing the problems of unobserved heterogeneity, sample selection, and endogeneity in one comprehensive framework. Using data from the German Socio-Economic Panel (GSOEP), we find the health variable to suffer from measurement error and a number of tests provide…

  1. Improving access to endogenous DNA in ancient bones and teeth

    PubMed Central

    Damgaard, Peter B.; Margaryan, Ashot; Schroeder, Hannes; Orlando, Ludovic; Willerslev, Eske; Allentoft, Morten E.

    2015-01-01

    Poor DNA preservation is the most limiting factor in ancient genomic research. In the majority of ancient bones and teeth, endogenous DNA molecules represent a minor fraction of the whole DNA extract, rendering shot-gun sequencing inefficient for obtaining genomic data. Based on ancient human bone samples from temperate and tropical environments, we show that an EDTA-based enzymatic ‘pre-digestion’ of powdered bone increases the proportion of endogenous DNA several fold. By performing the pre-digestion step between 30 min and 6 hours on five bones, we observe an asymptotic increase in endogenous DNA content, with a 2.7-fold average increase reached at 1 hour. We repeat the experiment using a brief pre-digestion (15 or 30 mins) on 21 ancient bones and teeth from a variety of archaeological contexts and observe an improvement in 16 of these. We here advocate the implementation of a brief pre-digestion step as a standard procedure in ancient DNA extractions. Finally, we demonstrate on 14 ancient teeth that by targeting the outer layer of the roots we obtain up to 14 times more endogenous DNA than when using the inner dentine. Our presented methods are likely to increase the proportion of ancient samples that are suitable for genome-scale characterization. PMID:26081994

  2. Class network routing

    DOEpatents

    Bhanot, Gyan; Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Steinmacher-Burow, Burkhard D.; Takken, Todd E.; Vranas, Pavlos M.

    2009-09-08

    Class network routing is implemented in a network such as a computer network comprising a plurality of parallel compute processors at nodes thereof. Class network routing allows a compute processor to broadcast a message to a range (one or more) of other compute processors in the computer network, such as processors in a column or a row. Normally this type of operation requires a separate message to be sent to each processor. With class network routing pursuant to the invention, a single message is sufficient, which generally reduces the total number of messages in the network as well as the latency to do a broadcast. Class network routing is also applied to dense matrix inversion algorithms on distributed memory parallel supercomputers with hardware class function (multicast) capability. This is achieved by exploiting the fact that the communication patterns of dense matrix inversion can be served by hardware class functions, which results in faster execution times.

  3. Functional Analysis of the env Open Reading Frame in Human Endogenous Retrovirus IDDMK1,222 Encoding Superantigen Activity

    PubMed Central

    Lapatschek, Matthias; Dürr, Susanne; Löwer, Roswitha; Magin, Christine; Wagner, Hermann; Miethke, Thomas

    2000-01-01

    Mice harbor a family of endogenous retroviruses, the mouse mammary tumor viruses (MMTV), which encode superantigens. These superantigens are responsible for the deletion of T cells expressing certain Vβ chains of the T-cell receptor in the thymus. Human T cells are able to recognize MMTV-encoded superantigens presented by human major histocompatibility complex class II-positive cells. Owing to this and to the similarity of the human and murine immune systems, it was speculated that human endogenous retroviruses might also code for superantigens. Recently, it was reported that a proviral clone (IDDMK1,222) of the human endogenous retrovirus family HTDV/HERV-K encodes a superantigen. The putative superantigen gene was located within the env region of the virus. Stimulated by these findings, we amplified by PCR and cloned into eucaryotic expression vectors open reading frames (ORFs) which were identical or very similar to IDDMK1,222. When we transfected these vectors into A20 cells, a murine B-cell lymphoma, we were able to demonstrate mRNA expression and protein production. However, we did not find any evidence that the ORF stimulated human or murine T cells in a Vβ-specific fashion, the most prominent feature of superantigens. PMID:10864649

  4. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules, which are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating cytotoxic lymphocytes (CTLs). The polymorp...

  5. Class and Gender

    ERIC Educational Resources Information Center

    Hart, Mechthild

    2005-01-01

    Everyone is dependent on caring labor. Because women's labor is financially beneficial to global capitalism, gender is inseparable from class, regardless of the specific national or cultural contexts.

  6. Online, Bigger Classes May Be Better Classes

    ERIC Educational Resources Information Center

    Parry, Marc

    2010-01-01

    In his work as a professor, Stephen Downes used to feel that he was helping those who least needed it. His students at places like the University of Alberta already had a leg up in life and could afford the tuition. When a colleague suggested they co-teach an online class in learning theory at the University of Manitoba, in 2008, Downes welcomed…

  7. Active site nanospace of aminoacyl tRNA synthetase: difference between the class I and class II synthetases.

    PubMed

    Dutta, Saheb; Choudhury, Kaberi; Banik, Sindrila Dutta; Nandi, Nilashis

    2014-03-01

    active sites of class I and class II aaRSs. The difference in mechanism in two classes as pointed out in recent study (S. Dutta Banik and N. Nandi, J. Biomol. Struct. Dyn. 30, 701 (2012)) is related with the fact that the relative arrangement of the ATP with respect to the AA is opposite in class I and class II aaRSs as explained in the present work. The charge population difference between the reacting centers (which are the alphaP atom of ATP (q(p)) and the attacking oxygen atom of carboxylic acid group (q(o)), respectively) denoted by delta(q), is a measure of the propensity of nucleophilic attack. The population analysis of the substrate AA shows that a non-negligible difference exists between the attacking oxygens of AA in class I (syn) and in class II (anti) which is one reason for the lower value of delta(q) in class II relative to class I. The population analysis of the AA, ATP, Mg+2 ions and active site residues shows that the difference in delta(q) values of the two classes is substantially reduced. When ions and residues are considered. Thus, the bent state of ATP, Mg+2 ions and active site residues complements it cognate AA to carry out the nucleophilic reaction in class I as efficiently as occurs in class I (with the extended state of ATP, single Mg+2 ion and active site residues). This could be one reason for the two different conformations of ATP in the two classes. The mutual arrangements of AA and ATP in each aaRS are guided by the spatial charge distribution of ATP (extended and bent). The present work shows that the construction of nanospace complements the arrangement of the substrate (AA and ATP). PMID:24745224

  8. Limits to Open Class Performance?

    NASA Technical Reports Server (NTRS)

    Bowers, Albion H.

    2007-01-01

    This viewgraph presentation describes the limits to open class performance. The contents include: 1) Standard Class; 2) 15m/Racing Class; 3) Open Class; and 4) Design Solutions associated with assumptions, limiting parameters, airfoil performance, current trends, and analysis.

  9. The Question of Class

    ERIC Educational Resources Information Center

    Gorski, Paul C.

    2007-01-01

    For too long, educators' approach to understanding the relationships between poverty, class and education has been framed by studying the behaviors and cultures of poor students and their families. If only we--in the middle and upper-middle classes--can understand "their" culture, why "those people" don't value education, why "those parents" don't…

  10. The Question of Class

    ERIC Educational Resources Information Center

    Gorski, Paul C.

    2007-01-01

    For too long, educators' approach to understanding the relationships between poverty, class and education has been framed by studying the behaviors and cultures of poor students and their families. If only people--in the middle and upper-middle classes--can understand "their" culture, why "those people" do not value education, why "those parents"…

  11. The Last Class

    ERIC Educational Resources Information Center

    Uhl, Christopher

    2005-01-01

    The last class of the semester is like a goodbye. It can be cold and perfunctory or warm and heartfelt. For many years, I erred on the side of "cold and perfunctory." No more. Now my last classes are a time of celebration and ritual as I invite students to focus on qualities such as acceptance and gratitude.

  12. The Class Size Debate.

    ERIC Educational Resources Information Center

    Mishel, Lawrence, Ed.; Rothstein, Richard, Ed.

    This collection of papers debates the merits of smaller class sizes and research methods used to evaluate the efficacy of this education reform measure. Four chapters focus on (1) "Understanding the Magnitude and Effect of Class Size on Student Achievement" (Alan B. Krueger), which discusses expenditures per student and economic criterion; (2)…

  13. Teaching Large Evening Classes

    ERIC Educational Resources Information Center

    Wambuguh, Oscar

    2008-01-01

    High enrollments, conflicting student work schedules, and the sheer convenience of once-a-week classes are pushing many colleges to schedule evening courses. Held from 6 to 9 pm or 7 to 10 pm, these classes are typically packed, sometimes with more than 150 students in a large lecture theater. How can faculty effectively teach, control, or even…

  14. Class Scheduling Preferences.

    ERIC Educational Resources Information Center

    Richards, Irving E.; And Others

    In order to ascertain students' preferences for the number of times a class should meet each week, 375 questionnaires administered to students during the 1989 summer session at Cuyahoga Community College, Western Campus (Ohio) were evaluated. Results indicated that 49% of respondents preferred classes meeting twice each week, and 29% preferred…

  15. Bayesian Hierarchical Classes Analysis

    ERIC Educational Resources Information Center

    Leenen, Iwin; Van Mechelen, Iven; Gelman, Andrew; De Knop, Stijn

    2008-01-01

    Hierarchical classes models are models for "N"-way "N"-mode data that represent the association among the "N" modes and simultaneously yield, for each mode, a hierarchical classification of its elements. In this paper we present a stochastic extension of the hierarchical classes model for two-way two-mode binary data. In line with the original…

  16. Teaching Social Class

    ERIC Educational Resources Information Center

    Tablante, Courtney B.; Fiske, Susan T.

    2015-01-01

    Discussing socioeconomic status in college classes can be challenging. Both teachers and students feel uncomfortable, yet social class matters more than ever. This is especially true, given increased income inequality in the United States and indications that higher education does not reduce this inequality as much as many people hope. Resources…

  17. Cutting Class Harms Grades

    ERIC Educational Resources Information Center

    Taylor, Lewis A., III

    2012-01-01

    An accessible business school population of undergraduate students was investigated in three independent, but related studies to determine effects on grades due to cutting class and failing to take advantage of optional reviews and study quizzes. It was hypothesized that cutting classes harms exam scores, attending preexam reviews helps exam…

  18. Salusin-β as a powerful endogenous antidipsogenic neuropeptide

    PubMed Central

    Suzuki-Kemuriyama, Noriko; Nakano-Tateno, Tae; Tani, Yuji; Hirata, Yukio; Shichiri, Masayoshi

    2016-01-01

    Salusin-β is an endogenous parasympathomimetic peptide, predominantly localized to the hypothalamus and posterior pituitary. Subcutaneously administered salusin-β (50 nmol/mouse) significantly increased water intake but did not affect locomotor activity or food intake. The salusin-β-induced increase in water intake was completely abrogated by pretreatment with muscarinic antagonist, atropine sulphate. In contrast, intracerebroventricular injection of salusin-β, at lower doses (10–100 fmol/mouse) caused a long-lasting decrease in water intake and locomotor activity throughout the entire dark phase of the diurnal cycle. Pre-injection of intracerebroventricular anti-salusin-β IgG completely abrogated the central salusin-β mediated suppression of water intake and locomotor activity. These results demonstrate contrasting actions of salusin-β in the control of water intake via the central and peripheral systems and highlight it as a potent endogenous antidipsogenic neuropeptide. PMID:26869388

  19. Exogenic and endogenic albedo and color patterns on Europa

    NASA Technical Reports Server (NTRS)

    Mcewen, A. S.

    1986-01-01

    New global and high-resolution multispectral mosaics of Europa have been produced from the Voyager imaging data. Photometric normalizations are based on multiple-image techniques that explicitly account for intrinsic albedo variations through pixel-by-pixel solutions. The exogenic color and albedo pattern on Europa is described by a second-order function of the cosine of the angular distance from the apex of orbital motion. On the basis of this second-order function and of color trends that are different on the leading and trailing hemispheres, the exogenic pattern is interpreted as being due to equilibrium between two dominant processes: (1) impact gardening and (2) magnetospheric interactions, including sulfur-ion implantation and sputtering redistribution. Removal of the model exogenic pattern in the mosaics reveals the endogenic variations, consisting of only two major units: darker (redder) and bright materials. Therefore Europa's visual spectral reflectivity is simple, having one continuous exogenic pattern and two discrete endogenic units.

  20. Interleukin-22 drives endogenous thymic regeneration in mice

    PubMed Central

    Dudakov, Jarrod A.; Hanash, Alan M.; Jenq, Robert R.; Young, Lauren F.; Ghosh, Arnab; Singer, Natalie V.; West, Mallory L.; Smith, Odette M.; Holland, Amanda M.; Tsai, Jennifer J.; Boyd, Richard L.; van den Brink, Marcel R.M.

    2013-01-01

    Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection or immunodepletion. The mechanisms governing this regeneration, however, remain poorly understood. Here we detail a framework of thymic regeneration centred on IL-22 and triggered by depletion of CD4+CD8+ double positive (DP) thymocytes. Intrathymic levels of IL-22 were increased following thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signalled through thymic epithelial cells (TECs) and promoted their proliferation and survival, was upregulated by radio-resistant RORγ(t)+CCR6+NKp46− lymphoid tissue-inducer cells (LTi) after thymic injury in an IL-23 dependent manner. Importantly, administration of IL-22 enhanced thymic recovery following total body irradiation (TBI). These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence. PMID:22383805

  1. Imaging transcription dynamics at endogenous genes in living Drosophila tissues.

    PubMed

    Yao, Jie; Zobeck, Katie L; Lis, John T; Webb, Watt W

    2008-07-01

    How transcription of individual genes is regulated in a single, intact, three-dimensionally organized cell nucleus remains mysterious. Recently, live cell imaging has become an essential tool to dissect the in vivo mechanisms of gene transcription. It not only examines functions of transcription factors at their gene targets within the chromatin context, but it also provides a non-disruptive approach for observing the dynamics of a transcription cycle in real time. However, the identification of any endogenous gene loci and their associated transcription factors remains technically difficult. Here, we describe the method of imaging the transcriptional dynamics of heat shock genes in Drosophila polytene chromosomes in living salivary gland tissues by multiphoton microscopy (MPM). This method has provided the experimental capability to visualize the assembly and dynamics of individual transcription factors and regulators and to dissect their functions at their endogenous gene targets in living cells. PMID:18586105

  2. Human herpes virus 6 and endogenous biotin in salivary glands.

    PubMed Central

    Green, M; Sviland, L; Taylor, C E; Peiris, M; McCarthy, A L; Pearson, A D; Malcolm, A J

    1992-01-01

    AIMS: To detect the presence of human herpes virus 6 (HHV6) and endogenous biotin in paraffin wax embedded and frozen salivary glands. METHODS: Two stage indirect and streptavidin-biotin immunoperoxidase techniques were used to visualise the antigens. RESULTS: HHV6 could not be shown in any of the tissues. However, considerable endogenous biotin antigenicity was detected in the glandular elements of the paraffin wax embedded material. CONCLUSIONS: Results obtained with avidin-biotin detection systems should be interpreted with caution, especially when glandular epithelium is being stained. This may apply to both immunoperoxidase and in situ hybridisation techniques. The use of an anti-biotin antibody as a standard control should be considered. Images PMID:1328329

  3. Endogenous Auxin and Ethylene in Pellia (Bryophyta) 1

    PubMed Central

    Thomas, Robert J.; Harrison, Marcia A.; Taylor, Jane; Kaufman, Peter B.

    1983-01-01

    The occurrence of endogenous indole-3-acetic acid and ethylene in bryophyte tissue was tentatively demonstrated using gas chromatography, high performance liquid chromatography, and double-standard isotope dilution techniques. Rapidly elongating stalks (or setae) of Pellia epiphylla (L.) Corda sporophytes contain approximately 2.5 to 2.9 micrograms per gram fresh weight of putative free IAA. Ethylene released by setae increases during growth from 0.027 to 0.035 nanoliter per seta per hour. Application of 5 microliters per liter ethylene inhibits auxin-stimulated elongation growth of this tissue, a result which suggests that both endogenously produced compounds act in tandem as natural growth modulators. Images Fig. 1 PMID:16663227

  4. Activation of endogenous neural stem cells for multiple sclerosis therapy.

    PubMed

    Michailidou, Iliana; de Vries, Helga E; Hol, Elly M; van Strien, Miriam E

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  5. [Proposal of endogenous anticholinergic hypothesis in Alzheimer disease].

    PubMed

    Hori, Koji; Konishi, Kimiko; Akita, Ryo; Tani, Masayuki; Tomioka, Hiroi; Kitajima, Yuka; Yokoyama, Sachiko; Azuma, Kazunari; Ikuse, Daisuke; Akashi, Norinao; Yuda, Hajime; Hachisu, Mitsugu

    2013-06-01

    We previously speculated that anticholinergic activity (AA) endogenously appeared in Alzheimer's disease (AD) and accelerated AD pathology. In this article we introduce manuscripts supporting the endogenous appearance of AA in AD and the acceleration of AD pathology. We speculate that acethylcholine (ACh) not only is related to cognitive functions but also regulates the inflammatory system. Therefore in AD, in which the ACh system is down-regulated, the hyperactivity of the inflammatory system may be caused and among cyctokines, substances having anticholinergic properties may appear. We also refer to a case in which serum anticholinergic activity (SAA) disappeared with the prescription of memantine (an antidementia agent that has the property of the N-methyl-D-aspartate (NMDA) receptor blocker) and speculate that because the hyperactivity of the inflammatory system occurs by way of the hyperactivity of NMDA receptor, memantine could abolish the AA. PMID:25069245

  6. Effect of irradiation and endogenous nucleases on rat liver chromatin

    SciTech Connect

    Gelderblom, D.; Smit, B.J.; Boehm, L.

    1984-08-01

    The assessment of the consequences of irradiation on chromatin is complicated by endogenous nucleases. Isolation and prolonged storage of rat liver nuclei in buffers containing divalent metal ions activates these enzymes and promotes the degradation of chromatin. Irradiation of rat liver nuclei to dose levels of 20,000 rad under conditions in which endogenous nucleases are inhibited and analysis of the irradiated chromatin by sucrose density gradient centrifugation gave no evidence for monosomes or oligosomes. When chromatin from irradiated nuclei was digested with micrococcal nuclease, the levels of monosomes and oligosomes were identical to those of micrococcal nuclease digests of unirradiated control nuclei. These results suggest that irradiation results in neither a direct fragmentation of linkers nor the sensitization of linkers for subsequent cleavage by micrococcal nuclease.

  7. Endogenous cost-effectiveness analysis and health care technology adoption.

    PubMed

    Jena, Anupam B; Philipson, Tomas J

    2013-01-01

    Increased health care spending has placed pressure on public and private payers to prioritize spending. Cost-effectiveness (CE) analysis is the main tool used by payers to prioritize coverage of new therapies. We argue that reimbursement based on CE is subject to a form of the "Lucas critique"; the goals of CE policies may not materialize when firms affected by the policies respond optimally to them. For instance, because 'costs' in CE analysis reflect prices set optimally by firms rather than production costs, observed CE levels will depend on how firm pricing responds to CE policies. Observed CE is therefore endogenous. When CE is endogenously determined, policies aimed at lowering spending and improving overall CE may paradoxically raise spending and lead to the adoption of more resource-costly treatments. We empirically illustrate whether this may occur using data on public coverage decisions in the United Kingdom. PMID:23202262

  8. Activation of endogenous neural stem cells for multiple sclerosis therapy

    PubMed Central

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  9. Endogenous pneumoconiosis: Analytical scanning electron microscopic analysis of a case.

    PubMed

    Galeotti, Jonathan; Sporn, Thomas A; Ingram, Peter; Wahidi, Momen M; Roggli, Victor L

    2016-01-01

    Pneumoconiosis is often considered a disease of the lung initiated by exposure to dust or other airborne particles, resulting in injury to the lungs. The term "endogenous pneumoconiosis" has been used in the literature to describe the deposition of compounds on the elastic fibers of the lung, usually in the setting of cardiac failure. In the case we present here, the patient aspirated a foreign body resulting in damage to the lung tissue and subsequent deposition of endogenous compounds on the elastic fibers of the pulmonary parenchyma and vasculature. We determined the composition of this mineral and mapped the distribution of elements using a combination of backscattered electron microscopy and energy dispersive spectrometry. PMID:27281119

  10. Long-distance transport of endogenous gibberellins in Arabidopsis

    PubMed Central

    Regnault, Thomas; Davière, Jean-Michel; Achard, Patrick

    2016-01-01

    Gibberellins (GAs) are phytohormones controlling major aspects of plant growth and development. Although previous studies suggested the existence of a transport of GAs in plants, the nature and properties associated with this transport were unknown. We recently showed through micrografting and biochemical approaches that the GA12 precursor is the chemical form of GA undergoing long-distance transport across plant organs in Arabidopsis. Endogenous GA12 moves through the plant vascular system from production sites to recipient tissues, in which GA12 can be converted to bioactive forms to support growth via the activation of GA-dependent processes. GAs are also essential to promote seed germination; hence GA biosynthesis mutants do not germinate without exogenous GA treatment. Our results suggest that endogenous GAs are not (or not sufficiently) transmitted to the offspring to successfully complete the germination under permissive conditions. PMID:26515330

  11. Photochemical control of endogenous ion channels and cellular excitability.

    PubMed

    Fortin, Doris L; Banghart, Matthew R; Dunn, Timothy W; Borges, Katharine; Wagenaar, Daniel A; Gaudry, Quentin; Karakossian, Movses H; Otis, Thomas S; Kristan, William B; Trauner, Dirk; Kramer, Richard H

    2008-04-01

    Light-activated ion channels provide a precise and noninvasive optical means for controlling action potential firing, but the genes encoding these channels must first be delivered and expressed in target cells. Here we describe a method for bestowing light sensitivity onto endogenous ion channels that does not rely on exogenous gene expression. The method uses a synthetic photoisomerizable small molecule, or photoswitchable affinity label (PAL), that specifically targets K+ channels. PALs contain a reactive electrophile, enabling covalent attachment of the photoswitch to naturally occurring nucleophiles in K+ channels. Ion flow through PAL-modified channels is turned on or off by photoisomerizing PAL with different wavelengths of light. We showed that PAL treatment confers light sensitivity onto endogenous K+ channels in isolated rat neurons and in intact neural structures from rat and leech, allowing rapid optical regulation of excitability without genetic modification. PMID:18311146

  12. Endogenous retroviruses: acquisition, amplification and taming of genome invaders.

    PubMed

    Dewannieux, Marie; Heidmann, Thierry

    2013-12-01

    Endogenous retroviruses are interspersed genomic elements that were generated after infectious retroviruses entered the germline of their host. They were initially identified as degenerate remnants of past infections, but new models of very recent or ongoing endogenisation are now emerging, allowing the real time investigation of the first steps of the coexistence between these elements and their host. Domestication of endogenous retroviruses involves several mechanisms, including transcriptional control of these elements and regulation of their mobility through the action of restriction factors. Recent studies also point towards an until-now unexpected role of the immune system for the control of these elements, even those that do not contain fully infectious copies. PMID:24004725

  13. Exogenous and endogenous shifts of attention in perihand space.

    PubMed

    Le Bigot, Nathalie; Grosjean, Marc

    2016-07-01

    While some studies have found that attentional orienting is altered in perihand space, most have not. One reason for such discrepancies may be related to the types of cues (uninformative and informative) that have been used, as they are known to induce different types of shifts of attention (exogenous and endogenous, respectively). To systematically address this question, two experiments were performed in which an uninformative peripheral cue (Experiment 1) or an informative central cue (Experiment 2) preceded a peripheral target with a short (100-150 ms) stimulus-onset asynchrony. Participants performed the task with their left hand, right hand, both hands, or no hands near the display. Cueing effects were obtained in both experiments, but they were only modulated by hand position in Experiment 1, with larger effects observed in the right- and both-hand conditions. These findings suggest that exogenous attention shifts are affected by hand proximity, while endogenous shifts are not. PMID:26134543

  14. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    EPA Science Inventory

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  15. Stochastic resonance in neuron models: Endogenous stimulation revisited

    NASA Astrophysics Data System (ADS)

    Plesser, Hans E.; Geisel, Theo

    2001-03-01

    The paradigm of stochastic resonance (SR)-the idea that signal detection and transmission may benefit from noise-has met with great interest in both physics and the neurosciences. We investigate here the consequences of reducing the dynamics of a periodically driven neuron to a renewal process (stimulation with reset or endogenous stimulation). This greatly simplifies the mathematical analysis, but we show that stochastic resonance as reported earlier occurs in this model only as a consequence of the reduced dynamics.

  16. Acute allograft rejection and immunosuppression: influence on endogenous melatonin secretion.

    PubMed

    Cardell, Markus; Jung, Florian Johannes; Zhai, Wei; Hillinger, Sven; Welp, Andre; Manz, Bernhard; Weder, Walter; Korom, Stephan

    2008-04-01

    Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo. Exogenous high-dose melatonin therapy exerted an immunosuppressive effect, abrogating acute rejection (AR), significantly prolonging transplant survival. Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft transplantation (Tx), was investigated during the AR response and under standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and rapamycin (RPM). Recipients of syngeneic transplants, and recipients of allogeneic grafts, either untreated or receiving immunosuppressive therapy constituted the experimental groups. Endogenous circadian melatonin levels were measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA) procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr; light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the challenge with a perfused allograft or the AR response influenced endogenous melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05), 14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx, as compared with naïve animals (155 +/- 25.8 pg/mL). In contrast, treatment with RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2 pg/mL; P < 0.001), compared with naïve animals (155 +/- 25.8 pg/mL). These findings imply a robust nature of the endogenous circadian melatonin secretion kinetics, even against the background of profound allogeneic stimuli. Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs. Further studies are necessary to disclose the long-term effect of immunosuppressive therapy on circadian melatonin secretion in transplant recipients. PMID:18339121

  17. Endogenous bacterial endophthalmitis masquerading as an intraocular tumor

    PubMed Central

    Salvetti, Anna Paola; Pellegrini, Marco; Bottoni, Ferdinando; Staurenghi, Giovanni

    2015-01-01

    A 40-year-old female patient referred for a possible intraocular tumor was found to have an endogenous bacterial endophthalmitis in her right eye. Fundus examination revealed an amelanotic dome shaped choroidal mass and an exudative retinal detachment. Enhanced Depth Imaging-Optical Coherence Tomography (EDI-OCT), fundus autofluorescence (FAF) and ultrasounds were suggestive of a possible choroidal melanoma. A multimodal imaging approach and a thorough anamnesis were instrumental in establishing the correct diagnosis. PMID:26949365

  18. Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis.

    PubMed

    Antoon, James W; Hernandez, Michelle L; Roehrs, Phillip A; Noah, Terry L; Leigh, Margaret W; Byerley, Julie S

    2016-03-01

    Pulmonary alveolar proteinosis (PAP) is an under-reported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti-granulocyte-macrophage colony-stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non-specific interstitial pneumonitis preceding the development of PAP. PMID:25103284

  19. Endogenous Protease Nexin-1 Protects against Cerebral Ischemia

    PubMed Central

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin’s endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1−/− mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

  20. Endogenous protease nexin-1 protects against cerebral ischemia.

    PubMed

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

  1. Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.

    PubMed

    Huang, Jeffrey K; Fancy, Stephen P J; Zhao, Chao; Rowitch, David H; Ffrench-Constant, Charles; Franklin, Robin J M

    2011-10-01

    Regeneration of myelin sheaths (remyelination) after central nervous system demyelination is important to restore saltatory conduction and to prevent axonal loss. In multiple sclerosis, the insufficiency of remyelination leads to the irreversible degeneration of axons and correlated clinical decline. Therefore, a regenerative strategy to encourage remyelination may protect axons and improve symptoms in multiple sclerosis. We highlight recent studies on factors that influence endogenous remyelination and potential promising pharmacological targets that may be considered for enhancing central nervous system remyelination. PMID:21904791

  2. A rapid and general assay for monitoring endogenous gene modification.

    PubMed

    Guschin, Dmitry Y; Waite, Adam J; Katibah, George E; Miller, Jeffrey C; Holmes, Michael C; Rebar, Edward J

    2010-01-01

    The development of zinc finger nucleases for targeted gene modification can benefit from rapid functional assays that directly quantify activity at the endogenous target. Here we describe a simple procedure for quantifying mutations that result from DNA double-strand break repair via non-homologous end joining. The assay is based on the ability of the Surveyor nuclease to selectively cleave distorted duplex DNA formed via cross-annealing of mutated and wild-type sequence. PMID:20680839

  3. Licensing endogenous cost-reduction in a differentiated Stackelberg model

    NASA Astrophysics Data System (ADS)

    Ferreira, Flávio; Bode, Oana R.

    2013-02-01

    In this paper we consider a differentiated Stackelberg model, when the leader firm engages in an R&D process that gives an endogenous cost-reducing innovation. The aim is to study the licensing of the cost-reduction by a two-part tariff. By using comparative static analysis, we conclude that the degree of the differentiation of the goods plays an important role in the results. We also do a direct comparison between our model and Cournot duopoly model.

  4. Endogenous galectin-1 exerts tonic inhibition on experimental arthritis.

    PubMed

    Iqbal, Asif J; Cooper, Dianne; Vugler, Alexander; Gittens, Beatrice R; Moore, Adrian; Perretti, Mauro

    2013-07-01

    Little is known about the role(s) of endogenous galectin-1 (Gal-1) in arthritis. In this study we queried whether antiarthritic functions for this effector of endogenous anti-inflammation could be unveiled by studying collagen-induced arthritis in Gal-1(-/-) mice. Gal-1(-/-) and C57BL/6J [wild-type (WT)] mice received an immunization of chicken type II collagen (CII) in CFA followed by a booster on day 21, which consisted of CII in IFA. Animals were monitored for signs of arthritis from day 14 onward. Clinical and histological signs of arthritis were recorded, and humoral and cellular immune responses against CII were analyzed. A distinct disease penetrance was apparent, with ~ 70% of Gal-1(-/-) mice developing arthritis compared with ~ 50% in WT animals. Gal-1(-/-) mice also exhibited an accelerated disease onset and more severe arthritis characterized by significantly elevated clinical scores. Postmortem analyses (day 42) revealed higher levels of IgG1 and IgG2b anti-CII Ig isotypes in the serum of Gal-1 null animals compared with WT. Finally, T cell responses following ex vivo stimulation with CII revealed a greater degree of proliferation in T cells of Gal-1(-/-) mice compared with WT, which was associated with increased production of IL-17 and IL-22. These data suggest the novel idea that endogenous Gal-1 is an inhibitory factor in the development of arthritis affecting disease severity. We have also highlighted the importance of endogenous Gal-1 in regulating T cell reactivity during experimental arthritis. PMID:23720814

  5. Characteristics of family functioning in patients with endogenous monopolar depression.

    PubMed

    Saeki, Toshinari; Asukai, Nozomu; Miyake, Yuko; Miguchi, Masahiro; Yamawaki, Shigeto

    2002-06-01

    The purpose of the study was to investigate dysfunctions in families with a member suffering from endogenous monopolar depression during the acute phase by means of a case-control study, and to consider the possibilities of psychiatric intervention for families with a patient in the course of monopolar depression. Twenty patients with monopolar depression during the acute phase and family members living in the same household (Depressive families) were compared with twenty-seven non-clinical college students and their family members (Control families) with regard to family functioning assessed by the Family Assessment Device (FAD). Depressive families reported significantly worse family functioning than Control families, especially in three areas: Problem Solving, Communication, and General Functioning. Members of Depressive families also perceived their family functioning to be significantly poorer than that of Control families, in the areas of Problem Solving, Communication, Roles, Affective Responsiveness, Affective Involvement and General Functioning, which yielded the same result as a comparison between depressive couples and control couples. The pattern of family dysfunction that was found in the present study, especially in the three areas of family functioning, Problem Solving, Communication, and General Functioning, emphasizes the importance of appropriate family intervention to improve the family's competence in problem solving and to promote better communication in the family during the acute phase of endogenous monopolar depression. Additionally such family dysfunction has been similarly observed in North American studies, indicating that diverse problems emerge beyond differences in the cultural background of families containing a patient with endogenous monopolar depression. PMID:12164346

  6. Drawing a fine line on endogenous retroelement activity

    PubMed Central

    Castro-Diaz, Nathaly; Friedli, Marc; Trono, Didier

    2015-01-01

    Endogenous retroelements (EREs) are essential motors of evolution yet require careful control to prevent genomic catastrophes, notably during the vulnerable phases of epigenetic reprogramming that occur immediately after fertilization and in germ cells. Accordingly, a variety of mechanisms restrict these mobile genetic units. Previous studies have revealed the importance of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor, KAP1, in the early embryonic silencing of endogenous retroviruses and so-called SVAs, but the implication of this transcriptional repression system in the control of LINE-1, the only known active autonomous retrotransposon in the human genome, was thought to be marginal. Two recent studies straighten the record by revealing that the KRAB/KAP system is key to the control of L1 in embryonic stem (ES) cells, and go further in demonstrating that DNA methylation and KRAB/KAP1-induced repression contribute to this process in an evolutionally dynamic fashion. These results shed light on the delicate equilibrium between higher vertebrates and endogenous retroelements, which are not just genetic invaders calling for strict control but rather a constantly renewed and nicely exploitable source of evolutionary potential. PMID:26442176

  7. Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

    PubMed Central

    Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H.; Konrad, Robert J.; Angelin, Bo

    2016-01-01

    Objective Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. Research design and methods We used a sensitive and specific dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. Results In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. Conclusions In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency. PMID:26866603

  8. The role of the endogenous opiates in zinc deficiency anorexia.

    PubMed

    Essatara, M B; Morley, J E; Levine, A S; Elson, M K; Shafer, R B; McClain, C J

    1984-03-01

    Anorexia is a major symptom of zinc deficiency, but the mechanism(s) for this anorexia are poorly defined. Recent studies have suggested an integral role for endogenous opiate peptides in appetite regulation. Dynorphin, a leucine-enkephalin containing opiate peptide, is a potent inducer of spontaneous feeding. In this study we showed that zinc deficient animals were relatively resistant to dynorphin-induced feeding. Measurement of dynorphin levels using a highly sensitive radioimmunoassay showed that zinc deficient animals had lower levels of dynorphin in the hypothalamus than did ad lib fed animals, with weight restricted animals having intermediate values. [3H]-naloxone binding was significantly increased to isolated brain membranes from zinc deficient animals using 1 nM unlabeled naloxone when compared to ad lib fed controls with the weight restricted animals again having intermediate values. These data suggest that abnormalities in endogenous opiate regulation of appetite may well play a role in the anorexia of zinc deficiency. The effects of zinc deficiency on endogenous opiate action appear to include alterations in receptor affinity, a post-receptor defect and alterations in the synthesis and/or release of dynorphin. PMID:6146993

  9. Endogenous galactose formation in galactose-1-phosphate uridyltransferase deficiency.

    PubMed

    Schadewaldt, Peter; Kamalanathan, Loganathan; Hammen, Hans-Werner; Kotzka, Jorg; Wendel, Udo

    2014-12-01

    Patients with classical galactosaemia (galactose-1-phosphate uridyltransferase (GALT) deficiency) manifest clinical complications despite strict dietary galactose restriction. Therefore the significance of endogenous galactose production has been assessed. Previous in vivo studies primarily focused on patients homozygous for the most common genetic variant Q188R but little is known about other genetic variants. In the present study the endogenous galactose release in a group of non-Q188R homozygous galactosaemic patients (n = 17; 4-34 years) exhibiting comparably low residual GALT activity in red blood cells was investigated. Primed continuous infusion studies with D-[1-(13)C]galactose as substrate were conducted under post-absorptive conditions and in good metabolic control. The results demonstrate that all patients exhibiting residual GALT activity of <1.5% of control showed a comparable pathological pattern of increased endogenous galactose release irrespective of the underlying genetic variations. Possible implications of the findings towards a more differentiated dietary regimen in galactosaemia are discussed. PMID:25268296

  10. Two-Stage Bayesian Model Averaging in Endogenous Variable Models.

    PubMed

    Lenkoski, Alex; Eicher, Theo S; Raftery, Adrian E

    2014-01-01

    Economic modeling in the presence of endogeneity is subject to model uncertainty at both the instrument and covariate level. We propose a Two-Stage Bayesian Model Averaging (2SBMA) methodology that extends the Two-Stage Least Squares (2SLS) estimator. By constructing a Two-Stage Unit Information Prior in the endogenous variable model, we are able to efficiently combine established methods for addressing model uncertainty in regression models with the classic technique of 2SLS. To assess the validity of instruments in the 2SBMA context, we develop Bayesian tests of the identification restriction that are based on model averaged posterior predictive p-values. A simulation study showed that 2SBMA has the ability to recover structure in both the instrument and covariate set, and substantially improves the sharpness of resulting coefficient estimates in comparison to 2SLS using the full specification in an automatic fashion. Due to the increased parsimony of the 2SBMA estimate, the Bayesian Sargan test had a power of 50 percent in detecting a violation of the exogeneity assumption, while the method based on 2SLS using the full specification had negligible power. We apply our approach to the problem of development accounting, and find support not only for institutions, but also for geography and integration as development determinants, once both model uncertainty and endogeneity have been jointly addressed. PMID:24223471

  11. A revised nomenclature for transcribed human endogenous retroviral loci

    PubMed Central

    2011-01-01

    Background Endogenous retroviruses (ERVs) and ERV-like sequences comprise 8% of the human genome. A hitherto unknown proportion of ERV loci are transcribed and thus contribute to the human transcriptome. A small proportion of these loci encode functional proteins. As the role of ERVs in normal and diseased biological processes is not yet established, transcribed ERV loci are of particular interest. As more transcribed ERV loci are likely to be identified in the near future, the development of a systematic nomenclature is important to ensure that all information on each locus can be easily retrieved. Results Here we present a revised nomenclature of transcribed human endogenous retroviral loci that sorts loci into groups based on Repbase classifications. Each symbol is of the format ERV + group symbol + unique number. Group symbols are based on a mixture of Repbase designations and well-supported symbols used in the literature. The presented guidelines will allow newly identified loci to be easily incorporated into the scheme. Conclusions The naming system will be employed by the HUGO Gene Nomenclature Committee for naming transcribed human ERV loci. We hope that the system will contribute to clarifying a certain aspect of a sometimes confusing nomenclature for human endogenous retroviruses. The presented system may also be employed for naming transcribed loci of human non-ERV repeat loci. PMID:21542922

  12. Endogenous Hepadnaviruses in the Genome of the Budgerigar (Melopsittacus undulatus) and the Evolution of Avian Hepadnaviruses

    PubMed Central

    Cui, Jie

    2012-01-01

    Endogenous hepadnaviruses (hepatitis B viruses [HBVs]) were recently discovered in the genomes of passerine birds. We mined six additional avian genomes and discovered multiple copies of endogenous HBVs in the budgerigar (order Psittaciformes), designated eBHBV. A phylogenetic analysis reveals that the endogenous hepadnaviruses are more diverse than their exogenous counterparts and that the endogenous and exogenous hepadnaviruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events. PMID:22553337

  13. Endogenous hepadnaviruses in the genome of the budgerigar (Melopsittacus undulatus) and the evolution of avian hepadnaviruses.

    PubMed

    Cui, Jie; Holmes, Edward C

    2012-07-01

    Endogenous hepadnaviruses (hepatitis B viruses [HBVs]) were recently discovered in the genomes of passerine birds. We mined six additional avian genomes and discovered multiple copies of endogenous HBVs in the budgerigar (order Psittaciformes), designated eBHBV. A phylogenetic analysis reveals that the endogenous hepadnaviruses are more diverse than their exogenous counterparts and that the endogenous and exogenous hepadnaviruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events. PMID:22553337

  14. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Clear channels; Class A, Class B and Class D stations. 73.25 Section 73.25 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES AM Broadcast Stations § 73.25 Clear channels; Class A, Class B and Class D stations. The frequencies in...

  15. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Clear channels; Class A, Class B and Class D stations. 73.25 Section 73.25 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES AM Broadcast Stations § 73.25 Clear channels; Class A, Class B and Class D stations. The frequencies in...

  16. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Clear channels; Class A, Class B and Class D stations. 73.25 Section 73.25 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES AM Broadcast Stations § 73.25 Clear channels; Class A, Class B and Class D stations. The frequencies in...

  17. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Clear channels; Class A, Class B and Class D stations. 73.25 Section 73.25 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES AM Broadcast Stations § 73.25 Clear channels; Class A, Class B and Class D stations. The frequencies in...

  18. 47 CFR 73.25 - Clear channels; Class A, Class B and Class D stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Clear channels; Class A, Class B and Class D stations. 73.25 Section 73.25 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES AM Broadcast Stations § 73.25 Clear channels; Class A, Class B and Class D stations. The frequencies in...

  19. Endogenous technological and demographic change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    Pande, Saket; Ertsen, Maurits; Sivapalan, Murugesu

    2014-05-01

    The ancient civilization in the Indus Valley civilization dispersed under extreme dry conditions; there are indications that the same holds for many other ancient societies. Even contemporary societies, such as the one in Murrumbidgee river basin in Australia, have started to witness a decline in overall population under increasing water scarcity. Hydroclimatic change may not be the sole predictor of the fate of contemporary societies in water scarce regions and many critics of such (perceived) hydroclimatic determinism have suggested that technological change may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. To study the role of technological change on the dynamics of coupled human-water systems, we develop a simple overlapping-generations model of endogenous technological and demographic change. We model technological change as an endogenous process that depends on factors such as the investments that are (endogenously) made in a society, the (endogenous) diversification of a society into skilled and unskilled workers, a society's patience in terms of its present consumption vs. future consumption, production technology and the (endogenous) interaction of all of these factors. In the model the population growth rate is programmed to decline once consumption per capita crosses a "survival" threshold. This means we do not treat technology as an exogenous random sequence of events, but instead assume that it results (endogenously) from societal actions. The model demonstrates that technological change may indeed ameliorate the effects of increasing water scarcity but typically it does so only to a certain extent. It is possible that technological change may allow a society to escape the effect of increasing water scarcity, leading to a (super)-exponential rise in technology and population. However, such cases require the rate of success of investment in technological advancement to be high. In other

  20. Endogenous technological and population change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    Pande, S.; Ertsen, M.; Sivapalan, M.

    2013-11-01

    The ancient civilization in the Indus Valley civilization dispersed under extreme dry conditions; there are indications that the same holds for many other ancient societies. Even contemporary societies, such as the one in Murrumbidgee river basin in Australia, have started to witness a decline in overall population under increasing water scarcity. Hydroclimatic change may not be the sole predictor of the fate of contemporary societies in water scarce regions and many critics of such (perceived) hydroclimatic determinism have suggested that technological change may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. To study the role of technological change on the dynamics of coupled human-water systems, we develop a simple overlapping-generations model of endogenous technological and demographic change. We model technological change as an endogenous process that depends on factors such as the investments that are (endogenously) made in a society, the (endogenous) diversification of a society into skilled and unskilled workers, a society's patience in terms of its present consumption vs. future consumption, production technology and the (endogenous) interaction of all of these factors. In the model the population growth rate is programmed to decline once consumption per capita crosses a "survival" threshold. This means we do not treat technology as an exogenous random sequence of events, but instead assume that it results (endogenously) from societal actions. The model demonstrates that technological change may indeed ameliorate the effects of increasing water scarcity but typically it does so only to a certain extent. It is possible that technological change may allow a society to escape the effect of increasing water scarcity, leading to a (super)-exponential rise in technology and population. However, such cases require the rate of success of investment in technological advancement to be high. In other

  1. Social Class Dialogues and the Fostering of Class Consciousness

    ERIC Educational Resources Information Center

    Madden, Meredith

    2015-01-01

    How do critical pedagogies promote undergraduate students' awareness of social class, social class identity, and social class inequalities in education? How do undergraduate students experience class consciousness-raising in the intergroup dialogue classroom? This qualitative study explores undergraduate students' class consciousness-raising in an…

  2. Universality classes of inflation

    SciTech Connect

    Roest, Diederik

    2014-01-01

    We investigate all single-field, slow-roll inflationary models whose slow-roll parameters scale as 1/N in the limit of a large number of e-folds N. We proof that all such models belong to two universality classes, characterised by a single parameter. One class contains small field models like hilltop inflation, while the other class consists of large field models like chaotic inflation. We give the leading expressions for the spectral index and tensor-to-scalar ratio r, which are universal for each class, plus subleading corrections for a number of models. This predicts r either to be unobservably small, r < 0.01, or close to the present observational limit, r ≈ 0.07.

  3. Aerobic Conditioning Class.

    ERIC Educational Resources Information Center

    Johnson, Neil R.

    1980-01-01

    An aerobic exercise class that focuses on the conditioning of the cardiovascular and muscular systems is presented. Students complete data cards on heart rate, pulse, and exercises to be completed during the forty minute course. (CJ)

  4. Teaching Heterogeneous Classes.

    ERIC Educational Resources Information Center

    Millrood, Radislav

    2002-01-01

    Discusses an approach to teaching heterogeneous English-as-a-Second/Foreign-Language classes. Draws on classroom research data to describe the features of a success-building lesson context. (Author/VWL)

  5. Automatic classification of endogenous seismic sources within a landslide body using random forest algorithm

    NASA Astrophysics Data System (ADS)

    Provost, Floriane; Hibert, Clément; Malet, Jean-Philippe; Stumpf, André; Doubre, Cécile

    2016-04-01

    Different studies have shown the presence of microseismic activity in soft-rock landslides. The seismic signals exhibit significantly different features in the time and frequency domains which allow their classification and interpretation. Most of the classes could be associated with different mechanisms of deformation occurring within and at the surface (e.g. rockfall, slide-quake, fissure opening, fluid circulation). However, some signals remain not fully understood and some classes contain few examples that prevent any interpretation. To move toward a more complete interpretation of the links between the dynamics of soft-rock landslides and the physical processes controlling their behaviour, a complete catalog of the endogeneous seismicity is needed. We propose a multi-class detection method based on the random forests algorithm to automatically classify the source of seismic signals. Random forests is a supervised machine learning technique that is based on the computation of a large number of decision trees. The multiple decision trees are constructed from training sets including each of the target classes. In the case of seismic signals, these attributes may encompass spectral features but also waveform characteristics, multi-stations observations and other relevant information. The Random Forest classifier is used because it provides state-of-the-art performance when compared with other machine learning techniques (e.g. SVM, Neural Networks) and requires no fine tuning. Furthermore it is relatively fast, robust, easy to parallelize, and inherently suitable for multi-class problems. In this work, we present the first results of the classification method applied to the seismicity recorded at the Super-Sauze landslide between 2013 and 2015. We selected a dozen of seismic signal features that characterize precisely its spectral content (e.g. central frequency, spectrum width, energy in several frequency bands, spectrogram shape, spectrum local and global maxima

  6. Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase-deficient rats

    SciTech Connect

    Gunnison, A.F.; Sellakumar, A.; Currie, D.; Snyder, E.A.

    1987-01-01

    We report on the distribution, metabolism, and toxicity of sulfite in the respiratory tract and other tissues of rats exposed to endogenously generated sulfite or to inhaled sulfur dioxide (SO/sub 2/). Graded sulfite oxidase deficiency was induced in several groups of rats by manipulating their tungsten to molybdenum intake ratio. Endogenously generated sulfite and S-sulfonate compounds (a class of sulfite metabolite) accumulated in the respiratory tract tissues and in the plasma of these rats in inverse proportion to hepatic sulfite oxidase activity. In contrast to this systemic mode of exposure, sulfite exposure of normal, sulfite oxidase-competent rats via inhaled SO/sub 2/ (10 and 30 ppm) was restricted to the airways. Minor pathological changes consisting of epithelial hyperplasia, mucoid degeneration, and desquamation of epithelium were observed only in the tracheas and bronchi of the rats inhaling SO/sub 2/, even though the concentration of sulfite plus S-sulfonates in the tracheas and bronchi of these rats was considerably lower than that in the endogenously exposed rats. We attribute this histological damage to hydrogen ions stemming from inhaled SO/sub 2/, not to the sulfite/bisulfite ions that are also a product of inhaled SO/sub 2/. In addition to the lungs and trachea, all other tissues examined, except the testes, appeared to be refractory to high concentrations of endogenously generated sulfite. The testes of grossly sulfite oxidase-deficient rats were severely atrophied and devoid of spermatogenic cells.

  7. Endogenous technological and demographic change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    Pande, S.; Ertsen, M.; Sivapalan, M.

    2013-12-01

    Many ancient civilizations such as the Indus Valley civilization dispersed under extreme dry conditions. Even contemporary societies such as the one in Murrumbidgee river basin, Australia, have started to witness a decline in overall population under increasing water scarcity. Skeptics of hydroclimatic determinism have often cautioned against the use of hydroclimatic change as the sole predictor of the fate of contemporary societies in water scarce regions by suggesting that technological change may ameliorate the effects of increasing water scarcity. We here develop a simple overlapping generations model of endogenous technological and demographic change. It models technological change not as an exogenous random sequence of events but as an endogenous process (as is widely accepted in contemporary literature) that depends on factors such as the investments that are (endogenously) made in a society, the endogenous diversification of a society into skilled and unskilled workers, individuals' patience in terms of its present consumption versus future consumption, the production technology and the (endogenous) interaction of these factors. The population growth rate is modeled to decline once consumption per capita crosses a ';survival' threshold. The model demonstrates that technological change may ameliorate the effects of increasing water scarcity but only to a certain extent in many cases. It is possible that technological change may allow a society to escape the effect of increasing water society, leading to an exponential rise in technology and population. However, such cases require that the rate of success of investment in technological advancement is high. In other more realistic cases of technological success, we find that endogenous technology change has an effect delaying the peak of population before it starts to decline. While the model is a rather simple model of societal growth, it is capable of replicating (not to scale) patterns of technological

  8. A comparative assessment of endogenous water institutional change

    NASA Astrophysics Data System (ADS)

    Pande, Saket; Ersten, Maurits

    2013-04-01

    This paper builds the theory of endogenous institutional change, first proposed by Greif and Laitin (2004), for water scarce regions in context of water institutions. The current emphasis on environmental change, including hydrological change, largely ignores the adaptation of human societies to change. Humans have mostly been considered as boundary conditions or parameters of the dynamics of hydrological change and are not considered as conduits of feedbacks. Nonetheless, the dynamical representation of hydrological change with feedbacks between various components of a system is assuring since it is reminiscent of processual ecological anthropology(Orlove, 1980), except that individual decision making is absent. This paper proposes to consider selected dryland basins of the world, to conceptualize proxies of water relevant socio-economic organisation, such as spatial scales of upstream-downstream cooperation in water use, synthesized over time and then proposes a comparative assessment to test regularities predicted by an extension of river game theory (Ambec and Ehlers, 2008; van der Brink et al, 2012) to endogenous institutional change. References: Orlove, B. S. (1980). Ecological Anthropology. Annual Review of Anthropology, Vol. 9 (1980), pp. 235-273. Greif. A. and D. D. Laitin (2004). A Theory of Endogenous Institutional Change. American Political Science Review, Vol. 98, No. 4 November 2004. Ambec, S. and L. Ehlers (2008). Sharing a river amongst satiable agents. Games and Economic Behavior, 64, 35-50. Van der Brink, G. van der Laan and N. Moes (2012). Fair agreements for sharing international rivers with multiple springs and externalities. Journal of Environmental Economics and Management, 63, 388-403.

  9. Harnessing endogenous growth factor activity modulates stem cell behavior

    PubMed Central

    Hudalla, Gregory A.; Kouris, Nicholas A.; Koepsel, Justin T.; Ogle, Brenda M.; Murphy, William L.

    2014-01-01

    The influence of specific serum-borne biomolecules (e.g. heparin) on growth factor-dependent cell behavior is often difficult to elucidate in traditional cell culture due to the random, non-specific nature of biomolecule adsorption from serum. We hypothesized that chemically well-defined cell culture substrates could be used to study the influence of sequestered heparin on human mesenchymal stem cell (hMSC) behavior. Specifically, we used bio-inert self-assembled monolayers (SAMs) chemically modified with a bioinspired heparin-binding peptide (termed “HEPpep”) and an integrin-binding peptide (RGDSP) as stem cell culture substrates. Our results demonstrate that purified heparin binds to HEPpep SAMs in a dose-dependent manner, and serum-borne heparin binds specifically and in a dose-dependent manner to HEPpep SAMs. These heparin-sequestering SAMs enhance hMSC proliferation by amplifying endogenous fibroblast growth factor (FGF) signaling, and enhance hMSC osteogenic differentiation by amplifying endogenous bone morphogenetic protein (BMP) signaling. The effects of heparin-sequestering are similar to the effects of supraphysiologic concentrations of recombinant FGF-2. hMSC phenotype is maintained over multiple population doublings on heparin-sequestering substrates in growth medium, while hMSC osteogenic differentiation is enhanced in a bone morphogenetic protein-dependent manner on the same substrates during culture in osteogenic induction medium. Together, these observations demonstrate that the influence of the substrate on stem cell phenotype is sensitive to the culture medium formulation. Our results also demonstrate that enhanced hMSC proliferation can be spatially localized by patterning the location of HEPpep on the substrate. Importantly, the use of chemically well-defined SAMs in this study eliminated the confounding factor of random, non-specific biomolecule adsorption, and identified serum-borne heparin as a key mediator of hMSC response to endogenous

  10. Sex-Dependent Influence of Endogenous Estrogen in Pulmonary Hypertension

    PubMed Central

    Mair, Kirsty M.; Wright, Audrey F.; Duggan, Nicholas; Rowlands, David J.; Hussey, Martin J.; Roberts, Sonia; Fullerton, Josephine; Nilsen, Margaret; Loughlin, Lynn; Thomas, Matthew

    2014-01-01

    Rationale: The incidence of pulmonary arterial hypertension is greater in women, suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males, exogenously administered estrogen can protect against pulmonary hypertension (PH). However, in models that display female susceptibility, estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and sex in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH: the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of sex on pulmonary expression of aromatase in these models and in lungs from patients with pulmonary arterial hypertension. Measurements and Main Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was caused by reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor α also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased bone morphogenetic protein receptor 2 and Id1 expression compared with male. Anastrozole treatment reversed the impaired bone morphogenetic protein receptor 2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared with male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential. PMID:24956156