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Sample records for class ii-related endogenous

  1. 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

  2. Alcoholytic cleavage of polyhydroxyalkanoate chains by class IV synthases induced by endogenous and exogenous ethanol.

    PubMed

    Hyakutake, Manami; Tomizawa, Satoshi; Mizuno, Kouhei; Abe, Hideki; Tsuge, Takeharu

    2014-02-01

    Polyhydroxyalkanoate (PHA)-producing Bacillus strains express class IV PHA synthase, which is composed of the subunits PhaR and PhaC. Recombinant Escherichia coli expressing PHA synthase from Bacillus cereus strain YB-4 (PhaRCYB-4) showed an unusual reduction of the molecular weight of PHA produced during the stationary phase of growth. Nuclear magnetic resonance analysis of the low-molecular-weight PHA revealed that its carboxy end structure was capped by ethanol, suggesting that the molecular weight reduction was the result of alcoholytic cleavage of PHA chains by PhaRCYB-4 induced by endogenous ethanol. This scission reaction was also induced by exogenous ethanol in both in vivo and in vitro assays. In addition, PhaRCYB-4 was observed to have alcoholysis activity for PHA chains synthesized by other synthases. The PHA synthase from Bacillus megaterium (PhaRCBm) from another subgroup of class IV synthases was also assayed and was shown to have weak alcoholysis activity for PHA chains. These results suggest that class IV synthases may commonly share alcoholysis activity as an inherent feature.

  3. 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.

  4. 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

  5. Sindbis virus induces the production of a novel class of endogenous siRNAs in Aedes aegypti mosquitoes.

    PubMed

    Adelman, Z N; Anderson, M A E; Liu, M; Zhang, L; Myles, K M

    2012-06-01

    Small RNA regulatory pathways are used to control the activity of transposons, regulate gene expression and resist infecting viruses. We examined the biogenesis of mRNA-derived endogenous short-interfering RNAs (endo-siRNAs) in the disease vector mosquito Aedes aegypti. Under standard conditions, mRNA-derived endo-siRNAs were produced from the bidirectional transcription of tail-tail overlapping gene pairs. Upon infection with the alphavirus, Sindbis virus (SINV), another class of mRNA-derived endo-siRNAs was observed. Genes producing SINV-induced endo-siRNAs were not enriched for overlapping partners or nearby genes, but were enriched for transcripts with long 3' untranslated regions. Endo-siRNAs from this class derived uniformly from the entire length of the target transcript, and were found to regulate the transcript levels of the genes from which they were derived. Strand-specific quantitative PCR experiments demonstrated that antisense strands of targeted mRNA genes were produced to exonic, but not intronic regions. Finally, small RNAs mapped to both sense and antisense strands of exon-exon junctions, suggesting double-stranded RNA precursors to SINV-induced endo-siRNAs may be synthesized from mature mRNA templates. These results suggest additional complexity in small RNA pathways and gene regulation in the presence of an infecting virus in disease vector mosquitoes.

  6. 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

  7. Endogenous galectin-1 enforces class I–restricted TCR functional fate decisions in thymocytes

    PubMed Central

    Liu, Scot D.; Whiting, Chan C.; Tomassian, Tamar; Pang, Mabel; Bissel, Stephanie J.; Baum, Linda G.; Mossine, Valeri V.; Poirier, Françoise; Huflejt, Margaret E.

    2008-01-01

    During thymocyte development, the T-cell receptor (TCR) can discriminate major histocompatibility complex (MHC)/peptide ligands over a narrow range of affinities and translate subtle differences into functional fate decisions. How small differences in TCR input are translated into absolute differences in functional output is unclear. We examined the effects of galectin-1 ablation in the context of class-I–restricted thymocyte development. Galectin-1 expression opposed TCR partial agonist-driven positive selection, but promoted TCR agonist-driven negative selection of conventional CD8+ T cells. Galectin-1 expression also promoted TCR agonist-driven CD8αα intestinal intraepithelial lymphocytes (IEL) development. Recombinant galectin-1 enhanced TCR binding to agonist/MHC complexes and promoted a negative-selection-signaling signature, reflected in intensified rapid and transient extracellular signal-regulated kinase (ERK) activation. In contrast, galectin-1 expression antagonized ERK activity in thymocytes undergoing positive selection. We propose that galectin-1 aids in discriminating TCR-directed fate decisions by promoting TCR binding to agonist/MHC complexes and enforcing agonist-driven signals, while opposing partial-agonist signals. In this way, galectin-1 widens the distinction between TCR-directed functional fate cues. PMID:18323414

  8. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection

    PubMed Central

    English, Luc; Chemali, Magali; Duron, Johanne; Rondeau, Christiane; Laplante, Annie; Gingras, Diane; Alexander, Diane; Leib, David; Norbury, Christopher; Lippé, Roger; Desjardins, Michel

    2013-01-01

    Viral proteins are usually processed by the ‘classical’ major histocompatibility complex (MHC) class I presentation pathway. Here we showed that although macrophages infected with herpes simplex virus type 1 (HSV-1) initially stimulated CD8+ T cells by this pathway, a second pathway involving a vacuolar compartment was triggered later during infection. Morphological and functional analyses indicated that distinct forms of autophagy facilitated the presentation of HSV-1 antigens on MHC class I molecules. One form of autophagy involved a previously unknown type of autophagosome that originated from the nuclear envelope. Whereas interferon-γ stimulated classical MHC class I presentation, fever-like hyperthermia and the pyrogenic cytokine interleukin 1β activated autophagy and the vacuolar processing of viral peptides. Viral peptides in autophagosomes were further processed by the proteasome, which suggests a complex interaction between the vacuolar and MHC class I presentation pathways. PMID:19305394

  9. Uracil excision by endogenous SMUG1 glycosylase promotes efficient Ig class switching and impacts on A:T substitutions during somatic mutation.

    PubMed

    Dingler, Felix A; Kemmerich, Kristin; Neuberger, Michael S; Rada, Cristina

    2014-07-01

    Excision of uracil introduced into the immunoglobulin loci by AID is central to antibody diversification. While predominantly carried out by the UNG uracil-DNA glycosylase as reflected by deficiency in immunoglobulin class switching in Ung(-/-) mice, the deficiency is incomplete, as evidenced by the emergence of switched IgG in the serum of Ung(-/-) mice. Lack of switching in mice deficient in both UNG and MSH2 suggested that mismatch repair initiated a backup pathway. We now show that most of the residual class switching in Ung(-/-) mice depends upon the endogenous SMUG1 uracil-DNA glycosylase, with in vitro switching to IgG1 as well as serum IgG3, IgG2b, and IgA greatly diminished in Ung(-/-) Smug1(-/-) mice, and that Smug1 partially compensates for Ung deficiency over time. Nonetheless, using a highly MSH2-dependent mechanism, Ung(-/-) Smug1(-/-) mice can still produce detectable levels of switched isotypes, especially IgG1. While not affecting the pattern of base substitutions, SMUG1 deficiency in an Ung(-/-) background further reduces somatic hypermutation at A:T base pairs. Our data reveal an essential requirement for uracil excision in class switching and in facilitating noncanonical mismatch repair for the A:T phase of hypermutation presumably by creating nicks near the U:G lesion recognized by MSH2.

  10. 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

  11. Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function

    PubMed Central

    1994-01-01

    To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS). PMID:7964466

  12. Presentation via the class I pathway by Leishmania amazonensis-infected macrophages of an endogenous leishmanial antigen to CD8+ T cells.

    PubMed

    Kima, P E; Ruddle, N H; McMahon-Pratt, D

    1997-08-15

    CD8+ T cells play a protective role in immunity to cutaneous leishmaniasis. However, it has been unclear how these cells execute this function, since results from several investigations attempting to demonstrate recognition of Leishmania-infected macrophages by CD8+ T cells have been contradictory. In this study, we report the generation of CD8+ T cell lines specific for GP46/M-2, a leishmanial Ag, previously shown to protectively immunize mice against a Leishmania amazonensis challenge. Using T cell cytolysis and IFN-gamma production to assess CD8+ T cell activation, we show that in addition to recognizing mammalian cells transfected with GP46/M-2, these CD8+ T cell lines also recognize macrophages infected with Leishmania amazonensis. MHC class I presentation of GP46/M-2 by infected macrophages can be blocked by treatment with brefeldin A and also by inhibitors of the cytosolic multicatalytic proteasome, N-acetyl-L-leucinyl-L-leucinal-L-norleucinal and N-acetyl-L-leucinyl-L-leucinylmethional. These results suggest that this leishmanial Ag is processed in the macrophage cytoplasm and is presented to CD8+ T cells via the classical pathway of MHC class I presentation. The relevance of these findings as they impact on our understanding of the biology of the parasite within the macrophage is discussed.

  13. 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

  14. 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

  15. Endogenous RNAi pathways in C. elegans.

    PubMed Central

    Billi, Allison C; Fischer, Sylvia E J; Kim, John K

    2014-01-01

    In addition to several hundred microRNAs, C. elegans produces thousands of other small RNAs targeting coding genes, pseudogenes, transposons, and other noncoding RNAs. Here we review what is currently known about these endogenous small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), providing an overview of their biogenesis, their associated protein factors, and their effects on mRNA dynamics and chromatin structure. Additionally, we describe how the molecular actions of these classes of endogenous small RNAs connect to their physiological roles in the organism. PMID:24816713

  16. 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

  17. [Endogenous venous thrombolysis].

    PubMed

    Porembskaya, O Ya; Khmelniker, S M; Shaidakov, E V

    2015-01-01

    Widely incorporated into vascular surgery pharmacological thrombolysis in treatment for deep vain thrombosis is fraught with a series of unsolved problems requiring further consideration. In spite of aggressive nature of treatment in a series of cases pharmacological thrombolysis sometimes turns out ineffective. Along with it, the results of experimental studies suggest a possibility of accelerating resorption of thrombotic masses and inhibiting remodelling of the venous wall by means of influencing effector cells of endogenous thrombolysis. A detailed study of the mechanisms of thrombolysis would make it possible to formulate strict criteria for carrying out pharmacological thrombolysis and to increase its efficacy. PMID:26355926

  18. [Genetics of endogenous psychoses].

    PubMed

    Zerbin-Rüdin, E

    1979-01-01

    As the endogeneous psychoses do not show a Mendelian mode of inheritance, empirical risk figures have to be calculated. They are heterogeneous and nurture as well as nature have a share in the manifestation of illness. The genetic basis of the schizophrenias is demonstrated by twin and adoption studies. The concordance rate in monozygotic twins is four times the rate in dizygotic twins. Schizophrenia is to be found in the biological families of schizophrenic adoptees but not in the adoptive families. However, despite their genetic identity, monozygotic twins do not show 100% concordance but 60% only. Nongenetic factors must be considered. Obviously they are nonspecific and vary between individuals. The same principles apply to the affective psychoses. At present research is most interested in the problem of heterogeneity. Do pure depressive and manic-depressive disease form one genetic entity, or two different ones, or have they in common part of their genetic basis? Some remarks on genetic counselling are made.

  19. Pushing the endogenous envelope

    PubMed Central

    Henzy, Jamie E.; Johnson, Welkin E.

    2013-01-01

    The majority of retroviral envelope glycoproteins characterized to date are typical of type I viral fusion proteins, having a receptor binding subunit associated with a fusion subunit. The fusion subunits of lentiviruses and alpha-, beta-, delta- and gammaretroviruses have a very conserved domain organization and conserved features of secondary structure, making them suitable for phylogenetic analyses. Such analyses, along with sequence comparisons, reveal evidence of numerous recombination events in which retroviruses have acquired envelope glycoproteins from heterologous sequences. Thus, the envelope gene (env) can have a history separate from that of the polymerase gene (pol), which is the most commonly used gene in phylogenetic analyses of retroviruses. Focusing on the fusion subunits of the genera listed above, we describe three distinct types of retroviral envelope glycoproteins, which we refer to as gamma-type, avian gamma-type and beta-type. By tracing these types within the ‘fossil record’ provided by endogenous retroviruses, we show that they have surprisingly distinct evolutionary histories and dynamics, with important implications for cross-species transmissions and the generation of novel lineages. These findings validate the utility of env sequences in contributing phylogenetic signal that enlarges our understanding of retrovirus evolution. PMID:23938755

  20. Endogenous Antibodies for Tumor Detection

    PubMed Central

    Rich, Barrie S.; Honeyman, Joshua N.; Darcy, David G.; Smith, Peter T.; Williams, Andrew R.; Lim, Irene Isabel P.; Johnson, Linda K.; Gönen, Mithat; Simon, Joel S.; LaQuaglia, Michael P.; Simon, Sanford M.

    2014-01-01

    The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies. PMID:24875800

  1. Endogenous Metabolism of Azotobacter agilis

    PubMed Central

    Sobek, J. M.; Charba, J. F.; Foust, W. N.

    1966-01-01

    Sobek, J. M. (University of Southwestern Louisiana, Lafayette), J. F. Charba, and W. N. Foust. Endogenous metabolism of Azotobacter agilis. J. Bacteriol. 92:687–695. 1966—Ribonucleic acid, deoxyribonucleic acid, cellular carbohydrate, and the cold trichloroacetic acid and acidic alcohol fractions of the cell do not appear to function as endogenous reserves for Azotobacter agilis. The immediate endogenous reserve of cells grown on glucose, acetate, or succinate was poly-β-hydroxybutyric acid (PHB). Viability of the cells during starvation was dependent upon the initial levels of PHB and the growth substrate. Cells with high initial PHB levels survived longer than cells with lower levels. Cells from succinate-grown cultures had lower PHB levels than cells from glucose-grown cultures, but were capable of maintaining their viability longer. Cellular protein may also serve as a secondary endogenous reserve substrate for this organism. PMID:5922542

  2. ENDOGENOUS RESPIRATION OF STAPHYLOCOCCUS AUREUS

    PubMed Central

    Ramsey, H. H.

    1962-01-01

    Ramsey, H. H. (Stanford University, Palo Alto, Calif.). Endogenous respiration of Staphylococcus aureus. J. Bacteriol. 83:507–514. 1962.—The endogenous respiration of Staphylococcus aureus is dependent upon the medium used to grow the cell suspension. Within wide ranges, the concentration of glucose in the medium has no effect upon subsequent endogenous respiration of the cells, but the concentration of amino acids in the medium, within certain limits, has a very marked effect. The total carbohydrate content of the cells does not decrease during endogenous respiration. As endogenous respiration proceeds, ammonia appears in the supernatant, and the concentration of glutamic acid in the free amino acid pool decreases. Organisms grown in the presence of labeled glutamic acid liberate labeled CO2 when allowed to respire without added substrate. The principal source of this CO2 is the free glutamate in the metabolic pool; its liberation is not suppressed by exogenous glucose or glutamate. With totally labeled cells, the free pool undergoes a rapid, but not total, depletion and remains at a low level for a long time. Activity of the protein fraction declines with time and shows the largest net decrease of all fractions. Exogenous glucose does not inhibit the release of labeled CO2 by totally labeled cells. Other amino acids in the free pool which can serve as endogenous substrates are aspartic acid and, to much lesser extents, glycine and alanine. The results indicate that both free amino acids and cellular protein may serve as endogenous substrates of S. aureus. PMID:14490204

  3. 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. PMID:26820249

  4. The Search for Endogenous Activators of the Aryl Hydrocarbon Receptor

    PubMed Central

    Nguyen, Linh P.; Bradfield, Christopher A.

    2008-01-01

    In its simplest aspect, this review is an attempt to describe the major ligand classes of the aryl hydrocarbon receptor (AHR). A grander objective is to provide models that may help define the physiological activator or “endogenous ligand” of the AHR. We begin by presenting evidence that supports a developmental function for the AHR. This is followed by proposing mechanisms by which an endogenous ligand and consequent AHR activation might be important during normal physiology and development. With this background, we then present a survey of the known xenobiotic, endogenous, dietary and “un-conventional” activators of the AHR. When possible, this includes information about their induction potency, receptor binding affinity and potential for exposure. Because of the essential function of the AHR in embryonic development, we discuss the candidacy of each of these compounds as physiologically important activators. PMID:18076143

  5. Development and pharmacological characterization of conformationally constrained urotensin II-related peptide agonists.

    PubMed

    Chatenet, David; Folch, Benjamin; Feytens, Debby; Létourneau, Myriam; Tourwé, Dirk; Doucet, Nicolas; Fournier, Alain

    2013-12-12

    Urotensin II (UII) and its paralog peptide, urotensin II-related peptide (URP), exert not only common but also divergent actions through the activation of UT, a specific membrane-bound receptor that belongs to the 1A G protein-coupled receptor subclass. In this study, we have designed and synthesized new URP analogues in which the intracyclic Trp residue was replaced with natural, unnatural, and constrained amino acids to determine important physicochemical features for receptor binding and activation. The biological data, highlighting the potent agonistic behavior of [Tiq(4)]URP and [Tpi(4)]URP, also suggest that the Trp residue, and more specifically the indole ring, is not critical for receptor interaction and could in fact be involved in the intramolecular stabilization of the bioactive conformation of URP. Finally, these analogues, which are intracyclic constrained URP-based agonists, could represent useful pharmacological tools for the study of the urotensinergic system. PMID:24251366

  6. Skeletal Fragility in Endogenous Hypercortisolism.

    PubMed

    Mazziotti, Gherardo; Delgado, Adriano; Maffezzoni, Filippo; Formenti, Annamaria; Giustina, Andrea

    2016-01-01

    Skeletal fragility is a frequent complication of endogenous hypercortisolism, and fragility fractures may be the first clinical manifestation of the disease. Fractures involve more frequently the vertebrae and may occur in 30-50% of the patients exposed to glucocorticoid excess, in close relationship with severity and duration of hypercortisolism. Although improvement of bone mineral density was reported after resolution of hypercortisolism, there are patients with persistently high fracture risk after the cure of hypercortisolism, and other patients in whom the resolution of hypercortisolism may take a long time, implying a multistep therapeutic approach. Since vertebral fractures tend to occur early during the natural history of disease, a skeletal-specific approach should be undertaken in these patients; however, the cost-effectiveness of this approach is still largely unknown since data on effectiveness and safety of bone-active drugs in endogenous hypercortisolism are scarce. PMID:27210111

  7. 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.

  8. 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.

  9. Genome-wide reexamination of endogenous retroviruses in Rattus norvegicus.

    PubMed

    Garcia-Etxebarria, Koldo; Jugo, Begoña M

    2016-07-01

    Endogenous retroviruses (ERVs) are remnants of retroviral infections that are present in a large number of vertebrate genomes. Based on the proposal that the rat could act as a reservoir of retroviruses, rat ERVs were analysed in silico using a whole-genome approach. To enrich the detected ERV groups, we applied an upgraded approach based on the hidden Markov model. We found 2637 elements that were classified into the following groups: 9 groups of Class I; 15 of Class II, 7 of them previously described; 1 of Class III; and 3 groups whose classification was unclear but were distantly related to Class I. Sixteen ERV groups seemed to be specific to rat. The high number of rat-specific groups might be related to the contact of rats with retroviruses and their role as a reservoir. In addition, the env gene of the more extended groups seemed to be undetectable.

  10. Identification, characterization and comparative genomics of chimpanzee endogenous retroviruses

    PubMed Central

    Polavarapu, Nalini; Bowen, Nathan J; McDonald, John F

    2006-01-01

    Background Retrotransposons, the most abundant and widespread class of eukaryotic transposable elements, are believed to play a significant role in mutation and disease and to have contributed significantly to the evolution of genome structure and function. The recent sequencing of the chimpanzee genome is providing an unprecedented opportunity to study the functional significance of these elements in two closely related primate species and to better evaluate their role in primate evolution. Results We report here that the chimpanzee genome contains at least 42 separate families of endogenous retroviruses, nine of which were not previously identified. All but two (CERV 1/PTERV1 and CERV 2) of the 42 families of chimpanzee endogenous retroviruses were found to have orthologs in humans. Molecular analysis (PCR and Southern hybridization) of CERV 2 elements demonstrates that this family is present in chimpanzee, bonobo, gorilla and old-world monkeys but absent in human, orangutan and new-world monkeys. A survey of endogenous retroviral positional variation between chimpanzees and humans determined that approximately 7% of all chimpanzee-human INDEL variation is associated with endogenous retroviral sequences. Conclusion Nine families of chimpanzee endogenous retroviruses have been transpositionally active since chimpanzees and humans diverged from a common ancestor. Seven of these transpositionally active families have orthologs in humans, one of which has also been transpositionally active in humans since the human-chimpanzee divergence about six million years ago. Comparative analyses of orthologous regions of the human and chimpanzee genomes have revealed that a significant portion of INDEL variation between chimpanzees and humans is attributable to endogenous retroviruses and may be of evolutionary significance. PMID:16805923

  11. Endogenous zinc in neurological diseases.

    PubMed

    Koh, Jae-Yong

    2005-10-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized.

  12. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  13. 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

  14. Endogenous Inhibitors of Kidney Inflammation

    PubMed Central

    Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Although inflammation is the physiological response to pathogen invasion and tissue damage, it can also be responsible for significant tissue damage. Therefore, the inflammatory response must be carefully regulated to prevent critical inflammatory damage to vital organs. Typically, local endogenous regulatory mechanisms adjust the magnitude of the response such that the injurious condition is resolved and homeostasis is mantained. Humoral mechanisms that restrain or inhibit inflammation include glucocorticoid hormones, anti-inflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β), and soluble cytokine receptors; other mediators facilitate tissue healing, like lipoxins and resolvins. There is growing evidence that inflammation plays a critical role in the development and progression of heart disease, cancer, stroke, diabetes, kidney diseases, sepsis, and several fibroproliferative disorders. Consequently, understanding the mechanisms that regulate inflammation may offer therapeutic targets for inhibiting the progression of several diseases. In this article, we review the significance of several novel endogenous anti-inflammatory mediators in the protection from kidney injury and the potential of these regulatory molecules as therapeutic targets for treatment of kidney inflammatory diseases. PMID:26779569

  15. Endogeneity in prison risk classification.

    PubMed

    Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber

    2013-10-01

    Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).

  16. "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…

  17. An analysis of cercopithecoid odontometrics. II. Relations between dental dimorphism, body size dimorphism and diet.

    PubMed

    Post, D; Goldstein, S; Melnick, D

    1978-11-01

    Odontometric, dietary, and body weight data were collected for a sample of 29 cercopithecoid species. Each species was assigned to one of three diet classes (frugivore, folivore, and omnivore) , and indices were constructed to estimate the extent of sexual dimorphism in body weight, postcanine area and incisor width in each of the species. Analysis proceeded by means of the analysis of covariance with the dental dimorphism indices as the dependent variables. Body weight dimorphism was not significantly related to either measure of dental dimorphism across the sample, and an analysis by diet alone revealed that omnivores show significantly higher dental dimorphism than do either of the other two diet classes. The relationship between this result and theories of sexual subniche differentiation is discussed.

  18. Generation of BAC Transgenic Tadpoles Enabling Live Imaging of Motoneurons by Using the Urotensin II-Related Peptide (ust2b) Gene as a Driver

    PubMed Central

    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

  19. The discovery of endogenous retroviruses

    PubMed Central

    Weiss, Robin A

    2006-01-01

    When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was not generally accepted, and reverse transcriptase was yet to be discovered. Nonetheless, the evidence that we accrued in the pre-molecular era has stood the test of time, and our hypothesis on ERV, which one reviewer described as 'impossible', proved to be correct. Here I recount some of the key observations in birds and mammals that led to the discovery of ERV, and comment on their evolution, cross-species dispersion, and what remains to be elucidated. PMID:17018135

  20. 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

  1. 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…

  2. 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.

  3. Population aging and endogenous economic growth.

    PubMed

    Prettner, Klaus

    2013-04-01

    We investigate the consequences of population aging for long-run economic growth perspectives. Our framework incorporates endogenous growth models and semi-endogenous growth models as special cases. We show that (1) increases in longevity have a positive impact on per capita output growth, (2) decreases in fertility have a negative impact on per capita output growth, (3) the positive longevity effect dominates the negative fertility effect in case of the endogenous growth framework, and (4) population aging fosters long-run growth in the endogenous growth framework, while its effect depends on the relative change between fertility and mortality in the semi-endogenous growth framework.Electronic supplementary material The online version of this article (doi:10.1007/s00148-012-0441-9) contains supplementary material, which is available to authorized users.

  4. Control of RFM strain endogenous retrovirus in RFM mouse cells.

    PubMed

    Tennant, R W; Otten, J A; Wang, T W; Liou, R S; Brown, A; Yang, W K

    1983-01-01

    RFM/Un mice express an endogenous type C retrovirus throughout their life span in many tissues; primary or established embryo fibroblast cell cultures do not express a virus but can be induced by exposure to 5-iodo-2'-deoxyuridine. All of our sources yielded a single ecotropic virus (RFV) which appeared to be related more closely to the endogenous N-tropic virus (WN1802N) of BALB/c mice than to Gross leukemia virus on the basis of two-dimensional gel electropherograms of virion proteins. No xenotropic or recombinant viruses were isolated by cocultivation techniques. RFV is N-tropic, and RFM/Un cells possess the Fv-1n allele, as indicated by restriction of B-tropic virus and susceptibility to Gross strain N-tropic virus. However, RFM cells are highly resistant to RFV and other endogenous N-tropic viruses. This resistance is expressed by two-hit titration kinetics and by inhibition of viral linear duplex DNA formation. This is similar to the effects of the Fv-1 locus, but preliminary work has shown no apparent genetic linkage between the two restrictions. The relative strength of the restriction, the presence of a single class of ecotropic virus, and the absence of recombinant viruses suggest that in RFM mice virus is expressed only in cells in which it is induced and not by cell-to-cell transmission.

  5. 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

  6. Class Size.

    ERIC Educational Resources Information Center

    Ellis, Thomas I.

    1985-01-01

    After a brief introduction identifying current issues and trends in research on class size, this brochure reviews five recent studies bearing on the relationship of class size to educational effectiveness. Part 1 is a review of two interrelated and highly controversial "meta-analyses" or statistical integrations of research findings on class size,…

  7. 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,…

  8. 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

  9. Overview of endogenous and synthetic melanocortin peptides.

    PubMed

    Wilson, K R; Todorovic, A; Proneth, B; Haskell-Luevano, C

    2006-01-01

    The melanocortin system consists of five seven-transmembrane spanning G-protein coupled (GPCRs) receptors (MC1R-MC5R), the endogenous agonists a-, B- and melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and the endogenous antagonists Agouti and Agouti-related protein (AGRP). Melanocortin agonists are involved in the regulation of feeding behavior and weight omeostasis in mammals. Structure-activity relationships (SAR) have been performed on the endogenous melanocortin receptor agonists and antagonists that have identified ligand amino acid residues implicated as important for receptor binding and stimulation. Knowledge of putative ligand-receptor interactions may help to design molecules as therapeutic agents for the treatment of physiological diseases. PMID:16914082

  10. Analysis of the Human Endogenous Coregulator Complexome

    PubMed Central

    Malovannaya, Anna; Lanz, Rainer B.; Jung, Sung Yun; Bulynko, Yaroslava; Le, Nguyen T.; Chan, Doug W.; Ding, Chen; Shi, Yi; Yucer, Nur; Krenciute, Giedre; Kim, Beom-Jun; Li, Chunshu; Chen, Rui; Li, Wei; Wang, Yi; O’Malley, Bert W.; Qin, Jun

    2011-01-01

    Summary Elucidation of endogenous cellular protein-protein interactions and their networks is most desirable for biological studies. Here we report our study of endogenous human coregulator protein complex networks obtained from integrative mass spectrometry-based analysis of 3,290 affinity purifications. By preserving weak protein interactions during complex isolation and utilizing high levels of reciprocity in the large dataset we identified many unreported protein associations, such as a transcriptional network formed by ZMYND8, ZNF687 and ZNF592. Furthermore, our work revealed a tiered interplay within networks that share common proteins, providing a conceptual organization of a cellular proteome composed of minimal endogenous modules (MEMOs), functional uniCOREs and regulatory complex-complex interaction networks (CCIs). This resource will effectively fill a void in linking correlative genomic studies with an understanding of transcriptional regulatory protein functions within the proteome for formulation and testing of new hypotheses. PMID:21620140

  11. 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.

  12. Natural mutagenesis of human genomes by endogenous retrotransposons

    PubMed Central

    Iskow, Rebecca C.; McCabe, Michael T.; Mills, Ryan E.; Torene, Spencer; Pittard, W. Stephen; Neuwald, Andrew F.; Van Meir, Erwin G.; Vertino, Paula M.; Devine, Scott E.

    2010-01-01

    SUMMARY Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine. Here, we describe new technologies for detecting these young retrotransposon insertions and demonstrate that such insertions indeed are abundant in human populations. We also found that new somatic L1 insertions occur at high frequencies in human lung cancer genomes. Genome-wide analysis suggests that altered DNA methylation may be responsible for the high levels of L1 mobilization observed in these tumors. Our data indicate that transposon-mediated mutagenesis is extensive in human genomes, and is likely to have a major impact on human biology and diseases. PMID:20603005

  13. Shiga-like toxin II-related cytotoxins in Citrobacter freundii strains from humans and beef samples.

    PubMed

    Schmidt, H; Montag, M; Bockemühl, J; Heesemann, J; Karch, H

    1993-02-01

    By hybridizing colonies grown from 928 individual stool samples of patients suffering from diarrhea with oligonucleotide probes 772 and 849 complementary to Shiga-like toxin I (SLT-I) and SLT-II gene sequences, respectively, we identified two strains that hybridized with probe 849, which biochemical identification revealed as Citrobacter freundii. An additional five slt-II probe-positive isolates were screened from 81 beef samples. Polymerase chain reaction analysis and restriction of amplified products provided evidence for slt-II-related genes in all seven strains. From C. freundii LM 76, the genes encoding the A and B subunits were cloned in pUC 18 vectors and sequenced. The gene encoding the A subunit differed from that of Escherichia coli slt-IIvhc in 4 bases, resulting in two amino acid residue differences. In 11, 13, and 11 nucleotides, differentiation of slt-IIA, slt-IIcA, and vtx2haA, respectively, was found. These differences affected the predicted amino acid sequence as follows: there were six amino acid differences with SLT-IIA, five with SLT-IIcA, and four with VTx2haA. The nucleotide sequence of the gene encoding the B subunit is identical to slt-IIvhcB and differed from slt-IIcB and vtx2haB by only a single nucleotide base, but this resulted in a predicted amino acid sequence identical to that reported for these toxins. We therefore termed the toxin genes C. freundii slt-IIcA and slt-IIcB. Culture filtrates inoculated with material from the colonies from primary cultures were cytotoxic to Vero cells. Neutralization assays with antisera to E. coli SLT-I, SLT-II, and SLT-IIvhc revealed that antibodies against SLT-IIvhc reduced the C. freundii cytotoxic activity specifically and to the same degree as with the E. coli SLT-IIvhc control strain. In five of the seven strains tested, subcultivation on both a liquid or solid medium resulted in loss of cytotoxic activity. With polymerase chain reaction, we demonstrated that loss of cytotoxic activity ran

  14. Exogenous and endogenous protease inhibitors in the gut of the fall armyworm larvae, Spodoptera frugiperda.

    PubMed

    Lwalaba, Digali; Weidlich, Sandy; Hoffmann, Klaus H; Woodring, Joseph

    2010-06-01

    A dose-dependent inhibition of endogenous trypsin and aminopeptidase occurs in the lumen of Spodoptera frugiperda after feeding L6 larvae exogenous inhibitors soybean trypsin inhibitor (SBTI), tosyl-L-lysine chloromethyl ketone-HCl (TLCK), or bestatin, respectively, for 3 days. TLCK inhibits trypsin in tissue extracts and in secretions more strongly than SBTI. The aminopeptidase released into the lumen (containing the peritrophic membrane) is strongly inhibited by bestatin, but the membrane-bound enzyme is not. A bound enzyme may be more resistant to an inhibitor than unbound. A cross-class elevation of aminopeptidase activity occurs in response to ingested trypsin inhibitor, but there was no cross-class effect of aminopeptidase inhibitor (bestatin) on trypsin activity. An endogenous trypsin and aminopeptidase inhibitor is present in the lumen and ventricular cells. The strength of the endogenous trypsin inhibition seems to be in the same range as that resulting from ingestion of the exogenous inhibitor SBTI. In some insect species, considerable trypsin secretion occurs in unfed as well as in fed animals, and endogenous protease inhibitors might function to protect the ventricular epithelium by inactivation of trypsin when less food is available. PMID:20513059

  15. Nicotine effects and the endogenous opioid system.

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.

  16. Shedding "UV" light on endogenous opioid dependence.

    PubMed

    Tejeda, Hugo A; Bonci, Antonello

    2014-06-19

    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state.

  17. Biochemical and physiological aspects of endogenous androgens.

    PubMed

    Kicman, Andrew T

    2010-01-01

    This review attempts to give a synopsis of the major aspects concerning the biochemistry of endogenous androgens, supplemented with several facets of physiology, particularly with respect to testosterone. Testosterone continues to be the most common adverse finding declared by World Anti-Doping Agency accredited laboratories, such samples having an augmented testosterone to epitestosterone ratio. Knowledge regarding the precursors and metabolism of endogenous testosterone is therefore fundamental to understanding many of the issues concerning doping with testosterone and its prohormones, including the detection of their administration. Further, adverse findings for nandrolone are frequent, but this steroid and 19-norandrostenedione are also produced endogenously, an appealing hypothesis being that they are minor by-products of the aromatization of androgens. At sports tribunals pertaining to adverse analytical findings of natural androgen administration, experts often raise issues that concern some aspect of steroid biochemistry and physiology. Salient topics included within this review are the origins and interconversion of endogenous androgens, the biosynthesis of testosterone and epitestosterone, the mechanism of aromatization, the molecular biology of the androgen receptor, the hypothalamic-pituitary-testicular axis, disturbances to this axis by anabolic steroid administration, the transport (binding) of androgens in blood, and briefly the metabolism and excretion of androgens.

  18. Shedding "UV" light on endogenous opioid dependence.

    PubMed

    Tejeda, Hugo A; Bonci, Antonello

    2014-06-19

    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state. PMID:24949960

  19. Nicotine effects and the endogenous opioid system.

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR. PMID:24882143

  20. Characterization of Endogenous Ethanol in the Mammal.

    PubMed

    McManus, I R; Contag, A O; Olson, R E

    1960-01-01

    Ethanol has been isolated from the tissues of several animal species in amounts ranging from 23 to 145 micromole/100 gm of tissue. Intestinal bacterial flora appear to be excluded as a source of this ethanol. Radioactivity from pyruvate-2-C(14) appeared in ethanol after incubation with liver slices; this finding indicates an endogenous synthesis.

  1. 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…

  2. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    PubMed Central

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  3. [Effect of female sex steroids on levels of endogenous ethanol].

    PubMed

    Garber, M R; Kovalenko, A E

    1988-01-01

    The authors presented the results of a study of the effect of female sex steroids on the level of endogenous ethanol. The time course of endogenous ethanol during the menstrual cycle was investigated. The concentration of endogenous ethanol was compared in the groups of women receiving and not receiving hormonal contraceptives. An increase in sex steroids during the menstrual cycle was accompanied by a decrease in the level of endogenous ethanol. The use of hormonal contraceptives caused an increase in the background concentration of endogenous ethanol. A possible effect of endogenous and exogenous female sex steroids on different levels of regulation of ethanol metabolism was assumed.

  4. 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)

  5. [Concentration of endogenous ethanol and alcoholic motivation].

    PubMed

    Burov, Iu V; Treskov, V G; Kampov-Polevoĭ, A B; Kovalenko, A E; Rodionov, A P

    1983-11-01

    Trials with patients suffering from stage II chronic alcoholism and normal test subjects as well as experiments made on male C57BL mice (with genetically determined alcoholic motivation) and CBA mice (with genetically determined alcoholic aversion) and random-bred male rats with different levels of initial alcoholic motivation have shown the presence of reverse proportional dependence between blood plasma endogenous ethanol and alcoholic motivation.

  6. HERVd: database of human endogenous retroviruses.

    PubMed

    Paces, Jan; Pavlícek, Adam; Paces, Václav

    2002-01-01

    The human endogenous retroviruses database (HERVd) is maintained at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, and is accessible via the World Wide Web at http://herv.img.cas.cz. The HERVd provides complex information on and analysis of retroviral elements found in the human genome. It can be used for searches of individual HERV families, identification of HERV parts, graphical output of HERV structures, comparison of HERVs and identification of retrovirus integration sites.

  7. Endogenous Retroviruses in the Genomics Era.

    PubMed

    Johnson, Welkin E

    2015-11-01

    Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations. PMID:26958910

  8. Endogenous growth of persistently active volcanoes

    NASA Astrophysics Data System (ADS)

    Francis, Peter; Oppenheimer, Clive; Stevenson, David

    1993-12-01

    LAVA lakes and active strombolian vents have persisted at some volcanoes for periods exceeding the historic record. They liberate prodigious amounts of volatiles and thermal energy but erupt little lava, a paradox that raises questions about how volcanoes grow. Although long-lasting surface manifestations can be sustained by convective exchange of magma with deeper reservoirs, residence times of magmas beneath several basaltic volcanoes are & sim10-100 years1,2, indicating that where surface activity continues for more than 100-1,000 years, the reservoirs are replenished by new magma. Endogenous growth of Kilauea volcano (Hawaii) through dyke intrusion and cumulate formation is a well-understood consequence of the steady supply of mantle-derived magma3,4. As we show here, inferred heat losses from the Halemaumau lava lake indicate a period of dominantly endogenous growth of Kilauea volcano during the nineteenth century. Moreover, heat losses and degassing rates for several other volcanoes, including Stromboli, also indicate cryptic influxes of magma that far exceed visible effluxes of lavas. We propose that persistent activity at Stromboli, and at other volcanoes in different tectonic settings, is evidence of endogenous growth, involving processes similar to those at Kilauea.

  9. 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.

  10. 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

  11. [Latest advances of SLA class I genes].

    PubMed

    Tao, Xuan; Li, Hua; Li, Xue-Wei; Yu, Hui; Zuo, Qi-Zhen

    2007-11-01

    The Swine leukocyte antigen (SLA) class I genes encode multi-glycoproteins on cell surface, which present endogenous antigenic peptides to T cells and thus initiate specific immune responses. In this article, latest advances on molecular structure, expression in tissues, regulation of expression, genotyping, polymorphism, and evolution of SLA class I genes were introduced, in which genotyping and polymorphism were emphasized. Molecular typing methods of SLA class I genes include serological method, DNA sequencing, PCR-SSP, PCR-SSOP and MS, of which PCR-SSP is frequently used in genotyping of SLA class I genes as a simple and rapid method. Future directions for the study and application of SLA class I genes on gene functions, peptide vaccine, xenotransplantation were also discussed.

  12. 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

  13. Endogenous morphine-like compound immunoreactivity increases in parkinsonism.

    PubMed

    Charron, Giselle; Doudnikoff, Evelyne; Laux, Alexis; Berthet, Amandine; Porras, Gregory; Canron, Marie-Hélène; Barroso-Chinea, Pedro; Li, Qin; Qin, Chuan; Nosten-Bertrand, Marika; Giros, Bruno; Delalande, François; Van Dorsselaer, Alain; Vital, Anne; Goumon, Yannick; Bezard, Erwan

    2011-08-01

    Morphine is endogenously synthesized in the central nervous system and endogenous dopamine is thought to be necessary for endogenous morphine formation. As Parkinson's disease results from the loss of dopamine and is associated with central pain, we considered how endogenous morphine is regulated in the untreated and l-DOPA-treated parkinsonian brain. However, as the cellular origin and overall distribution of endogenous morphine remains obscure in the pathological adult brain, we first characterized the distribution of endogenous morphine-like compound immunoreactive cells in the rat striatum. We then studied changes in the endogenous morphine-like compound immunoreactivity of medium spiny neurons in normal, Parkinson's disease-like and l-DOPA-treated Parkinson's disease-like conditions in experimental (rat and monkey) and human Parkinson's disease. Our results reveal an unexpected dramatic upregulation of neuronal endogenous morphine-like compound immunoreactivity and levels in experimental and human Parkinson's disease, only partially normalized by l-DOPA treatment. Our data suggest that endogenous morphine formation is more complex than originally proposed and that the parkinsonian brain experiences a dramatic upregulation of endogenous morphine immunoreactivity. The functional consequences of such endogenous morphine upregulation are as yet unknown, but based upon the current knowledge of morphine signalling, we hypothesize that it is involved in fatigue, depression and pain symptoms experienced by patients with Parkinson's disease.

  14. Endogenous formation of morphine in human cells.

    PubMed

    Poeaknapo, Chotima; Schmidt, Jürgen; Brandsch, Matthias; Dräger, Birgit; Zenk, Meinhart H

    2004-09-28

    Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of (18)O(2) led to the [(18)O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in (16)O(2), indicating the presence of two atoms of (18)O per molecule of morphine. Growth of DAN-G cells in an (18)O(2) atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-(13)C(6)]-tyramine, [1-(13)C, N-(13)CH(3)]-(S)-reticuline and [N-CD(3)]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of "endogenous morphine" in the neurosciences and immunosciences.

  15. 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.

  16. Endogenous Synthesis of Coenzyme Q in Eukaryotes

    PubMed Central

    Tran, UyenPhuong C.; Clarke, Catherine F.

    2007-01-01

    Coenzyme Q (Q) functions in the mitochondrial respiratory chain and serves as a lipophilic antioxidant. There is increasing interest in the use of Q as a nutritional supplement. Although the physiological significance of Q is extensively investigated in eukaryotes, ranging from yeast to human, the eukaryotic Q biosynthesis pathway is best characterized in the budding yeast Saccharomyces cerevisiae. At least ten genes (COQ1-COQ10) have been shown to be required for Q biosynthesis and function in respiration. This review highlights recent knowledge about the endogenous synthesis of Q in eukaryotes, with emphasis on S. cerevisiae as a model system. PMID:17482885

  17. Human endogenous retroviruses: friend or foe?

    PubMed

    Weiss, Robin A

    2016-01-01

    The integration of proviral DNA into host chromosomal DNA as an obligatory step in the replication cycle of retroviruses is a natural event of genetic recombination between virus and host. When integration occurs in cells of the germ line, it results in mendelian inheritance of viral sequences that we call endogenous retroviruses (ERV) and HERV for humans. HERVs and host often establish a symbiotic relationship, especially in the placenta and in pluripotent embryonic stem cells, but HERVs occasionally have deleterious consequences for the host. This special issue of APMIS features the fascinating relationships between HERV and humans in health and disease. PMID:26818257

  18. Endogenous cannabinoid signaling at inhibitory interneurons

    PubMed Central

    Younts, Thomas J.; Castillo, Pablo E.

    2014-01-01

    Significant progress has been made in our understanding of how endogenous cannabinoids (eCBs) signal at excitatory and inhibitory synapses in the central nervous system (CNS). This review discusses how eCBs regulate inhibitory interneurons, their synapses, and the networks in which they are embedded. eCB signaling plays a pivotal role in brain physiology by means of their synaptic signal transduction, spatiotemporal signaling profile, routing of information through inhibitory microcircuits, and experience-dependent plasticity. Understanding the normal processes underlying eCB signaling is beginning to shed light on how their dysregulation contributes to disease. PMID:24650503

  19. Leishmania-infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells.

    PubMed

    Kima, P E; Soong, L; Chicharro, C; Ruddle, N H; McMahon-Pratt, D

    1996-12-01

    CD4+ T cell lines raised against the protective leishmanial antigens GP46 and P8 were used to study the presentation of endogenously synthesized Leishmania antigens by infected cells. Using two different sources of macrophages, the I4.07 macrophage cell line (H-2k) which constitutively expresses major histocompatibility complex (MHC) class II molecules, and elicited peritoneal exudate cells, we found that cells infected with Leishmania amastigotes presented little, if any endogenously synthesized parasite antigens to CD4+ T cells. In contrast, promastigote-infected macrophages did present endogenous parasite molecules to CD4+ T cells, although only for a limited time, with maximal presentation occurring within 24 h of infection and decreasing to minimal antigen presentation at 72 h post-infection. These observations suggest that once within the macrophage, Leishmania amastigote antigens are sequestered from the MHC class II pathway of antigen presentation. This allows live parasites to persist in infected hosts by evading the activation of CD4+ T cells, a major and critical anti-leishmanial component of the host immune system. Studies with drugs that modify fusion patterns of phagosomes suggest that the mechanism of this antigen sequestration includes targeted fusion of the parasitophorous vacuole with certain endocytic compartments.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

    2016-07-20

    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.

  8. Endogenous Group Formation via Unproductive Costs.

    PubMed

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

    2013-10-01

    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

  9. 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

  10. [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

  11. 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

  12. 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

  13. 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

  14. Endogenous cardiotonic steroids in chronic renal failure

    PubMed Central

    Kolmakova, Elena V.; Haller, Steven T.; Kennedy, David J.; Isachkina, Alina N.; Budny, George V.; Frolova, Elena V.; Piecha, Grzegorz; Nikitina, Elena R.; Malhotra, Deepak; Fedorova, Olga V.; Shapiro, Joseph I.

    2011-01-01

    Background. Previous reports demonstrated that digitalis-like cardiotonic steroids (CTS) contribute to the pathogenesis of end-stage renal disease. The goal of the present study was to define the nature of CTS in patients with chronic kidney disease (CKD) and in partially nephrectomized (PNx) rats. Methods. In patients with CKD and in healthy controls, we determined plasma levels of marinobufagenin (MBG) and endogenous ouabain (EO) and erythrocyte Na/K-ATPase activity in the absence and in the presence of 3E9 anti-MBG monoclonal antibody (mAb) and Digibind. Levels of MBG and EO were also determined in sham-operated Sprague–Dawley rats and in rats following 4 weeks of PNx. Results. In 25 patients with CKD plasma, MBG but not EO was increased (0.86 ± 0.07 versus 0.28 ± 0.02 nmol/L, P < 0.01) and erythrocyte Na/K-ATPase was inhibited (1.24 ± 0.10 versus 2.80 ± 0.09 μmol Pi/mL/h, P < 0.01) as compared to that in 19 healthy subjects. Ex vivo, 3E9 mAb restored Na/K-ATPase in erythrocytes from patients with CKD but did not affect Na/K-ATPase from control subjects. Following chromatographic fractionation of uremic versus normal plasma, a competitive immunoassay based on anti-MBG mAb detected a 3-fold increase in the level of endogenous material having retention time similar to that seen with MBG. A similar pattern of CTS changes was observed in uremic rats. As compared to sham-operated animals, PNx rats exhibited 3-fold elevated levels of MBG but not that of EO. Conclusions. In chronic renal failure, elevated levels of a bufadienolide CTS, MBG, contribute to Na/K-ATPase inhibition and may represent a potential target for therapy. PMID:21292813

  15. Strategies for endogenous spinal cord repair: HPMA hydrogel to recruit migrating endogenous stem cells.

    PubMed

    Espinosa-Jeffrey, Araceli; Oregel, Karlos; Wiggins, Laurent; Valera, Remelyn; Bosnoyan, Kathrin; Agbo, Chioma; Awosika, Oluwole; Zhao, Paul M; de Vellis, Jean; Woerly, Stéphane

    2012-01-01

    Injury to the spinal cord disrupts ascending and descending axonal pathways and causes tissue damage with a subsequent limited cellular regeneration. Successful treatment would encompass the restoration of the cytoarchitecture, homeostasis and function all in dear need. Transplantation-based treatments using exogenous cells are the most favoured approach. Yet, with the advent of the stem cell concept and continuous progress in the field it became clear that the endogenous potential for repair is greater than previously thought. As an alternative to neural grafting, we and other researchers have aimed at understanding what are the elements needed for a successful repair with self progenitors that would give rise to the cell types needed to restore function of the central nervous system. Some studies involve both scaffolds and cell grafts. Here we describe studies on spinal cord repair using what we call "endogenous tissue engineering for regenerative medicine". The approach involves a hydrogel that mimics the natural milieu where endogenous pre-existing and newly formed cells populate the gel progressively allowing for the integration of CNS self populations leading to a successful recovery of function. Highlight aspects learned from this type of studies are that: Endogenous reconstruction of the injured spinal cord is possible by using the adequate support. The contribution of nestin-expressing progenitors to spinal cord regeneration is continuous and substantial both, in the reconstructed segment as well as, along the distal and caudal segments of the reconstructed spinal cord. Most of these cells appear to have been in a quiescent state until the injury occurred and only a small fraction of these neural progenitors was produced via cell proliferation. The hydrogel combined with exercise was necessary and sufficient to restore locomotor function in cats that underwent spinal transaction followed by reconstructive surgery. This recovery of function was first seen

  16. 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 ...

  17. 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…

  18. On the Endogeneity of the Mean-Variance Efficient Frontier.

    ERIC Educational Resources Information Center

    Somerville, R. A.; O'Connell, Paul G. J.

    2002-01-01

    Explains that the endogeneity of the efficient frontier in the mean-variance model of portfolio selection is commonly obscured in portfolio selection literature and in widely used textbooks. Demonstrates endogeneity and discusses the impact of parameter changes on the mean-variance efficient frontier and on the beta coefficients of individual…

  19. 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…

  20. 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

  1. Endogenous ethanol--its metabolic, behavioral and biomedical significance.

    PubMed

    Ostrovsky YuM

    1986-01-01

    Ethanol is constantly formed endogenously from acetaldehyde, and level of the former can be measured in both human beings and animals. Acetaldehyde can be generated in situ from the metabolism of pyruvate, threonine, deoxyribose-5-phosphate, phosphoethanolamine, alanine and presumably from other substrates. The levels of blood and tissue endogenous ethanol change as a function of various physiologic and experimental conditions such as starvation, aging, stress, cooling, adrenalectomy, etc. and are regulated by many exogenous compounds such as antimetabolites, derivatives of amino acids, lithium salts, disulfiram, cyanamide, etc. Under free choice alcohol selection situations, the levels of endogenous ethanol in rat blood and alcohol preference by the animals are negatively correlated. Similar negative correlations have been found between the levels of blood endogenous ethanol and the frequency of delirium in alcoholic patients undergoing alcohol withdrawal. Endogenous ethanol and acetaldehyde can therefore be regarded as compounds which fulfil substrate, regulatory and modulator functions.

  2. Retinal photodamage by endogenous and xenobiotic agents.

    PubMed

    Wielgus, Albert R; Roberts, Joan E

    2012-01-01

    The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm and therefore light absorbed by the eye must be benign. However, exposure to the very intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age. There are age-related changes in the endogenous (natural) chromophores (lipofuscin, A2E and all-trans-retinal derivatives) in the human retina that makes it more susceptible to visible light damage. Intense visible light sources that do not filter short blue visible light (400-440 nm) used for phototherapy of circadian imbalance (i.e. seasonal affective disorder) increase the risk for age-related light damage to the retina. Moreover, many drugs, dietary supplements, nanoparticles and diagnostic dyes (xenobiotics) absorb ocular light and have the potential to induce photodamage to the retina, leading to transient or permanent blinding disorders. This article will review the underlying reasons why visible light in general and short blue visible light in particular dramatically raises the risk of photodamage to the human retina.

  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. 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

  5. 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

  6. Endogenous neural noise and stochastic resonance

    NASA Astrophysics Data System (ADS)

    Emberson, Lauren; Kitajo, Keiichi; Ward, Lawrence M.

    2007-06-01

    We discuss the relationship of endogenous neural noise (ENN) to performance of behavioral tasks and to information processing in the brain. Spontaneous neural activity is closely linked to development and perception, and is correlated with behavior. Some of this activity is probably related to internal processing of task- and goal-relevant information, but some is simply noise. Two previous studies have reported correlations between performance on behavioral tasks and measures of neural noise and have characterized these relationships as intrinsic stochastic resonance (SR). We argue that neither of these studies demonstrated intrinsic SR, and discuss several alternative ways of measuring ENN in humans from EEG or MEG records. Using one of these, random-phase power in the 30-50 Hz range 1 sec before the onset of the signal, we demonstrate a kind of intrinsic SR that optimizes detection of weak visual signals. Minimum response time was obtained when this EEG measure of ENN was in a middle decile. No other measure of ENN was related either to response time or to an unbiased measure of detection accuracy (e.g., d'). A discussion of the implications of these findings for the study of intrinsic SR concludes the paper.

  7. Spontaneous endogenous hypermelatoninemia: a new disease?

    PubMed

    Duman, Ozgur; Durmaz, Erdem; Akcurin, Sema; Serteser, Mustafa; Haspolat, Senay

    2010-01-01

    Melatonin, a major photoperiod-dependent hormone, regulates circadian rhythms and biological rhythms and acts as a prominent sleep promoter. Symptoms related to hypermelatoninemia have been reported in individuals supplemented with melatonin. However, spontaneous endogenous hypermelatoninemia has not been reported previously. A 6-year-old girl previously diagnosed with Shapiro's syndrome was admitted to our hospital on several occasions during a 1-year period with complaints of altered consciousness, syncope, hypothermia and episodes of sweating. The episodes occurred daily and during sleep and lasted for 1-6 h. During these episodes, she sweated profusely and felt faint and her skin was pale and cool. Other complaints included recurrent abdominal pain, urge incontinence and myopia. She was shown to have hypermelatoninemia (>1,000 pg/ml, normal range 0-150 pg/ml) during these episodes. The duration of her attacks decreased with phototherapy and she was successfully treated with propranolol. To our knowledge, this is the first case of hypermelatoninemia without any detectable organic pathology. We did not determine the exact mechanism of hypermelatoninemia in this patient; however, it might have been related to irregular control of pinealocytes by the suprachiasmatic nucleus or related pathways. Hypermelatoninemia should be considered in patients with spontaneous periodic hypothermia and hyperhidrosis, and also in patients with Shapiro's syndrome. PMID:21041995

  8. Absolute Quantification of Endogenous Ras Isoform Abundance

    PubMed Central

    Mageean, Craig J.; Griffiths, John R.; Smith, Duncan L.; Clague, Michael J.; Prior, Ian A.

    2015-01-01

    Ras proteins are important signalling hubs situated near the top of networks controlling cell proliferation, differentiation and survival. Three almost identical isoforms, HRAS, KRAS and NRAS, are ubiquitously expressed yet have differing biological and oncogenic properties. In order to help understand the relative biological contributions of each isoform we have optimised a quantitative proteomics method for accurately measuring Ras isoform protein copy number per cell. The use of isotopic protein standards together with selected reaction monitoring for diagnostic peptides is sensitive, robust and suitable for application to sub-milligram quantities of lysates. We find that in a panel of isogenic SW48 colorectal cancer cells, endogenous Ras proteins are highly abundant with ≥260,000 total Ras protein copies per cell and the rank order of isoform abundance is KRAS>NRAS≥HRAS. A subset of oncogenic KRAS mutants exhibit increased total cellular Ras abundance and altered the ratio of mutant versus wild type KRAS protein. These data and methodology are significant because Ras protein copy number is required to parameterise models of signalling networks and informs interpretation of isoform-specific Ras functional data. PMID:26560143

  9. 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

  10. 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…

  11. Reversing Endogenous Alloreactive B cell GC Responses with Anti-CD154 or CTLA-4Ig

    PubMed Central

    Chen, Jianjun; Yin, Hao; Xu, Jing; Wang, Qiang; Edelblum, Karen L.; Sciammas, Roger; Chong, Anita

    2013-01-01

    Alloantibodies mediate acute antibody-mediated rejection as well as chronic allograft rejection in clinical transplantation. To better understand the cellular dynamics driving antibody production, we focused on the activation and differentiation of alloreactive B cells in the draining lymph nodes and spleen following sensitization to allogeneic cells or hearts. We used a modified staining approach with a single MHC Class I tetramer (Kd) bound to two different fluorochromes to discriminate between the Class I-binding and fluorochrome-streptavidin-binding B cells with a high degree of specificity and binding efficiency. By day 7-8 post-sensitization, there was a 1.5-3.2-fold increase in the total numbers of Kd-binding B cells. Within this Kd-binding B cell population, approximately half were IgDlow, MHC Class IIhigh and CD86+, 30-45 % expressed a germinal center (Fas+GL7+) phenotype, and 3-12 % were IRF4hi plasma cells. Remarkably, blockade with anti-CD40 or CTLA-4Ig, starting on day 7 post-immunization for 1 or 4 weeks, completely dissolved established GCs and halted further development of the alloantibody response. Thus MHC Class I tetramers can specifically track the in vivo fate of endogenous, Class I-specific B cells, and was used to demonstrate the ability of delayed treatment with anti-CD154 and CTLA-4Ig to halt established allo-B cell responses. PMID:23855587

  12. Receptors on lymphocytes for endogenous splenic glycosaminoglycans.

    PubMed Central

    Bradbury, M G; Parish, C R

    1989-01-01

    Previous studies have shown that lymphocytes carry cell surface receptors for sulphated polysaccharides (SPS), and SPS recognition may play a role in lymphocyte migration and positioning in vivo. This paper describes attempts to isolate and characterize the endogenous glycosaminoglycans (GAGs) of murine spleen and determine whether splenic lymphocytes carry cell surface receptors for these GAGs. A procedure was devised for isolating GAGs from murine spleen in good yield and high purity and the GAG preparation was then radiolabelled for subsequent binding studies. It was found that the splenic GAGs bound to murine splenocytes in a saturable, rapid and reversible manner with only a small subpopulation of the splenic GAG preparation being involved in binding. This reactive species was chondroitinase ABC-resistant and nitrous acid-sensitive, indicative of a heparan sulphate/heparin-like molecule. Furthermore, using immunofluorescent flow cytometry studies it was demonstrated that the majority of spleen cells have receptors for these GAGs. Subsequent ion-exchange fractionation and SDS-PAGE analysis of chondroitinase ABC-resistant GAGs confirmed that the splenic GAG recognized by splenocytes was a heparan sulphate/heparin molecule of approximately 20,000 MW with a binding affinity to splenocytes of approximately 5 X 10(-8) M. Additional binding inhibition studies indicated two possible binding sites for splenic GAGs on the splenocyte surface, one being fully inhibited by a range of SPS such as heparin (both coagulant and anticoagulant forms), pentosan sulphate, fucoidan, dextran sulphate, lambda- and iota-carrageenan, and the second being partially inhibited by kappa-carrageenan. The possible relevance of these heparan sulphate/heparin receptors on splenocytes to lymphocyte positioning in vivo is discussed. Images Figure 6 PMID:2541072

  13. 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

  14. 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

  15. Mitochondrial respiratory function induces endogenous hypoxia.

    PubMed

    Prior, Sara; Kim, Ara; Yoshihara, Toshitada; Tobita, Seiji; Takeuchi, Toshiyuki; Higuchi, Masahiro

    2014-01-01

    Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions. PMID:24586439

  16. Functional epialleles at an endogenous human centromere.

    PubMed

    Maloney, Kristin A; Sullivan, Lori L; Matheny, Justyne E; Strome, Erin D; Merrett, Stephanie L; Ferris, Alyssa; Sullivan, Beth A

    2012-08-21

    Human centromeres are defined by megabases of homogenous alpha-satellite DNA arrays that are packaged into specialized chromatin marked by the centromeric histone variant, centromeric protein A (CENP-A). Although most human chromosomes have a single higher-order repeat (HOR) array of alpha satellites, several chromosomes have more than one HOR array. Homo sapiens chromosome 17 (HSA17) has two juxtaposed HOR arrays, D17Z1 and D17Z1-B. Only D17Z1 has been linked to CENP-A chromatin assembly. Here, we use human artificial chromosome assembly assays to show that both D17Z1 and D17Z1-B can support de novo centromere assembly independently. We extend these in vitro studies and demonstrate, using immunostaining and chromatin analyses, that in human cells the centromere can be assembled at D17Z1 or D17Z1-B. Intriguingly, some humans are functional heterozygotes, meaning that CENP-A is located at a different HOR array on the two HSA17 homologs. The site of CENP-A assembly on HSA17 is stable and is transmitted through meiosis, as evidenced by inheritance of CENP-A location through multigenerational families. Differences in histone modifications are not linked clearly with active and inactive D17Z1 and D17Z1-B arrays; however, we detect a correlation between the presence of variant repeat units of D17Z1 and CENP-A assembly at the opposite array, D17Z1-B. Our studies reveal the presence of centromeric epialleles on an endogenous human chromosome and suggest genomic complexities underlying the mechanisms that determine centromere identity in humans.

  17. Phylogenetic distribution of the novel avian endogenous provirus family EAV-0.

    PubMed Central

    Resnick, R M; Boyce-Jacino, M T; Fu, Q; Faras, A J

    1990-01-01

    A new family of related endogenous proviruses, existing at 50 to 100 copies per haploid genome and distinguishable by remarkably short long terminal repeats, has been described for domestic chickens (Gallus gallus subsp domesticus). In this communication, by using Southern blot analysis and probes derived from both internal viral sequences and locus-specific, cellular flanking sequences, we studied the genetic distribution of this family of moderately repetitive avian endogenous retroviruses within the genomes of four Gallus species. Eight inbred lines of domestic chickens, the evolutionary progenitor to the domestic chicken (red jungle fowl), and two more distantly related species (grey and green jungle fowl) were studied. All Gallus species harbored this class of elements, although the different lines of domestic chickens and different species of jungle fowl bore distinguishable complements of the proviral loci. Jungle fowl appeared to have fewer copies than domestic chickens. For three randomly isolated proviral loci, domestic chickens (G. gallus subsp. domesticus) and red jungle fowl (G. gallus subsp. gallus) showed only a proviral state, whereas the most primitive and divergent of the jungle fowl, the green jungle fowl (G. varius), consistently demonstrated only preintegration states or disparate alleles. The presence of this family in all Gallus species and of related sequences in other genera suggests that a primordial founding integration event occurred prior to the evolutionary separation of Gallus species and possibly related genera. Additionally, at least one proviral locus has been acquired subsequent to speciation, indicating that this family was actively infectious after the primary founding event. This conserved, repetitive proviral family appears to represent the vestigial remnant of an avian retrovirus class related to and evolutionarily more ancient than the Rous-associated virus-0 family of avian endogenous retroviruses. Images PMID:2398526

  18. 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

  19. Demonstration of endogenous imipramine like material in rat brain

    SciTech Connect

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  20. Endogenous allergen upregulation: transgenic vs. traditionally bred crops.

    PubMed

    Herman, Rod A; Ladics, Gregory S

    2011-10-01

    The safety assessment for transgenic food crops currently includes an evaluation of the endogenous allergy potential (via serum IgE screening) when the non-transgenic counterpart is a commonly allergenic food. The value of this analysis in the safety assessment of transgenic crops, especially with reference to recent requests to quantify individual allergen concentrations in raw commodities, is examined. We conclude that the likelihood of upregulating an endogenous allergen due to transgenesis is no greater than from traditional breeding which has a history of safety and is largely unregulated. The potential consequences of upregulating an endogenous allergen are also unclear.

  1. 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)

  2. Endogenous Protease Activation of ENaC

    PubMed Central

    Adebamiro, Adedotun; Cheng, Yi; Johnson, John P.; Bridges, Robert J.

    2005-01-01

    Endogenous serine proteases have been reported to control the reabsorption of Na+ by kidney- and lung-derived epithelial cells via stimulation of electrogenic Na+ transport mediated by the epithelial Na+ channel (ENaC). In this study we investigated the effects of aprotinin on ENaC single channel properties using transepithelial fluctuation analysis in the amphibian kidney epithelium, A6. Aprotinin caused a time- and concentration-dependent inhibition (84 ± 10.5%) in the amiloride-sensitive sodium transport (INa) with a time constant of 18 min and half maximal inhibition constant of 1 μM. Analysis of amiloride analogue blocker–induced fluctuations in INa showed linear rate–concentration plots with identical blocker on and off rates in control and aprotinin-inhibited conditions. Verification of open-block kinetics allowed for the use of a pulse protocol method (Helman, S.I., X. Liu, K. Baldwin, B.L. Blazer-Yost, and W.J. Els. 1998. Am. J. Physiol. 274:C947–C957) to study the same cells under different conditions as well as the reversibility of the aprotinin effect on single channel properties. Aprotinin caused reversible changes in all three single channel properties but only the change in the number of open channels was consistent with the inhibition of INa. A 50% decrease in INa was accompanied by 50% increases in the single channel current and open probability but an 80% decrease in the number of open channels. Washout of aprotinin led to a time-dependent restoration of INa as well as the single channel properties to the control, pre-aprotinin, values. We conclude that protease regulation of INa is mediated by changes in the number of open channels in the apical membrane. The increase in the single channel current caused by protease inhibition can be explained by a hyperpolarization of the apical membrane potential as active Na+ channels are retrieved. The paradoxical increase in channel open probability caused by protease inhibition will require further

  3. Ketoconazole and endogenous Cushing's syndrome. Effective but tricky to use.

    PubMed

    2016-03-01

    Endogenous Cushing's syndrome is a rare but serious disease. Ketoconazole was effective in over 50% of cases in non-comparative series in a total of 800 patients. However, ketoconazole is hepatotoxic and interacts with many other drugs. PMID:27152395

  4. Expression and function of endogenous retroviruses in the placenta.

    PubMed

    Denner, Joachim

    2016-01-01

    Although the expression of endogenous retroviruses in the placenta of numerous species was observed a long time ago, their physiological function during gestation was demonstrated only very recently. Expression of retroviral envelope proteins, also called syncytins, in the placenta allows generation of the multinuclear syncytiotrophoblast as an outer cellular layer of the placenta by fusion of the trophoblast cells. This fusion process is crucial for the development of the placenta and for successful pregnancy. It is still unclear whether the immunosuppressive properties of the transmembrane envelope protein of the endogenous retroviruses expressed in the placenta contribute to immunosuppression to prevent the rejection of the semiallotransplant embryo. The presence of placenta cells expressing retroviral envelope proteins surrounded by immune cells deep in the maternal tissue supports an immunosuppressive function. It is important to emphasize that during evolution different species utilized ('enslaved') different endogenous retroviruses and that two or more endogenous retroviruses are involved in placentogenesis in each species.

  5. The endogenous opioid system in Gilles de la Tourette syndrome.

    PubMed

    Gillman, M A; Sandyk, R

    1986-04-01

    The various neurotransmitter systems postulated to be involved in the pathogenesis of Gilles de la Tourette syndrome(GTS) are described with special reference to the endogenous opioid system(EOS). Malfunction of the opioid system is proposed as the underlying disturbance in this disease causing secondary dysfunction of the other systems. Furthermore, the various symptoms of the illness are examined also in terms of dysfunction of the endogenous opioid system.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Evolutionary Spread and Recombination of Porcine Endogenous Retroviruses in the Suiformes

    PubMed Central

    Niebert, Marcus; Tönjes, Ralf R.

    2005-01-01

    Different Suiformes with increasing phylogenetic distance to the common pig (Sus scrofa) were assayed for the presence of porcine endogenous retroviruses (PERV) in general (pol gene), while the distribution of long terminal repeat (LTR) types (with or without repeats in U3) and env genes (classes A, B, and C) were determined in detail. PERV was not detectable in the most distantly related species, while classes PERV-A and PERV-B are present in Suiformes originating in the Pliocene epoch, and class PERV-C was detectable only in S. scrofa and in closely related species originating in the Holocene epoch. This distribution pattern of PERV classes is in line with our previous study on the age of PERV (45) and suggests an African origin of about 7.5 million years ago (MYA) and a gradual spread of PERV through the Suiformes. It seems likely that PERV-C originated more recently (1.5 to 3.5 MYA) by recombination with a homologue of unknown descent, while the origin of the repeatless LTR was a separate event approximately 3.5 MYA. PMID:15596862

  11. Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen

    PubMed Central

    Mamalaki, Clio; Elliott, James; Norton, Trisha; Yannoutsos, Nicholas; Townsend, Alain R.; Chandler, Phillip; Simpson, Elizabeth

    1993-01-01

    A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8+ and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC Db (Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2k and BALB/c H-2d) and the endogenous Mtv ligands. Positive selection of CD8+ T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period of in vitro culture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+ peripheral T-cells in these (H-2k or H-2d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2d scid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired. PMID:8281031

  12. 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

  13. Recognition of Endogenous Nucleic Acids by the Innate Immune System.

    PubMed

    Roers, Axel; Hiller, Björn; Hornung, Veit

    2016-04-19

    Recognition of DNA and RNA by endosomal and cytosolic sensors constitutes a central element in the detection of microbial invaders by the innate immune system. However, the capacity of these sensors to discriminate between microbial and endogenous nucleic acids is limited. Over the past few years, evidence has accumulated to suggest that endogenous DNA or RNA species can engage nucleic-acid-sensing pattern-recognition receptors that can trigger or sustain detrimental pathology. Here, we review principles of how the activation of innate sensors by host nucleic acids is prevented in the steady state and discuss four important determinants of whether a nucleic-acid-driven innate response is mounted. These include structural features of the ligand being sensed, the subcellular location and quantity of pathogen-derived or endogenous nucleic acids, and the regulation of sensor-activation thresholds. Furthermore, we emphasize disease mechanisms initiated by failure to discriminate self from non-self in nucleic acid detection.

  14. Expression of baboon endogenous virus in exogenously infected baboon cells.

    PubMed

    Lavelle, G; Foote, L; Heberling, R L; Kalter, S S

    1979-04-01

    Strains of low-passage, fetal diploid, baboon (Papio cynocephalus) fibroblasts were susceptible to exogenous infection with three independent isolates of baboon endogenous virus, as measured by an immunofluorescence assay specific for viral p28. Infectivity of the M7 strain of baboon endogenous virus for baboon cells of fetal skin muscle origin was equivalent to that for human and dog cells in that similar, linear, single-hit titration patterns were obtained. The assay for supernatant RNA-dependent DNA polymerase, however, showed that baboon cells produced only low levels of virus after infection compared with the production by heterologous cells. The results showed that baboon endogenous virus was capable of penetrating baboon cells and that viral genes were expressed in infected cells. Replication of complete infectious virus was restricted, however, indicating that in this primate system homologous cells differentially regulated the expression of viral genes.

  15. Endogenous Lentiviral Elements in the Weasel Family (Mustelidae)

    PubMed Central

    Han, Guan-Zhu; Worobey, Michael

    2012-01-01

    Endogenous retroviruses provide molecular fossils for studying the ancient evolutionary history of retroviruses. Here, we report our independent discovery and analysis of endogenous lentiviral insertions (Mustelidae endogenous lentivirus [MELV]) within the genomes of weasel family (Mustelidae). Genome-scale screening identified MELV elements in the domestic ferret (Mustela putorius furo) genome (MELVmpf). MELVmpf exhibits a typical lentiviral genomic organization. Phylogenetic analyses position MELVmpf basal to either primate lentiviruses or feline immunodeficiency virus. Moreover, we verified the presence of MELV insertions in the genomes of several species of the Lutrinae and Mustelinae subfamilies but not the Martinae subfamily, suggesting that the invasion of MELV into the Mustelidae genomes likely took place between 8.8 and 11.8 Ma. The discovery of MELV in weasel genomes extends the host range of lentiviruses to the Caniformia (order Carnivora) and provides important insights into the prehistoric diversity of lentiviruses. PMID:22522310

  16. 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

  17. 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

  18. Endogenous lentiviral elements in the weasel family (Mustelidae).

    PubMed

    Han, Guan-Zhu; Worobey, Michael

    2012-10-01

    Endogenous retroviruses provide molecular fossils for studying the ancient evolutionary history of retroviruses. Here, we report our independent discovery and analysis of endogenous lentiviral insertions (Mustelidae endogenous lentivirus [MELV]) within the genomes of weasel family (Mustelidae). Genome-scale screening identified MELV elements in the domestic ferret (Mustela putorius furo) genome (MELVmpf). MELVmpf exhibits a typical lentiviral genomic organization. Phylogenetic analyses position MELVmpf basal to either primate lentiviruses or feline immunodeficiency virus. Moreover, we verified the presence of MELV insertions in the genomes of several species of the Lutrinae and Mustelinae subfamilies but not the Martinae subfamily, suggesting that the invasion of MELV into the Mustelidae genomes likely took place between 8.8 and 11.8 Ma. The discovery of MELV in weasel genomes extends the host range of lentiviruses to the Caniformia (order Carnivora) and provides important insights into the prehistoric diversity of lentiviruses.

  19. 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.

  20. Reassociation with beta 2-microglobulin is necessary for Kb class I major histocompatibility complex binding of exogenous peptides.

    PubMed Central

    Rock, K L; Rothstein, L E; Gamble, S R; Benacerraf, B

    1990-01-01

    T lymphocytes recognize endogenously produced antigenic peptides in association with major histocompatibility complex (MHC)-encoded molecules. Peptides from the extracellular fluid can be displayed in association with class I and class II MHC molecules. Here we report that mature Kb class I MHC molecules bind peptides upon dissociation and reassociation of their light chain. Intact Kb heterodimers, unlike class II MHC molecules, are relatively unreceptive to binding peptides. This property may maintain segregation of class I and class II MHC-restricted peptides and has implications for the use of peptides as vaccines. Images PMID:2217182

  1. SNIPER peptide-mediated degradation of endogenous proteins.

    PubMed

    Fan, Xuelai; Wang, Yu Tian

    2015-03-02

    Rapid and reversible methods for altering the function of endogenous proteins are not only indispensable tools for probing complex biological systems, but may potentially drive the development of new therapeutics for the treatment of human diseases. Genetic approaches have provided insights into protein function, but are limited in speed, reversibility and spatiotemporal control. To overcome these limitations, we have developed a peptide-based method (SNIPER: Selective Native Protein Eradication) to degrade any given endogenous protein at the post-translational level by harnessing chaperone-mediated autophagy, a major intracellular protein degradation pathway. This unit presents a typical strategy in the design and validation of a protein-knockdown peptide.

  2. The first full-length endogenous hepadnaviruses: identification and analysis.

    PubMed

    Liu, Wei; Pan, Shaokun; Yang, Huijuan; Bai, Weiya; Shen, Zhongliang; Liu, Jing; Xie, Youhua

    2012-09-01

    In silico screening of metazoan genome data identified multiple endogenous hepadnaviral elements in the budgerigar (Melopsittacus undulatus) genome, most notably two elements comprising about 1.3 × and 1.0 × the full-length genome. Phylogenetic and molecular dating analyses show that endogenous budgerigar hepatitis B viruses (eBHBV) share an ancestor with extant avihepadnaviruses and infiltrated the budgerigar genome millions of years ago. Identification of full-length genomes with preserved key features like ε signals could enable resurrection of ancient BHBV. PMID:22718817

  3. Pilot Class Testing: Statistics.

    ERIC Educational Resources Information Center

    Washington Univ., Seattle. Washington Foreign Language Program.

    Statistics derived from test score data from the pilot classes participating in the Washington Foreign Language Program are presented in tables in this report. An index accompanies the tables, itemizing the classes by level (FLES, middle, and high school), grade test, language skill, and school. MLA-Coop test performances for each class were…

  4. 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,…

  5. 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…

  6. 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.

  7. 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.

  8. Social class and body weight among Chinese urban adults: the role of the middle classes in the nutrition transition.

    PubMed

    Bonnefond, Céline; Clément, Matthieu

    2014-07-01

    While a plethoric empirical literature addresses the relationship between socio-economic status and body weight, little is known about the influence of social class on nutritional outcomes, particularly in developing countries. The purpose of this article is to contribute to the analysis of the social determinants of adult body weight in urban China by taking into account the influence of social class. More specifically, we propose to analyse the position of the Chinese urban middle class in terms of being overweight or obese. The empirical investigations conducted as part of this research are based on a sample of 1320 households and 2841 adults from the China Health and Nutrition Survey for 2009. For the first step, we combine an economic approach and a sociological approach to identify social classes at household level. First, households with an annual per capita income between 10,000 Yuan and the 95th income percentile are considered as members of the middle class. Second, we strengthen the characterization of the middle class using information on education and employment. By applying clustering methods, we identify four groups: the elderly and inactive middle class, the old middle class, the lower middle class and the new middle class. For the second step, we implement an econometric analysis to assess the influence of social class on adult body mass index and on the probability of being overweight or obese. We use multinomial treatment regressions to deal with the endogeneity of the social class variable. Our results show that among the four subgroups of the urban middle class, the new middle class is the only one to be relatively well-protected against obesity. We suggest that this group plays a special role in adopting healthier food consumption habits and seems to be at a more advanced stage of the nutrition transition.

  9. 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...

  10. 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…

  11. 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.

  12. Endogenous Depression in the Elderly: Prevalence and Agreement among Measures.

    ERIC Educational Resources Information Center

    Gallagher-Thompson, Dolores; And Others

    1992-01-01

    Examined agreement among diagnoses made according to 5 definitions of endogenous depression in 99 depressed elders. Poor to fair agreement was generally demonstrated, except for Research Diagnostic Criteria and Diagnostic and Statistical Manual of Mental Disorders, which demonstrated excellent agreement. Mostly, demographic and clinical variables…

  13. 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…

  14. [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.

  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. 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...

  17. A population of endogenous pararetrovirus genomes in carrizo citrange

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complete genomes of three related endogenous pararetroviruses (EPRVs) were obtained by 454 sequencing of nucleic acid extracts from ‘Carrizo’citrange, used as a citrus rootstock. Numerous homologous sequences have been found in the sweet orange genome. The new EPRVs are most closely related to...

  18. New horizons for newborn brain protection: enhancing endogenous neuroprotection.

    PubMed

    Hassell, K Jane; Ezzati, Mojgan; Alonso-Alconada, Daniel; Hausenloy, Derek J; Robertson, Nicola J

    2015-11-01

    Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade. PMID:26063194

  19. 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

  20. 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…

  1. 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,"...

  2. 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…

  3. Role of endogenous angiogenesis inhibitors in Down syndrome.

    PubMed

    Ryeom, Sandra; Folkman, Judah

    2009-03-01

    New blood vessel growth via angiogenesis is a fundamental process in both physiological and pathological conditions. Physiological angiogenesis is critical during embryogenesis and placental development, whereas pathological angiogenesis plays an important role in the progression of many diseases, most notably tumor growth. Tumor angiogenesis is well accepted to be regulated by a balance of proangiogenic and antiangiogenic factors produced both by tumor cells and surrounding stromal cells. For many years, investigation of antiangiogenic therapies for cancer has focused on the proangiogenic cytokine, vascular endothelial growth factor; its receptors; or downstream signaling pathways. However, more recently with the identification of endogenous angiogenesis inhibitors, studies have turned toward understanding the role of endogenous antiangiogenic proteins in preventing disease progression. Clinical clues have suggested that specific populations may have dysregulated angiogenesis due to differential expression of endogenous angiogenesis regulators. For example, individuals with Down syndrome may possess a systemic antiangiogenic state with a significantly decreased incidence of angiogenesis-dependent diseases. Our work suggests that endogenous angiogenesis inhibitors may be the master regulators controlling progression of angiogenesis-dependent diseases such as vascular anomalies and cancer. The molecular regulation of angiogenesis is not yet fully understood; however, the Down syndrome population may give us insights toward novel therapies for controlling angiogenesis in disease.

  4. 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

  5. New horizons for newborn brain protection: enhancing endogenous neuroprotection

    PubMed Central

    Hassell, K Jane; Ezzati, Mojgan; Alonso-Alconada, Daniel; Hausenloy, Derek J; Robertson, Nicola J

    2015-01-01

    Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy. There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade. PMID:26063194

  6. 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.

  7. Inhibition of endogenous lactate turnover with lactate infusion in humans

    SciTech Connect

    Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C. )

    1989-11-01

    The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U-{sup 14}C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production.

  8. 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…

  9. Endogenous methicillin-resistant Staphylococcus aureus endophthalmitis after leg trauma.

    PubMed

    Larson, Katie E; Carrillo-Marquez, Maria

    2015-08-01

    We present a case of endogenous endophthalmitis in a 13-year-old boy with methicillin-resistant Staphylococcus aureus sepsis. The patient underwent magnetic resonance imaging of the brain after intermittent anisocoria was noted on examination, leading to a diagnosis of endophthalmitis with a chorodial abscess.

  10. Inhibition of cellular respiration by endogenously produced carbon monoxide.

    PubMed

    D'Amico, Gabriela; Lam, Francis; Hagen, Thilo; Moncada, Salvador

    2006-06-01

    Endogenously produced nitric oxide (NO) interacts with mitochondrial cytochrome c oxidase, leading to inhibition of cellular respiration. This interaction has been shown to have important physiological and pathophysiological consequences. Exogenous carbon monoxide (CO) is also known to inhibit cytochrome c oxidase in vitro; however, it is not clear whether endogenously produced CO can inhibit cellular respiration and, if so, what the significance of this might be. In this study, we show that exogenous CO inhibits respiration in a moderate but persistent manner in HEK293 cells under ambient (21%) oxygen concentrations (K(i) = 1.44 microM). This effect of CO was increased (K(i) = 0.35 microM) by incubation in hypoxic conditions (1% oxygen). Endogenous CO, generated by HEK293 cells transfected with the inducible isoform of haem oxygenase (haem oxygenase-1; HO-1), also inhibited cellular respiration moderately (by 12%) and this was accompanied by inhibition (23%) of cytochrome c oxidase activity. When the cells were incubated in hypoxic conditions during HO-1 induction, the inhibitory effect of CO on cell respiration was markedly increased to 70%. Furthermore, endogenously produced CO was found to be responsible for the respiratory inhibition that occurs in RAW264.7 cells activated in hypoxic conditions with lipopolysaccharide and interferon-gamma, in the presence of N-(iminoethyl)-L-ornithine to prevent the synthesis of NO. Our results indicate that CO contributes significantly to the respiratory inhibition in activated cells, particularly under hypoxic conditions. Inhibition of cell respiration by endogenous CO through its interaction with cytochrome c oxidase might have an important role in inflammatory and hypoxic conditions.

  11. Relevance of tryptophan and tyrosine availability in endogenous and 'non-endogenous' depressives treated with imipramine or clomipramine.

    PubMed

    Møller, S E; Reisby, N; Ortmann, J; Elley, J; Krautwald, O

    1981-09-01

    This study was performed on 65 depressed in-patients who were included in previously reported trials of imipramine and clomipramine. Before and during treatment, blood samples were collected for estimation of the availability of tryptophan and tyrosine by measurement of their plasma ratios to competing amino acids, and for determination of plasma steady-state concentrations of imipramine, clomipramine and their demethylated metabolites. The patients were classified as endogenous or 'non-endogenous' depressives by means of diagnostic rating scales, and therapeutic efficacy was evaluated by means of the Hamilton rating scales. Neither imipramine nor clomipramine increased the availability of tryptophan or tyrosine. Three biochemical regions were defined: a low region including mostly patients with subnormal availability of both tryptophan and tyrosine, a medium region, and a high region including mostly patients with supernormal precursor availabilities. Endogenous depressives showed about the same biochemical distribution as controls whereas there tended to be a proportionately higher number of 'non-endogenous' depressives within the low region. Patients in the low region, irrespective of diagnostic classification, improved faster and more on imipramine than patients in the medium and high regions with comparable plasma drug levels. Patients on clomipramine tended to show a relationship between precursor availabilities and clinical response but no definite conclusion could be drawn from these data. The results suggest that determination of the pre-treatment tryptophan and tyrosine availability may be superior to diagnostic classification in predicting response to imipramine. The possible mode of action of tricyclic antidepressants is briefly discussed. PMID:6456290

  12. Mass-tag labeling reveals site-specific and endogenous levels of protein S-fatty acylation.

    PubMed

    Percher, Avital; Ramakrishnan, Srinivasan; Thinon, Emmanuelle; Yuan, Xiaoqiu; Yount, Jacob S; Hang, Howard C

    2016-04-19

    Fatty acylation of cysteine residues provides spatial and temporal control of protein function in cells and regulates important biological pathways in eukaryotes. Although recent methods have improved the detection and proteomic analysis of cysteine fatty (S-fatty) acylated proteins, understanding how specific sites and quantitative levels of this posttranslational modification modulate cellular pathways are still challenging. To analyze the endogenous levels of protein S-fatty acylation in cells, we developed a mass-tag labeling method based on hydroxylamine-sensitivity of thioesters and selective maleimide-modification of cysteines, termed acyl-PEG exchange (APE). We demonstrate that APE enables sensitive detection of protein S-acylation levels and is broadly applicable to different classes of S-palmitoylated membrane proteins. Using APE, we show that endogenous interferon-induced transmembrane protein 3 is S-fatty acylated on three cysteine residues and site-specific modification of highly conserved cysteines are crucial for the antiviral activity of this IFN-stimulated immune effector. APE therefore provides a general and sensitive method for analyzing the endogenous levels of protein S-fatty acylation and should facilitate quantitative studies of this regulated and dynamic lipid modification in biological systems.

  13. Mass-tag labeling reveals site-specific and endogenous levels of protein S-fatty acylation.

    PubMed

    Percher, Avital; Ramakrishnan, Srinivasan; Thinon, Emmanuelle; Yuan, Xiaoqiu; Yount, Jacob S; Hang, Howard C

    2016-04-19

    Fatty acylation of cysteine residues provides spatial and temporal control of protein function in cells and regulates important biological pathways in eukaryotes. Although recent methods have improved the detection and proteomic analysis of cysteine fatty (S-fatty) acylated proteins, understanding how specific sites and quantitative levels of this posttranslational modification modulate cellular pathways are still challenging. To analyze the endogenous levels of protein S-fatty acylation in cells, we developed a mass-tag labeling method based on hydroxylamine-sensitivity of thioesters and selective maleimide-modification of cysteines, termed acyl-PEG exchange (APE). We demonstrate that APE enables sensitive detection of protein S-acylation levels and is broadly applicable to different classes of S-palmitoylated membrane proteins. Using APE, we show that endogenous interferon-induced transmembrane protein 3 is S-fatty acylated on three cysteine residues and site-specific modification of highly conserved cysteines are crucial for the antiviral activity of this IFN-stimulated immune effector. APE therefore provides a general and sensitive method for analyzing the endogenous levels of protein S-fatty acylation and should facilitate quantitative studies of this regulated and dynamic lipid modification in biological systems. PMID:27044110

  14. 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.

  15. 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

  16. 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.

  17. 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...

  18. 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…

  19. 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.

  20. Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids

    PubMed Central

    Louw-du Toit, Renate; Perkins, Meghan S.; Snoep, Jacky L.; Storbeck, Karl-Heinz; Africander, Donita

    2016-01-01

    Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis. PMID:27706226

  1. Competition between endogenous and exogenous orienting of visual attention.

    PubMed

    Berger, Andrea; Henik, Avishai; Rafal, Robert

    2005-05-01

    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 their validity was manipulated orthogonally to examine whether attention mechanisms are mediated by separate systems and whether they have additive and independent effects on visual detection and discrimination. The results showed that each orienting mechanism developed its typical and independent effect in every case except for the difficult identification task. A theoretical framework for understanding the relationship between endogenous and exogenous orienting of attention is proposed, tested, and confirmed.

  2. 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.

  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. The endogenous opioid system: a common substrate in drug addiction.

    PubMed

    Trigo, José Manuel; Martin-García, Elena; Berrendero, Fernando; Robledo, Patricia; Maldonado, Rafael

    2010-05-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.

  5. Endogenous RNAi and adaptation to environment in C. elegans

    PubMed Central

    Grishok, Alla

    2012-01-01

    The contributions of short RNAs to the control of repetitive elements are well documented in animals and plants. Here, the role of endogenous RNAi and AF10 homolog ZFP-1 in the adaptation of C. elegans to the environment is discussed. First, modulation of insulin signaling through regulation of transcription of the PDK-1 kinase (Mansisidor et al., PLoS Genetics, 2011) is reviewed. Second, an siRNA-based natural selection model is proposed in which variation in endogenous siRNA pools between individuals is subject to natural selection similarly to DNA-based genetic variation. The value of C. elegans for the research of siRNA-based epigenetic variation and adaptation is highlighted. PMID:24058837

  6. Endogenous K-ras signaling in erythroid differentiation.

    PubMed

    Zhang, Jing; Lodish, Harvey F

    2007-08-15

    K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.

  7. Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors.

    PubMed

    Pomorska, Dorota K; Gach, Katarzyna; Janecka, Anna

    2014-01-01

    The main role of endogenous opioid peptides is the modulation of pain. Opioid peptides exert their analgesic activity by binding to the opioid receptors distributed widely in the central nervous system (CNS). However, opioid receptors are also found on tissues and organs outside the CNS, including the cells of the immune system, indicating that opioids are capable of exerting additional effects in periphery. Morphine, which is a gold standard in the treatment of chronic pain, is well-known for its immunosuppressive effects. Much less is known about the immunomodulatory effects exerted by endogenous (enkephalins, endorphins, dynorphins and endomorphins) and synthetic peptides activating opioid receptors. In this review we tried to summarize opioid peptide-mediated modulation of immune cell functions which can be stimulatory as well as inhibitory. PMID:25553430

  8. 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.

  9. [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.

  10. Diet-induced obese mice retain endogenous leptin action.

    PubMed

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-01

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.

  11. 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

  12. THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES

    PubMed Central

    Snell, E. S.; Atkins, Elisha

    1965-01-01

    Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated. PMID:14319400

  13. Endogenous CO dynamics monitoring in breath by tunable diode laser

    NASA Astrophysics Data System (ADS)

    Kouznetsov, Andrian I.; Stepanov, Eugene V.; Shulagin, Yurii A.; Skrupskii, Vladimir A.

    1996-04-01

    High sensitive CO gas analyzer based on tunable diode laser (TDL) was used as a real time monitor of endogenous carbon monoxide in a set of breath physiology experiments. The measurements of the CO content dynamics in exhaled air with 10 ppb sensitivity were attended with detection of carbon dioxide and O2 in breath, lung ventilation parameters, heart rate and blood analysis using conventional techniques. Variations of endogenous CO in human breath caused by hyperoxia, hypoxia, hyperventilation as well as sport loading were studied in real time. Scattering of the CO variation time constants was observed for different tested persons. Possible reasons for this scattering related with the organisms' physiology peculiarities are discussed.

  14. 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

  15. 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.

  16. The Conversation Class

    ERIC Educational Resources Information Center

    Jackson, Acy L.

    2012-01-01

    The conversation class occupies a unique place in the process of learning English as a second or foreign language. From the author's own experience in conducting special conversation classes with Persian-speaking adults, he has drawn up a number of simple but important guidelines, some of which he hopes may provide helpful suggestions for the…

  17. 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…

  18. 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)…

  19. 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…

  20. 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

  1. 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

    2013-08-14

    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.

  2. 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.

  3. [The immunological mechanisms of the tissue lesions in endogenous uveitis].

    PubMed

    Todea, V

    1994-01-01

    The endogenous uveitis is essentially an immunologic disease, although it has a very variable immunology. During the immune response are implied the reactions of tardive hypersensibility (by immune complexes), hypersensibility through antibodies produced intraocularly or transported by the overall circulation and rarely, immediate hypersensibility reaction. The absence of lymphatics in the eye and of the antigenic cells in the tissues which limit the anterior chamber, implies an active, deviated immunity response, denoted by the term ACAID. PMID:8060956

  4. Pseudogene-derived endogenous siRNAs and their function.

    PubMed

    Chan, Wen-Ling; Chang, Jan-Gowth

    2014-01-01

    Pseudogenes were once considered genomic fossils, but recent studies indicate that they may function as gene regulators through the generation of endogenous small interfering RNAs (esiRNAs), antisense RNAs, and decoys for microRNAs. In this review, we summarize pseudogene study methods, emphasizing relevant publicly available resources, and we describe a systematic pipeline to identify pseudogene-derived esiRNAs and their targets, which can lead to a deeper understanding of pseudogene function.

  5. 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

  6. Peptic ulcer disease in endogenous hypercortisolism: myth or reality?

    PubMed

    Hatipoglu, Esra; Caglar, Asli Sezgin; Caglar, Erkan; Ugurlu, Serdal; Tuncer, Murat; Kadioglu, Pinar

    2015-11-01

    Many clinicians believe hypercortisolism is ulcerogenic. However, data from clinical studies show that prophylaxis for peptic ulcer disease is no longer recommended in patients receiving corticosteroid treatment. This has not yet been verified in endogenous hypercortisolism by controlled clinical studies. The purpose of the current study was to evaluate the relationship between endogenous Cushing's syndrome (CS) and peptic ulcer disease and Helicobacter pylori infection. The study group contained 20 cases with CS resulting from ACTH-dependent endogenous hypercortisolism. The control groups consisted of 14 age- and gender-matched cases receiving exogenous corticosteroid therapy and 100 cases of dyspepsia with non-cushingoid features. Upper gastrointestinal endoscopy was performed on all cases. Biopsies were taken from five different points: two samples from the antrum, two samples from the corpus, and one sample from the fundus. A histological diagnosis of Helicobacter pylori infection was also obtained from evaluation of biopsy specimens. The frequency of stomach and duodenal ulcers did not vary between the groups (p = 0.5 and p = 0.7). Antral gastritis was less frequent and pangastritis was more common in cases with CS compared to the healthy controls (p = 0.001 and p < 0.001). The incidence of Candida esophagitis was more frequent in cases with CS compared to cases with corticosteroid treatment and healthy controls (p = 0.03). Histopathological findings and frequency of Helicobacter pylori based on pathology results did not vary between the three groups. It is possible that neither exogenous nor endogenous corticosteroid excess directly causes peptic ulcer or Helicobacter pylori infection. Prophylactic use of proton pump inhibitors is not compulsory for hypercortisolism of any type.

  7. 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.

  8. Behavioral fractality in marine copepods: Endogenous rhythms versus exogenous stressors

    NASA Astrophysics Data System (ADS)

    Seuront, Laurent

    2011-01-01

    The presence of endogenous rhythms in the swimming behavior of five common species of copepods (i.e. minute marine crustaceans) was investigated through comparisons of the scaling properties of their three-dimensional trajectories and cumulative probability distribution functions of move lengths recorded during the day and at night. Beside clear inter-specific differences in their behavioral scaling properties, the five species exhibited an increase in path tortuosity at night, consistent with an increase in food foraging activity. Given the absence of food under all experimental conditions, this suggests the presence of an endogenous swimming rhythm consistent with the widely reported pattern of ascent at dusk resulting in copepods entering the food-rich surface layer at night. The impact of the stress exerted on swimming behavior by changes in the light regime (i.e. light and dark conditions respectively experienced at night and during the day) and the related copepod behavioral adaptivity was also investigated. The low and high fractal dimensions respectively observed during daytime in the dark and during night-time under conditions of simulated daytime indicate that these organisms have the ability to adjust the complexity of their swimming path depending on exogenous factors, independent of their actual endogenous rhythms. The scaling exponents of the cumulative probability distribution function of move lengths exhibit a significant decrease during daylight hours under simulated night-time conditions and during the night under simulated daytime conditions, suggesting an increase in the stress levels experienced by the five species considered. It is finally shown that the stress exerted on endogenous behavioral diel variability by exogenous cues has a species-specific effect on copepods.

  9. 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 ...

  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.

  11. ENDOGENOUS CARDIOTONIC STEROIDS AND SALT-SENSITIVE HYPERTENSION

    PubMed Central

    Fedorova, Olga V.; Shapiro, Joseph I.; Bagrov, Alexei Y.

    2010-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis like factors, have been postulated to play important roles in pathogenesis of hypertension for nearly half of a century. For the past 50 years biomedical scientists have been in quest of an unidentified factor or hormone that both increases blood pressure and renal sodium excretion; this “natriuretic hormone” was, in fact, postulated to interact with the Na/K-ATPase. Recent discoveries have led to the identification of steroid molecules which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other systems that regulate renal salt handling and contribute to the salt-sensitivity of blood pressure. Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CTS can signal through the Na/K-ATPase. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the central regulation of blood pressure and regulation of cell growth, and development of cardiovascular and renal fibrosis in particular. PMID:20347967

  12. Endogenous Cardioprotective Agents: Role in Pre and Postconditioning.

    PubMed

    Penna, Claudia; Granata, Riccarda; Tocchetti, Carlo Gabriele; Gallo, Maria Pia; Alloatti, Giuseppe; Pagliaro, Pasquale

    2015-01-01

    Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful effects of acute myocardial ischemia and subsequent reperfusion injury. Cardioprotection against acute ischemia/ reperfusion injury is made possible by the "conditioning protocols." Conditioning is obtained by applying a few periods of brief ischemia and reperfusion in the event of prolonged (index) ischemia that may cause myocardial infarction. Whilst the conditioning stimulus is applied before the index ischemia in ischemic pre-conditioning, it is applied after the event in post-conditioning. Pre and post- conditioning stimuli can be applied in a different/remote organ (remote pre- and post-conditioning); in this case conditioning stimulus can also be applied during the index event, in the so called remote per-conditioning. All these endogenous cardioprotective strategies recruit endogenous cytoprotective agents and factors that elicit specific cardioprotective pathways. Here, we discuss many of these cardioprotective factors compared to literature and highlight their main characteristics and mechanisms of action. Enphasis is given to endogenous cardioprotective agents acting or not on surface receptors, including chromogranin A derivatives, ghrelin-associated peptides, growth factors and cytokines, and to microvesicles and exosomes. Moreover the cardioprotective effects of gasotransmitters nitric oxide, hydrogen sulphide and carbon monoxide are reviewed. The possible clinical translation of these knowledge for future successful therapies is briefly and critically discussed.

  13. 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

  14. Determination of endogenous faecal phosphorus loss in goats.

    PubMed

    Tayo, Grace Oluwatoyin; Tang, Shao Xun; Tan, Zhi Liang; Sun, Zhi Hong; Wang, Min; Zhou, Chuan She; Han, Xue Feng

    2009-04-01

    Four black Liuyang wether goats were fed with corn stover and concentrate formulated to contain four levels of dietary phosphorus (P), including 0.129, 0.140, 0.162 and 0.180% of P. In a 4 x 4 Latin square experiment the endogenous faecal P loss was determined by the regression technique and the substitution method. Treatment effects on faecal and urinary P output, apparent P digestibility and P retention, and saliva P secretion were not significant. A linear relationship was observed between apparent faecal digestible P (Y, g/kg DMI) and P intake (X, g/kg DMI), which was described by the equation: Y = 0.4799 X -0.9209, r2 = 0.9869, (p < 0.05). The true P digestibility determined by the regression technique and the substitution method amounted to 48.0 and 48.9%, respectively; the recorded endogenous faecal P losses were 0.92 and 0.93 g/kg DMI, respectively. The study demonstrated the potential of the regression method as well as the substitution method for estimation of true P digestibility and endogenous faecal P losses in goats.

  15. 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

  16. Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

    PubMed Central

    Bagrov, Alexei Y.; Shapiro, Joseph I.; Fedorova, Olga V.

    2009-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, have been postulated to play important roles in health and disease for nearly half a century. Recent discoveries, which include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of an alternative mechanism by which CTS can signal through the Na+/K+-ATPase, have increased the interest in this field substantially. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the regulation of cell growth, differentiation, apoptosis, and fibrosis, the modulation of immunity and of carbohydrate metabolism, and the control of various central nervous functions and even behavior. This review focuses on the physiological interactions between CTS and other regulatory systems that may be important in the pathophysiology of essential hypertension, preeclampsia, end-stage renal disease, congestive heart failure, and diabetes mellitus. Based on our increasing understanding of the regulation of CTS as well as the molecular mechanisms of these hormone increases, we also discuss potential therapeutic strategies. PMID:19325075

  17. 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

  18. 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

  19. 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

  20. Sphingosine Lysolipids in the CNS: Endogenous Cannabinoid Antagonists or a Parallel Pain Modulatory System?

    PubMed Central

    Selley, Dana E.; Welch, Sandra P.; Sim-Selley, Laura J.

    2014-01-01

    A significant number of patients experience chronic pain and the intractable side effects of currently prescribed pain medications. Recent evidence indicates important pain modulatory roles for two classes of G-protein-coupled receptors that are activated by endogenous lipid ligands, the endocannabinoid (eCB) and sphingosine-1-phosphate (S1P) receptors, which are widely expressed in both the immune and nervous systems. In the central nervous system (CNS), CB1 cannabinoid and S1P1 receptors are most abundantly expressed and exhibit overlapping anatomical distributions and similar signaling mechanisms. The eCB system has emerged as a potential target for treatment of chronic pain, but comparatively little is known about the roles of S1P in pain regulation. Both eCB and S1P systems modulate pain perception via the central and peripheral nervous systems. In most paradigms studied, the eCB system mainly inhibits pain perception. In contrast, S1P acting peripherally at S1P1 and S1P3 receptors can enhance sensitivity to various pain stimuli or elicit spontaneous pain. However, S1P acting at S1P1 receptors and possibly other targets in the CNS can attenuate sensitivity to various pain stimuli. Interestingly, other endogenous sphingolipid derivatives might play a role in central pain sensitization. Moreover, these sphingolipids can also act as CB1 cannabinoid receptor antagonists, but the physiological relevance of this interaction is unknown. Overall, both eCB and sphingolipid systems offer promising targets for the treatment of chronic pain. This review compares and contrasts the eCB and S1P systems with a focus on their roles in pain modulation, and considers possible points of interaction between these systems. PMID:23782998

  1. 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

  2. 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

  3. 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…

  4. 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

  5. Venture Class Launch Services

    NASA Technical Reports Server (NTRS)

    Wiese, Mark

    2016-01-01

    Provide an introduction to the Launch Services Program, and specifically the strategic initiative that drove the Venture Class Launch Services contracts. Provide information from the VCLS request for proposals, as well as the Agency's CubeSat Launch Initiative.

  6. Class, health and justice.

    PubMed

    Marchand, S; Wikler, D; Landesman, B

    1998-01-01

    Class inequalities in health are intuitively unjust. Although the link between social class and health status has been fully documented, the precise nature of the injustice has not been made clear. Four alternative views are presented, corresponding to four goals: (1) maximizing the sum total of health; (2) equalizing the health status of higher and lower social classes; (3) maximizing the health status of the lowest social class; and (4) maximizing the health status of the sickest individuals in society. The nature of the injustice is further obscured by several theoretical and empirical questions, like the degree and significance of personal responsibility for illness and the relation of the degree of economic inequality to sum total of health.

  7. 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)

  8. 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)

  9. 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.

  10. A class in astrobiology

    NASA Astrophysics Data System (ADS)

    Airieau, S. A.

    1999-09-01

    The goal of this class is to provide basic astrobiology knowledge to upper division science students. The scope is broad and in-depth coverage is not possible in this introductory course. Instead, science students from various branches of academia can acquire a broad basis and understanding of the other fields: astronomy, biology, geology, biochemistry, planetary and space sciences. The class is highly modular and allows instructors to concentrate on or eliminate topics according to their priorities and preferences.

  11. 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

  12. 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.

  13. Trafficking of an endogenous potassium channel in adult ventricular myocytes

    PubMed Central

    Wang, Tiantian; Cheng, Yvonne; Dou, Ying; Goonesekara, Charitha; David, Jens-Peter; Steele, David F.; Huang, Chen

    2012-01-01

    The roles of several small GTPases in the expression of an endogenous potassium current, Ito,f, in adult rat ventricular myocytes have been investigated. The results indicate that forward trafficking of newly synthesized Kv4.2, which underlies Ito,f in these cells, requires both Rab1 and Sar1 function. Expression of a Rab1 dominant negative (DN) reduced Ito,f current density by roughly one-half relative to control, mCherry-transfected myocytes. Similarly, expression of a Sar1DN nearly halved Ito,f current density. Rab11 is not essential to trafficking of Kv4.2, as expression of a Rab11DN had no effect on Ito,f over the time frames investigated here. In a process dependent on intact endoplasmic reticulum (ER)-to-Golgi transport, however, overexpression of wild-type Rab11 resulted in a doubling of Ito,f density; block of ER-to-Golgi traffic by Brefeldin A completely abrogated the effect. Also implicated in the trafficking of Kv4.2 are Rab5 and Rab4. Rab5DN expression increased endogenous Ito,f by two- to threefold, nonadditively with inhibition of dynamin-dependent endocytosis. And, in a phenomenon similar to that previously reported for myoblast-expressed Kv1.5, Rab4DN expression roughly doubled endogenous peak transient currents. Colocalization experiments confirmed the involvement of Rab4 in postinternalization trafficking of Kv4.2. There was little role evident for the lysosome in the degradation of internalized Kv4.2, as overexpression of neither wild-type nor DN isoforms of Rab7 had any effect on Ito,f. Instead, degradation may depend largely on the proteasome; the proteasome inhibitor MG132 significantly increased Ito,f density. PMID:22914645

  14. Visualization of an endogenous retinoic acid gradient across embryonic development.

    PubMed

    Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya; Higashijima, Shin-Ichi; Miyawaki, Atsushi

    2013-04-18

    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and

  15. Prostanoids inhibit release of endogenous norepinephrine from rat isolated trachea.

    PubMed

    Racké, K; Bähring, J; Langer, C; Bräutigam, M; Wessler, I

    1992-11-01

    Prostanoids, of epithelial origin, are known as modulators of several processes in the airways. The present study examined whether prostanoids are involved in the local control of sympathetic neurotransmission. The release of endogenous norepinephrine from rat isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine, and tyrosine. In different series of experiments, indomethacin (3 mumol/L) increased the evoked release of endogenous norepinephrine by 70 to 80%. In the presence of indomethacin, prostaglandin E2 (PGE2) and several prostanoid receptor agonists inhibited the evoked release of norepinephrine in a concentration-dependent manner, maximally by 60 to 70%. According to the concentration producing 35% inhibition of norepinephrine release (half-maximal effect), the following rank order of potencies was observed (EC35): nocloprost (8 nmol/L), sulprostone (30 nmol/L), PGE2 (308 nmol/L), iloprost (2 mumol/L), and U46619 (> 10 mumol/L). The EP1 receptor antagonist AH 6809 (3 mumol/L) had no effect on the evoked norepinephrine release and did not affect the inhibitory effect of 1 mumol/L of sulprostone. In the absence of indomethacin, the inhibitory effect of PGE2 was similar to that observed in the presence of indomethacin. After removal of the epithelium, the evoked norepinephrine release was markedly reduced. However, no significant effect of indomethacin was observed in epithelium-denuded tracheae. In conclusion, norepinephrine release in the rat trachea is inhibited via prostaglandin receptors that have the pharmacologic characteristics of the EP3 subtype. Endogenous eicosanoids, most likely of epithelial origin, are involved in the local control of the release of norepinephrine. PMID:1443867

  16. Endogenous Bioactive Lipids and the Regulation of Conventional Outflow Facility

    PubMed Central

    Wan, Zhou; Woodward, David F.; Stamer, W. Daniel

    2009-01-01

    Summary Perturbation of paracrine signaling within the human conventional outflow pathway influences tissue homeostasis and outflow function. For example, exogenous introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or prostaglandin F2α, to conventional outflow tissues alters the rate of drainage of aqueous humor through the trabecular meshwork, and into Schlemm’s canal. This review summarizes recent data that characterizes endogenous bioactive lipids, their receptors and associated signaling partners in the conventional outflow tract. We also discuss the potential of targeting such signaling pathways as a strategy for the development of therapeutics to treat ocular hypertension and glaucoma. PMID:19381354

  17. Endogenous RNA viruses of plants in insect genomes

    PubMed Central

    Cui, Jie; Holmes, Edward C.

    2013-01-01

    Endogenous viral elements (EVEs) derived from RNA viruses with no DNA stage are rare, especially those where the parental viruses possess single-strand positive-sense (ssRNA+) genomes. Here we provide evidence that EVEs that share a sequence similarity to ssRNA+viruses of plants are integrated into the genomes of a number of insects, including mosquito, fruit flies, bees, ant, silkworm, pea aphid, Monarch butterfly, and wasps. A preliminary phylogenetic analysis places these EVEs as divergent relatives of the Virgaviridae and three currently unclassified plant viral species. PMID:22410578

  18. Imaging of endogenous RNA using genetically encoded probes.

    PubMed

    Ozawa, Takeaki; Umezawa, Yoshio

    2011-03-01

    Imaging of RNAs in single cells revealed their localized transcription and specific function. Such information cannot be obtained from bulk measurements. This unit contains a protocol of an imaging method capable of visualizing endogenous RNAs bound to genetically encoded fluorescent probes in single living cells. The protocol includes methods of design and construction of the probes, their characterization, and imaging a target RNA in living cells. The methods for RNA imaging are generally applicable to many kinds of RNAs and may allow for elucidating novel functions of localized RNAs and understanding their dynamics in living cells. Curr. Protoc. Chem. Biol. 3:27-37 © 2011 by John Wiley & Sons, Inc.

  19. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

    NASA Technical Reports Server (NTRS)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.

    1988-01-01

    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  20. Divergent cardio-ventilatory and locomotor effects of centrally and peripherally administered urotensin II and urotensin II-related peptides in trout

    PubMed Central

    Vanegas, Gilmer; Leprince, Jérôme; Lancien, Frédéric; Mimassi, Nagi; Vaudry, Hubert; Le Mével, Jean-Claude

    2015-01-01

    The urotensin II (UII) gene family consists of four paralogous genes called UII, UII-related peptide (URP), URP1 and URP2. UII and URP peptides exhibit the same cyclic hexapeptide core sequence (CFWKYC) while the N- and C-terminal regions are variable. UII, URP1, and URP2 mRNAs are differentially expressed within the central nervous system of teleost fishes, suggesting that they may exert distinct functions. Although the cardiovascular, ventilatory and locomotor effects of UII have been described in teleosts, much less is known regarding the physiological actions of URPs. The goal of the present study was to compare the central and peripheral actions of picomolar doses (5–500 pmol) of trout UII, URP1, and URP2 on cardio-ventilatory variables and locomotor activity in the unanesthetized trout. Compared to vehicle, intracerebroventricular injection of UII, URP1 and URP2 evoked a gradual increase in total ventilation (VTOT) reaching statistical significance for doses of 50 and 500 pmol of UII and URP1 but for only 500 pmol of URP2. In addition, UII, URP1 and URP2 provoked an elevation of dorsal aortic blood pressure (PDA) accompanied with tachycardia. All peptides caused an increase in locomotor activity (ACT), at a threshold dose of 5 pmol for UII and URP1, and 50 pmol for URP2. After intra-arterial (IA) injection, and in contrast to their central effects, only the highest dose of UII and URP1 significantly elevated VTOT and ACT. UII produced a dose-dependent hypertensive effect with concomitant bradycardia while URP1 increased PDA and heart rate after injection of only the highest dose of peptide. URP2 did not evoke any cardio-ventilatory or locomotor effect after IA injection. Collectively, these findings support the hypothesis that endogenous UII, URP1 and URP2 in the trout brain may act as neurotransmitters and/or neuromodulators acting synergistically or differentially to control the cardio-respiratory and locomotor systems. In the periphery, the only

  1. Divergent cardio-ventilatory and locomotor effects of centrally and peripherally administered urotensin II and urotensin II-related peptides in trout.

    PubMed

    Vanegas, Gilmer; Leprince, Jérôme; Lancien, Frédéric; Mimassi, Nagi; Vaudry, Hubert; Le Mével, Jean-Claude

    2015-01-01

    The urotensin II (UII) gene family consists of four paralogous genes called UII, UII-related peptide (URP), URP1 and URP2. UII and URP peptides exhibit the same cyclic hexapeptide core sequence (CFWKYC) while the N- and C-terminal regions are variable. UII, URP1, and URP2 mRNAs are differentially expressed within the central nervous system of teleost fishes, suggesting that they may exert distinct functions. Although the cardiovascular, ventilatory and locomotor effects of UII have been described in teleosts, much less is known regarding the physiological actions of URPs. The goal of the present study was to compare the central and peripheral actions of picomolar doses (5-500 pmol) of trout UII, URP1, and URP2 on cardio-ventilatory variables and locomotor activity in the unanesthetized trout. Compared to vehicle, intracerebroventricular injection of UII, URP1 and URP2 evoked a gradual increase in total ventilation (V TOT) reaching statistical significance for doses of 50 and 500 pmol of UII and URP1 but for only 500 pmol of URP2. In addition, UII, URP1 and URP2 provoked an elevation of dorsal aortic blood pressure (P DA) accompanied with tachycardia. All peptides caused an increase in locomotor activity (A CT), at a threshold dose of 5 pmol for UII and URP1, and 50 pmol for URP2. After intra-arterial (IA) injection, and in contrast to their central effects, only the highest dose of UII and URP1 significantly elevated V TOT and A CT. UII produced a dose-dependent hypertensive effect with concomitant bradycardia while URP1 increased P DA and heart rate after injection of only the highest dose of peptide. URP2 did not evoke any cardio-ventilatory or locomotor effect after IA injection. Collectively, these findings support the hypothesis that endogenous UII, URP1 and URP2 in the trout brain may act as neurotransmitters and/or neuromodulators acting synergistically or differentially to control the cardio-respiratory and locomotor systems. In the periphery, the only

  2. Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs

    SciTech Connect

    Oetomo, S.B.; Lewis, J.; Ikegami, M.; Jobe, A.H. )

    1990-04-01

    The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radiolabeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

  3. Intergenerational redistribution in a small open economy with endogenous fertility.

    PubMed

    Kolmar, M

    1997-08-01

    The literature comparing fully funded (FF) and pay-as-you-go (PAYG) financed public pension systems in small, open economies stresses the importance of the Aaron condition as an empirical measure to decide which system can be expected to lead to a higher long-run welfare. A country with a PAYG system has a higher level of utility than a country with a FF system if the growth rate of total wage income exceeds the interest rate. Endogenizing population growth makes one determinant of the growth rate of wage incomes endogenous. The author demonstrates why the Aaron condition ceases to be a good indicator in this case. For PAYG-financed pension systems, claims can be calculated according to individual contributions or the number of children in a family. Analysis determined that for both structural determinants there is no interior solution of the problem of intergenerational utility maximization. Pure systems are therefore always welfare maximizing. Moreover, children-related pension claims induce a fiscal externality which tends to be positive. The determination of the optimal contribution rate shows that the Aaron condition is generally a misleading indicator for the comparison of FF and PAYG-financed pension systems.

  4. Presynaptic Control of Corticostriatal Synapses by Endogenous GABA

    PubMed Central

    Logie, Christopher; Bagetta, Vincenza

    2013-01-01

    Corticostriatal terminals have presynaptic GABAB receptors that limit glutamate release, but how these receptors are activated by endogenous GABA released by different types of striatal neurons is still unknown. To address this issue, we used single and paired whole-cell recordings combined with stimulation of corticostriatal fibers in rats and mice. In the presence of opioid, GABAA, and NK1 receptor antagonists, antidromic stimulation of a population of striatal projection neurons caused suppression of subsequently evoked EPSPs in projection neurons. These effects were larger at intervals of 500 ms than 1 or 2 s, and were fully blocked by the selective GABAB receptor antagonist CGP 52432. Bursts of spikes in individual projection neurons were not able to inhibit evoked EPSPs. Similarly, spikes in fast spiking interneurons and low-threshold spike interneurons failed to elicit detectable effects mediated by GABAB receptors. Conversely, spikes in individual neurogliaform interneurons suppressed evoked EPSPs, and these effects were blocked by CGP 52432. These results provide the first demonstration of how GABAB receptors are activated by endogenous GABA released by striatal neuronal types. PMID:24068811

  5. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

    PubMed Central

    Zhang, Wei; Zecca, Luigi; Wilson, Belinda; Ren, RW; Wang, Yong-jun; Wang, Xiao-min; Hong, Jau-Shyong

    2013-01-01

    Substantial evidence indicates that neuroinflammation caused by over-activation of microglial in the substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in the death of dopaminergic neurons. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of the substantia nigra, on microglial activation and associated dopaminergic neurotoxicity were investigated. Using multiple well-established primary mesencephalic cultures, we tested whether human NM (HNM) could activate microglia, thereby provoking dopaminergic neurodegeneration. The results demonstrated that in primary mesencephalic neuron-glia cultures, HNM caused dopaminergic neuronal damage characterized by the decreased dopamine uptake and reduced numbers and shorted dendrites of dopaminergic neurons. HNM-induced degeneration was relatively selective to dopaminergic neurons since the other types of neurons determined by either gamma-aminobutyric acid uptake and total neuronal numbers after staining showed smaller decrease. We demonstrated that HNM produced modest dopaminergic neurotoxicity in neuron-enriched cultures; in contrast, much greater neurotoxicity was observed in the presence of microglia. HNM-induced microglial activation was shown by morphological changes and production of proinflammatory and neurotoxic factors. These results suggest that HNM, once released from damaged dopaminergic neurons, can be an potent endogenous activator involved in the reactivation of microglia, which may mediate disease progression. Thus, inhibition of reactive microglia can be a useful strategy for PD therapy. PMID:23276965

  6. Endogenous change: on cooperation and water in ancient history

    NASA Astrophysics Data System (ADS)

    Pande, S.; Ertsen, M.

    2013-04-01

    We propose and test the theory of endogenous change based on historical reconstructions of two ancient civilizations, Indus and Hohokam, in two water scarce basins, the Indus basin in the Indian subcontinent and the Lower Colorado basin in Southwestern United States. The endogenous institutional change sees changes in institutions as a sequence of equilibria brought about by changes in "quasi-parameters" such as rainfall, population density, soil and land use induced water resource availability. In the historical reconstructions of ancient civilizations, institutions are proximated by the scale of cooperation be it in the form of the extent of trade, sophisticated irrigation network, a centrally planned state or a loosely held state with a common cultural identity. The "quasi-parameters" either change naturally or are changed by humans and the changes affect the stability of cooperative structures over time. However, human influenced changes in the quasi-parameters itself are conditioned on the scale of existing cooperative structures. We thus provide insights into the quantitative dimensions of water access by ancient populations and its co-evolution with the socioeconomic and sociopolitical organization of the human past. We however do not suggest that water manipulation was the single most significant factor in stimulating social development and complexity - clearly this has been shown as highly reductionist, even misleading. The paper cautiously contributes to proximate prediction of hydrological change by attempting to understand the complexity of coupled human-hydrological systems.

  7. Cellular responses to endogenous electrochemical gradients in morphological development

    NASA Technical Reports Server (NTRS)

    Desrosiers, M. F.

    1996-01-01

    Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: (1) intercellular organization and development through their effects on the membrane potential, (2) direct effects such as electrophoresis of membrane components, and (3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: (1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, (2) the ionic conductance changes within seconds showing altered transport between the tissues, and (3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

  8. Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein

    PubMed Central

    Much, Christian; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O’Carroll, Dónal

    2016-01-01

    Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse. PMID:27254021

  9. Endogenous cannabinoid system as a modulator of food intake.

    PubMed

    Cota, D; Marsicano, G; Lutz, B; Vicennati, V; Stalla, G K; Pasquali, R; Pagotto, U

    2003-03-01

    The ability of Cannabis sativa (marijuana) to increase hunger has been noticed for centuries, although intensive research on its molecular mode of action started only after the characterization of its main psychoactive component Delta(9)-tetrahydrocannabinol in the late 1960s. Despite the public concern related to the abuse of marijuana and its derivatives, scientific studies have pointed to the therapeutic potentials of cannabinoid compounds and have highlighted their ability to stimulate appetite, especially for sweet and palatable food. Later, the discovery of specific receptors and their endogenous ligands (endocannabinoids) suggested the existence of an endogenous cannabinoid system, providing a physiological basis for biological effects induced by marijuana and other cannabinoids. Epidemiological reports describing the appetite-stimulating properties of cannabinoids and the recent insights into the molecular mechanisms underlying cannabinoid action have proposed a central role of the cannabinoid system in obesity. The aim of this review is to provide an extensive overview on the role of this neuromodulatory system in feeding behavior by summarizing the most relevant data obtained from human and animal studies and by elucidating the interactions of the cannabinoid system with the most important neuronal networks and metabolic pathways involved in the control of food intake. Finally, a critical evaluation of future potential therapeutical applications of cannabinoid antagonists in the therapy of obesity and eating disorders will be discussed.

  10. Cellular responses to endogenous electrochemical gradients in morphological development.

    PubMed

    Desrosiers, M F

    1996-01-01

    Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: 1) intercellular organization and development through their effects on the membrane potential, 2) direct effects such as electrophoresis of membrane components, and 3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: 1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, 2) the ionic conductance changes within seconds showing altered transport between the tissues, and 3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature. PMID:11538627

  11. Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of endothelial cells.

    PubMed

    Zhao, Xingyu; Jin, Lianhai; Shen, Nan; Xu, Bin; Zhang, Wei; Zhu, Hongli; Luo, Zhengli

    2013-01-01

    Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Herein, we investigated the protective effects of salidroside against hydrogen peroxide (H2O2)-induced oxidative damage in human endothelial cells (EVC-304). EVC-304 cells were incubated in the presence or absence of low steady states of H2O2 (3-4 µM) generated by glucose oxidase (GOX) with or without salidroside. 3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) assays were performed, together with Hoechst 33258 staining and flow cytometric analysis using Annexin-V and propidium iodide (PI) label. The results indicated that salidroside pretreatment attenuated endogenous H2O2 induced apoptotic cell death in EVC-304 cells in a dose-dependent pattern. Furthermore, Western blot data revealed that salidroside inhibited activation of caspase-3, 9 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by endogenous H2O2. It also decreased the expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. All these results demonstrated that salidroside may present a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases.

  12. Discovery and characterization of an endogenous CXCR4 antagonist.

    PubMed

    Zirafi, Onofrio; Kim, Kyeong-Ae; Ständker, Ludger; Mohr, Katharina B; Sauter, Daniel; Heigele, Anke; Kluge, Silvia F; Wiercinska, Eliza; Chudziak, Doreen; Richter, Rudolf; Moepps, Barbara; Gierschik, Peter; Vas, Virag; Geiger, Hartmut; Lamla, Markus; Weil, Tanja; Burster, Timo; Zgraja, Andreas; Daubeuf, Francois; Frossard, Nelly; Hachet-Haas, Muriel; Heunisch, Fabian; Reichetzeder, Christoph; Galzi, Jean-Luc; Pérez-Castells, Javier; Canales-Mayordomo, Angeles; Jiménez-Barbero, Jesus; Giménez-Gallego, Guillermo; Schneider, Marion; Shorter, James; Telenti, Amalio; Hocher, Berthold; Forssmann, Wolf-Georg; Bonig, Halvard; Kirchhoff, Frank; Münch, Jan

    2015-05-01

    CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation. PMID:25921529

  13. Endogenous cortisol levels influence exposure therapy in spider phobia.

    PubMed

    Lass-Hennemann, Johanna; Michael, Tanja

    2014-09-01

    Previous research in patients with phobia showed that the administration of glucocorticoids reduces fear in phobic situations and enhances exposure therapy. Glucocorticoids underlie a daily cycle with a peak in the morning and low levels during the evening and night. The aim of the present study was to investigate whether exposure is more effective when conducted in the morning when endogenous cortisol levels are high. Sixty patients meeting DSM IV criteria for specific phobia (animal type) were randomly assigned to one-session exposure treatment either at 08.00 a.m. (high cortisol group) or at 06.00 p.m. (low cortisol group). Participants returned for a posttreatment assessment one week after therapy and a follow-up assessment three months after therapy. Both groups showed good outcome, but patients treated in the morning exhibited significantly less fear of spiders in the behavioral approach test (BAT) and a trend for lower scores on the Fear of Spiders Questionnaire (FSQ) than patients treated in the evening. This effect was present at posttreatment and follow-up. Our findings indicate that exposure therapy is more effective in the morning than in the evening. We suggest that this may be due to higher endogenous cortisol levels in the morning group that enhance extinction memory.

  14. Spatial models of political competition with endogenous political parties.

    PubMed

    Laver, Michael; Schilperoord, Michel

    2007-09-29

    Two important human action selection processes are the choice by citizens of parties to support in elections and the choice by party leaders of policy 'packages' offered to citizens in order to attract this support. Having reviewed approaches analysing these choices and the reasons for doing this using the methodology of agent-based modelling, we extend a recent agent-based model of party competition to treat the number and identity of political parties as an output of, rather than an input to, the process of party competition. Party birth is modelled as an endogenous change of agent type from citizen to party leader, which requires describing citizen dissatisfaction with the history of the system. Endogenous birth and death of parties transforms into a dynamic system even in an environment where all agents have otherwise non-responsive adaptive rules. A key parameter is the survival threshold, with lower thresholds leaving citizens on average less dissatisfied. Paradoxically, the adaptive rule most successful for party leaders in winning votes makes citizens on average less happy than under other policy-selection rules.

  15. Coevolution of endogenous Betaretroviruses of sheep and their host

    PubMed Central

    Arnaud, F.; Varela, M.; Spencer, T. E.

    2014-01-01

    Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. Jaagsiekte sheep retrovirus (JSRV) is a pathogenic exogenous retrovirus and the causative agent of ovine pulmonary adenocarcinoma. The sheep genome contains at least 27 copies of endogenous retroviruses (enJSRVs) highly related to JSRV. enJSRVs have played several roles in the evolution of the domestic sheep as they are able to block the JSRV replication cycle and play a critical role in sheep conceptus development and placental morphogenesis. Available data strongly suggest that some dominant negative enJSRV proviruses (i.e. able to block JSRV replication) have been positively selected during evolution. Interestingly, viruses escaping the transdominant enJSRV loci have recently emerged (less than 200 years ago). Thus, endogenization of these retroviruses may still be occurring today. Therefore, sheep provide an exciting and unique system to study retrovirus-host coevolution. (Part of a Multi-author Review) PMID:18818869

  16. Dynamic nuclear polarization of nucleic acid with endogenously bound manganese.

    PubMed

    Wenk, Patricia; Kaushik, Monu; Richter, Diane; Vogel, Marc; Suess, Beatrix; Corzilius, Björn

    2015-09-01

    We report the direct dynamic nuclear polarization (DNP) of (13)C nuclei of a uniformly [(13)C,(15)N]-labeled, paramagnetic full-length hammerhead ribozyme (HHRz) complex with Mn(2+) where the enhanced polarization is fully provided by the endogenously bound metal ion and no exogenous polarizing agent is added. A (13)C enhancement factor of ε = 8 was observed by intra-complex DNP at 9.4 T. In contrast, "conventional" indirect and direct DNP experiments were performed using AMUPol as polarizing agent where we obtained a (1)H enhancement factor of ε ≈ 250. Comparison with the diamagnetic (Mg(2+)) HHRz complex shows that the presence of Mn(2+) only marginally influences the (DNP-enhanced) NMR properties of the RNA. Furthermore two-dimensional correlation spectra ((15)N-(13)C and (13)C-(13)C) reveal structural inhomogeneity in the frozen, amorphous state indicating the coexistence of several conformational states. These demonstrations of intra-complex DNP using an endogenous metal ion as well as DNP-enhanced MAS NMR of RNA in general yield important information for the development of new methods in structural biology. PMID:26219517

  17. Endogenous ouabain in renal Na(+) handling and related diseases.

    PubMed

    Manunta, Paolo; Messaggio, Elisabetta; Casamassima, Nunzia; Gatti, Guido; Carpini, Simona Delli; Zagato, Laura; Hamlyn, John M

    2010-12-01

    The Na(+) pump and its Endogenous modulator Ouabain (EO) can be considered as an ancestral enzymatic system, conserved among species ranging from Drosophila to humans, related to Na handling. In this review, we examine how EO is linked with vascular function in hypertension and if it impacts the pathogenesis of heart and renal failure. Moreover, the molecular mechanism of endogenous ouabain-linked hypertension involves the sodium pump/sodium-calcium exchanger duet. Biosynthesis of EO occurs in adrenal glands and is under the control of angiotensin II, ACTH and epinephrine. Elevated concentrations of EO and in the sub-nanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure. Experimental data suggest that the Na/K-ATPase α(2)-catalytic subunit causes EO-induced vasoconstriction. Finally, maneuvers that promote Na depletion, as diuretic therapy or reduced Na intake, raise the EO levels. Taken together, these findings suggest a key role for EO in body Na homeostasis.

  18. Studies on endogenous circulating calcium entry blocker and stimulator

    SciTech Connect

    Pang, P.K.T.; Yang, M.C.M.

    1986-03-01

    Several synthetic compounds have been studied extensively for their calcium entry blockade and stimulation in smooth muscles. It is hypothesized that there should be endogenous substances which control calcium entry into cells. We recently investigated the effect of some vasoactive hormones on calcium entry. Our studies on rat tail artery helical strip showed that the in vitro vasoconstriction produced by arginine vasopressin (AVP) decreased stepwise with decreasing concentration of both calcium. After exposure of the tail artery to calcium-free Ringer's solution for 1 minute or longer, the tissue lost its ability to respond to AVP. Subsequent addition of calcium to the medium produced immediate contraction. Measurements of low affinity lanthanum resistant pool of calcium with /sup 45/Ca showed that AVP increased calcium uptake by tail artery in a dose-dependent manner. In another study rat tail artery helical strip indicated that the vasorelaxing action of parathyroid hormone (PTH) was related to an inhibition of calcium uptake. AVP or 60 mM potassium chloride increased the low affinity lanthanum resistant pool of calcium in rate tail artery and PTH inhibited the increase. In conclusion, AVP and PTH may behave like endogenous calcium entry stimulator and inhibitor respectively in vascular tissues.

  19. Endogenous triacylglycerol utilization by the isolated rat atria.

    PubMed

    Varela, A; Savino, E A

    1988-03-01

    The isolated atria from 24 h fasted rats, either in the presence of glucose or in a substrate-free medium containing 2-deoxyglucose, mobilized the endogenous triacylglycerol (TG) to a greater extent than those from fed rats. The TG of the fasted atria had almost disappeared at the end of the 90 min incubation in the substrate-free plus 2-deoxyglucose medium, whereas in those from fed rats a mobilization-resistant portion of about 40% of the TG pool remained. This finding coincided with a lower decay of the contractile and pacemaker activities in the atria from fasted rats. Insulin abolished the TG mobilization in the atria from fed rats in the presence of glucose, but it was ineffective in the fasted atria. These data suggest that the endogenous-TG and glucose share in supporting the atrial functions, that insulin is involved in the control of TG consumption only in the fed state and that the greater TG mobilization in the fasted atria, at least partly, meets the energy requirements of the tissue.

  20. Harnessing endogenous stem/progenitor cells for tendon regeneration

    PubMed Central

    Lee, Chang H.; Lee, Francis Y.; Tarafder, Solaiman; Kao, Kristy; Jun, Yena; Yang, Guodong; Mao, Jeremy J.

    2015-01-01

    Current stem cell–based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues. PMID:26053662

  1. MALDI imaging mass spectrometry and analysis of endogenous peptides.

    PubMed

    Chatterji, Bijon; Pich, Andreas

    2013-08-01

    In recent years, MALDI imaging mass spectrometry (MALDI-IMS) has developed as a promising tool to investigate the spatial distribution of biomolecules in intact tissue specimens. Ion densities of various molecules can be displayed as heat maps while preserving anatomical structures. In this short review, an overview of different biomolecules that can be analyzed by MALDI-IMS is given. Many reviews have covered imaging of lipids, small metabolites, whole proteins and enzymatically digested proteins in the past. However, little is known about imaging of endogenous peptides, for example, in the rat brain, and this will therefore be highlighted in this review. Furthermore, sample preparation of frozen or formalin-fixed, paraffin-embedded (FFPE) tissue is crucial for imaging experiments. Therefore, some aspects of sample preparation will be addressed, including washing and desalting, the choice of MALDI matrix and its deposition. Apart from mapping endogenous peptides, their reliable identification in situ still remains challenging and will be discussed as well. PMID:23992420

  2. Effects of endogenous antidiuretic hormone (ADH) on macrophage phagocytosis

    SciTech Connect

    Fernandez-Repollet, E.; Opava-Stitzer, S.; Tiffany, S.; Schwartz, A.

    1983-07-01

    Although several studies have indicated that antidiuretic hormone (ADH) enhances the phagocytic function of the reticuloendothelial system (RES) in shock syndromes, it remains unknown what influence ADH exerts upon the individual phagocytic components of this system. The present investigation was designed to evaluate the effects of endogenous ADH on the phagocytic activity of peritoneal macrophage cells. As a phagocytic stimuli, fluorescent methacrylate microbeads were injected intraperitoneally into Brattleboro (ADH deficient) and normal Long Evans rats in the presence and absence of exogenous ADH. Peritoneal cells were harvested 19-22 hr after the administration of the microbeads and the percent phagocytosis was determined in macrophage cells using a fluorescence-activated cell sorter (FACS II). Our results indicate that the percentage of peritoneal macrophages ingesting the fluorescent methacrylate microbeads was significantly reduced in the absence of ADH (Brattleboro rats: 5.4 +/- 0.6% versus Long Evans rats: 16.8 +/- 2.3%; p less than 0.001). In addition, our data demonstrate that exogenous administration of ADH significantly enhanced macrophage phagocytosis in Brattleboro (14.7 +/- 2.2%) and normal Long Evans (49.6 +/- 4.5%) rats. These data suggest, for the first time, that endogenous ADH might play a modulatory role in the phagocytic activity of a specific component of the RES, namely, the macrophage cell.

  3. Endogenous repair after spinal cord contusion injuries in the rat.

    PubMed

    Beattie, M S; Bresnahan, J C; Komon, J; Tovar, C A; Van Meter, M; Anderson, D K; Faden, A I; Hsu, C Y; Noble, L J; Salzman, S; Young, W

    1997-12-01

    Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. It was noted that the cavities often developed a dense cellular matrix that became partially filled with nerve fibers and associated Schwann cells. The amount of fiber and Schwann cell ingrowth was inversely related to the severity of injury and amount of peripheral fiber sparing. The source of the ingrowing fibers was not determined, but many of them clearly originated in the dorsal roots. In addition to signs of regeneration, we noted evidence for the proliferation of cells located in the ependymal zone surrounding the central canal at early times following contusion injuries. These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury. PMID:9417825

  4. The role of endogenous H2S in cardiovascular physiology.

    PubMed

    Skovgaard, Nini; Gouliaev, Anja; Aalling, Mathilde; Simonsen, Ulf

    2011-09-01

    Recent research has shown that the endogenous gas hydrogen sulphide (H2S) is a signalling molecule of considerable biological potential and has been suggested to be involved in a vast number of physiological processes. In the vascular system, H2S is synthesized from cysteine by cystathionine-γ-lyase (CSE) in smooth muscle cells (SMC) and 3- mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H2S induces relaxation and/or contraction dependent on the concentration of H2S, type of vessel and species. H2S relaxes SMC through a direct effect on KATP-channels or Kv-channels causing hyperpolarization and closure of voltage-dependent Ca2+-channels followed by a reduction in intracellular calcium. H2S also relaxes SMC through the release of endothelium- derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H2S contracts SMC through a reduction in nitric oxide (NO) availability by reacting with NO forming a nitrosothiol compound and through an inhibitory effect on endothelial nitric oxide synthase (eNOS) as well as a reduction in SMC cyclic AMP concentration. Evidence supports a role for H2S in oxygen sensing. Furthermore, reduced endogenous H2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease.

  5. Silent no more: Endogenous small RNA pathways promote gene expression.

    PubMed

    Wedeles, Christopher J; Wu, Monica Z; Claycomb, Julie M

    2014-01-01

    Endogenous small RNA pathways related to RNA interference (RNAi) play a well-documented role in protecting host genomes from the invasion of foreign nucleic acids. In C. elegans, the PIWI type Argonaute, PRG-1, through an association with 21U-RNAs, mediates a genome surveillance process by constantly scanning the genome for potentially deleterious invading elements. Upon recognition of foreign nucleic acids, PRG-1 initiates a cascade of cytoplasmic and nuclear events that results in heritable epigenetic silencing of these transcripts and their coding genomic loci. If the PRG-1/21U-RNA genome surveillance pathway has the capacity to target most of the C. elegans transcriptome, what mechanisms exist to protect endogenous transcripts from being silenced by this pathway? In this commentary, we discuss three recent publications that implicate the CSR-1 small RNA pathway in the heritable activation of germline transcripts, propose a model as to why not all epialleles behave similarly, and touch on the practical implications of these findings.

  6. Cellular responses to endogenous electrochemical gradients in morphological development

    NASA Astrophysics Data System (ADS)

    Desrosiers, M. F.

    Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: 1) intercellular organization and development through their effects on the membrane potential, 2) direct effects such as electrophoresis of membrane components, and 3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: 1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, 2) the ionic conductance changes within seconds showing altered transport between the tissues, and 3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

  7. Endogenous patterns of mechanical stress are required for branching morphogenesis

    PubMed Central

    Gjorevski, Nikolce; Nelson, Celeste M.

    2011-01-01

    Spatial patterning of cell behaviors establishes the regional differences within tissues that collectively develop branched organs into their characteristic treelike shapes. Here we show that the pattern of branching morphogenesis of three-dimensional (3D) engineered epithelial tissues is controlled in part by gradients of endogenous mechanical stress. We used microfabrication to build model mammary epithelial tissues of defined geometry that branched in a stereotyped pattern when induced with growth factors. Branches initiated from sites of high mechanical stress within the tissues, as predicted numerically and measured directly using 3D traction force microscopy. Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. Stress, FAK activation, and branching were all altered by manipulating cellular contractility, matrix stiffness, intercellular cohesion and tissue geometry. These data suggest that the pattern and magnitude of mechanical stress across epithelial tissues cooperate with biochemical signals to specify branching pattern. Insight, innovation, integration Morphogenesis is ultimately a physical process wherein tissues are sculpted into their final three-dimensional (3D) patterns. Mechanical stresses from the microenvironment can also play regulatory roles, but their influence on pattern is difficult to ascertain in 3D systems in vivo. Here we integrate 3D microscale engineered tissues with insight from biological mechanics to understand the role of endogenous mechanical stresses in patterning tissue development. The innovation lies in the use of numerical modeling to design experiments that can predict the stress distribution and resulting morphogenesis of model tissues. PMID:20717570

  8. Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells

    PubMed Central

    Ziberna, Lovro; Martelanc, Mitja; Franko, Mladen; Passamonti, Sabina

    2016-01-01

    Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9–1.5 pmol mg−1 protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3–5 pmol mg−1 protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5–13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID:27381978

  9. Why do cannabinoid receptors have more than one endogenous ligand?

    PubMed Central

    Di Marzo, Vincenzo; De Petrocellis, Luciano

    2012-01-01

    The endocannabinoid system was revealed following the understanding of the mechanism of action of marijuana's major psychotropic principle, Δ9-tetrahydrocannabinol, and includes two G-protein-coupled receptors (GPCRs; the cannabinoid CB1 and CB2 receptors), their endogenous ligands (the endocannabinoids, the best studied of which are anandamide and 2-arachidonoylglycerol (2-AG)), and the proteins that regulate the levels and activity of these receptors and ligands. However, other minor lipid metabolites different from, but chemically similar to, anandamide and 2-AG have also been suggested to act as endocannabinoids. Thus, unlike most other GPCRs, cannabinoid receptors appear to have more than one endogenous agonist, and it has been often wondered what could be the physiological meaning of this peculiarity. In 1999, it was proposed that anandamide might also activate other targets, and in particular the transient receptor potential of vanilloid type-1 (TRPV1) channels. Over the last decade, this interaction has been shown to occur both in peripheral tissues and brain, during both physiological and pathological conditions. TRPV1 channels can be activated also by another less abundant endocannabinoid, N-arachidonoyldopamine, but not by 2-AG, and have been proposed by some authors to act as ionotropic endocannabinoid receptors. This article will discuss the latest discoveries on this subject, and discuss, among others, how anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis. PMID:23108541

  10. Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

    PubMed

    Much, Christian; Auchynnikava, Tania; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O'Carroll, Dónal

    2016-06-01

    Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse. PMID:27254021

  11. Elevations of Endogenous Kynurenic Acid Produce Spatial Working Memory Deficits

    PubMed Central

    Chess, Amy C.; Simoni, Michael K.; Alling, Torey E.; Bucci, David J.

    2007-01-01

    Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the α7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed. PMID:16920787

  12. Endogenous allergens in the regulatory assessment of genetically engineered crops.

    PubMed

    Graf, Lynda; Hayder, Hikmat; Mueller, Utz

    2014-11-01

    A scientific approach to the assessment of foods derived from genetically engineered (GE) crops is critical to maintaining objectivity and public confidence in regulatory decisions. Principles developed at the international level support regulators and enable robust and transparent safety assessments. A comparison of key constituents in the GE crop with a suitable comparator is an important element of an assessment. In Europe, endogenous allergens would be included in the comparative analysis, however this approach has been hindered by technical limitations on the ability to accurately measure identified allergenic proteins. Over recent years, improved proteomic methods have enabled researchers to focus on major allergenic proteins in conventional food crops, as information on natural variability is largely lacking. Emerging data for soybean indicate that variability in levels of major allergens already in the food supply is broad. This raises questions about the biological interpretation of differences between a GE plant and its conventional counterpart, in particular, whether any conclusions about altered allergenicity could be inferred. This paper discusses the scientific justification for requiring proteomic analysis of endogenous allergens as part of the evaluation. Ongoing scientific review and corresponding international discussion are integral to ensuring that data requirements address legitimate risk assessment questions.

  13. Noncanonical MicroRNAs and Endogenous siRNAs in Lytic Infection of Murine Gammaherpesvirus

    PubMed Central

    Xia, Jing; Zhang, Weixiong

    2012-01-01

    MicroRNA (miRNA) and endogenous small interfering RNA (endo-siRNA) are two essential classes of small noncoding RNAs (sncRNAs) in eukaryotes. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68 (MHV68). In addition to three novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from transfer RNAs, small nucleolar RNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from that of canonical miRNAs in lengths of hairpins, base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. Besides several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to produce endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs). Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data and virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative targets of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation, and localized to membranes, suggesting their potential role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new light on their potential functions of lytic infection of MHV68. PMID:23110115

  14. A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy.

    PubMed

    Johnsen, Kasper Bendix; Gudbergsson, Johann Mar; Skov, Martin Najbjerg; Pilgaard, Linda; Moos, Torben; Duroux, Meg

    2014-08-01

    Exosomes denote a class of secreted nanoparticles defined by size, surface protein and lipid composition, and the ability to carry RNA and proteins. They are important mediators of intercellular communication and regulators of the cellular niche, and their altered characteristics in many diseases, such as cancer, suggest them to be important both for diagnostic and therapeutic purposes, prompting the idea of using exosomes as drug delivery vehicles, especially for gene therapy. This review covers the current status of evidence presented in the field of exosome-based drug delivery systems. Components for successful exosome-based drug delivery, such as choice of donor cell, therapeutic cargo, use of targeting peptide, loading method and administration route are highlighted and discussed with a general focus pertaining to the results obtained in models of different cancer types. In addition, completed and on-going clinical trials are described, evaluating exosome-based therapies for the treatment of different cancer types. Due to their endogenous origin, exosome-based drug delivery systems may have advantages in the treatment of cancer, but their design needs further refinement to justify their usage on the clinical scale.

  15. Endogenous murine leukemia virus-encoded proteins in radiation leukemias of BALB/c mice

    SciTech Connect

    Tress, E.; Pierotti, M.; DeLeo, A.B.; O'Donnell, P.V.; Fleissner, E.

    1982-02-01

    To explore the role of endogenous retroviruses in radiation-induced leukemogenesis in the mouse, we have examined virus-encoded proteins in nine BALB/c leukemias by pulsechase labeling procedures and serological typing with monospecific and monoclonal antibodies. The major gag precursor protein, Pr65/sup gag/, was observed in all cases, but only three leukemias expressed detectable amounts of the glycosylated gag species, gP95/sup gag/, or its precursor, Pr75/sup gag/. No evidence was found for synthesis of gag-host fusion proteins. None of the leukemias released infectious xenotropic or dualtropic virus, but all nine expressed at least one env protein with xenotropic properties. In two instances a monoclonal antibody, 35/56, which is specific for the NuLV G/sub IX/ antigen, displayed a distinctive reactivity with this class of env protein, although this antibody is unreactive with replicating xenotropic viruses. An ecotropic/xenotropic recombinant env protein with the same 35/56 phenotype was observed in a leukemia induced by a strongly leukemogenic virus isolated from a BALB/c radiation leukemia.

  16. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications. PMID:27117099

  17. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-03-18

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications.

  18. Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans

    PubMed Central

    Kumar, Neeraj; Jagtap, Urmila; Verma, Sonia; Mukhopadhyay, Arnab

    2015-01-01

    Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of ‘core’ direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway. PMID:26539642

  19. A Cell-Based Assay for Measuring Endogenous BcrAbl Kinase Activity and Inhibitor Resistance.

    PubMed

    Ouellette, Steven B; Noel, Brett M; Parker, Laurie L

    2016-01-01

    Kinase enzymes are an important class of drug targets, particularly in cancer. Cell-based kinase assays are needed to understand how potential kinase inhibitors act on their targets in a physiologically relevant context. Current cell-based kinase assays rely on antibody-based detection of endogenous substrates, inaccurate disease models, or indirect measurements of drug action. Here we expand on previous work from our lab to introduce a 96-well plate compatible approach for measuring cell-based kinase activity in disease-relevant human chronic myeloid leukemia cell lines using an exogenously added, multi-functional peptide substrate. Our cellular models natively express the BcrAbl oncogene and are either sensitive or have acquired resistance to well-characterized BcrAbl tyrosine kinase inhibitors. This approach measures IC50 values comparable to established methods of assessing drug potency, and its robustness indicates that it can be employed in drug discovery applications. This medium-throughput assay could bridge the gap between single target focused, high-throughput in vitro assays and lower-throughput cell-based follow-up experiments. PMID:27598410

  20. Retroviral safety: analyses of phylogeny, prevalence and polymorphisms of porcine endogenous retroviruses.

    PubMed

    Niebert, Marcus; Kurth, Reinhard; Tönjes, Ralf R

    2003-01-01

    Porcine endogenous retroviruses (PERV) are discussed as putative infectious agents in xenotransplantation (XTx). PERV classes A, B, and C harboring different envelope proteins and two types of long terminal repeat (LTR) structures exist. One type of LTR contains a distinct repeat structure in U3, while the other is repeat-less and confers poor transcriptional activity. As the different LTR structures were found to be distributed unequally among the proviruses, we were interested in determining which LTR is the ancestor. Since replication-competent PERV can still be found today suggesting an evolutionary recent origin, we investigated the distribution and prevalence of six well-characterized and chromosomally assigned PERV in individuals of five different pig (Suidae, Sus scrofa) subspecies. Our studies revealed a heterogenous distribution of replication-competent PERV among individuals as well as among subspecies. The age of PERV was calculated to be 7.6 x 10(6) years, whereby the repeat-less LTR type evolved approximately 3.4 x 10(6) years ago being the phylogenetically younger structure. The age correlates with the time of separation between pigs and their closest relatives, american-borne peccaries (Tayassuidae, Pecari tajacu), 7.4 x 10(6) years ago.

  1. Radioprotective Action of Low-Intensity Light into the Red Absorption Band of Endogenous Molecular Oxygen

    NASA Astrophysics Data System (ADS)

    Ivanov, A. V.; Mashalov, A. A.; Zakharov, S. D.

    2016-08-01

    Application of ionizing radiation in oncology (radiation therapy) is a widespread way to eliminate malignant tumors. Normal tissues are inevitable included in any radiation field, and their reliable protection is actual till now. All attempts to solve the problem are based on search of effective radioprotectors, i.e. chemical compounds of various classes, which should be entered into the patient. To date about 50,000 compounds with some radioprotection properties had been tested, but the most effective of them have been simultaneously the most toxic. Here the preliminary results of researches devoted to development of an optical technique on basis of the light-oxygen effect for the protection of women with breast cancer from side effects of the radiation therapy are presented. A low intensity emission of the semiconductor laser in a red spectral interval was used to excite a very small quantity of endogenous molecular oxygen in O2(1Δg) state. It is shown, that application of the method at occurrence of earliest signs of radiation injury allows notably reducing dangerous breaks in radiation therapy course.

  2. A Cell-Based Assay for Measuring Endogenous BcrAbl Kinase Activity and Inhibitor Resistance

    PubMed Central

    Ouellette, Steven B.; Noel, Brett M.; Parker, Laurie L.

    2016-01-01

    Kinase enzymes are an important class of drug targets, particularly in cancer. Cell-based kinase assays are needed to understand how potential kinase inhibitors act on their targets in a physiologically relevant context. Current cell-based kinase assays rely on antibody-based detection of endogenous substrates, inaccurate disease models, or indirect measurements of drug action. Here we expand on previous work from our lab to introduce a 96-well plate compatible approach for measuring cell-based kinase activity in disease-relevant human chronic myeloid leukemia cell lines using an exogenously added, multi-functional peptide substrate. Our cellular models natively express the BcrAbl oncogene and are either sensitive or have acquired resistance to well-characterized BcrAbl tyrosine kinase inhibitors. This approach measures IC50 values comparable to established methods of assessing drug potency, and its robustness indicates that it can be employed in drug discovery applications. This medium-throughput assay could bridge the gap between single target focused, high-throughput in vitro assays and lower-throughput cell-based follow-up experiments. PMID:27598410

  3. Coming out in Class

    ERIC Educational Resources Information Center

    McKinnon, Rachel

    2012-01-01

    This article shares how the author explained her trans status to her students. Everyone has been extremely supportive of her decision to come out in class and to completely mask the male secondary-sex characteristics, especially in the workplace. The department chair and the faculty in general have been willing to do whatever they can to assist…

  4. Shrinking Your Class

    ERIC Educational Resources Information Center

    Herron-Thorpe, Farren L.; Olson, Jo Clay; Davis, Denny

    2010-01-01

    Toys in the classroom was the result of a National Science Foundation grant that brought two engineering graduate students to a middle school math class. The graduate students and teachers collaborated in an effort to enhance students' mathematical learning. An engineering context was theorized as a way to further develop students' understanding…

  5. IQ and Social Class.

    ERIC Educational Resources Information Center

    Fischbein, Siv

    1980-01-01

    Swedish longitudinal studies of twins support Scarr-Salapatek's explanation of nature-nurture influences on intelligence. This model predicts more genetic variance in test results for advantaged than disadvantaged groups. Jensen's work, however, suggests equal amounts of variance among different social classes. (Author/CP)

  6. Financing Class Size Reduction

    ERIC Educational Resources Information Center

    Achilles, C. M.

    2005-01-01

    Class size reduction has been shown to, among other things, improve academic achievement for all students and particularly for low-income and minority students. With the No Child Left Behind Act's heavy emphasis on scientifically based research, adequate yearly progress, and disaggregated results, one wonders why all children aren't enrolled in…

  7. Virtual Classes, Real Policy

    ERIC Educational Resources Information Center

    Beem, Kate

    2010-01-01

    As Internet technology encroached on the public school classroom about a decade ago, Kim Ross, superintendent of the Houston School District in Houston, Minnesota, saw an opportunity. At first, he and his administrative team simply wanted to offer students in the district of 1,300 access to more classes via the web than what a district that size…

  8. Class D sucker rods

    SciTech Connect

    Woodings, R. T.

    1984-10-23

    It has been found that API Class D sucker rods can be made inexpensively from low-alloy, low-cost steel by following a suitable induction-normalizing process and using a suitable steel to which there has been added 0.07 to 0.15 percent of vanadium.

  9. Openers for Biology Classes.

    ERIC Educational Resources Information Center

    Gridley, C. Robert R.

    This teaching guide contains 200 activities that are suitable for openers and demonstrations in biology classes. Details are provided regarding the use of these activities. Some of the broad topics under which the activities are organized include algae, amphibians, bacteria, biologists, crustaceans, dinosaurs, ecology, evolution, flowering plants,…

  10. Microarrays for Undergraduate Classes

    ERIC Educational Resources Information Center

    Hancock, Dale; Nguyen, Lisa L.; Denyer, Gareth S.; Johnston, Jill M.

    2006-01-01

    A microarray experiment is presented that, in six laboratory sessions, takes undergraduate students from the tissue sample right through to data analysis. The model chosen, the murine erythroleukemia cell line, can be easily cultured in sufficient quantities for class use. Large changes in gene expression can be induced in these cells by…

  11. Class Attitudes among Dental Students.

    ERIC Educational Resources Information Center

    Gardiner, James F.; Lancaster, Diana M.

    Class attitudes among dental students were studied at Louisiana State University in spring 1986, with attention to attitudes toward leadership, faculty and administration, study habits, labs and clinics, information acquisition, social life, and class unification. Class attitudes became more uniform and deeply held as the classes progressed…

  12. The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation

    SciTech Connect

    Serafino, A. Balestrieri, E.; Pierimarchi, P.; Matteucci, C.; Moroni, G.; Oricchio, E.; Rasi, G.; Mastino, A.; Spadafora, C.; Garaci, E.; Vallebona, P. Sinibaldi

    2009-03-10

    Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.

  13. A New Endogenous Overexpression System of Multidrug Transporters of Candida albicans Suitable for Structural and Functional Studies

    PubMed Central

    Banerjee, Atanu; Khandelwal, Nitesh K.; Sanglard, Dominique; Prasad, Rajendra

    2016-01-01

    Fungal pathogens have a robust array of multidrug transporters which aid in active expulsion of drugs and xenobiotics to help them evade toxic effects of drugs. Thus, these transporters impose a major impediment to effective chemotherapy. Although the Saccharomyces cerevisiae strain AD1-8u− has catered well to the need of an overexpression system to study drug transport by multidrug transporters of Candida albicans, artifacts associated with a heterologous system could not be excluded. To avoid the issue, we exploited a azole-resistant clinical isolate of C. albicans to develop a new system devoid of three major multidrug transporters (Cdr1p, Cdr2p, and Mdr1p) for the overexpression of multidrug transporters under native hyperactive CDR1 promoter due to gain of function (GOF) mutation in TAC1. The study deals with overexpression and functional characterization of representatives of two major classes of multidrug transporters, Cdr1p and Mdr1p, to prove the functionality of this newly developed endogenous expression system. Expression of native Cdr1 and Mdr1 protein in C. albicans cells was confirmed by confocal microscopy and immunodetection and resulted in increased resistance to the putative substrates as compared to control. The system was further validated by overexpressing a few key mutant variants of Cdr1p and Mdr1p. Together, our data confirms the utility of new endogenous overexpression system which is devoid of artifactual factors as most suited for functional characterization of multidrug transporter proteins of C. albicans. PMID:26973635

  14. Upregulating endogenous genes by an RNA-programmable artificial transactivator

    PubMed Central

    Fimiani, Cristina; Goina, Elisa; Mallamaci, Antonello

    2015-01-01

    To promote expression of endogenous genes ad libitum, we developed a novel, programmable transcription factor prototype. Kept together via an MS2 coat protein/RNA interface, it includes a fixed, polypeptidic transactivating domain and a variable RNA domain that recognizes the desired gene. Thanks to this device, we specifically upregulated five genes, in cell lines and primary cultures of murine pallial precursors. Gene upregulation was small, however sufficient to robustly inhibit neuronal differentiation. The transactivator interacted with target gene chromatin via its RNA cofactor. Its activity was restricted to cells in which the target gene is normally transcribed. Our device might be useful for specific applications. However for this purpose, it will require an improvement of its transactivation power as well as a better characterization of its target specificity and mechanism of action. PMID:26152305

  15. [Evaluation of the endogenous intoxication syndrome in food toxic infections].

    PubMed

    Marzhokhova, M Iu; Zhelikhazheva, Zh M

    2009-01-01

    To study the endogenous intoxication syndrome in patients with food toxic infections is essential in revealing the pathogenetic mechanisms underlying this disease. For this, the authors measured the level of low and average molecular weight, as well as their protein component--oligopeptides in plasma, red blood cells, and urine in the course of the disease. There were increased levels of the study parameters, which depended on the stage and degree of a pathological process. The determination of the level of low and average molecular weight and oligopeptides in plasma, red blood cells, and urine may serve as a marker of the intoxication syndrome; the level of the study parameters may be used as additional criteria for the severity of the process, the prediction of disease development and comorbidity, and as a criterion for recovery completeness.

  16. Endogenous opioids: a proximate reward mechanism for kin selection?

    PubMed

    D'Amato, F R; Pavone, F

    1993-07-01

    The kin selection theory predicts that individuals would behave differently toward one another, depending on their genetic relatedness. Proximate mechanisms have been postulated to exist helping the individual to discriminate what is good or bad for him. Opioids have been discovered to be involved in the mediation of reinforcement, in particular they underlay social emotion. In this study it is shown that pain sensitivity decreased in male mice interacting with siblings following 2 months of separation; this analgesic response was antagonized by naloxone administration. Interaction with unknown and unrelated subjects did not change the nociceptive threshold. These results suggest that interacting with kin is an adaptive situation reinforced, at the neural level, by the release of endogenous opioids.

  17. Pluripotency and the endogenous retrovirus HERVH: Conflict or serendipity?

    PubMed

    Izsvák, Zsuzsanna; Wang, Jichang; Singh, Manvendra; Mager, Dixie L; Hurst, Laurence D

    2016-01-01

    Remnants of ancient retroviral infections during evolution litter all mammalian genomes. In modern humans, such endogenous retroviral (ERV) sequences comprise at least 8% of the genome. While ERVs and other types of transposable elements undoubtedly contribute to the genomic "junk yard", functions for some ERV sequences have been demonstrated, with growing evidence that ERVs can be important players in gene regulatory processes. Here we focus on one particular large family of human ERVs, termed HERVH, which several recent studies suggest has a key regulatory role in human pluripotent stem cells. Remarkably, this is not the first instance of an ERV controlling pluripotency. We speculate as to why this convergent evolution might have come about, suggesting that it may reflect selection on the virus to extend the time available for transposition. Alternatively it may reflect serendipity alone. PMID:26735931

  18. Human endogenous retrovirus K10 encodes a functional integrase.

    PubMed Central

    Kitamura, Y; Ayukawa, T; Ishikawa, T; Kanda, T; Yoshiike, K

    1996-01-01

    We cloned a human endogenous retrovirus K1O DNA fragment encoding integrase and expressed it as a fusion protein with Escherichia coli maltose-binding protein. Integrase activities were measured in vitro by using a double-stranded oligonucleotide as a substrate mimicking viral long terminal repeats (LTR). The fusion protein was highly active for both terminal cleavage and strand transfer in the presence of Mn2+ on the K1O LTR substrate. It was also active on both Rous sarcoma virus and human immunodeficiency virus type 1 LTR substrates, whereas Rous sarcoma virus and human immunodeficiency virus type 1 integrases were active only on their corresponding LTR substrates. The results strongly suggest that K1O encodes a functional integrase with relaxed substrate specificity. PMID:8627815

  19. Light-induced suppression of endogenous circadian amplitude in humans

    NASA Technical Reports Server (NTRS)

    Jewett, Megan; Czeisler, Charles A.; Kronauer, Richard E.

    1991-01-01

    A recent demonstration that the phase of the human circadian pacemaker could be inverted using an unconventional three-cycle stimulus has led to an investigation of whether critically timed exposure to a more moderate stimulus could drive that oscillator toward its singularity, a phaseless position at which the amplitude of circadian oscillation is zero. It is reported here that exposure of humans to fewer cycles of bright light, centered around the time at which the human circadian pacemaker is most sensitive to light-induced phase shifts, can markedly attenuate endogenous cicadian amplitude. In some cases this results in an apparent loss of rhythmicity, as expected to occur in the region of singularity.

  20. Serratia marcescens endogenous endophthalmitis in an immunocompetent host.

    PubMed

    Memon, Muhammad; Raman, Vasant

    2016-01-01

    A systemically well 66-year-old white Caucasian man presented to the urgent care department with a short history of progressive pain and blurring of vision in his left eye. He denied a history of trauma, intraocular surgery or use of illicit drugs. He was diagnosed with endogenous endophthalmitis. Vitreous biopsy grew Serratia marcescens, a Gram negative bacteria. In spite of extensive investigation, there was no obvious source of infection. He had an indwelling urine catheter for prostate hypertrophy, but urine culture was negative. There was no evidence of immunocompromise. He was treated with systemic as well as intravitreal antibiotics. In spite of appropriate treatment, the patient lost vision. S. marcescens endophthalmitis, seen even in immunocompetent people, carries a poor visual prognosis. PMID:26791115

  1. Excretion of artifactual endogenous digitalis-like factors

    SciTech Connect

    Kelly, R.A.

    1986-07-01

    Radioimmunoassays have been used to detect digoxin-like immunoreactive factors (DLF) in the plasma and urine of hypertensive patients and rats with deoxycorticosterone acetate (DOCA)-salt hypertension. DLF, partially purified from DOCA-HS urine by antidigoxin antibody immunoaffinity chromatography, was found to have a molecular weight <2000. When DOCA-HS rats were switched to the low-sodium chow, DLF excretion dropped precipitously. No measurable DLF was detected in the plasma of rats eating either chow. However, >95% of the urinary DLF could be attributed to a contaminant in the standard laboratory chow. These data document the importance of excluding nonspecific compounds and exogenous sources of DLF when sensitive radioligand and biologic assays are used to detect endogenous inhibitors of the sodium pump.

  2. Endogenous siRNAs, regulators of internal affairs

    PubMed Central

    Piatek, Monica J; Werner, Andreas

    2015-01-01

    Endogenous short interfering RNAs (endo-siRNAs) have recently emerged as versatile regulators of gene expression. They derive from double stranded intrinsic transcripts and are processed by Dicer and associate with Argonaute proteins. In Caenorhabditis elegans, endo-siRNAs are known as 22G and 26G RNAs and are involved in genome protection and gene regulation. Drosophila melanogaster endo-siRNAs are produced with the help of specific Dicer and Argonaute isoforms and play an essential role in transposon control and the protection from viral infections. Biological functions of endo-siRNAs in vertebrates include repression of transposable elements, chromatin organisation as well as gene regulation at transcriptional and post-transcriptional level. PMID:25110021

  3. Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs)

    SciTech Connect

    Kaulitz, Danny; Fiebig, Uwe; Eschricht, Magdalena; Wurzbacher, Christian; Kurth, Reinhard; Denner, Joachim

    2011-03-01

    Antibodies neutralising porcine endogenous retroviruses (PERVs) were induced in different animal species by immunisation with the transmembrane envelope protein p15E. These antibodies recognised epitopes, designated E1, in the fusion peptide proximal region (FPPR) of p15E, and E2 in the membrane proximal external region (MPER). E2 is localised in a position similar to that of an epitope in the transmembrane envelope protein gp41 of the human immunodeficiency virus-1 (HIV-1), recognised by the monoclonal antibody 4E10 that is broadly neutralising. To detect neutralising antibodies specific for PERV, a novel assay was developed, which is based on quantification of provirus integration by real-time PCR. In addition, for the first time, highly effective neutralising antibodies were obtained by immunisation with the surface envelope protein of PERV. These data indicate that neutralising antibodies can be induced by immunisation with both envelope proteins.

  4. CYTOCHEMICAL LOCALIZATION OF ENDOGENOUS PEROXIDASE IN THYROID FOLLICULAR CELLS

    PubMed Central

    Strum, Judy M.; Karnovsky, Morris J.

    1970-01-01

    Endogenous peroxidase activity in rat thyroid follicular cells is demonstrated cytochemically. Following perfusion fixation of the thyroid gland, small blocks of tissue are incubated in a medium containing substrate for peroxidase, before being postfixed in osmium tetroxide, and processed for electron microscopy. Peroxidase activity is found in thyroid follicular cells in the following sites: (a) the perinuclear cisternae, (b) the cisternae of the endoplasmic reticulum, (c) the inner few lamellae of the Golgi complex, (d) within vesicles, particularly those found apically, and (e) associated with the external surfaces of the microvilli that project apically from the cell into the colloid. In keeping with the radioautographic evidence of others and the postulated role of thyroid peroxidase in iodination, it is suggested that the microvillous apical cell border is the major site where iodination occurs. However, that apical vesicles also play a role in iodination cannot be excluded. The in vitro effect of cyanide, aminotriazole, and thiourea is also discussed. PMID:4190069

  5. Endogenous coresidence and program incidence: South Africa's Old Age Pension.

    PubMed

    Hamoudi, Amar; Thomas, Duncan

    2014-07-01

    We investigate whether living arrangements respond to an arguably exogenous shift in the distribution of power in family economic decision-making. In the early 1990s, the South African Old Age Pension was expanded to cover most black South Africans above a sex-specific age cut-off resulting in a substantial increase in the income of older South Africans and potentially their say in the economic decisions of their families. Beneficiaries of the program are more likely to coreside with adults who have less human capital as measured by height and education. Since height and education are fixed for adults, this cannot be an effect of the pension income but reflects selective changes in living arrangements resulting from the pension. The findings highlight the endogeneity of living arrangements and illustrate the potential value of moving beyond theory and data that are confined to a spatially determined definition of the household.

  6. Serratia marcescens endogenous endophthalmitis in an immunocompetent host.

    PubMed

    Memon, Muhammad; Raman, Vasant

    2016-01-20

    A systemically well 66-year-old white Caucasian man presented to the urgent care department with a short history of progressive pain and blurring of vision in his left eye. He denied a history of trauma, intraocular surgery or use of illicit drugs. He was diagnosed with endogenous endophthalmitis. Vitreous biopsy grew Serratia marcescens, a Gram negative bacteria. In spite of extensive investigation, there was no obvious source of infection. He had an indwelling urine catheter for prostate hypertrophy, but urine culture was negative. There was no evidence of immunocompromise. He was treated with systemic as well as intravitreal antibiotics. In spite of appropriate treatment, the patient lost vision. S. marcescens endophthalmitis, seen even in immunocompetent people, carries a poor visual prognosis.

  7. Endogenously determined cycles: empirical evidence from livestock industries.

    PubMed

    McCullough, Michael P; Huffaker, Ray; Marsh, Thomas L

    2012-04-01

    This paper applies the techniques of phase space reconstruction and recurrence quantification analysis to investigate U.S. livestock cycles in relation to recent literature on the business cycle. Results are presented for pork and cattle cycles, providing empirical evidence that the cycles themselves have slowly diminished. By comparing the evolution of production processes for the two livestock cycles we argue that the major cause for this moderation is largely endogenous. The analysis suggests that previous theoretical models relying solely on exogenous shocks to create cyclical patterns do not fully capture changes in system dynamics. Specifically, the biological constraint in livestock dynamics has become less significant while technology and information are relatively more significant. Concurrently, vertical integration of the supply chain may have improved inventory management, all resulting in a small, less deterministic, cyclical effect.

  8. Human Endogenous Retrovirus Group E and Its Involvement in Diseases

    PubMed Central

    Le Dantec, Christelle; Vallet, Sophie; Brooks, Wesley H.; Renaudineau, Yves

    2015-01-01

    Human endogenous retrovirus group E (HERV-E) elements are stably integrated into the human genome, transmitted vertically in a Mendelian manner, and are endowed with transcriptional activity as alternative promoters or enhancers. Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C. Moreover, HERV-E expression is tissue-specific, and silenced by epigenetic constraints that may be disrupted in cancer, autoimmunity, and human placentation. Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production. Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy. PMID:25785516

  9. Unusual productions of endogenous alcohol: report of two autopsy cases.

    PubMed

    Moriya, F; Ishizu, H; Miyaishi, S

    1991-10-01

    We experienced two autopsy cases in which endogenous alcohol productions by saprogens had been unusual. Case 1 is a victim found in a mountain stream 3 to 4 weeks after his death. Since ethanol and n-propanol concentrations in the right intrathoracic bloody fluid, pericardial sac fluid, and blood in the right side of the heart were 0.41 mg/g and 0.052 mg/g, 0.42 mg/g and 0.032 mg/g, and 0.45 mg/g and 0.025 mg/g, respectively. The ethanol detected in those specimens appeared to have been produced postmortem. The femoral muscle and urine, however, contained very little n-propanol though the ethanol levels were 0.21 mg/g and 0.05 mg/g, respectively. Thus, we judged the victim might have died soon after drinking a little alcohol. Case 2 is a victim who was stabbed in the abdomen (liver) with a knife and died due to hemorrhagic shock after 26.5 hours in spite of a peritoneotomy. It was probable that metabolic activities of the liver had decreased significantly after getting a wound. Almost 1 mg/g of ethanol and little n-propanol were detected in the heart blood. In the intraabdominal bloody fluid, however, 2.45 mg/g of ethanol and 0.079 mg/g of n-propanol were detected. n-Propanol level in the bloody fluid is equal to that in severely decomposed body and indicates that a large amount of ethanol was endogenously produced. It may be considered that the unusual ethanol production was caused by the severe peritonitis after the operation.

  10. Endogenous nociceptin modulates diet preference independent of motivation and reward.

    PubMed

    Koizumi, Miwako; Cagniard, Barbara; Murphy, Niall P

    2009-04-20

    Previous studies show that the opioid peptide nociceptin stimulates food intake. Here, we studied nociceptin receptor knockout (NOP KO) mice in various behavioral paradigms designed to differentiate psychological and physiological loci at which endogenous nociceptin might control feeding. When presented a choice under food restriction, NOP KO mice displayed reduced preference for high sucrose diet, but lower intake of high fat diet under no-choice conditions. These responses were absent under ad libitum feeding conditions. Conditioned place preference to high fat diet under food-deprived conditions was unaltered in NOP KO mice, suggesting no difference in reward responses. Furthermore, operant food self-administration under a variety of conditions showed no genotype-dependent differences, suggesting no differences in the motivational properties of food. Taste reactivity to sucrose was unchanged in NOP KO mice, though NOP KO mice had altered aversive reactions to quinine solutions under ad libitum feeding, suggesting minor differences in the affective impact of palatable and unpalatable tastants. Although NOP KO mice re-fed following food-deprivation showed normal increases in plasma glucose and insulin, multidimensional scaling analysis showed that the relationship between these measures, body weight and plasma leptin was substantially disrupted in NOP KO, particularly in fasted mice. Additionally, the typical positive relationship between body weight and plasma leptin was considerably weaker in NOP KO mice. Together, these findings suggest that endogenous nociceptin differentially modulates diet preference depending on macronutrient content and homeostatic state, independently of the motivating, rewarding or orosensory properties of food, but may involve metabolic or postingestive processes. PMID:19138695

  11. Endogenous technological and population change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    Ancient civilizations may have dispersed or collapsed under extreme dry conditions. There are indications that the same may hold for modern societies. However, hydroclimatic change cannot be the sole predictor of the fate of contemporary societies in water-scarce regions. This paper focuses on technological change as a factor that may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. We study the role of technological change on the dynamics of coupled human-water systems, and model technological change as an endogenous process that depends on many factors intrinsic to coupled human-water dynamics. We do not treat technology as an exogenous random sequence of events, but assume that it results from societal actions. While the proposed model is a rather simple model of a coupled human-water system, it is shown to be capable of replicating patterns of technological, population, production and consumption per capita changes. 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. In general we find that endogenous technology change under increasing water scarcity helps to delay the peak of population size before it inevitably starts to decline. We also analyze the case when water remains constant over time and find that co-evolutionary trajectories can never grow at a constant rate; rather the rate itself grows with time. Thus our model does not predict a co-evolutionary trajectory of a socio-hydrological system where technological innovation harmoniously provides for a growing population. It allows either for an explosion or an eventual dispersal of population. The latter occurs only under increasing water scarcity. As a result, we draw the conclusion that declining consumption per capita despite technological advancement and increase in aggregate production may serve as a useful predictor of upcoming

  12. Hypobromous acid, a powerful endogenous electrophile: Experimental and theoretical studies.

    PubMed

    Ximenes, Valdecir Farias; Morgon, Nelson Henrique; de Souza, Aguinaldo Robinson

    2015-05-01

    Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold lower than that of chloride anion (Cl(-)). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3×10(2)M(-1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3×10(6)M(-1)s(-1), HOCl, 5.2×10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0×10(4)M(-1)s(-1), non-reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9×10(4)M(-1)s(-1), HOCl, k2=1.1×10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3×10(3)M(-1)s(-1), HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile. PMID:25771434

  13. Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

    SciTech Connect

    Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

    2008-01-18

    Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

  14. Remodeling of Endogenous Mammary Epithelium by Breast Cancer Stem Cells

    PubMed Central

    Parashurama, Natesh; Lobo, Neethan A.; Ito, Ken; Mosley, Adriane R.; Habte, Frezghi G.; Zabala, Maider; Smith, Bryan R.; Lam, Jessica; Weissman, Irving L.; Clarke, Michael F.; Gambhir, Sanjiv S.

    2014-01-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  15. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    PubMed

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  16. Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin.

    PubMed

    Ito, Yoshikiyo; Miyamoto, Toshihiro; Chong, Yong; Maki, Toshinobu; Akashi, Koichi; Kamimura, Tomohiko

    2013-01-01

    We report a 74-year-old female with chronic myelogenous leukemia (CML) in accelerated phase with pre-existing severe type 2 diabetes (T2D) and hemorrhagic gastric ulcers who was successfully treated with nilotinib. We first considered second-generation tyrosine kinase inhibitors for the treatment of this patient, as they elicit a superior response compared with imatinib. We next selected nilotinib, rather than dasatinib, since the increased risk of bleeding associated with dasatinib represented a greater risk of fatality than aggravation of T2D with nilotinib. After improvement of hemorrhagic gastric ulcers and T2D with exogenous insulin therapy, we began nilotinib administration; insulin dose was increased to maintain her glucose levels whereas urine C-peptide level decreased. Conversely, when nilotinib was discontinued due to liver dysfunction, the dosage of injected insulin was decreased and urine C-peptide levels increased. After re-starting nilotinib, the required dose of insulin gradually increased again, and urine C-peptide level decreased, indicating that nilotinib may have impaired secretion of endogenous insulin. The patient obtained a complete cytogenetic response after 3 months of nilotinib treatment. Her T2D has since been well controlled by insulin therapy. To our knowledge, this is the first report that nilotinib treatment for patients with severe T2D may induce a reversible decrease in endogenous insulin secretion, although the precise underlying mechanisms remain unknown. We highly recommend sufficient screening and early intervention with exogenous insulin therapy for diabetic CML patients who receive nilotinib.

  17. Relationship between endogenous 3-methylhistidine excretion and body composition.

    PubMed

    Lukaski, H C; Mendez, J; Buskirk, E R; Cohn, S H

    1981-03-01

    Fourteen healthy men (aged 20-30 yr) consumed two isocaloric, isonitrogenous diets in the sequence of a 4-day meat diet (MD) followed by a 7-day meal-free diet (MFD). Urinary 3-methylhistidine (3MH) excretion during the MD (513 +/- 21 mumol . day-1, mean +/- SE) was significantly higher (P less than 0.01) than day 3 of the MFD (230 +/- 10 mumol . day-1), after which the mean daily 3MH output was constant with a mean coefficient of variation of 4.5%. There was no change in fat-free body mass (FFBM) determined by densitometry at the start (62.3 +/- 1.8 kg) and the end (62.2 +/- 1.9 kg) of the 11-day dietary period. Mean muscle mass (MM) calculated from measurements of total-body potassium and nitrogen was 23.4 +/- 1.3 kg. Endogenous 3MH excretion was related more closely to MM (r = 0.91, P less than 0.001) than to FFBM measured by densitometry (r = 0.81, P less than 0.001). Only a low correlation coefficient (r = 0.33, P less than 0.05) was observed between 3MH and the nonmuscle component of FFBM. Urinary creatinine output also was correlated significantly with 3MH (r = 0.87; P less than 0.001) and MM (r = 0.79; P less than 0.01). It is concluded that because endogenous 3MH is significantly related to MM in man, it can be used as a marker to study in vivo total-body muscle protein degradation provided that the necessary dietary restrictions are observed.

  18. Bringing Far-Field Subdiffraction Optical Imaging to Electronically Coupled Optoelectronic Molecular Materials Using Their Endogenous Chromophores.

    PubMed

    Penwell, Samuel B; Ginsberg, Lucas D S; Ginsberg, Naomi S

    2015-07-16

    We demonstrate that subdiffraction resolution can be achieved in fluorescence imaging of functional materials with densely packed, endogenous, electronically coupled chromophores by modifying stimulated emission depletion (STED) microscopy. This class of chromophores is not generally compatible with STED imaging due to strong two-photon absorption cross sections. Yet, we achieve 90 nm resolution and high contrast in images of clusters of conjugated polymer polyphenylenevinylene-derivative nanoparticles by modulating the excitation intensity in the material. This newfound capability has the potential to significantly broaden the range of fluorophores that can be employed in super-resolution fluorescence imaging. Moreover, solution-processed optoelectronics and photosynthetic or other naturally luminescent biomaterials exhibit complex energy and charge transport characteristics and luminescence variations in response to nanoscale heterogeneity in their complex, physical structures. Our discovery will furthermore transform the current understanding of these materials' structure-function relationships that have until now made them notoriously challenging to characterize on their native, subdiffraction scales.

  19. Economy class syndrome.

    PubMed

    Sahiar, F; Mohler, S R

    1994-10-01

    A recent case of the "Economy Class Syndrome" is presented, emphasizing the syndrome's aeromedical implications and prevention. The clinical presentation, current modes of prophylaxis and therapy, plus a brief but pertinent historical background, are described. The syndrome is potentially fatal, and the authors stress that the condition needs to be recognized as a preventable hazard of air travel. Adoption of the preventive measures described herein can assist in promoting healthy air travel.

  20. Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins.

    PubMed

    Bao, Peng; Chen, Song-Can; Xiao, Ke-Qing

    2015-12-01

    Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance. PMID:26456389

  1. Melatonin and farm animals: endogenous rhythms and exogenous applications.

    PubMed

    Paterson, A M; Foldes, A

    1994-05-01

    Studies on farm animals have contributed significantly to our increased understanding of basic melatonin-related physiological mechanisms, as well as to the regulation of reproduction and pelage in individual domestic species. This review concentrates on recent work on the role of melatonin in the regulation of porcine reproduction, cervine endocrine, and behavioral cycles and wool and cashmere production which has added to this knowledge base. Early studies of the domestic pig indicated that melatonin secretion in this species differed markedly from that in other domestic and laboratory animals. There is now clear evidence that this is not the case and that the domestic pig uses a circadian rhythm of melatonin release for the transduction of photoperiodic information. Apparent inconsistencies among reports may be due, in part, to differences in the conditions under which the experiments were performed and to the assay systems employed to measure circulating melatonin, the concentrations of which are much lower than in other domestic species. Appropriately administered exogenous melatonin advances the onset of puberty in gilts, and may prove to be effective in overcoming seasonal infertility in female pigs. Appropriately timed melatonin and/or photoperiod treatments, administered to ruminants in utero, influence the reproductive physiology of the offspring, indicating that even in species which don't develop an endogenous melatonin rhythm till some weeks postnatally, awareness of photoenvironment, presumably via maternal melatonin, predates birth. Pre- or early postnatal melatonin-related treatments also influence the development/cycle frequency of pelage. Areas requiring further investigation include the hormonal/growth factors involved, reasons for the transient nature of the effects in sheep and goats, and the reason for similar effects on pelage of augmenting or inactivating melatonin. Aspects of endogenous melatonin rhythms in farm species which require

  2. Endogenous ethanol production in trauma victims associated with medical treatment.

    PubMed

    Moriya, F; Hashimoto, Y

    1996-08-01

    Four cases of trauma, where endogenous ethanol production was suspected to have been occurred in association with medical treatment, are reported. To discriminate endogenous ethanol produced de novo by bacteria from exogenous ethanol by drinking, various tissues and body fluids, such as brain and cerebrospinal fluid, together with blood obtained from various locations, were subjected to analysis for both ethanol and n-propanol. The first individual was a 40-year-old man who had been stabbed in the abdomen with a knife and had died of bleeding about 12 h after peritoneotomy, and autopsied 12 h later. In the heart blood, 0.44 mg/g ethanol and 0.005 mg/g n-propanol were detected. Ethanol levels in the cerebrospinal fluid, vitreous humor and brain, reflecting exogenous ethanol levels, were 0.08-0.16 mg/g, and no n-propanol was detected in any of the specimens. The second individual was a 45-year-old man who had been punched hard in the head and face and had died of traumatic shock about 12 h after hospitalization, and autopsied 12 h later. The heart blood concentrations of ethanol and n-propanol were 0.15 and 0.008 mg/g respectively, and a subdural hematoma contained only 0.05 mg/g ethanol and non n-propanol. The third individual was a 34-year-old man who suffered incised wounds of the left arm and head with a sickle and had died of hemorrhagic shock. In the heart blood, 0.30 mg/g ethanol and 0.026 mg/g n-propanol were detected; there was 0.04 mg/g ethanol and no n-propanol in the brain. The fourth individual was a 76-year-old woman who had been hit by a motorcycle and had died of liver rupture about 1 h after admission to a hospital. The heart blood contained 0.22 mg/g ethanol and 0.002 mg/g n-propanol. Only a trace of ethanol and no n-propanol were detected in the pericardial sac fluid and cerebrospinal fluid.

  3. Endogenous and exogenous progesterone influence body temperature in dairy cows.

    PubMed

    Suthar, V S; Burfeind, O; Bonk, S; Dhami, A J; Heuwieser, W

    2012-05-01

    Three experiments were conducted to determine the effect of endogenous progesterone (P4) on body temperature comparing lactating, pregnant with lactating, nonpregnant cows, and to study the effect of exogenous P4 administered via a controlled internal drug release (CIDR) insert on body temperature in lactating dairy cows. Body temperature was measured vaginally and rectally using temperature loggers and a digital thermometer, respectively. In experiment 1, 10 cyclic lactating cows (3 primiparous, 7 multiparous) and 10 lactating, pregnant cows (3 primiparous, 7 multiparous) were included. Vaginal temperatures and serum P4 concentrations were greater in pregnant cows (vaginal: 0.3±0.01°C; P4: 5.5±0.4 ng/mL) compared with nonpregnant cows. In experiment 2, estrous cycles of 14 postpartum healthy, cyclic, lactating cows (10 primiparous, 4 multiparous) were synchronized, and cows were assigned randomly to 1 of 2 treatments (CIDR-P4 or CIDR-blank). A temperature logger was inserted 1 d after ovulation using a P4-free CIDR (CIDR-blank) and a CIDR containing 1.38g of P4 (CIDR-P4) in the control (n=7) and the P4-treated group (n=7), respectively. On d 3 after P4 treatment, vaginal temperature was 0.3±0.03°C greater compared with that on d 1 and d 5. In experiment 3, 9 cyclic multiparous lactating cows were enrolled 1±1 d after confirmed ovulation and a temperature logger inserted. Two days later, a CIDR-P4 was inserted on top of the CIDR-blank. On d 5±1 and d 7±1, respectively, the CIDR-P4 and CIDR-blank with the temperature logger were removed. During the CIDR-P4 treatment (48h), vaginal temperature was 0.2±0.05°C and 0.1±0.05°C greater than during the pre- and post-treatment periods (48h), respectively. Serum P4 concentration peaked during CIDR-P4 treatment (2.2±0.8 ng/mL) and was greater than during the pre-treatment period (0.2±0.2 ng/mL) for 48h. An increase in vaginal temperature could be due to endogenous and exogenous P4. However, a correlation between

  4. Class Participation: Promoting In-Class Student Engagement

    ERIC Educational Resources Information Center

    O'Connor, Kevin J.

    2013-01-01

    Class participation has long been valued by faculty members interested in engaging students in the learning process. This paper discusses class participation and shares participation techniques that promote active student engagement during class meetings. Emphasis is placed on techniques that invite a larger number of students into a course's…

  5. Melatonin in Children with Autism Spectrum Disorders: Endogenous and Pharmacokinetic Profiles in Relation to Sleep

    ERIC Educational Resources Information Center

    Goldman, Suzanne E.; Adkins, Karen W.; Calcutt, M. Wade; Carter, Melissa D.; Goodpaster, Robert L.; Wang, Lily; Shi, Yaping; Burgess, Helen J.; Hachey, David L.; Malow, Beth A.

    2014-01-01

    Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (C[subscript max]) and…

  6. [Do enkephalins and other endogenous opioids participate in regulation of cancer growth?].

    PubMed

    Kajdaniuk, D; Marek, B; Buntner, B; Zwirska-Korczala, K

    2000-01-01

    Attempts are interesting exploratory trend to define precisely relations between endogenous opioid system and neoplastic process development. Mechanism in which enkephalins and other endogenous opioides could influence on cancer growth is not clear. Several hypothesis were put and presented in the paper.

  7. Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

    ERIC Educational Resources Information Center

    Peck, Laura R.

    2015-01-01

    Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

  8. Class prediction for high-dimensional class-imbalanced data

    PubMed Central

    2010-01-01

    Background The goal of class prediction studies is to develop rules to accurately predict the class membership of new samples. The rules are derived using the values of the variables available for each subject: the main characteristic of high-dimensional data is that the number of variables greatly exceeds the number of samples. Frequently the classifiers are developed using class-imbalanced data, i.e., data sets where the number of samples in each class is not equal. Standard classification methods used on class-imbalanced data often produce classifiers that do not accurately predict the minority class; the prediction is biased towards the majority class. In this paper we investigate if the high-dimensionality poses additional challenges when dealing with class-imbalanced prediction. We evaluate the performance of six types of classifiers on class-imbalanced data, using simulated data and a publicly available data set from a breast cancer gene-expression microarray study. We also investigate the effectiveness of some strategies that are available to overcome the effect of class imbalance. Results Our results show that the evaluated classifiers are highly sensitive to class imbalance and that variable selection introduces an additional bias towards classification into the majority class. Most new samples are assigned to the majority class from the training set, unless the difference between the classes is very large. As a consequence, the class-specific predictive accuracies differ considerably. When the class imbalance is not too severe, down-sizing and asymmetric bagging embedding variable selection work well, while over-sampling does not. Variable normalization can further worsen the performance of the classifiers. Conclusions Our results show that matching the prevalence of the classes in training and test set does not guarantee good performance of classifiers and that the problems related to classification with class-imbalanced data are exacerbated when

  9. The Class of '34

    PubMed Central

    Cairney, Richard

    1995-01-01

    The Great Depression raged, governments were beleaguered, the unemployment rate stood at 30%, scurvy stalked the poor and no one was immune to contagious diseases such as scarlet fever, polio and measles when the University of Alberta School of Medicine's Class of '34 graduated. For four alumni who recently gathered in Edmonton—Drs. Morley Hodgson, Melvin Gaudin, John McLurg and Edmund Cairns—their 60th-anniversary reunion was a time to recall the changes they have witnessed in medicine, including the arrival of antibiotic drugs and the medicare system. Imagesp558-a

  10. The role of human endogenous retroviruses in brain development and function.

    PubMed

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established.

  11. Endogenous and exogenous ligands of aryl hydrocarbon receptor: current state of art.

    PubMed

    Stejskalova, Lucie; Dvorak, Zdenek; Pavek, Petr

    2011-02-01

    Aryl hydrocarbon receptor (AhR) is an important transcriptional regulator of drug metabolizing enzymes that dominantly controls the expression of cytochrome P450 CYP1 family genes and some phase II enzymes. AhR also has many endogenous functions including cell cycle control, immune response, and cell differentiation. In addition, AhR is well-known to be involved in chemically-induced carcinogenesis. AhR is activated by a variety of endogenous and exogenous ligands. While exogenous activation of AhR has deleterious effects on human organism, sustained activation of AhR by endogenous ligands is indispensable for proper cell functions. Therefore, the effects of exogenous and endogenous ligands on AhR resemble the Dr. Jekyll and Mr. Hyde story. The aim of the current paper is to summarize and update the knowledge on exogenous and endogenous AhR ligands. PMID:21395538

  12. A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca).

    PubMed

    Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix; Avila-Arcos, María; Stenglein, Mark D; Chen, Wei; Sun, Wei; Mazzoni, Camila J; Osterrieder, Nikolaus; Greenwood, Alex D

    2013-08-15

    Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs. Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant panda sequences U. maritimus endogenous retrovirus (UmaERV) and A. melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary history within the HERV-K group. All individual remnants of proviral sequences contain numerous frameshifts and stop codons and thus, the virus is likely non-infectious.

  13. Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks

    PubMed Central

    Mizuno, Shiro; Ishizaki, Takeshi; Toga, Hirohisa; Sakai, Akio; Isakova, Jainagul; Taalaibekova, Elnura; Baiserkeev, Zamirbek; Kojonazarov, Baktybek; Aldashev, Almaz

    2015-01-01

    Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks. Although the yaks are hypoxemic, cardiac function and pulmonary arterial pressures are almost normal, and we found decreased DDAH expression and activity in association with reduced plasma ADMA concentrations. The eNOS expression was significantly higher in yaks. These results indicate that augmented endogenous NO activity in yaks through the ADMA-DDAH pathway and eNOS upregulation account for the low pulmonary vascular tone observed in high altitude adapted yaks. PMID:26380264

  14. Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets

    PubMed Central

    Mukhitov, Nikita; Roper, Michael G.; Bertram, Richard

    2016-01-01

    Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal’s ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion. PMID:27788129

  15. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus.

    PubMed

    Zhang, Dali; Xiong, Wei; Jackson, Michael F; Parkinson, Fiona E

    2016-07-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. PMID:27189965

  16. [Neuropeptide thyroliberin--an endogenous anticonvulsant in the brain].

    PubMed

    Chepurnov, S A; Chepurnova, N E; Abbasova, K R; Goncharov, O B

    2002-01-01

    Thyroliberin (TRH) promoting endogenous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application. This application TRH in ultra-low doses contrast the method of systemic TRH administration (i.v., i.m. or oral in the large doses--mg). In our experiments intranasal application of 10(-9) M, 10(-10) M and 10(-12) M TRH significantly inhibited the severe epileptic motor fits in rats induced by pentylenetetrazole (PTZ). Beneficent effect of TRH is also confirmed by EEG (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide cHis-Pro-NH2 (10(-10) M, 10(-5) M). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology. PMID:11881332

  17. Endogenous nociceptin system involvement in stress responses and anxiety behavior.

    PubMed

    Fulford, Allison Jane

    2015-01-01

    The mechanisms underpinning stress-related behavior and dysfunctional events leading to the expression of neuropsychiatric disorders remain incompletely understood. Novel candidates involved in the neuromodulation of stress, mediated both peripherally and centrally, provide opportunities for improved understanding of the neurobiological basis of stress disorders and may represent targets for novel therapeutic development. This chapter provides an overview of the mechanisms by which the opioid-related peptide, nociceptin, regulates the neuroendocrine stress response and stress-related behavior. In our research, we have employed nociceptin receptor antagonists to investigate endogenous nociceptin function in tonic control over stress-induced activity of the hypothalamo-pituitary-adrenal axis. Nociceptin demonstrates a wide range of functions, including modulation of psychological and inflammatory stress responses, modulation of neurotransmitter release, immune homeostasis, in addition to anxiety and cognitive behaviors. Greater appreciation of the complexity of limbic-hypothalamic neuronal networks, together with attention toward gender differences and the roles of steroid hormones, provides an opportunity for deeper understanding of the importance of the nociceptin system in the context of the neurobiology of stress and behavior.

  18. Copper is an endogenous modulator of neural circuit spontaneous activity

    PubMed Central

    Dodani, Sheel C.; Firl, Alana; Chan, Jefferson; Nam, Christine I.; Aron, Allegra T.; Onak, Carl S.; Ramos-Torres, Karla M.; Paek, Jaeho; Webster, Corey M.; Feller, Marla B.; Chang, Christopher J.

    2014-01-01

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu+ sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling. PMID:25378701

  19. Two endogenous proteins that induce cell wall extension in plants

    NASA Technical Reports Server (NTRS)

    McQueen-Mason, S.; Durachko, D. M.; Cosgrove, D. J.

    1992-01-01

    Plant cell enlargement is regulated by wall relaxation and yielding, which is thought to be catalyzed by elusive "wall-loosening" enzymes. By employing a reconstitution approach, we found that a crude protein extract from the cell walls of growing cucumber seedlings possessed the ability to induce the extension of isolated cell walls. This activity was restricted to the growing region of the stem and could induce the extension of isolated cell walls from various dicot stems and the leaves of amaryllidaceous monocots, but was less effective on grass coleoptile walls. Endogenous and reconstituted wall extension activities showed similar sensitivities to pH, metal ions, thiol reducing agents, proteases, and boiling in methanol or water. Sequential HPLC fractionation of the active wall extract revealed two proteins with molecular masses of 29 and 30 kD associated with the activity. Each protein, by itself, could induce wall extension without detectable hydrolytic breakdown of the wall. These proteins appear to mediate "acid growth" responses of isolated walls and may catalyze plant cell wall extension by a novel biochemical mechanism.

  20. Endogenous opioid peptides and the control of gonadotrophin secretion.

    PubMed

    Brooks, A N; Lamming, G E; Haynes, N B

    1986-11-01

    The endogenous opioid peptides are a group of recently discovered compounds which occur in the brain of a wide variety of species. Originally named because of their opiate-like activity, they have since been demonstrated to have multifaceted actions, one of which appears to be the modulation of luteinising hormone (LH) secretion. Because of the prime position of LH in the ovulatory process, this role for the opioids has attracted considerable interest. Their mode of action is essentially one of suppression and they work by inhibiting the release of hypothalamic gonadotrophin releasing hormone. Through this mechanism they have been implicated in the suppression of LH secretion during the prepubertal period and the modulation of LH during the oestrous cycle. It is well established that gonadal steroids suppress LH secretion by negative feedback upon the hypothalamic-pituitary axis, and this action may be brought about, in part, through intermediary opioidergic neurones. Much of the research to date has been carried out upon laboratory rodents and primates, but there is evidence now accruing that the opioids have similar actions in domestic animals. Knowledge of the role of these compounds may therefore aid in the understanding of an area of commercial importance, namely the control of ovulation in farm livestock.

  1. An Eleven-Year Retrospective Study of Endogenous Bacterial Endophthalmitis

    PubMed Central

    Nishida, Takashi; Ishida, Kyoko; Niwa, Yoshiaki; Kawakami, Hideaki; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi

    2015-01-01

    Purpose. To determine the clinical features, microbial profiles, treatment outcomes, and prognostic factors for endogenous bacterial endophthalmitis (EBE). Methods. The medical records of 27 eyes of 21 patients diagnosed with EBE for 11 years were reviewed. Collected data included age, site of infection, visual acuities (VAs), microbial profiles, and treatment regimen. Results. The mean age was 68.5 years. Gram-positive organisms accounted for 76.2%, while gram-negative ones accounted for 19.0%. Staphylococcus aureus was the most common causative organism (52.3%) of which 72.7% was methicillin-resistant S. aureus. A final VA of ≥20/40 was achieved in 44% and 20/200 or better was in 64%. Eyes with initial VA of ≥20/200 (P = 0.003) and focal involvements (P = 0.011) had significantly better final VA. Initial VA (P = 0.001) and the interval between onset of ocular symptoms and intravitreal antibiotic injection (P = 0.097) were associated with final VA in eyes receiving intravitreal antibiotics. Conclusions. EBE is generally associated with poor visual outcome; however the prognosis may depend on initial VA, extent of ocular involvement, and an interval between onset of ocular symptoms and intravitreal antibiotic injection. Early diagnosis and early intravitreal injection supplement to systemic antibiotics might lead to a relatively good visual outcome. PMID:25802752

  2. Endogenous lipolytic activities during autolysis of highly enriched hepatic lysosomes.

    PubMed

    Beckman, J K; Owens, K; Weglicki, W B

    1981-11-01

    High enriched (50- to 70-fold) fractions of "native" lysosomes were isolated using continuous flow electrophoresis from livers of rats which had not been pretreated with Triton WR-1339. Incubation of lysosomes for 30 min at pH 5.0 in the presence of 5 mM EDTA resulted in a dramatic loss in the content of fatty acids bound to triacylglycerols (137 down to 10 mumol/mg protein) and to phospholipids and an elevation in the level of unesterified fatty acid. Phosphatidylcholine, phosphatidylethanolamine and sphingomyelin concentrations decreased whereas those of lysophosphatidylethanolamine (0.8 up to 8.5% of total lipid-P) and lysophosphatidylcholine (1.9 up to 16.7%) rose in a manner parallel to their respective, fully acylated lipids. Other phospholipids, including phosphatidylinositol, did not change in concentration during incubation. These results indicate that lysosomal phospholipase A, sphingomyelin and triacylglycerol lipase are activated by incubation at acid pH, enabling them to hydrolyze endogenous lysosomal lipids. However, lysosomal phosphatidylinositol-directed phospholipase C is apparently unable to interact with phosphatidylinositol of the lysosomal membrane. PMID:7311738

  3. Endogenous Groups and Dynamic Selection in Mechanism Design*

    PubMed Central

    Madeira, Gabriel A.; Townsend, Robert M.

    2010-01-01

    We create a dynamic theory of endogenous risk sharing groups, with good internal information, and their coexistence with relative performance, individualistic regimes, which are informationally more opaque. Inequality and organizational form are determined simultaneously. Numerical techniques and succinct re-formulations of mechanism design problems with suitable choice of promised utilities allow the computation of a stochastic steady state and its transitions. Regions of low inequality and moderate to high wealth (utility promises) produce the relative performance regime, while regions of high inequality and low wealth produce the risk sharing group regime. If there is a cost to prevent coalitions, risk sharing groups emerge at high wealth levels also. Transitions from the relative performance regime to the group regime tend to occur when rewards to observed outputs exacerbate inequality, while transitions from the group regime to the relative performance regime tend to come with a decrease in utility promises. Some regions of inequality and wealth deliver long term persistence of organization form and inequality, while other regions deliver high levels of volatility. JEL Classification Numbers: D23,D71,D85,O17. PMID:20107614

  4. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-19

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

  5. Involvement of endogenous neuromedin U and neuromedin S in thermoregulation.

    PubMed

    Nakahara, Keiko; Akagi, Ai; Shimizu, Seiya; Tateno, Satoshi; Qattali, Abdul Wahid; Mori, Kenji; Miyazato, Mikiya; Kangawa, Kenji; Murakami, Noboru

    2016-02-19

    We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icv) injection of NMU or NMS increased the back surface temperature (BS-T) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the β3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icv injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BS-T was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and β3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU.

  6. Opening of Iris flowers is regulated by endogenous auxins.

    PubMed

    van Doorn, Wouter G; Dole, Isabelle; Celikel, Fisun G; Harkema, Harmannus

    2013-01-15

    Flower opening in Iris (Iris×hollandica) requires elongation of the pedicel and ovary. This moves the floral bud upwards, thereby allowing the tepals to move laterally. Flower opening is requires with elongation of the pedicel and ovary. In cv. Blue Magic, we investigated the possible role of hormones other than ethylene in pedicel and ovary elongation and flower opening. Exogenous salicylic acid (SA) and the cytokinins benzyladenine (N6-benzyladenine, BA) and zeatin did not affect opening. Jasmonic acid (JA) and abscisic acid (ABA) were slightly inhibitory, but an inhibitor of ABA synthesis (norflurazon) was without effect. Flower opening was promoted by gibberellic acid (GA(3)), but two inhibitors of gibberellin synthesis (4-hydroxy-5-isopropyl-2-methylphenyltrimethyl ammonium chloride-1-piperidine carboxylate, AMO-1618; ancymidol) did not change opening. The auxins indoleacetic acid (IAA) and naphthaleneacetic acid (NAA) strongly promoted elongation and opening. An inhibitor of auxin transport (2,3,5-triodobenzoic acid, TIBA) and an inhibitor of auxin effects [α-(p-chlorophenoxy)-isobutyric acid; PCIB] inhibited elongation and opening. The data suggest that endogenous auxins are among the regulators of the pedicel and ovary elongation and thus of flower opening in Iris. PMID:23218543

  7. Endogenizing geopolitical boundaries with agent-based modeling

    PubMed Central

    Cederman, Lars-Erik

    2002-01-01

    Agent-based modeling promises to overcome the reification of actors. Whereas this common, but limiting, assumption makes a lot of sense during periods characterized by stable actor boundaries, other historical junctures, such as the end of the Cold War, exhibit far-reaching and swift transformations of actors' spatial and organizational existence. Moreover, because actors cannot be assumed to remain constant in the long run, analysis of macrohistorical processes virtually always requires “sociational” endogenization. This paper presents a series of computational models, implemented with the software package REPAST, which trace complex macrohistorical transformations of actors be they hierarchically organized as relational networks or as collections of symbolic categories. With respect to the former, dynamic networks featuring emergent compound actors with agent compartments represented in a spatial grid capture organizational domination of the territorial state. In addition, models of “tagged” social processes allows the analyst to show how democratic states predicate their behavior on categorical traits. Finally, categorical schemata that select out politically relevant cultural traits in ethnic landscapes formalize a constructivist notion of national identity in conformance with the qualitative literature on nationalism. This “finite-agent method”, representing both states and nations as higher-level structures superimposed on a lower-level grid of primitive agents or cultural traits, avoids reification of agency. Furthermore, it opens the door to explicit analysis of entity processes, such as the integration and disintegration of actors as well as boundary transformations. PMID:12011409

  8. Endogenous ethanol affects biopolyester molecular weight in recombinant Escherichia coli.

    PubMed

    Hiroe, Ayaka; Hyakutake, Manami; Thomson, Nicholas M; Sivaniah, Easan; Tsuge, Takeharu

    2013-11-15

    In biopolyester synthesis, polyhydroxyalkanoate (PHA) synthase (PhaC) catalyzes the polymerization of PHA in bacterial cells, followed by a chain transfer (CT) reaction in which the PHA polymer chain is transferred from PhaC to a CT agent. Accordingly, the frequency of CT reaction determines PHA molecular weight. Previous studies have shown that exogenous alcohols are effective CT agents. This study aimed to clarify the effect of endogenous ethanol as a CT agent for poly[(R)-3-hydroxybutyrate] [P(3HB)] synthesis in recombinant Escherichia coli, by comparing with that of exogenous ethanol. Ethanol supplementation to the culture medium reduced P(3HB) molecular weights by up to 56% due to ethanol-induced CT reaction. NMR analysis of P(3HB) polymers purified from the culture supplemented with (13)C-labeled ethanol showed the formation of a covalent bond between ethanol and P(3HB) chain at the carboxyl end. Cultivation without ethanol supplementation resulted in the reduction of P(3HB) molecular weight with increasing host-produced ethanol depending on culture aeration. On the other hand, production in recombinant BW25113(ΔadhE), an alcohol dehydrogenase deletion strain, resulted in a 77% increase in molecular weight. Analysis of five E. coli strains revealed that the estimated number of CT reactions was correlated with ethanol production. These results demonstrate that host-produced ethanol acts as an equally effective CT agent as exogenous ethanol, and the control of ethanol production is important to regulate the PHA molecular weight.

  9. Curbing Inflammation through Endogenous Pathways: Focus on Melanocortin Peptides

    PubMed Central

    Ahmed, Tazeen J.; Montero-Melendez, Trinidad; Perretti, Mauro; Pitzalis, Costantino

    2013-01-01

    The resolution of inflammation is now known to be an active process, armed with a multitude of mediators both lipid and protein in nature. Melanocortins are peptides endowed with considerable promise with their proresolution and anti-inflammatory effects in preclinical models of inflammatory disease, with tissue protective effects. These peptides and their targets are appealing because they can be seen as a natural way of inducing these effects as they harness endogenous pathways of control. Whereas most of the information generated about these mediators derives from several acute models of inflammation (such as zymosan induced peritonitis), there is some indication that these mediators may inhibit chronic inflammation by modulating cytokines, chemokines, and leukocyte apoptosis. In addition, proresolving mediators and their mimics have often been tested alongside therapeutic protocols, hence have been tested in settings more relevant to real life clinical scenarios. We provide here an overview on some of these mediators with a focus on melanocortin peptides and receptors, proposing that they may unveil new opportunities for innovative treatments of inflammatory arthritis. PMID:23738228

  10. Interchromosomal gene conversion at an endogenous human cell locus.

    PubMed Central

    Quintana, P J; Neuwirth, E A; Grosovsky, A J

    2001-01-01

    To examine the relationship between gene conversion and reciprocal exchange at an endogenous chromosomal locus, we developed a reversion assay in a thymidine kinase deficient mutant, TX545, derived from the human lymphoblastoid cell line TK6. Selectable revertants of TX545 can be generated through interchromosomal gene conversion at the site of inactivating mutations on each tk allele or by reciprocal exchange that alters the linkage relationships of inactivating polymorphisms within the tk locus. Analysis of loss of heterozygosity (LOH) at intragenic polymorphisms and flanking microsatellite markers was used to initially evaluate allelotypes in TK(+) revertants for patterns associated with either gene conversion or crossing over. The linkage pattern in a subset of convertants was then unambiguously established, even in the event of prereplicative recombinational exchanges, by haplotype analysis of flanking microsatellite loci in tk(-/-) LOH mutants collected from the tk(+/-) parental convertant. Some (7/38; 18%) revertants were attributable to easily discriminated nonrecombinational mechanisms, including suppressor mutations within the tk coding sequence. However, all revertants classified as a recombinational event (28/38; 74%) were attributed to localized gene conversion, representing a highly significant preference (P < 0.0001) over gene conversion with associated reciprocal exchange, which was never observed. PMID:11404339

  11. Endogenous and exogenous control of gametogenesis and spawning in echinoderms.

    PubMed

    Mercier, Annie; Hamel, Jean-François

    2009-01-01

    Most echinoderms display seasonal or other temporal cycles of reproduction that presumably result from the complex interplay of endogenous and exogenous signals. Various environmental, chemical and hormonal factors, acting directly or indirectly, individually or in combination, have been proposed to cue, favour or modulate a suite of reproductive functions from the onset of gametogenesis to gamete release. From as early as the nineteenth century, an astonishing array of studies has been published on topics related to the control of reproduction in echinoderms, ranging from fortuitous behavioural observations to complex experimental demonstrations and molecular analyses. Although the exact pathways involved in the perception of external signals and their transduction into coordinated spawning events remain obscure for most species, significant advances have been made that shed new light on the information gathered over decades of research. By compiling the existing literature (over 1000 references), interpreting the main results, critically assessing the methodologies used and reviewing the emerging hypotheses, we endeavour to draw a clearer picture of the existing knowledge and to provide a framework for future investigation of the mechanisms that underlie reproductive strategies in echinoderms and, by extension, in other marine invertebrates.

  12. Discovery of unfixed endogenous retrovirus insertions in diverse human populations

    PubMed Central

    Wildschutte, Julia Halo; Williams, Zachary H.; Montesion, Meagan; Subramanian, Ravi P.; Kidd, Jeffrey M.; Coffin, John M.

    2016-01-01

    Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity. PMID:27001843

  13. Copper is an endogenous modulator of neural circuit spontaneous activity.

    PubMed

    Dodani, Sheel C; Firl, Alana; Chan, Jefferson; Nam, Christine I; Aron, Allegra T; Onak, Carl S; Ramos-Torres, Karla M; Paek, Jaeho; Webster, Corey M; Feller, Marla B; Chang, Christopher J

    2014-11-18

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.

  14. Influence of endogenous prostaglandins on mTAL injury.

    PubMed

    Silva, P; Rosen, S; Spokes, K; Taylor, M; Epstein, F H

    1990-11-01

    We altered renal prostaglandin production by isolated rat kidneys in several ways to see if this would influence the susceptibility of cells lining the medullary thick ascending limb to injury. Rats were fed a diet containing either safflower oil (high in linoleic acid) or fish oil (low in arachidonate precursors) as a source of fat. After 90 min of perfusion, the kidneys of rats fed safflower oil showed only 32.7 +/- 6.7% of medullary thick ascending limb cells near the inner medulla with severe damage, whereas the same zone in perfused kidneys of rats fed fish oil showed 96.6 +/- 1.3% severely damaged cells (P less than 0.01). The protection afforded by safflower oil was accompanied by a doubling of urinary excretion of PGE2 and 6-keto-PGF1 alpha, and was eliminated by indomethacin, which suppressed prostaglandin synthesis. Perfusion with bradykinin also greatly increased prostaglandin excretion and reduced severe medullary thick ascending limb damage in the deepest zone of the outer medulla from 51.3 +/- 6.6% in controls to 28.5 +/- 5.9% (P less than 0.02). The protection provided by bradykinin was also completely reversed by indomethacin. The results suggest that endogenous prostaglandins serve a protective function against hypoxic injury for cells of the medullary thick ascending limb.

  15. Deletion of endogenous Tau proteins is not detrimental in Drosophila.

    PubMed

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer's disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.

  16. Endogenous lipoid pneumonia in a cachectic patient after brain injury.

    PubMed

    Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei

    2015-01-01

    Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP. PMID:26097618

  17. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus

    PubMed Central

    Zhang, Dali; Xiong, Wei; Jackson, Michael F.

    2016-01-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5′-nucleotidase activity. Wild-type (CD73+/+) and ecto-5′-nucleotidase-deficient (CD73−/−) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73+/+ mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73+/+ mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg2+ conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5′-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73−/− mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5′-nucleotidase activity. PMID:27189965

  18. Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth.

    PubMed

    Li, Hai; Kuwajima, Takaaki; Oakley, Derek; Nikulina, Elena; Hou, Jianwei; Yang, Wan Seok; Lowry, Emily Rhodes; Lamas, Nuno Jorge; Amoroso, Mackenzie Weygandt; Croft, Gist F; Hosur, Raghavendra; Wichterle, Hynek; Sebti, Said; Filbin, Marie T; Stockwell, Brent; Henderson, Christopher E

    2016-07-12

    Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT) and geranylgeranyl transferase I (PGGT-1). Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS). Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early- versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans. PMID:27373155

  19. Deletion of endogenous Tau proteins is not detrimental in Drosophila

    PubMed Central

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions. PMID:26976084

  20. Do polyunsaturated fatty acids behave like an endogenous "polypill"?

    PubMed

    Das, Undurti N

    2008-01-01

    Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin - called as polypill - was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites and other products prevent platelet aggregation, lower blood pressure, reduce LDL-C, and ameliorate the adverse actions of homocysteine. Thus, EFAs and their metabolites show all the actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules, have no significant side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and children; and have been shown to reduce the incidence cardiovascular diseases. I propose that a rational combination of omega-3 and omega-6 fatty acids is as beneficial as that of the "polypill"; and may even show additional benefit in the prevention of depression, schizophrenia, Alzheimer's disease, and enhance cognitive function. PMID:17624683

  1. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  2. Endogenous or exogenous origin of vaginal candidiasis in Polish women?

    PubMed

    Mnichowska-Polanowskai, Magdalena; Wojciechowska-Koszko, Iwona; Klimowicz, Bogumia; Szymaniak, Ludmia; Krasnodebska-Szponder, Barbara; Szych, Zbigniew; Giedrys-Kalemba, Stefania

    2013-01-01

    Vaginal candidiasis is a common problem of clinical practice. Many studies have been conducted to explain its origin but only a few have included Polish women. The aim of the study was to determine the prevalence and similarity of oral, anal and vaginal Candida albicans strains isolated from Polish women with vaginal candidiasis. The study involved 20 from 37 recruited women. Swab samples were collected from their vagina, anus, and oral cavity at two-month intervals. All the women were treated with nystatin. Yeast were recovered and identified by the germ-tube test, API /Vitek system, typed by API ZYM and RAPD-PCR. Chi-square test was used to analyze the data. A total of 170 Candida albicans isolates were recovered from 180 samples collected 3 times from 3 sites of 20 women. Positive yeast vaginal cultures were found in all patients before administration of nystatin. Vaginal yeast recovery rate was decreased statistically significant in both follow-up visits (p= 0.001; p= 0.003). The same and different genotypes/biotypes were found concomitantly in a few body sites and/ or repeatedly at time interval from the same body site. The results support the concept of dynamic exchange of yeast within one woman and endogenous or exogenous origin of vaginal candidiasis.

  3. Discovery of unfixed endogenous retrovirus insertions in diverse human populations.

    PubMed

    Wildschutte, Julia Halo; Williams, Zachary H; Montesion, Meagan; Subramanian, Ravi P; Kidd, Jeffrey M; Coffin, John M

    2016-04-19

    Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity.

  4. Endogenous surfactant turnover in preterm infants measured with stable isotopes.

    PubMed

    Bunt, J E; Zimmermann, L J; Wattimena, J L; van Beek, R H; Sauer, P J; Carnielli, V P

    1998-03-01

    We studied surfactant synthesis and turnover in vivo in preterm infants using the stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/- 244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC, obtained from tracheal aspirates, was measured by gas chromatography-combustion interface-isotope ratio mass spectrometry. We observed a significant incorporation of carbon-13 from glucose into surfactant PC palmitate. PC palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7 +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2 mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous surfactant production and turnover were obtained for the first time in human infants with the use of stable isotopes. This novel and safe method could be applied to address many important issues concerning surfactant metabolism in preterm infants, children, and adults.

  5. Strategies to Detect Endogenous Ubiquitination of a Target Mammalian Protein.

    PubMed

    Sigismund, Sara; Polo, Simona

    2016-01-01

    Different biochemical techniques are well established to investigate target's ubiquitination in mammals without overexpressing a tagged version of ubiquitin (Ub). The simplest and more direct approach is to immunoprecipitate (IP) your target protein from cell lysate (stimulated and/or properly treated), followed by western blot analysis utilizing specific antibodies against Ub (see Subheading 3.1). This approach requires a good antibody against the target working in IP; alternatively, one could express a tagged version of the protein, possibly at the endogenous level. Another approach consists in IP ubiquitinated proteins from total cell lysate followed by detection with the antibody against the protein of interest. This second method relies on the availability of specific and very efficient antibodies against Ub (see Subheading 3.2). A more quantitative approach is the DELFIA assay (Perkin Elmer), an ELISA-based assay, which allows comparing more samples and conditions (see Subheading 3.3). Cross-validation with more than one approach is usually recommended in order to prove that your protein is modified by ubiquitin.Here we will use the EGFR as model system but protocols can be easily modified according to the protein of interest. PMID:27613032

  6. Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

    PubMed Central

    Tönjes, Ralf R.

    2012-01-01

    Summary: Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference. PMID:22491774

  7. Inhibition of cyclic gonadotropin secretion by endogenous human prolactin.

    PubMed

    Tyson, J E; Khojandi, M; Huth, J; Smith, B; Thomas, P

    1975-02-01

    The resumption of cyclic uterine bleeding reportedly accompanies the use of human prolactin (HPRL)-suppressing agents in postpill galactorrhea-amenorrhea. In this laboratory, HPRL suppression with L-dopa was variable and short lived. Basal plasma HPRL levels were elevated before and after as much as five months of therapy. Galactorrhea persisted and mean gonadotropin concentrations were subnormal. An immediate and sustained attenuation of HPRL secretion ( less than 200 per cent) followed the use of 2-Br-alpha-ergocryptine (CB-154). Cyclic gonadotropin secretion resumed and was accompanied by ovulation and, in one instance, pregnancy. The cessation of galactorrhea was positively correlated with the rise in the daily concentration of 17 beta-estradiol. Cyclic postovulatory menstruation continued after the cessation of CB-154 treatment. HPRL levels remained normal. The daily patterns of human follicle-stimulating hormone (HFSH) and human tuteinizing hormone (HLH) secretion created by the suppression of HPRL displayed an inherent rhythmicity identical to that observed at the time of menarche. The inhibitory effects of HPRL appeared directed at cyclic rather than tonic gonadotropin secretion. At the same time, diminished ovarian estrogen production seemed to increase mammary gland sensitivity to HPRL, leading to lactation. One may postulate, therefore, that the ingestion of sex steroids is associated with an over-all suppression of endogenous cyclic and, to a lesser extent, tonic gonadotropin secretion secondary to which ovarian function is attenuated. Without physiologic concentration of circulating estrogen, HPRL induces mammary alveolar function with the production of a milklike secretion.

  8. Local properties of patterned vegetation: quantifying endogenous and exogenous effects.

    PubMed

    Penny, Gopal G; Daniels, Karen E; Thompson, Sally E

    2013-12-13

    Dryland ecosystems commonly exhibit periodic bands of vegetation, thought to form due to competition between individual plants for heterogeneously distributed water. In this paper, we develop a Fourier method for locally identifying the pattern wavenumber and orientation, and apply it to aerial images from a region of vegetation patterning near Fort Stockton, TX, USA. We find that the local pattern wavelength and orientation are typically coherent, but exhibit both rapid and gradual variation driven by changes in hillslope gradient and orientation, the potential for water accumulation, or soil type. Endogenous pattern dynamics, when simulated for spatially homogeneous topographic and vegetation conditions, predict pattern properties that are much less variable than the orientation and wavelength observed in natural systems. Our local pattern analysis, combined with ancillary datasets describing soil and topographic variation, highlights a largely unexplored correlation between soil depth, pattern coherence, vegetation cover and pattern wavelength. It also, surprisingly, suggests that downslope accumulation of water may play a role in changing vegetation pattern properties.

  9. Local properties of patterned vegetation: quantifying endogenous and exogenous effects.

    PubMed

    Penny, Gopal G; Daniels, Karen E; Thompson, Sally E

    2013-01-01

    Dryland ecosystems commonly exhibit periodic bands of vegetation, thought to form due to competition between individual plants for heterogeneously distributed water. In this paper, we develop a Fourier method for locally identifying the pattern wavenumber and orientation, and apply it to aerial images from a region of vegetation patterning near Fort Stockton, TX, USA. We find that the local pattern wavelength and orientation are typically coherent, but exhibit both rapid and gradual variation driven by changes in hillslope gradient and orientation, the potential for water accumulation, or soil type. Endogenous pattern dynamics, when simulated for spatially homogeneous topographic and vegetation conditions, predict pattern properties that are much less variable than the orientation and wavelength observed in natural systems. Our local pattern analysis, combined with ancillary datasets describing soil and topographic variation, highlights a largely unexplored correlation between soil depth, pattern coherence, vegetation cover and pattern wavelength. It also, surprisingly, suggests that downslope accumulation of water may play a role in changing vegetation pattern properties.

  10. [Correlations between endogenous intoxication and excessive body weight].

    PubMed

    Abylaĭuly, Zh; Oshakbaev, K P; Kozhabekova, B N; Erdesova, G E; Imantaeva, G M; Uberbaeva, G K

    2005-01-01

    The aim of the study was to analyze correlations between endogenous intoxication (EI) and lipid peroxidation (LP) indices in patients with cardiovascular and endocrine diseases and healthy individuals, taking into account the presence of excessive body weight (EBW), as well as to compare EI and LP indices in practically healthy people with and without excessive body weight (EBW). The subjects were 165 people, including 36 healthy individuals and 129 patients with cardiovascular and endocrine disease. The healthy ones were divided into two groups: 20 with and 16 without EBW. To evaluate the degree of EI, the concentration of middle-molecular-weight peptides (MMWP) was measured by the method offered by N. I. Gabrielyan et al. in 1984. To evaluate LP processes, serum levels of the secondary LP product, malonic dialdehyde, and two antioxidative enzymes, superoxide dismutase and catalase, were measured. The results show that treatment aimed at LP suppression is not appropriate; it should be aimed at the cause of LP activation instead, which is the increase of MMWP level due to EBW. LP activation significantly correlates with increase of MMWP blood level (p < 0.05). EBW worsens EI and activates LP in healthy people, thus being a stress factor to the organism. Increased MMWP level and LP activation in healthy individuals with EBW may be a premorbid diagnostic marker.

  11. Optogenetic control of endogenous Ca(2+) channels in vivo.

    PubMed

    Kyung, Taeyoon; Lee, Sangkyu; Kim, Jung Eun; Cho, Taesup; Park, Hyerim; Jeong, Yun-Mi; Kim, Dongkyu; Shin, Anna; Kim, Sungsoo; Baek, Jinhee; Kim, Jihoon; Kim, Na Yeon; Woo, Doyeon; Chae, Sujin; Kim, Cheol-Hee; Shin, Hee-Sup; Han, Yong-Mahn; Kim, Daesoo; Heo, Won Do

    2015-10-01

    Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we present OptoSTIM1, an optogenetic tool for manipulating intracellular Ca(2+) levels through activation of Ca(2+)-selective endogenous Ca(2+) release-activated Ca(2+) (CRAC) channels. Using OptoSTIM1, which combines a plant photoreceptor and the CRAC channel regulator STIM1 (ref. 4), we quantitatively and qualitatively controlled intracellular Ca(2+) levels in various biological systems, including zebrafish embryos and human embryonic stem cells. We demonstrate that activating OptoSTIM1 in the CA1 hippocampal region of mice selectively reinforced contextual memory formation. The broad utility of OptoSTIM1 will expand our mechanistic understanding of numerous Ca(2+)-associated processes and facilitate screening for drug candidates that antagonize Ca(2+) signals.

  12. Biofortification of rice with lysine using endogenous histones.

    PubMed

    Wong, H W; Liu, Q; Sun, S S M

    2015-02-01

    Rice is the most consumed cereal grain in the world, but deficient in the essential amino acid lysine. Therefore, people in developing countries with limited food diversity who rely on rice as their major food source may suffer from malnutrition. Biofortification of stable crops by genetic engineering provides a fast and sustainable method to solve this problem. In this study, two endogenous rice lysine-rich histone proteins, RLRH1 and RLRH2, were over-expressed in rice seeds to achieve lysine biofortification. Their protein sequences passed an allergic sequence-based homology test. Their accumulations in rice seeds were raised to a moderate level by the use of a modified rice glutelin 1 promoter with lowered expression strength to avoid the occurrence of physiological abnormalities like unfolded protein response. The expressed proteins were further targeted to protein storage vacuoles for stable storage using a glutelin 1 signal peptide. The lysine content in the transgenic rice seeds was enhanced by up to 35 %, while other essential amino acids remained balanced, meeting the nutritional standards of the World Health Organization. No obvious unfolded protein response was detected. Different degrees of chalkiness, however, were detected in the transgenic seeds, and were positively correlated with both the levels of accumulated protein and lysine enhancement. This study offered a solution to the lysine deficiency in rice, while at the same time addressing concerns about food safety and physiological abnormalities in biofortified crops.

  13. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

    PubMed Central

    Akram, Khondoker M.; Patel, Neil; Spiteri, Monica A.; Forsyth, Nicholas R.

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  14. Quantitating protein synthesis, degradation, and endogenous antigen processing.

    PubMed

    Princiotta, Michael F; Finzi, Diana; Qian, Shu-Bing; Gibbs, James; Schuchmann, Sebastian; Buttgereit, Frank; Bennink, Jack R; Yewdell, Jonathan W

    2003-03-01

    Using L929 cells, we quantitated the macroeconomics of protein synthesis and degradation and the microeconomics of producing MHC class I associated peptides from viral translation products. To maintain a content of 2.6 x 10(9) proteins, each cell's 6 x 10(6) ribosomes produce 4 x 10(6) proteins min(-1). Each of the cell's 8 x 10(5) proteasomes degrades 2.5 substrates min(-1), creating one MHC class I-peptide complex for each 500-3000 viral translation products degraded. The efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo. Proteasomes create antigenic peptides at different efficiencies from two distinct substrate pools: rapidly degraded newly synthesized proteins that clearly represent defective ribosomal products (DRiPs) and a less rapidly degraded pool in which DRiPs may also predominate. PMID:12648452

  15. Combination Classes and Educational Achievement

    ERIC Educational Resources Information Center

    Thomas, Jaime L.

    2012-01-01

    Using the ECLS-K and considering first graders in single-grade and K-1 and 1-2 combination classes, I discuss the mechanisms underlying the combination-class effect and address the systematic school-, teacher-, and student-level differences that confound estimates of this effect. I find evidence for positive selection into 1-2 classes, but using a…

  16. A Class Traitor in Academe

    ERIC Educational Resources Information Center

    Benton, Thomas H.

    2007-01-01

    In this article, the author reflects on his feelings as a working-class transplant into academic culture and the middle class. He draws on his feelings of alienation from the people who surround him and his observations of the cultural subordination necessary to succeed in the middle class world to explain his desire to do more to help other…

  17. Team Learning in Large Classes.

    ERIC Educational Resources Information Center

    Roueche, Suanne D., Ed.

    1984-01-01

    Information and suggestions are provided on the use of team learning in large college classes. Introductory material discusses the negative cycle of student-teacher interaction that may be provoked by large classes, and the use of permanent, heterogeneous, six- or seven-member student learning groups as the central focus of class activity as a…

  18. Multimethod latent class analysis

    PubMed Central

    Nussbeck, Fridtjof W.; Eid, Michael

    2015-01-01

    Correct and, hence, valid classifications of individuals are of high importance in the social sciences as these classifications are the basis for diagnoses and/or the assignment to a treatment. The via regia to inspect the validity of psychological ratings is the multitrait-multimethod (MTMM) approach. First, a latent variable model for the analysis of rater agreement (latent rater agreement model) will be presented that allows for the analysis of convergent validity between different measurement approaches (e.g., raters). Models of rater agreement are transferred to the level of latent variables. Second, the latent rater agreement model will be extended to a more informative MTMM latent class model. This model allows for estimating (i) the convergence of ratings, (ii) method biases in terms of differential latent distributions of raters and differential associations of categorizations within raters (specific rater bias), and (iii) the distinguishability of categories indicating if categories are satisfyingly distinct from each other. Finally, an empirical application is presented to exemplify the interpretation of the MTMM latent class model. PMID:26441714

  19. Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine Deaminases ▿

    PubMed Central

    Dörrschuck, Eva; Fischer, Nicole; Bravo, Ignacio G.; Hanschmann, Kay-Martin; Kuiper, Heidi; Spötter, Andreas; Möller, Ronny; Cichutek, Klaus; Münk, Carsten; Tönjes, Ralf R.

    2011-01-01

    Xenotransplantation of porcine cells, tissues, and organs shows promise to surmount the shortage of human donor materials. Among the barriers to pig-to-human xenotransplantation are porcine endogenous retroviruses (PERV) since functional representatives of the two polytropic classes, PERV-A and PERV-B, are able to infect human embryonic kidney cells in vitro, suggesting that a xenozoonosis in vivo could occur. To assess the capacity of human and porcine cells to counteract PERV infections, we analyzed human and porcine APOBEC3 (A3) proteins. This multigene family of cytidine deaminases contributes to the cellular intrinsic immunity and act as potent inhibitors of retroviruses and retrotransposons. Our data show that the porcine A3 gene locus on chromosome 5 consists of the two single-domain genes A3Z2 and A3Z3. The evolutionary relationships of the A3Z3 genes reflect the evolutionary history of mammals. The two A3 genes encode at least four different mRNAs: A3Z2, A3Z3, A3Z2-Z3, and A3Z2-Z3 splice variant A (SVA). Porcine and human A3s have been tested toward their antiretroviral activity against PERV and murine leukemia virus (MuLV) using novel single-round reporter viruses. The porcine A3Z2, A3Z3 and A3Z2-Z3 were packaged into PERV particles and inhibited PERV replication in a dose-dependent manner. The antiretroviral effect correlated with editing by the porcine A3s with a trinucleotide preference for 5′ TGC for A3Z2 and A3Z2-Z3 and 5′ CAC for A3Z3. These results strongly imply that human and porcine A3s could inhibit PERV replication in vivo, thereby reducing the risk of infection of human cells by PERV in the context of pig-to-human xenotransplantation. PMID:21307203

  20. Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential.

    PubMed

    Ohnuki, Mari; Tanabe, Koji; Sutou, Kenta; Teramoto, Ito; Sawamura, Yuka; Narita, Megumi; Nakamura, Michiko; Tokunaga, Yumie; Nakamura, Masahiro; Watanabe, Akira; Yamanaka, Shinya; Takahashi, Kazutoshi

    2014-08-26

    Pluripotency can be induced in somatic cells by overexpressing transcription factors, including POU class 5 homeobox 1 (OCT3/4), sex determining region Y-box 2 (SOX2), Krüppel-like factor 4 (KLF4), and myelocytomatosis oncogene (c-MYC). However, some induced pluripotent stem cells (iPSCs) exhibit defective differentiation and inappropriate maintenance of pluripotency features. Here we show that dynamic regulation of human endogenous retroviruses (HERVs) is important in the reprogramming process toward iPSCs, and in re-establishment of differentiation potential. During reprogramming, OCT3/4, SOX2, and KLF4 transiently hyperactivated LTR7s--the long-terminal repeats of HERV type-H (HERV-H)--to levels much higher than in embryonic stem cells by direct occupation of LTR7 sites genome-wide. Knocking down LTR7s or long intergenic non-protein coding RNA, regulator of reprogramming (lincRNA-RoR), a HERV-H-driven long noncoding RNA, early in reprogramming markedly reduced the efficiency of iPSC generation. KLF4 and LTR7 expression decreased to levels comparable with embryonic stem cells once reprogramming was complete, but failure to resuppress KLF4 and LTR7s resulted in defective differentiation. We also observed defective differentiation and LTR7 activation when iPSCs had forced expression of KLF4. However, when aberrantly expressed KLF4 or LTR7s were suppressed in defective iPSCs, normal differentiation was restored. Thus, a major mechanism by which OCT3/4, SOX2, and KLF4 promote human iPSC generation and reestablish potential for differentiation is by dynamically regulating HERV-H LTR7s.

  1. Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs.

    PubMed

    Ranoa, Diana Rose E; Parekh, Akash D; Pitroda, Sean P; Huang, Xiaona; Darga, Thomas; Wong, Anthony C; Huang, Lei; Andrade, Jorge; Staley, Jonathan P; Satoh, Takashi; Akira, Shizuo; Weichselbaum, Ralph R; Khodarev, Nikolai N

    2016-05-01

    Emerging evidence indicates that ionizing radiation (IR) and chemotherapy activate Type I interferon (IFN) signaling in tumor and host cells. However, the mechanism of induction is poorly understood. We identified a novel radioprotective role for the DEXH box RNA helicase LGP2 (DHX58) through its suppression of IR-induced cytotoxic IFN-beta [1]. LGP2 inhibits activation of the RIG-I-like receptor (RLR) pathway upon binding of viral RNA to the cytoplasmic sensors RIG-I (DDX58) and MDA5 (IFIH1) and subsequent IFN signaling via the mitochondrial adaptor protein MAVS (IPS1). Here we show that MAVS is necessary for IFN-beta induction and interferon-stimulated gene expression in the response to IR. Suppression of MAVS conferred radioresistance in normal and cancer cells. Germline deletion of RIG-I, but not MDA5, protected mice from death following total body irradiation, while deletion of LGP2 accelerated the death of irradiated animals. In human tumors depletion of RIG-I conferred resistance to IR and different classes of chemotherapy drugs. Mechanistically, IR stimulated the binding of cytoplasmic RIG-I with small endogenous non-coding RNAs (sncRNAs), which triggered IFN-beta activity. We demonstrate that the small nuclear RNAs U1 and U2 translocate to the cytoplasm after IR treatment, thus stimulating the formation of RIG-I: RNA complexes and initiating downstream signaling events. Taken together, these findings suggest that the physiologic responses to radio-/chemo-therapy converge on an antiviral program in recruitment of the RLR pathway by a sncRNA-dependent activation of RIG-I which commences cytotoxic IFN signaling. Importantly, activation of interferon genes by radiation or chemotherapy is associated with a favorable outcome in patients undergoing treatment for cancer. To our knowledge, this is the first demonstration of a cell-intrinsic response to clinically relevant genotoxic treatments mediated by an RNA-dependent mechanism.

  2. Essential Role for endogenous siRNAs during meiosis in mouse oocytes.

    PubMed

    Stein, Paula; Rozhkov, Nikolay V; Li, Fan; Cárdenas, Fabián L; Davydenko, Olga; Davydenk, Olga; Vandivier, Lee E; Gregory, Brian D; Hannon, Gregory J; Schultz, Richard M

    2015-02-01

    The RNase III enzyme DICER generates both microRNAs (miRNAs) and endogenous short interfering RNAs (endo-siRNAs). Both small RNA species silence gene expression post-transcriptionally in association with the ARGONAUTE (AGO) family of proteins. In mammals, there are four AGO proteins (AGO1-4), of which only AGO2 possesses endonucleolytic activity. siRNAs trigger endonucleolytic cleavage of target mRNAs, mediated by AGO2, whereas miRNAs cause translational repression and mRNA decay through association with any of the four AGO proteins. Dicer deletion in mouse oocytes leads to female infertility due to defects during meiosis I. Because mouse oocytes express both miRNAs and endo-siRNAs, this phenotype could be due to the absence of either class of small RNA, or both. However, we and others demonstrated that miRNA function is suppressed in mouse oocytes, which suggested that endo-siRNAs, not miRNAs, are essential for female meiosis. To determine if this was the case we generated mice that express a catalytically inactive knock-in allele of Ago2 (Ago2ADH) exclusively in oocytes and thereby disrupted the function of siRNAs. Oogenesis and hormonal response are normal in Ago2ADH oocytes, but meiotic maturation is impaired, with severe defects in spindle formation and chromosome alignment that lead to meiotic catastrophe. The transcriptome of these oocytes is widely perturbed and shows a highly significant correlation with the transcriptome of Dicer null and Ago2 null oocytes. Expression of the mouse transcript (MT), the most abundant transposable element in mouse oocytes, is increased. This study reveals that endo-siRNAs are essential during meiosis I in mouse females, demonstrating a role for endo-siRNAs in mammals.

  3. Endogenous ligands of the aryl hydrocarbon receptor regulate lung dendritic cell function.

    PubMed

    Thatcher, Thomas H; Williams, Marc A; Pollock, Stephen J; McCarthy, Claire E; Lacy, Shannon H; Phipps, Richard P; Sime, Patricia J

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a transcription factor that has been extensively studied as a regulator of toxicant metabolism. However, recent evidence indicates that the AhR also plays an important role in immunity. We hypothesized that the AhR is a novel, immune regulator of T helper type 2 (Th2) -mediated allergic airway disease. Here, we report that AhR-deficient mice develop increased allergic responses to the model allergen ovalbumin (OVA), which are driven in part by increased dendritic cell (DC) functional activation. AhR knockout (AhR(-/-) ) mice sensitized and challenged with OVA develop an increased inflammatory response in the lung compared with wild-type controls, with greater numbers of inflammatory eosinophils and neutrophils, greater T-cell proliferation, greater production of Th2 cytokines, and higher levels of OVA-specific IgE and IgG1. Lung DCs from AhR(-/-) mice stimulated antigen-specific proliferation and Th2 cytokine production by naive T cells in vitro. Additionally, AhR(-/-) DCs produced higher levels of tumour necrosis factor-α and interleukin-6, which promote Th2 differentiation, and expressed higher cell surface levels of stimulatory MHC Class II and CD86 molecules. Overall, loss of the AhR was associated with enhanced T-cell activation by pulmonary DCs and heightened pro-inflammatory allergic responses. This suggests that endogenous AhR ligands are involved in the normal regulation of Th2-mediated immunity in the lung via a DC-dependent mechanism. Therefore, the AhR may represent an important target for therapeutic intervention in allergic airways inflammation.

  4. Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs

    PubMed Central

    Ranoa, Diana Rose E.; Parekh, Akash D.; Pitroda, Sean P.; Huang, Xiaona; Darga, Thomas; Wong, Anthony C.; Huang, Lei; Andrade, Jorge; Staley, Jonathan P.; Satoh, Takashi; Akira, Shizuo

    2016-01-01

    Emerging evidence indicates that ionizing radiation (IR) and chemotherapy activate Type I interferon (IFN) signaling in tumor and host cells. However, the mechanism of induction is poorly understood. We identified a novel radioprotective role for the DEXH box RNA helicase LGP2 (DHX58) through its suppression of IR-induced cytotoxic IFN-beta [1]. LGP2 inhibits activation of the RIG-I-like receptor (RLR) pathway upon binding of viral RNA to the cytoplasmic sensors RIG-I (DDX58) and MDA5 (IFIH1) and subsequent IFN signaling via the mitochondrial adaptor protein MAVS (IPS1). Here we show that MAVS is necessary for IFN-beta induction and interferon-stimulated gene expression in the response to IR. Suppression of MAVS conferred radioresistance in normal and cancer cells. Germline deletion of RIG-I, but not MDA5, protected mice from death following total body irradiation, while deletion of LGP2 accelerated the death of irradiated animals. In human tumors depletion of RIG-I conferred resistance to IR and different classes of chemotherapy drugs. Mechanistically, IR stimulated the binding of cytoplasmic RIG-I with small endogenous non-coding RNAs (sncRNAs), which triggered IFN-beta activity. We demonstrate that the small nuclear RNAs U1 and U2 translocate to the cytoplasm after IR treatment, thus stimulating the formation of RIG-I: RNA complexes and initiating downstream signaling events. Taken together, these findings suggest that the physiologic responses to radio-/chemo-therapy converge on an antiviral program in recruitment of the RLR pathway by a sncRNA-dependent activation of RIG-I which commences cytotoxic IFN signaling. Importantly, activation of interferon genes by radiation or chemotherapy is associated with a favorable outcome in patients undergoing treatment for cancer. To our knowledge, this is the first demonstration of a cell-intrinsic response to clinically relevant genotoxic treatments mediated by an RNA-dependent mechanism. PMID:27034163

  5. Endogenous short RNAs generated by Dicer 2 and RNA-dependent RNA polymerase 1 regulate mRNAs in the basal fungus Mucor circinelloides

    SciTech Connect

    Grigoriev, Igor; Nicolas, Francisco; Moxon, Simon; Haro, Juan de; Calo, Silvia; Torres-Martinez, Santiago; Moulton, Vincent; Ruiz-Vazquez, Rosa; Dalmay, Tamas

    2011-09-01

    Endogenous short RNAs (esRNAs) play diverse roles in eukaryotes and usually are produced from double-stranded RNA (dsRNA) by Dicer. esRNAs are grouped into different classes based on biogenesis and function but not all classes are present in all three eukaryotic kingdoms. The esRNA register of fungi is poorly described compared to other eukaryotes and it is not clear what esRNA classes are present in this kingdom and whether they regulate the expression of protein coding genes. However, evidence that some dicer mutant fungi display altered phenotypes suggests that esRNAs play an important role in fungi. Here, we show that the basal fungus Mucor circinelloides produces new classes of esRNAs that map to exons and regulate the expression of many protein coding genes. The largest class of these exonic-siRNAs (ex-siRNAs) are generated by RNA-dependent RNA Polymerase 1 (RdRP1) and dicer-like 2 (DCL2) and target the mRNAs of protein coding genes from which they were produced. Our results expand the range of esRNAs in eukaryotes and reveal a new role for esRNAs in fungi

  6. Functional classes and equivalence relations

    PubMed Central

    Sidman, Murray; Wynne, Constance K.; Maguire, Russell W.; Barnes, Thomas

    1989-01-01

    Three adult subjects were taught a set of two-choice simultaneous discriminations, with three positive and three negative stimuli; all possible combinations of positive and negative stimuli yielded nine different pairs. The discriminations were repeatedly reversed and rereversed, the former positive stimuli becoming negative and the former negative stimuli becoming positive. With all subjects, a reversal of the contingencies for one pair of stimuli became sufficient to change their responses to all of the other pairs. The reversals had produced functional stimulus classes. Then, all subjects showed conditional discriminations emerging between members of a functional class; given a sample from one class and comparisons from both classes, they selected the comparison that was in the same class as the sample. Next, 2 of the subjects showed that the within-class conditional relations possessed the symmetric and transitive properties of equivalence relations; after having been taught to relate new stimuli to existing class members, the subjects then matched other class members to the new stimuli. Subsequent tests of two-choice discriminations showed that the conditional discriminations had transferred functional class membership to the new stimuli. The 3rd subject, who did not show equivalence relations among functional class members, was also found to have lost the within-class conditional relations after the equivalence tests. PMID:16812597

  7. Class Differences in Cohabitation Processes

    PubMed Central

    Sassler, Sharon; Miller, Amanda J.

    2012-01-01

    Despite the burgeoning cohabitation literature, research has failed to examine social class variation in processes of forming and advancing such unions. Drawing upon in-depth interviews with 122 working- and middle-class cohabitors, we examine the duration between dating and moving in together, reasons for cohabiting, and subsequent plans. Transitions to cohabitation are more rapid among the working class. Respondents often cohabited for practical reasons—out of financial necessity, because it was convenient, or to meet a housing need. Regardless of social class status, few couples move in together as a “trial marriage.” Nonetheless, middle-class cohabitors were more likely to have become engaged than their working-class counterparts. Our findings indicate the need to reassess common beliefs regarding the role served by cohabitation and suggest that cohabitation has become another location where family outcomes are diverging by social class. PMID:23504506

  8. Class Differences in Cohabitation Processes.

    PubMed

    Sassler, Sharon; Miller, Amanda J

    2011-04-01

    Despite the burgeoning cohabitation literature, research has failed to examine social class variation in processes of forming and advancing such unions. Drawing upon in-depth interviews with 122 working- and middle-class cohabitors, we examine the duration between dating and moving in together, reasons for cohabiting, and subsequent plans. Transitions to cohabitation are more rapid among the working class. Respondents often cohabited for practical reasons-out of financial necessity, because it was convenient, or to meet a housing need. Regardless of social class status, few couples move in together as a "trial marriage." Nonetheless, middle-class cohabitors were more likely to have become engaged than their working-class counterparts. Our findings indicate the need to reassess common beliefs regarding the role served by cohabitation and suggest that cohabitation has become another location where family outcomes are diverging by social class.

  9. Exogenous and endogenous contributions to nitrogen fluxes in the digestive tract of pigs fed a casein diet. III. Recycling of endogenous nitrogen.

    PubMed

    Souffrant, W B; Rérat, A; Laplace, J P; Darcy-Vrillon, B; Köhler, R; Corring, T; Gebhardt, G

    1993-01-01

    The aim of the present study was to measure the incorporation of infused 15N in blood fractions, urine, digesta, faeces and in the exocrine pancreatic and biliary secretions, in order to estimate the endogenous part of nitrogen in the ileal digesta and in the faeces of pigs fed a casein diet and to calculate the total endogenous nitrogen secretion as well as its recycling in the digestive tract. For 8 d 11 Large White female pigs (50.1 +/- 1.8 kg) received a continuous infusion of L-[15N]leucine via a catheter in the jugular vein. The 15N-enrichment was measured in several fractions. The 15N-level of the pancreatic juice was higher than that in the biliary secretion, TCA-blood fractions, and urine during the whole experimental period. Using the 15N-isotope dilution method it was found that casein was completely digested up to the terminal ileum and that all the nitrogen in the ileal digesta was of endogenous origin. The total endogenous secretion was estimated at approximately 11 g N/d. The reabsorption of endogenous nitrogen amounted to 79% up to the end of the small intestine and 88% over the whole digestive tract. PMID:8240681

  10. Pseudo Class III malocclusion

    PubMed Central

    Al-Hummayani, Fadia M.

    2016-01-01

    The treatment of deep anterior crossbite is technically challenging due to the difficulty of placing traditional brackets with fixed appliances. This case report represents a none traditional treatment modality to treat deep anterior crossbite in an adult pseudo class III malocclusion complicated by severely retruded, supraerupted upper and lower incisors. Treatment was carried out in 2 phases. Phase I treatment was performed by removable appliance “modified Hawley appliance with inverted labial bow,” some modifications were carried out to it to suit the presented case. Positive overbite and overjet was accomplished in one month, in this phase with minimal forces exerted on the lower incisors. Whereas, phase II treatment was performed with fixed appliances (braces) to align teeth and have proper over bite and overjet and to close posterior open bite, this phase was accomplished within 11 month. PMID:27052290

  11. Endogenous Market-Clearing Prices and Reference Point Adaptation

    NASA Astrophysics Data System (ADS)

    Dragicevic, Arnaud Z.

    When prices depend on the submitted bids, i.e. with endogenous market-clearing prices in repeated-round auction mechanisms, the assumption of independent private values that underlines the property of incentive-compatibility is to be brought into question; even if these mechanisms provide active involvement and market learning. In its orthodox view, adaptive bidding behavior imperils incentive-compatibility. We relax the assumption of private values' independence in the repeated-round auctions, when the market-clearing prices are made public at the end of each round. Instead of using game-theory learning models, we introduce a behavioral model that shows that bidders bid according to the anchoring-and-adjustment heuristic, which neither ignores the rationality and incentive-compatibility constraints, nor rejects the posted prices issued from others' bids. Bidders simply weight information at their disposal and adjust their discovered value using reference points encoded in the sequential price weighting function. Our model says that bidders and offerers are sincere boundedly rational utility maximizers. It lies between evolutionary dynamics and adaptive heuristics and we model the concept of inertia as high weighting of the anchor, which stands for truthful bidding and high regard to freshly discovered preferences. Adjustment means adaptive rule based on adaptation of the reference point in the direction of the posted price. It helps a bidder to maximize her expected payoff, which is after all the only purpose that matters to rationality. The two components simply suggest that sincere bidders are boundedly rational. Furthermore, by deviating from their anchor in the direction of the public signal, bidders operate in a correlated equilibrium. The correlation between bids comes from the commonly observed history of play and each bidder's actions are determined by the history. Bidders are sincere if they have limited memory and confine their reference point adaptation

  12. Can Neural Activity Propagate by Endogenous Electrical Field?

    PubMed

    Qiu, Chen; Shivacharan, Rajat S; Zhang, Mingming; Durand, Dominique M

    2015-12-01

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2-6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5-5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds.

  13. Visualization of Epicardial Cryoablation Lesions using Endogenous Tissue Fluorescence

    PubMed Central

    Swift, Luther; Gil, Daniel A.B.; Jaimes, Rafael; Kay, Matthew; Mercader, Marco; Sarvazyan, Narine

    2014-01-01

    Background Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures. Methods and Results Cryoablation of either blood-perfused or saline-perfused hearts was associated with a marked decrease in NADH fluorescence leading to a 60-70% loss of signal intensity at the lesion site. The total lesion area observed on the NADH channel exhibited a strong correlation with the area identified by triphenyl tetrazolium staining (r=0.89, p<0.001). At physiological temperatures, loss of NADH became visually apparent within 26±8 sec after detachment of the cryoprobe from the epicardial surface and plateaued within minutes after which the boundaries of the lesions remained stable for several hours. The loss of electrical activity within the cryoablation site exhibited a close spatial correlation with the loss of NADH (r=0.84±0.06, p<0.001). Cryoablation led to a decrease in diffuse reflectance across the entire visible spectrum which was in stark contrast to radiofrequency ablation that markedly increased the intensity of reflected light at the lesion sites. Conclusions We confirmed the feasibility of using endogenous NADH fluorescence for the real-time visualization of cryoablation lesions in blood-perfused cardiac muscle preparations and revealed similarities and differences between imaging cryo- and radiofrequency ablation lesions when using ultraviolet and visible light illumination. PMID:25141861

  14. Nicotine and endogenous opioids: neurochemical and pharmacological evidence.

    PubMed

    Hadjiconstantinou, Maria; Neff, Norton H

    2011-06-01

    Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

  15. Diffuse fluorescence tomography of exo- and endogenously labeled tumors

    NASA Astrophysics Data System (ADS)

    Balalaeva, Irina V.; Turchin, Ilya V.; Orlova, Anna G.; Plekhanov, Vladimir I.; Shirmanova, Marina V.; Kleshnin, Michail S.; Fiks, Ilya I.; Zagainova, Elena V.; Kamensky, Vladislav A.

    2007-06-01

    Strong light scattering and absorption limit observation of the internal structure of biological tissue. Only special tools for turbid media imaging, such as optical diffuse tomography, enable noninvasive investigation of the internal biological tissues, including visualization and intravital monitoring of deep tumors. In this work the preliminary results of diffuse fluorescence tomography (DFT) of small animals are presented. Usage of exogenous fluorophores, targeted specifically at tumor cells, and fluorescent proteins expressed endogenously can significantly increase the contrast of obtained images. Fluorescent compounds of different nature, such as sulphonated aluminium phthalocyanine (Photosens), red fluorescing proteins and CdTe/CdSe-core/shell nanocrystals (quantum dots) were applied. We tested diffuse fluorescence tomography method at model media, in post mortem and in vivo experiments. The animal was scanned in transilluminative configuration by low-frequency modulated light (1 kHz) from Nd:YAG laser with second harmonic generation at wavelength of 532 nm or semiconductor laser at wavelength of 655 nm. Quantum dots or protein DsRed2 in glass capsules (inner diameter 2-3 mm) were placed post mortem inside the esophagus of 7-day-old hairless rats to simulate marked tumors. Photosens was injected intravenously to linear mice with metastazing Lewis lung carcinoma. The reconstruction algorithm, based on Algebraic Reconstruction Technique, was created and tested numerically in model experiments. High contrast images of tumor simulating capsules with DsRed2 concentrations about 10 -6 M and quantum dots about 5x10 -11 M have been obtained. Organ distribution of Photosens and its accumulation in tumors and surrounding tissues of animals has been examined. We have conducted the monitoring of tumors, exogenously labeled by photosensitizer. This work demonstrates potential capabilities of DFT method for intravital detection and monitoring of deep fluorescent

  16. Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy

    PubMed Central

    Park, Yongsoo; Kim, Hyunok; Park, Leejin; Min, Dongsoo; Park, Jinseu; Choi, Sooyoung; Park, Moon Hyang

    2015-01-01

    Background Diabetic nephropathy (DN) is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by inhibiting extracellular matrix expression) in these patients. Methods Using techniques for intra-cellular delivery of peptides, we made metallothionein (MT) and superoxide dismutase (SOD), potent endogenous antioxidants, readily transducible into cell membrane and tested their protective effect against the development of DN in OLETF rats. Herein, we study antioxidant peptides for their ability to prevent oxidative damage to primary rat mesangial cells (MCs), which are important constituents of renal glomeruli. Results Intraperitoneal administration of these antioxidants resulted in delivery to the kidney and decreased ROS and the expression of downstream signals in renal cells and postponed the usual progression to DN. In in vitro experiments, MT and SOD were efficiently transferred to MCs, and the increased removal of ROS by MT and SOD was proportional to the degree of scavenging enzymes delivered. MT and SOD decreased three major oxidative injuries (hyperglycemia, AGE and ROS exposure) and also injuries directly mediated by angiotensin II in MCs while changing downstream signal transduction. Conclusions The protective effects of MT and SOD for the progression of DN in experimental animals may be associated with the scavenging of ROS by MT and SOD and correlated changes in signal transduction downstream. Concomitant administration of these antioxidant peptides may prove to be a new approach for the prevention and therapy of DN. PMID:26114547

  17. The endogenous cannabinoid system protects against colonic inflammation

    PubMed Central

    Massa, Federico; Marsicano, Giovanni; Hermann, Heike; Cannich, Astrid; Monory, Krisztina; Cravatt, Benjamin F.; Ferri, Gian-Luca; Sibaev, Andrei; Storr, Martin; Lutz, Beat

    2004-01-01

    Excessive inflammatory responses can emerge as a potential danger for organisms’ health. Physiological balance between pro- and anti-inflammatory processes constitutes an important feature of responses against harmful events. Here, we show that cannabinoid receptors type 1 (CB1) mediate intrinsic protective signals that counteract proinflammatory responses. Both intrarectal infusion of 2,4-dinitrobenzene sulfonic acid (DNBS) and oral administration of dextrane sulfate sodium induced stronger inflammation in CB1-deficient mice (CB1–/–) than in wild-type littermates (CB1+/+). Treatment of wild-type mice with the specific CB1 antagonist N-(piperidino-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-pyrazole-3-carboxamide (SR141716A) mimicked the phenotype of CB1–/– mice, showing an acute requirement of CB1 receptors for protection from inflammation. Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Δ6-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis. Electrophysiological recordings from circular smooth muscle cells, performed 8 hours after DNBS treatment, revealed spontaneous oscillatory action potentials in CB1–/– but not in CB1+/+ colons, indicating an early CB1-mediated control of inflammation-induced irritation of smooth muscle cells. DNBS treatment increased the percentage of myenteric neurons expressing CB1 receptors, suggesting an enhancement of cannabinoid signaling during colitis. Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses. PMID:15085199

  18. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors.

    PubMed Central

    Dalgard, Clifton Lee; Lu, Huasheng; Mohyeldin, Ahmed; Verma, Ajay

    2004-01-01

    Adaptations to change in oxygen availability are crucial for survival of multi-cellular organisms and are also implicated in several disease states. Such adaptations rely upon gene expression regulated by the heterodimeric transcription factors HIFs (hypoxia-inducible factors). Enzymes that link changes in oxygen tensions with the stability and transcriptional activity of HIFs are considered as oxygen sensors. These enzymes are oxygen-, iron- and 2-oxoglutarate-dependent dioxygenases that hydroxylate key proline and asparagine residues in HIFalpha subunits. The constitutive inhibitory action of these enzymes on HIFs is relieved by hypoxia and by agents that displace iron or 2-oxoglutarate. Two of the enzymes, HPH (HIF prolyl hydroxylase)-1 and HPH-2, are known to be inducible by hypoxia in a HIF-dependent manner. This suggests the existence of a novel feedback loop for adjusting hypoxia-regulated gene expression. We have recently shown that HIF-1alpha stability, HIF-1 nuclear translocation and HIF-mediated gene expression in human glioma cell lines can be stimulated by pyruvate independently of hypoxia. In the present study we show that the endogenous 2-oxoacid oxaloacetate can also activate HIF-mediated gene expression. Pyruvate and oxaloacetate treatment of cells also up-regulates HPH-1 and HPH-2, but not HPH-3 or the HIF asparaginyl hydroxylase FIH-1 (factor inhibiting HIF). Regulation of HIF-1 and the expression of HPH homologue genes can thus be influenced by specific glycolytic and tricarboxylic acid cycle metabolites. These findings may underlie important interactions between oxygen homoeostasis, glycolysis, the tricarboxylic acid cycle and gluconeogenesis. PMID:14984367

  19. Estimating endogenous changes in task performance from EEG

    PubMed Central

    Touryan, Jon; Apker, Gregory; Lance, Brent J.; Kerick, Scott E.; Ries, Anthony J.; McDowell, Kaleb

    2014-01-01

    Brain wave activity is known to correlate with decrements in behavioral performance as individuals enter states of fatigue, boredom, or low alertness.Many BCI technologies are adversely affected by these changes in user state, limiting their application and constraining their use to relatively short temporal epochs where behavioral performance is likely to be stable. Incorporating a passive BCI that detects when the user is performing poorly at a primary task, and adapts accordingly may prove to increase overall user performance. Here, we explore the potential for extending an established method to generate continuous estimates of behavioral performance from ongoing neural activity; evaluating the extended method by applying it to the original task domain, simulated driving; and generalizing the method by applying it to a BCI-relevant perceptual discrimination task. Specifically, we used EEG log power spectra and sequential forward floating selection (SFFS) to estimate endogenous changes in behavior in both a simulated driving task and a perceptual discrimination task. For the driving task the average correlation coefficient between the actual and estimated lane deviation was 0.37 ± 0.22 (μ ± σ). For the perceptual discrimination task we generated estimates of accuracy, reaction time, and button press duration for each participant. The correlation coefficients between the actual and estimated behavior were similar for these three metrics (accuracy = 0.25 ± 0.37, reaction time = 0.33 ± 0.23, button press duration = 0.36 ± 0.30). These findings illustrate the potential for modeling time-on-task decrements in performance from concurrent measures of neural activity. PMID:24994968

  20. Network Class Superposition Analyses

    PubMed Central

    Pearson, Carl A. B.; Zeng, Chen; Simha, Rahul

    2013-01-01

    Networks are often used to understand a whole system by modeling the interactions among its pieces. Examples include biomolecules in a cell interacting to provide some primary function, or species in an environment forming a stable community. However, these interactions are often unknown; instead, the pieces' dynamic states are known, and network structure must be inferred. Because observed function may be explained by many different networks (e.g., for the yeast cell cycle process [1]), considering dynamics beyond this primary function means picking a single network or suitable sample: measuring over all networks exhibiting the primary function is computationally infeasible. We circumvent that obstacle by calculating the network class ensemble. We represent the ensemble by a stochastic matrix , which is a transition-by-transition superposition of the system dynamics for each member of the class. We present concrete results for derived from Boolean time series dynamics on networks obeying the Strong Inhibition rule, by applying to several traditional questions about network dynamics. We show that the distribution of the number of point attractors can be accurately estimated with . We show how to generate Derrida plots based on . We show that -based Shannon entropy outperforms other methods at selecting experiments to further narrow the network structure. We also outline an experimental test of predictions based on . We motivate all of these results in terms of a popular molecular biology Boolean network model for the yeast cell cycle, but the methods and analyses we introduce are general. We conclude with open questions for , for example, application to other models, computational considerations when scaling up to larger systems, and other potential analyses. PMID:23565141

  1. Network class superposition analyses.

    PubMed

    Pearson, Carl A B; Zeng, Chen; Simha, Rahul

    2013-01-01

    Networks are often used to understand a whole system by modeling the interactions among its pieces. Examples include biomolecules in a cell interacting to provide some primary function, or species in an environment forming a stable community. However, these interactions are often unknown; instead, the pieces' dynamic states are known, and network structure must be inferred. Because observed function may be explained by many different networks (e.g., ≈ 10(30) for the yeast cell cycle process), considering dynamics beyond this primary function means picking a single network or suitable sample: measuring over all networks exhibiting the primary function is computationally infeasible. We circumvent that obstacle by calculating the network class ensemble. We represent the ensemble by a stochastic matrix T, which is a transition-by-transition superposition of the system dynamics for each member of the class. We present concrete results for T derived from boolean time series dynamics on networks obeying the Strong Inhibition rule, by applying T to several traditional questions about network dynamics. We show that the distribution of the number of point attractors can be accurately estimated with T. We show how to generate Derrida plots based on T. We show that T-based Shannon entropy outperforms other methods at selecting experiments to further narrow the network structure. We also outline an experimental test of predictions based on T. We motivate all of these results in terms of a popular molecular biology boolean network model for the yeast cell cycle, but the methods and analyses we introduce are general. We conclude with open questions for T, for example, application to other models, computational considerations when scaling up to larger systems, and other potential analyses. PMID:23565141

  2. Influence of Glutamic Acid on the Endogenous Respiration of Bacillus subtilis

    PubMed Central

    Clifton, C. E.; Cherry, John

    1966-01-01

    Clifton, C. E. (Stanford University, Stanford, Calif.), and John Cherry. Influence of glutamic acid on the endogenous respiration of Bacillus subtilis. J. Bacteriol. 91:546–550. 1966.—Amino acids serve as the major initial endogenous substrate for Bacillus subtilis. The endogenous activity of freshly harvested washed cells is high and falls off rapidly with time of shaking at 30 C to lower but still significant levels. The rate of O2 consumption after the addition of glutamic acid also decreases as the cells age, but more slowly than noted for endogenous respiration. When cells were fed glutamate as soon as possible after harvesting, an apparent stimulation of endogenous respiration was noted. However, endogenous activity was inhibited if the cell suspensions were shaken for at least 1 hr before addition of the glutamate. Similar results were obtained with glycerol or glucose as exogenous substrates. Variation in rates of respiration with age of the cells, inherent instability of B. subtilis, and possible utilization of substances initially excreted by the cells appear to account for the variations noted regarding the influence of an exogenous substrate on endogenous respiration. PMID:4956754

  3. Differences between endogenous and exogenous emotion inhibition in the human brain.

    PubMed

    Kühn, Simone; Haggard, Patrick; Brass, Marcel

    2014-05-01

    The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

  4. Gastrointestinal Endogenous Proteins as a Source of Bioactive Peptides - An In Silico Study

    PubMed Central

    Dave, Lakshmi A.; Montoya, Carlos A.; Rutherfurd, Shane M.; Moughan, Paul J.

    2014-01-01

    Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein. PMID:24901416

  5. Degradation of endogenous and exogenous genes of roundup-ready soybean during food processing.

    PubMed

    Chen, Ying; Wang, Yuan; Ge, Yiqiang; Xu, Baoliang

    2005-12-28

    Roundup-Ready soybeans have been genetically modified to resist the effects of the herbicidal glyphosate and have become the most prevalent transgenic crop in the world. In this work, Roundup-Ready soybeans were used as raw material to study the effects of critical processing procedures such as grinding, cooking, blending, homogenization, sterilization, and spray-drying on the length of DNA fragments of an endogenous gene (lectin) and an exogenous gene (epsps) examined in material from three soybean foods of bean curd, soy milk, and soy powder and from samples taken during their processing. The results showed that various processing procedures caused degradations of both the endogenous and exogenous genes to different degrees. In the grinding procedure, endogenous gene DNA was degraded from 1883 to approximately 836 bp, and exogenous gene DNA was degraded from 1512 to approximately 408 bp. In the blending and squeeze-molding procedures, exogenous gene DNA was also degraded from about 408 to 190 bp, but there was no obvious action on the endogenous gene. After the endogenous and exogenous genes had been degraded to some degree, such as 836 and 408 bp, respectively, they were not evidently affected by cooking procedure at 100 degrees C for 15 min. However, the endogenous gene was further considerably degraded from around 836 to 162 bp in the sterilization procedure at 121 degrees C for 30 s. The effect of the homogenization step on endogenous and exogenous genes was similar to that of the cooking procedure. The coagulation procedure, principally a biochemical reaction, did not greatly affect the exogenous gene but did affect endogenous gene, reducing DNA size from about 836 to 407 bp. Furthermore, the spray-drying procedure, a process of physical shearing, high temperature, and sudden high pressure, distinctly caused degradation of both the lectin and epsps genes, rapidly decreasing the sizes from about 836 to 162 bp for the endogenous gene and from about 408 to 190

  6. Exploring social class: voices of inter-class couples.

    PubMed

    McDowell, Teresa; Melendez-Rhodes, Tatiana; Althusius, Erin; Hergic, Sara; Sleeman, Gillian; Ton, Nicky Kieu My; Zimpfer-Bak, A J

    2013-01-01

    Social class is not often discussed or examined in-depth in couple and family therapy research and literature even though social class shapes familial relationships and is considered an important variable in marital satisfaction. In this qualitative study, we explored the perceptions of eight couples who made lasting commitments across class lines by asking them about the impact of their social class backgrounds on their relationships. Three categories of themes emerged including: (a) differences and similarities in values and attitudes toward education, work, money, and class awareness/classism, (b) relationship issues involving families of origin, friends, and class-based couple conflict, and (c) differences in economic resources, social capital and privileges/opportunities. Implications for assessment and treatment of couples are included. PMID:25073843

  7. Endogenous DNA-directed DNA synthesising system in a microsomal fraction of embryonic chick brain.

    PubMed Central

    Smith, J; Soriano, L

    1977-01-01

    A DNA polymerising complex directed by endogenous DNA has been partially purified from 11-day-old embryonic chick brain microsomes by DEAE-cellulose and phosphocellulose column chromatography. The active fractions are eluted together with an exogenous DNA-directed DNA polymerase; after Sephadex gel filtration, the endogenous activity remains associated with a high molecular weight DNA-directed DNA polymerase. The endogenous activity of the complex has been shown to be RNase-resistant and actinomycin-sensitive. It requires potassium, an ATP-regenerating system and all four deoxyribonucleoside triphosphates for full activity. The significance of this activity with regard to the protovirus hypothesis is discussed. PMID:866184

  8. Erbium-doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis.

    PubMed

    Chaptini, Cassandra; Huilgol, Shyamala C

    2015-08-01

    Ochronosis is a rare disease characterised clinically by bluish-grey skin discolouration and histologically by yellow-brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium-doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment.

  9. Isolated group B streptococcal endogenous endophthalmitis simulating retinoblastoma or persistent fetal vasculature in a healthy full-term infant.

    PubMed

    McCourt, Emily A; Hink, Eric M; Durairaj, Vikram D; Oliver, Scott C N

    2010-08-01

    Group B streptococcus (GBS) is a potentially devastating neonatal pathogen that most commonly causes meningitis, sepsis, and pneumonia. It is also a very rare cause of endogenous endophthalmitis. We present the second case of endogenous endophthalmitis caused by GBS in a healthy newborn and the first case of endogenous endophthalmitis by GBS in a newborn mimicking retinoblastoma and resulting in enucleation. PMID:20637664

  10. Actions of Xanthurenic acid, a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus.

    PubMed

    Copeland, C S; Neale, S A; Salt, T E

    2013-03-01

    Xanthurenic acid (XA), a molecule arising from tryptophan metabolism by transamination of 3-hydroxykynurenine, has recently been identified as an endogenous Group II (mGlu2 and mGlu3) metabotropic glutamate (mGlu) receptor ligand in vitro. Impairments in Group II mGlu receptor expression and function have been implicated in the pathophysiology of schizophrenia, as have multiple steps in the kynurenine metabolism pathway. Therefore, we examined XA in vivo to further investigate its potential as a Group II mGlu receptor ligand using a preparation that has been previously demonstrated to efficiently reveal the action of other Group II mGlu receptor ligands in vivo. Extracellular single-neurone recordings were made in the rat ventrobasal thalamus (VB) in conjunction with iontophoresis of agonists, an antagonist and a positive allosteric modulator and/or intravenous (i.v.) injection of XA. We found the XA effect on sensory inhibition, when applied iontophoretically and i.v., was similar to that of other Group II mGlu receptor agonists in reducing inhibition evoked in the VB from the thalamic reticular nucleus upon physiological sensory stimulation. Furthermore, we postulate that XA may be the first potential endogenous allosteric agonist (termed 'endocoid') for the mGlu receptors. As the Group II receptors and kynurenine metabolism pathway have both been heavily implicated in the pathophysiology of schizophrenia, XA could play a pivotal role in antipsychotic research as this potential endocoid represents both a convergence within these two biological parameters and a novel class of Group II mGlu receptor ligand. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. PMID:22491023

  11. Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

    PubMed Central

    Faucard, Raphaël; Madeira, Alexandra; Gehin, Nadège; Authier, François-Jérôme; Panaite, Petrica-Adrian; Lesage, Catherine; Burgelin, Ingrid; Bertel, Mélanie; Bernard, Corinne; Curtin, François; Lang, Aloïs B.; Steck, Andreas J.; Perron, Hervé; Kuntzer, Thierry; Créange, Alain

    2016-01-01

    Background Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects. Methods 50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs). Findings In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env. Interpretation The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1

  12. Can Neural Activity Propagate by Endogenous Electrical Field?

    PubMed Central

    Qiu, Chen; Shivacharan, Rajat S.; Zhang, Mingming

    2015-01-01

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2–6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5–5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds. SIGNIFICANCE STATEMENT Neural activity (waves or spikes) can propagate using well documented mechanisms such as synaptic transmission, gap junctions, or diffusion. However, the purpose of this paper is to provide an explanation for experimental data showing that neural signals can propagate by means other than synaptic

  13. Induction of Endogenous Reactive Oxygen Species in Mitochondria by Fullerene-Based Photodynamic Therapy.

    PubMed

    Li, Qian; Liu, Chenguang; Li, Hongguang

    2016-06-01

    The production of ROS in mitochondria plays critical role in photodynamic therapy (PDT). The aim of this study was to investigate whether fullerene-based PDT can induce generation of additional endogenous ROS in mitochondria. Chitosan oligosaccharide grafted fullerene conjugate (CS-C60) was synthesized as a model water-soluble fullerene. The relationship among photodynamic cytotoxicity, intracellular ROS and CS-C60 amount demonstrated that low dose fullerene could induce generation of endogenous ROS in human malignant melanoma (A375) cells. Laser scanning microscope (LSM) image shows that considerable amount of endogenous ROS was generated in mitochondria even CS-C60 could not localize into mitochondria. Assay with rotenone shows that PDT-induced endogenous ROS was generated via electron transport chain (ETC).

  14. In between: Gypsy in Drosophila melanogaster Reveals New Insights into Endogenous Retrovirus Evolution

    PubMed Central

    Touret, Franck; Guiguen, François; Greenland, Timothy; Terzian, Christophe

    2014-01-01

    Retroviruses are RNA viruses that are able to synthesize a DNA copy of their genome and insert it into a chromosome of the host cell. Sequencing of different eukaryote genomes has revealed the presence of many such endogenous retroviral sequences. The mechanisms by which these retroviral sequences have colonized the genome are still unknown, and the endogenous retrovirus gypsy of Drosophila melanogaster is a powerful experimental model for deciphering this process in vivo. Gypsy is expressed in a layer of somatic cells, and then transferred into the oocyte by an unknown mechanism. This critical step is the start of the endogenization process. Moreover gypsy has been shown to have infectious properties, probably due to its envelope gene acquired from a baculovirus. Recently we have also shown that gypsy maternal transmission is reduced in the presence of the endosymbiotic bacterium Wolbachia. These studies demonstrate that gypsy is a unique and powerful model for understanding the endogenization of retroviruses. PMID:25502325

  15. Quantifying the time scales over which exogenous and endogenous conditions affect soil respiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding how exogenous and endogenous factors and aboveground-belowground linkages modulate carbon dynamics is difficult because of influences of antecedent conditions. For example, there are variable lags between aboveground assimilation and belowground efflux, and the duration of antecedent p...

  16. The validity of four definitions of endogenous depression. II. Clinical, demographic, familial, and psychosocial correlates.

    PubMed

    Zimmerman, M; Coryell, W; Pfohl, B; Stangl, D

    1986-03-01

    Based on a survey of the classic literature and studies examining the correlates of a clinical diagnosis of endogenous or nonendogenous depression, we found 14 variables that should discriminate endogenous and nonendogenous depressives. We applied four definitions of endogenous depression (Feinberg and Carroll, DSM-III, Research Diagnostic Criteria, and Newcastle) to a consecutive series of 152 unipolar major depressive inpatients. We examined the concordance between the definitions and the relationship between each definition and clinical, demographic, family history, and psychosocial factors. The DSM-III and Newcastle definitions were less inclusive than the other two definitions. We found some support for the validity of each of the four definitions. The validity of the Newcastle scale was the most frequently supported, with the endogenous depressives having a lower rate of personality disorder, marital separations and divorces, familial alcoholism, life events, and nonserious suicide attempts. PMID:3954543

  17. Excretion of low-molecular weight volatile substances in human breath: focus on endogenous ethanol.

    PubMed

    Jones, A W

    1985-01-01

    This paper describes a gas chromatographic method suitable for the analysis of low-molecular endogenous volatiles in human breath. The use of an on-column gas sampling device allowed serial determinations at 10-min intervals. With a flame ionization detector and Porapak Q as stationary phase, the four major endogenous breath volatiles were methanol, ethanol, acetone, and isoprene (2-methyl-1,3-butadiene). These same compounds were present in the breath of healthy individuals and abstinent alcoholics. In 10 healthy men, the breath concentration of endogenous ethanol, methanol, and acetone ranged from 0.07 to 0.39 microgram/L, 0.21 to 0.07 microgram/L, and 0.57 to 4.01 micrograms/L, respectively. When a man drank 5 g of exogenous ethanol, the blood concentration increased 200 times above the endogenous level. This small dose of ethanol was eliminated with a half-life of 16 min.

  18. Lack of differences in blood and tissue concentrations of endogenous ethanol in conventional and germfree rats.

    PubMed

    Jones, A W; Ostrovsky YuM; Wallin, A; Midtvedt, T

    1984-01-01

    Headspace gas chromatography was used to determine the concentrations of endogenous ethanol in blood and tissue of conventional and germfree rats. In all biological specimens analysed, the four principal volatile endogenous substances were identified as methanol, acetaldehyde, ethanol and acetone. No statistically significant differences in the concentrations of endogenous ethanol were noted between conventional and germfree animals. In whole blood, liver, kidney, and brain of germfree rats the concentrations of endogenous ethanol were 4.2 +/- 0.19 microM, 5.1 +/- 0.55 microM, 8.2 +/- 0.59 microM and 4.4 +/- 0.17 microM (means +/- SE), respectively. The higher concentration in kidney was also observed in conventional rats. Our results suggest that ethanol is a normal metabolic intermediate in rats and does not exclusively arise from microbial fermentation reactions in the gastrointestinal tract.

  19. Lens regeneration using endogenous stem cells with gain of visual function.

    PubMed

    Lin, Haotian; Ouyang, Hong; Zhu, Jie; Huang, Shan; Liu, Zhenzhen; Chen, Shuyi; Cao, Guiqun; Li, Gen; Signer, Robert A J; Xu, Yanxin; Chung, Christopher; Zhang, Ying; Lin, Danni; Patel, Sherrina; Wu, Frances; Cai, Huimin; Hou, Jiayi; Wen, Cindy; Jafari, Maryam; Liu, Xialin; Luo, Lixia; Zhu, Jin; Qiu, Austin; Hou, Rui; Chen, Baoxin; Chen, Jiangna; Granet, David; Heichel, Christopher; Shang, Fu; Li, Xuri; Krawczyk, Michal; Skowronska-Krawczyk, Dorota; Wang, Yujuan; Shi, William; Chen, Daniel; Zhong, Zheng; Zhong, Sheng; Zhang, Liangfang; Chen, Shaochen; Morrison, Sean J; Maas, Richard L; Zhang, Kang; Liu, Yizhi

    2016-03-17

    The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

  20. Induction of Endogenous Reactive Oxygen Species in Mitochondria by Fullerene-Based Photodynamic Therapy.

    PubMed

    Li, Qian; Liu, Chenguang; Li, Hongguang

    2016-06-01

    The production of ROS in mitochondria plays critical role in photodynamic therapy (PDT). The aim of this study was to investigate whether fullerene-based PDT can induce generation of additional endogenous ROS in mitochondria. Chitosan oligosaccharide grafted fullerene conjugate (CS-C60) was synthesized as a model water-soluble fullerene. The relationship among photodynamic cytotoxicity, intracellular ROS and CS-C60 amount demonstrated that low dose fullerene could induce generation of endogenous ROS in human malignant melanoma (A375) cells. Laser scanning microscope (LSM) image shows that considerable amount of endogenous ROS was generated in mitochondria even CS-C60 could not localize into mitochondria. Assay with rotenone shows that PDT-induced endogenous ROS was generated via electron transport chain (ETC). PMID:27427601

  1. Lens regeneration using endogenous stem cells with gain of visual function.

    PubMed

    Lin, Haotian; Ouyang, Hong; Zhu, Jie; Huang, Shan; Liu, Zhenzhen; Chen, Shuyi; Cao, Guiqun; Li, Gen; Signer, Robert A J; Xu, Yanxin; Chung, Christopher; Zhang, Ying; Lin, Danni; Patel, Sherrina; Wu, Frances; Cai, Huimin; Hou, Jiayi; Wen, Cindy; Jafari, Maryam; Liu, Xialin; Luo, Lixia; Zhu, Jin; Qiu, Austin; Hou, Rui; Chen, Baoxin; Chen, Jiangna; Granet, David; Heichel, Christopher; Shang, Fu; Li, Xuri; Krawczyk, Michal; Skowronska-Krawczyk, Dorota; Wang, Yujuan; Shi, William; Chen, Daniel; Zhong, Zheng; Zhong, Sheng; Zhang, Liangfang; Chen, Shaochen; Morrison, Sean J; Maas, Richard L; Zhang, Kang; Liu, Yizhi

    2016-03-17

    The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells. PMID:26958831

  2. 47 CFR 80.1053 - Prohibition on certification, manufacture, importation, sale or use of Class A, Class B, Class S...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Prohibition on certification, manufacture... certification, manufacture, importation, sale or use of Class A, Class B, Class S, and INMARSAT-E EPIRBs. The manufacture, importation, or sale in the United States of Class A, Class B, Class S, or INMARSAT-E EPIRBs...

  3. Class Matters in the Interview Setting? Positionality, Situatedness and Class

    ERIC Educational Resources Information Center

    Mellor, Jody; Ingram, Nicola; Abrahams, Jessie; Beedell, Phoebe

    2014-01-01

    In this article we argue that despite methodological and analytical advancements in the field of social class research, these developments have not led to a wholehearted discussion about class positionality and situatedness in relation to interviewer-participant dynamics. Despite--or perhaps due to--this methodological gap, there remains an…

  4. Class Counts: Education, Inequality, and the Shrinking Middle Class

    ERIC Educational Resources Information Center

    Ornstein, Allan

    2007-01-01

    Class differences and class warfare have existed since the beginning of western civilization, but the gap in income and wealth between the rich (top 10 percent) and the rest has increased steadily in the last twenty-five years. The U.S. is heading for a financial oligarchy much worse than the aristocratic old world that our Founding Fathers feared…

  5. The role of the endogenous cannabinoid system in drug addiction.

    PubMed

    Parolaro, D; Rubino, T

    2008-04-01

    This review aims to present the more recent knowledge on the role of the endocannabinoid system in drug addiction. For a long time, dopamine has been consistently associated with the reinforcing effects of most drugs of abuse but, recently, pharmacological evidence points to the possibility that pharmacological management of the endocannabinoid system might not only block the direct reinforcing effect of cannabis, opioids, nicotine and ethanol, but also prevent the relapse to various drugs of abuse including opioids, cocaine, nicotine, alcohol and amphetamine. Preclinical and clinical studies suggest that the manipulation of the endocannabinoid system through the CB(1) receptor antagonist SR-141716A (rimonabant) might constitute a new therapeutical strategy for treating addiction across different classes of abused drugs. PMID:18560613

  6. [Antibodies to endogenous bioregulators and their association with age and sex in chronic pain syndrome].

    PubMed

    Myagkova, M A; Petrochenko, S N; Morozova, V S; Moseikin, I A; Shypitsin, V V; Polyvyanaya, O Yu

    2013-01-01

    Authors studied changes in the levels of antibodies to endogenous bioregulators (Ab) to Β-endorphin, orphanin, serotonin, dopamine and angiotensin in 36 healthy people and 109 patients with dorsopathy with chronic pain syndrome. The association of these immunological indicators with age and sex was found. It has been concluded that the levels of Ab to endogenous bioregulators may be considered as a marker of algic system pathology that does not depend on age and is sex-related.

  7. [Antibodies to endogenous bioregulators and their association with age and sex in chronic pain syndrome].

    PubMed

    Myagkova, M A; Petrochenko, S N; Morozova, V S; Moseikin, I A; Shypitsin, V V; Polyvyanaya, O Yu

    2013-01-01

    Authors studied changes in the levels of antibodies to endogenous bioregulators (Ab) to Β-endorphin, orphanin, serotonin, dopamine and angiotensin in 36 healthy people and 109 patients with dorsopathy with chronic pain syndrome. The association of these immunological indicators with age and sex was found. It has been concluded that the levels of Ab to endogenous bioregulators may be considered as a marker of algic system pathology that does not depend on age and is sex-related. PMID:23739439

  8. Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

    PubMed

    Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell

    2015-08-01

    Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. PMID:26013541

  9. Parvovirus-derived endogenous viral elements in two South American rodent genomes.

    PubMed

    Arriagada, Gloria; Gifford, Robert J

    2014-10-01

    We describe endogenous viral elements (EVEs) derived from parvoviruses (family Parvoviridae) in the genomes of the long-tailed chinchilla (Chinchilla lanigera) and the degu (Octodon degus). The novel EVEs include dependovirus-related elements and representatives of a clearly distinct parvovirus lineage that also has endogenous representatives in marsupial genomes. In the degu, one dependovirus-derived EVE was found to carry an intact reading frame and was differentially expressed in vivo, with increased expression in the liver.

  10. Movement of endogenous calcium in the elongating zone of graviresponding roots of Zea mays

    NASA Technical Reports Server (NTRS)

    Moore, R.; Cameron, I. L.; Smith, N. K.

    1989-01-01

    Endogenous calcium (Ca) accumulates along the lower side of the elongating zone of horizontally oriented roots of Zea mays cv. Yellow Dent. This accumulation of Ca correlates positively with the onset of gravicurvature, and occurs in the cytoplasm, cell walls and mucilage of epidermal cells. Corresponding changes in endogenous Ca do not occur in cortical cells of the elongating zone of intact roots. These results indicate that the calcium asymmetries associated with root gravicurvature occur in the outermost layers of the root.

  11. The induction of free proline accumulation by endogenous ABA in Arabidopsis thaliana during drought

    SciTech Connect

    Gottlieb, M.L.; Bray, E.A. )

    1991-05-01

    Endogenous levels of abscisic acid (ABA) and free proline increase in response to drought stress. Exogenous ABA has been shown to induce proline accumulation, suggesting that ABA triggers the amino acid response. To determine if endogenous ABA induces free proline accumulation, increases in ABA and proline during drought stress were compared between wild type (WT), ABA-insensitive (abi) and ABA-deficient (aba) mutants of Arabidopsis thaliana. If elevated levels of endogenous ABA signal the proline response, then the mutants would not be expected to accumulate proline during stress. abi should be unable to respond to increased levels of endogenous ABA, while aba should be unable to accumulate sufficient ABA to elicit a proline response. Drought-stressed three week old shoots of WT, abi, and aba exhibited different patterns of endogenous ABA accumulation, but similar patterns of proline accumulation over 24 hours. Although the patterns of endogenous ABA accumulation differed, maximum levels were similar in WT and abi, but aba produced approximately 25% less. However, free proline accumulated in all three plant lines. abi exhibited a greater, more rapid increase in free proline over that in either WT or aba. aba, however, showed the same pattern and levels of accumulation as that in WT. Since free proline accumulated to at least similar levels in both WT and mutants, regardless of the levels of ABA accumulation, it may be that only a small endogenous ABA accumulation is required for proline accumulation. Alternatively, endogenous ABA may not be the direct signal for the proline response during drought stress.

  12. Endogenization of mouse mammary tumor virus (MMTV)-like elements in genomes of pikas (Ochotona sp.).

    PubMed

    Lemos de Matos, Ana; de Sousa-Pereira, Patrícia; Lissovsky, Andrey A; van der Loo, Wessel; Melo-Ferreira, José; Cui, Jie; Esteves, Pedro J

    2015-12-01

    Despite the finding in European rabbit and other leporid genomes of the first ever described endogenous lentivirus and of a European rabbit exclusive endogenous gammaretrovirus, until now no exogenous retroviruses have been isolated in Lagomorpha species. Nevertheless, looking for the presence of endogenous retroviruses (ERVs) in the species genomes could lead to the discovery of retroviral lineages yet to be found in Lagomorpha. Different mammalian genomes harbor endogenous viral sequences phylogenetically close to the betaretrovirus mouse mammary tumor virus (MMTV), propelling us to look for such retroviral "fossil" in American pika (Ochotona princeps) and European rabbit (Oryctolagus cuniculus) genomes. By performing genomic mining using MMTV gag and LTR as query sequences, we found that such viral elements were absent from the European rabbit genome. Oppositely, significant matches were found in American pika, and more importantly, a nearly complete MMTV-like virus (Pika-BERV) was identified. Using Pika-BERV gag and LTR as templates, we found similar sequences endogenized in different pika (Ochotona sp.) species. The orthology of the LTR flanking region between some pika species supported shared ancestry of specific endogenous betaretroviruses, while in other pika species similar sequences, but not orthologous, should have resulted from independent insertions. Our study supports the possible existence of infecting exogenous betaretroviruses for a long term, after the divergence of Ochotonidae from Leporidae, but yet to be identified. PMID:26151606

  13. Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

    SciTech Connect

    Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao; Lu, Meili; Che, Yanqiu

    2015-01-15

    This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

  14. Determination of endogenous ethanol in blood and breath by gas chromatography-mass spectrometry.

    PubMed

    Jones, A W; Mårdh, G; Anggård, E

    1983-01-01

    We describe methods for the determination of endogenous ethanol in biological specimens from healthy abstaining subjects. The analytical methods were headspace gas chromatography (GC) for plasma samples and gas chromatography-mass spectometry (GC/MS) with deuterium labelled species 2H3-ethanol and 2H5-ethanol as internal standards for breath analysis. Ethanol in rebreathed air was about 10% higher than in directly analysed end-expired alveolar air. Known volumes of rebreathed air were passed through a liquid-N2 freeze trap and the volatile constituents of breath were concentrated prior to analysis by GC or GC/MS. Besides endogenous ethanol, peaks were seen on the chromatograms for methanol, acetone and acetaldehyde as well as several as yet unidentified substances. The endogenous alcohols ethanol and methanol were confirmed from their mass chromatograms and the GC/MS profile also indicated the presence of endogenous propan-1-ol. The concentration of endogenous ethanol in plasma showed wide inter-subject variations ranging from below detection limits to 1.6 micrograms/ml (34.8 mumol/l) and with mean +/- SD of 0.39 +/- 0.45 micrograms/ml (8.5 +/- 9.8 mumol/l). We aim to characterise further the role of endogenous ethanol with the main focus on dynamic aspects such as the rate of formation and turnover.

  15. A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis.

    PubMed

    Saintigny, Yannick; Chevalier, François; Bravard, Anne; Dardillac, Elodie; Laurent, David; Hem, Sonia; Dépagne, Jordane; Radicella, J Pablo; Lopez, Bernard S

    2016-07-11

    Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [(3)H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [(3)H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.

  16. Discrepancy of neural response between exogenous and endogenous task switching: an event-related potentials study.

    PubMed

    Miyajima, Maki; Toyomaki, Atsuhito; Hashimoto, Naoki; Kusumi, Ichiro; Murohashi, Harumitsu; Koyama, Tsukasa

    2012-08-01

    Task switching is a well-known cognitive paradigm to explore task-set reconfiguration processes such as rule shifting. In particular, endogenous task switching is thought to differ qualitatively from stimulus-triggered exogenous task switching. However, no previous study has examined the neural substrate of endogenous task switching. The purpose of the present study is to explore the differences between event-related potential responses to exogenous and endogenous rule switching at cue stimulus. We modified two patterns of cued switching tasks: exogenous (bottom-up) rule switching and endogenous (top-down) rule switching. In each task cue stimulus was configured to induce switching or maintaining rule. In exogenous switching tasks, late positive deflection was larger in the switch rule condition than in the maintain rule condition. However, in endogenous switching tasks late positive deflection was unexpectedly larger in the maintain-rule condition than in the switch-rule condition. These results indicate that exogenous rule switching is explicit stimulus-driven processes, whereas endogenous rule switching is implicitly parallel processes independent of external stimulus.

  17. A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis

    PubMed Central

    Saintigny, Yannick; Chevalier, François; Bravard, Anne; Dardillac, Elodie; Laurent, David; Hem, Sonia; Dépagne, Jordane; Radicella, J. Pablo; Lopez, Bernard S.

    2016-01-01

    Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [3H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [3H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses. PMID:27406380

  18. CAPEOPEN.NET CLASS LIBRARY

    EPA Science Inventory

    The Cape-Open for .Net class library is a collection of classes that implement the Cape-Open v.1.0 interfaces in the .Net framework. This is a tool to aid process modeling component (PMC) developers in producing CAPE-OPEN compliant objects using the latest version of the Visual S...

  19. Automatic discovery of optimal classes

    NASA Technical Reports Server (NTRS)

    Cheeseman, Peter; Stutz, John; Freeman, Don; Self, Matthew

    1986-01-01

    A criterion, based on Bayes' theorem, is described that defines the optimal set of classes (a classification) for a given set of examples. This criterion is transformed into an equivalent minimum message length criterion with an intuitive information interpretation. This criterion does not require that the number of classes be specified in advance, this is determined by the data. The minimum message length criterion includes the message length required to describe the classes, so there is a built in bias against adding new classes unless they lead to a reduction in the message length required to describe the data. Unfortunately, the search space of possible classifications is too large to search exhaustively, so heuristic search methods, such as simulated annealing, are applied. Tutored learning and probabilistic prediction in particular cases are an important indirect result of optimal class discovery. Extensions to the basic class induction program include the ability to combine category and real value data, hierarchical classes, independent classifications and deciding for each class which attributes are relevant.

  20. Class and SLA: Making Connections

    ERIC Educational Resources Information Center

    Block, David

    2012-01-01

    This article explores how class might be brought to the fore as an identity inscription in studies of second language learning, alongside other identity inscriptions such as gender, ethnicity and national identity, which have been the focus of rather more research. It begins by clarifying what is meant by class through a brief discussion of the…

  1. [Modified Class II tunnel preparation].

    PubMed

    Rimondini, L; Baroni, C

    1991-05-15

    Tunnel preparations for restoration of Class II carious lesions in primary molars preserve the marginal ridge and minimize sacrifice of healthy tooth substructure. Materials with improved bonding to tooth structure and increase potential for fluoride release allow Class II restorations without "extension for prevention". PMID:1864420

  2. Visions of the Special Class.

    ERIC Educational Resources Information Center

    Safford, Philip L.; Safford, Elizabeth J.

    1998-01-01

    Discusses how the advent of public school special day-classes for children with disabilities marked a major shift in the service model in the direction of educational and societal inclusion. The different visions of the classes as cluster, clinic, and clearinghouse are explained. (Author/CR)

  3. A Touch of...Class!

    ERIC Educational Resources Information Center

    Netten, Joan W., Ed.

    1984-01-01

    A collection of ideas for class activities in elementary and secondary language classes includes a vocabulary review exercise and games of memory, counting, vocabulary, flashcard tic-tac-toe, dice, trashcans, questioning, and spelling. Some are designed specifically for French. (MSE)

  4. Eustace Tilley Comes to Class

    ERIC Educational Resources Information Center

    Arin, Jennifer

    2009-01-01

    Of all the reasons to use "The New Yorker" in a college writing class, the most compelling may be that its articles go beyond--well beyond--the five-paragraph model. Why, oh why, did that paradigm become such a fixture in composition courses? Students in the author's writing classes invariably suppose they can compose a quick introduction, add…

  5. Class Differences in Cohabitation Processes

    ERIC Educational Resources Information Center

    Sassler, Sharon; Miller, Amanda J.

    2011-01-01

    Despite the burgeoning cohabitation literature, research has failed to examine social class variation in processes of forming and advancing such unions. Drawing upon in-depth interviews with 122 working- and middle-class cohabitors, we examine the duration between dating and moving in together, reasons for cohabiting, and subsequent plans.…

  6. Tucker2 Hierarchical Classes Analysis

    ERIC Educational Resources Information Center

    Ceulemans, Eva; Van Mechelen, Iven

    2004-01-01

    This paper presents a new hierarchical classes model, called Tucker2-HICLAS, for binary three-way three-mode data. As any three-way hierarchical classes model, the Tucker2-HICLAS model includes a representation of the association relation among the three modes and a hierarchical classification of the elements of each mode. A distinctive feature of…

  7. Translanguaging in a Reading Class

    ERIC Educational Resources Information Center

    Vaish, Viniti; Subhan, Aidil

    2015-01-01

    Using translanguaging as a theoretical foundation, this paper analyses findings from a Grade 2 reading class for low achieving students, where Malay was used as a scaffold to teach English. Data come from one class in one school in Singapore and its Learning Support Programme (LSP), which is part of a larger research project on biliteracy. The LSP…

  8. Class, Identity, and Teacher Education

    ERIC Educational Resources Information Center

    Van Galen, Jane A.

    2010-01-01

    This paper explores the possibilities of working with White, working-class teacher education students to explore the "complex social trajectory" (Reay in Women's Stud Int Forum 20(2):225-233, 1997a, p. 19) of class border crossing as they progress through college. Through analysis of a course that I have developed, "Education and the American…

  9. Student Engagement and Marketing Classes

    ERIC Educational Resources Information Center

    Taylor, Steven A.; Hunter, Gary L.; Melton, Horace; Goodwin, Stephen A.

    2011-01-01

    A study is reported that investigates the goals underlying undergraduate students' engagement in their major classes, nonmajor classes, and in extracurricular activities. The qualitative study employs both focus groups and goal-mapping exercises. The results suggest that students tend to focus on utilitarian, attribute-level considerations mainly…

  10. Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases

    PubMed Central

    Lahm, A.; Paolini, C.; Pallaoro, M.; Nardi, M. C.; Jones, P.; Neddermann, P.; Sambucini, S.; Bottomley, M. J.; Lo Surdo, P.; Carfí, A.; Koch, U.; De Francesco, R.; Steinkühler, C.; Gallinari, P.

    2007-01-01

    Previous findings have suggested that class IIa histone deacetylases (HDACs) (HDAC4, -5, -7, and -9) are inactive on acetylated substrates, thus differing from class I and IIb enzymes. Here, we present evidence supporting this view and demonstrate that class IIa HDACs are very inefficient enzymes on standard substrates. We identified HDAC inhibitors unable to bind recombinant human HDAC4 while showing inhibition in a typical HDAC4 enzymatic assay, suggesting that the observed activity rather reflects the involvement of endogenous copurified class I HDACs. Moreover, an HDAC4 catalytic domain purified from bacteria was 1,000-fold less active than class I HDACs on standard substrates. A catalytic Tyr is conserved in all HDACs except for vertebrate class IIa enzymes where it is replaced by His. Given the high structural conservation of HDAC active sites, we predicted the class IIa His-Nε2 to be too far away to functionally substitute the class I Tyr-OH in catalysis. Consistently, a Tyr-to-His mutation in class I HDACs severely reduced their activity. More importantly, a His-976-Tyr mutation in HDAC4 produced an enzyme with a catalytic efficiency 1,000-fold higher than WT, and this “gain of function phenotype” could be extended to HDAC5 and -7. We also identified trifluoroacetyl-lysine as a class IIa-specific substrate in vitro. Hence, vertebrate class IIa HDACs may have evolved to maintain low basal activities on acetyl-lysines and to efficiently process restricted sets of specific, still undiscovered natural substrates. PMID:17956988

  11. Notes on the Comparison Class

    NASA Astrophysics Data System (ADS)

    Solt, Stephanie

    This paper investigates the role of comparison classes in the semantics of gradable adjectives in the positive form, focusing on the case where the comparison class is expressed overtly via a for-phrase (e.g. John is tall for a jockey). Two central questions are addressed: what information does the comparison class provide, and how is this information integrated compositionally? It is shown that the standard of comparison invoked by the positive form can be analyzed as a range of values whose width is based on the degree of dispersion in the comparison class. Compositionally, the comparison class can be analyzed as an argument of a null positive morpheme (contra Kennedy [13]), in parallel to recent proposals for the superlative (e.g. Heim [9]). The implications of the analysis for the choice between degree- and delineation-based analyses of gradable adjectives are discussed.

  12. Control Class Summaries and Control Class IV from April 1990

    SciTech Connect

    Wu, J.; /Fermilab

    1991-02-22

    The D0 cryogenic control system is a complicated system with many facets. Because of the large number and variety of features in the system, a series of ongoing control system training seminars, or control classes, were created in order to keep people up to date on the operation of the system. As of the writing of this engineering note, there have been four classes. The original lecture notes from each class can be found in the cryogenic control room at the D0 Assembly Building, or in the Co-op office. This note provides a summary of the first three control classes, and it includes the entire set of notes from the fourth class, which was held in April of 1990. This class was taught by Jeff Wendlandt and Dan Markley. Dan should be consulted for more complete explanations than those given in the notes. The notes are, in fact, more of a reference for someone who has some experience with the system, than they are a training manual. Most of the pages include pictures and printouts of different menus and functions, useful for finding details without searching through the actual program. In general, this note serves as a pointer to the existence of the control class lecture notes, and as an explanation of their overall contents and purpose.

  13. Selective inhibition of class I but not class IIb histone deacetylases exerts cardiac protection from ischemia reperfusion.

    PubMed

    Aune, Sverre E; Herr, Daniel J; Mani, Santhosh K; Menick, Donald R

    2014-07-01

    While inhibition of class I/IIb histone deacetylases (HDACs) protects the mammalian heart from ischemia reperfusion (IR) injury, class selective effects remain unexamined. We hypothesized that selective inhibition of class I HDACs would preserve left ventricular contractile function following IR in isolated hearts. Male Sprague Dawley rats (n=6 per group) were injected with vehicle (dimethylsulfoxide, 0.63mg/kg), the class I/IIb HDAC inhibitor trichostatin A (1mg/kg), the class I HDAC inhibitor entinostat (MS-275, 10mg/kg), or the HDAC6 (class IIb) inhibitor tubastatin A (10mg/kg). After 24h, hearts were isolated and perfused in Langendorff mode for 30min (Sham) or subjected to 30min global ischemia and 120min global reperfusion (IR). A saline filled balloon attached to a pressure transducer was placed in the LV to monitor contractile function. After perfusion, LV tissue was collected for measurements of antioxidant protein levels and infarct area. At the conclusion of IR, MS-275 pretreatment was associated with significant preservation of developed pressure, rate of pressure generation, rate of pressure relaxation and rate pressure product, as compared to vehicle treated hearts. There was significant reduction of infarct area with MS-275 pretreatment. Contractile function was not significantly restored in hearts treated with trichostatin A or tubastatin A. Mitochondrial superoxide dismutase (SOD2) and catalase protein and mRNA in hearts from animals pretreated with MS-275 were increased following IR, as compared to Sham. This was associated with a dramatic enrichment of nuclear FOXO3a transcription factor, which mediates the expression of SOD2 and catalase. Tubastatin A treatment was associated with significantly decreased catalase levels after IR. Class I HDAC inhibition elicits protection of contractile function following IR, which is associated with increased expression of endogenous antioxidant enzymes. Class I/IIb HDAC inhibition with trichostatin A or

  14. Endogenous and exogenous ice-nucleating agents constrain supercooling in the hatchling painted turtle.

    PubMed

    Costanzo, Jon P; Baker, Patrick J; Dinkelacker, Stephen A; Lee, Richard E

    2003-02-01

    Hatchlings of the painted turtle (Chrysemys picta) commonly hibernate in their shallow, natal nests. Survival at temperatures below the limit of freeze tolerance (approximately -4 degrees C) apparently depends on their ability to remain supercooled, and, whereas previous studies have reported that supercooling capacity improves markedly with cold acclimation, the mechanistic basis for this change is incompletely understood. We report that the crystallization temperature (T(c)) of recently hatched (summer) turtles acclimated to 22 degrees C and reared on a substratum of vermiculite or nesting soil was approximately 5 degrees C higher than the T(c) determined for turtles acclimated to 4 degrees C and tested in winter. This increase in supercooling capacity coincided with elimination of substratum (and, in fewer cases, eggshell) that the hatchlings had ingested; however, this association was not necessarily causal because turtles reared on a paper-covered substratum did not ingest exogenous matter but nevertheless showed a similar increase in supercooling capacity. Our results for turtles reared on paper revealed that seasonal development of supercooling capacity fundamentally requires elimination of ice-nucleating agents (INA) of endogenous origin: summer turtles, but not winter turtles, produced feces (perhaps derived from residual yolk) that expressed ice-nucleating activity. Ingestion of vermiculite or eggshell, which had modest ice-nucleating activity, had no effect on the T(c), whereas ingestion of nesting soil, which contained two classes of potent INA, markedly reduced the supercooling capacity of summer turtles. This effect persisted long after the turtles had purged their guts of soil particles, because the T(c) of winter turtles reared on nesting soil (mean +/- S.E.M.=-11.6+/-1.4 degrees C) was approximately 6 degrees C higher than the T(c) of winter turtles reared on vermiculite or paper. Experiments in which winter turtles were fed INA commonly found in

  15. Diversification of Fungal Specific Class A Glutathione Transferases in Saprotrophic Fungi

    PubMed Central

    Favier, Frédérique; Harvengt, Luc; Didierjean, Claude; Jacquot, Jean-Pierre; Morel-Rouhier, Mélanie; Gelhaye, Eric

    2013-01-01

    Glutathione transferases (GSTs) form a superfamily of multifunctional proteins with essential roles in cellular detoxification processes and endogenous metabolism. The distribution of fungal-specific class A GSTs was investigated in saprotrophic fungi revealing a recent diversification within this class. Biochemical characterization of eight GSTFuA isoforms from Phanerochaete chrysosporium and Coprinus cinereus demonstrated functional diversity in saprotrophic fungi. The three-dimensional structures of three P. chrysosporium isoforms feature structural differences explaining the functional diversity of these enzymes. Competition experiments between fluorescent probes, and various molecules, showed that these GSTs function as ligandins with various small aromatic compounds, derived from lignin degradation or not, at a L-site overlapping the glutathione binding pocket. By combining genomic data with structural and biochemical determinations, we propose that this class of GST has evolved in response to environmental constraints induced by wood chemistry. PMID:24278272

  16. Selenium inhibits root elongation by repressing the generation of endogenous hydrogen sulfide in Brassica rapa.

    PubMed

    Chen, Yi; Mo, Hai-Zhen; Zheng, Mei-Yu; Xian, Ming; Qi, Zhong-Qiang; Li, You-Qin; Hu, Liang-Bin; Chen, Jian; Yang, Li-Fei

    2014-01-01

    Selenium (Se) has been becoming an emerging pollutant causing severe phytotoxicity, which the biochemical mechanism is rarely known. Although hydrogen sulfide (H2S) has been suggested as an important exogenous regulator modulating plant physiological adaptions in response to heavy metal stress, whether and how the endogenous H2S regulates Se-induce phytotoxicity remains unclear. In this work, a self-developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S in situ in the roots of Brassica rapa under Se(IV) stress. Se(IV)-induced root growth stunt was closely correlated with the inhibition of endogenous H2S generation in root tips. Se(IV) stress dampened the expression of most LCD and DCD homologues in the roots of B. rapa. By using various specific fluorescent probes for bio-imaging root tips in situ, we found that the increase in endogenous H2S by the application of H2S donor NaHS could significantly alleviate Se(IV)-induced reactive oxygen species (ROS) over-accumulation, oxidative impairment, and cell death in root tips, which further resulted in the recovery of root growth under Se(IV) stress. However, dampening the endogenous H2S could block the alleviated effect of NaHS on Se(IV)-induced phytotoxicity. Finally, the increase in endogenous H2S resulted in the enhancement of glutathione (GSH) in Se(IV)-treated roots, which may share the similar molecular mechanism for the dominant role of H2S in removing ROS by activating GSH biosynthesis in mammals. Altogether, these data provide the first direct evidences confirming the pivotal role of endogenous H2S in modulating Se(IV)-induced phytotoxicity in roots.

  17. Selenium Inhibits Root Elongation by Repressing the Generation of Endogenous Hydrogen Sulfide in Brassica rapa

    PubMed Central

    Zheng, Mei-Yu; Xian, Ming; Qi, Zhong-Qiang; Li, You-Qin; Hu, Liang-Bin; Chen, Jian; Yang, Li-Fei

    2014-01-01

    Selenium (Se) has been becoming an emerging pollutant causing severe phytotoxicity, which the biochemical mechanism is rarely known. Although hydrogen sulfide (H2S) has been suggested as an important exogenous regulator modulating plant physiological adaptions in response to heavy metal stress, whether and how the endogenous H2S regulates Se-induce phytotoxicity remains unclear. In this work, a self-developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S in situ in the roots of Brassica rapa under Se(IV) stress. Se(IV)-induced root growth stunt was closely correlated with the inhibition of endogenous H2S generation in root tips. Se(IV) stress dampened the expression of most LCD and DCD homologues in the roots of B. rapa. By using various specific fluorescent probes for bio-imaging root tips in situ, we found that the increase in endogenous H2S by the application of H2S donor NaHS could significantly alleviate Se(IV)-induced reactive oxygen species (ROS) over-accumulation, oxidative impairment, and cell death in root tips, which further resulted in the recovery of root growth under Se(IV) stress. However, dampening the endogenous H2S could block the alleviated effect of NaHS on Se(IV)-induced phytotoxicity. Finally, the increase in endogenous H2S resulted in the enhancement of glutathione (GSH) in Se(IV)-treated roots, which may share the similar molecular mechanism for the dominant role of H2S in removing ROS by activating GSH biosynthesis in mammals. Altogether, these data provide the first direct evidences confirming the pivotal role of endogenous H2S in modulating Se(IV)-induced phytotoxicity in roots. PMID:25333279

  18. Mapping Lunar Chemistry with CLASS

    NASA Astrophysics Data System (ADS)

    Sreekumar, P.

    2012-07-01

    The Chandrayaan-2 Large Area Soft x-ray Spectrometer (CLASS) is planned to be flown on the second Indian lunar mission Chandrayaan-2. It aims to map elemental abundance on the lunar surface by measuring X-ray Fluorescence emission when solar x-rays are incident. The primary objective of CLASS is to quantitatively estimate the abundance of the major elements Mg, Al, Si, Ca, Ti and Fe on the lunar surface at a spatial resolution of 25 km. CLASS will be able to detect Mg, Al and Si signatures at this scale even during a low intensity A-class solar flare, quantify abundance from B-class flares and above, and obtain high Z elemental abundance during brighter flares (C-class and above). This instrument is a follow up to C1XS payload flown earlier on Chandrayaan-1, but with enhanced sensitivity and finer spatial resolution. CLASS will also study particle-induced x-ray emission in the lunar orbit. We will discuss the instrument configuration and developmental status.

  19. Simplified Design Equations for Class-E Neural Prosthesis Transmitters

    PubMed Central

    Troyk, Philip; Hu, Zhe

    2013-01-01

    Extreme miniaturization of implantable electronic devices is recognized as essential for the next generation of neural prostheses, owing to the need for minimizing the damage and disruption of the surrounding neural tissue. Transcutaneous power and data transmission via a magnetic link remains the most effective means of powering and controlling implanted neural prostheses. Reduction in the size of the coil, within the neural prosthesis, demands the generation of a high-intensity radio frequency magnetic field from the extracoporeal transmitter. The Class-E power amplifier circuit topology has been recognized as a highly effective means of producing large radio frequency currents within the transmitter coil. Unfortunately, design of a Class-E circuit is most often fraught by the need to solve a complex set of equations so as to implement both the zero-voltage-switching and zero-voltage-derivative-switching conditions that are required for efficient operation. This paper presents simple explicit design equations for designing the Class-E circuit topology. Numerical design examples are presented to illustrate the design procedure. PMID:23292784

  20. 7 CFR 1006.51 - Class I differential, adjustments to Class I prices, and Class I price.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... MILK IN THE FLORIDA MARKETING AREA Order Regulating Handling Class Prices § 1006.51 Class I... 7 Agriculture 9 2012-01-01 2012-01-01 false Class I differential, adjustments to Class I prices, and Class I price. 1006.51 Section 1006.51 Agriculture Regulations of the Department of...

  1. Endogenously and exogenously driven selective sustained attention: Contributions to learning in kindergarten children.

    PubMed

    Erickson, Lucy C; Thiessen, Erik D; Godwin, Karrie E; Dickerson, John P; Fisher, Anna V

    2015-10-01

    Selective sustained attention is vital for higher order cognition. Although endogenous and exogenous factors influence selective sustained attention, assessment of the degree to which these factors influence performance and learning is often challenging. We report findings from the Track-It task, a paradigm that aims to assess the contribution of endogenous and exogenous factors to selective sustained attention within the same task. Behavioral accuracy and eye-tracking data on the Track-It task were correlated with performance on an explicit learning task. Behavioral accuracy and fixations to distractors during the Track-It task did not predict learning when exogenous factors supported selective sustained attention. In contrast, when endogenous factors supported selective sustained attention, fixations to distractors were negatively correlated with learning. Similarly, when endogenous factors supported selective sustained attention, higher behavioral accuracy was correlated with greater learning. These findings suggest that endogenously and exogenously driven selective sustained attention, as measured through different conditions of the Track-It task, may support different kinds of learning.

  2. Identification of diverse groups of endogenous gammaretroviruses in mega- and microbats.

    PubMed

    Cui, Jie; Tachedjian, Gilda; Tachedjian, Mary; Holmes, Edward C; Zhang, Shuyi; Wang, Lin-Fa

    2012-09-01

    A previous phylogenetic study suggested that mammalian gammaretroviruses may have originated in bats. Here we report the discovery of RNA transcripts from two putative endogenous gammaretroviruses in frugivorous (Rousettus leschenaultii retrovirus, RlRV) and insectivorous (Megaderma lyra retrovirus, MlRV) bat species. Both genomes possess a large deletion in pol, indicating that they are defective retroviruses. Phylogenetic analysis places RlRV and MlRV within the diversity of mammalian gammaretroviruses, with the former falling closer to porcine endogenous retroviruses and the latter to Mus dunni endogenous virus, koala retrovirus and gibbon ape leukemia virus. Additional genomic mining suggests that both microbat (Myotis lucifugus) and megabat (Pteropus vampyrus) genomes harbour many copies of endogenous retroviral forms related to RlRV and MlRV. Furthermore, phylogenetic analysis reveals the presence of three genetically diverse groups of endogenous gammaretroviruses in bat genomes, with M. lucifugus possessing members of all three groups. Taken together, this study indicates that bats harbour distinct gammaretroviruses and may have played an important role as reservoir hosts during the diversification of mammalian gammaretroviruses. PMID:22694899

  3. A MALDI-MS-based quantitative analytical method for endogenous estrone in human breast cancer cells

    PubMed Central

    Kim, Kyoung-Jin; Kim, Hee-Jin; Park, Han-Gyu; Hwang, Cheol-Hwan; Sung, Changmin; Jang, Kyoung-Soon; Park, Sung-Hee; Kim, Byung-Gee; Lee, Yoo-Kyung; Yang, Yung-Hun; Jeong, Jae Hyun; Kim, Yun-Gon

    2016-01-01

    The level of endogenous estrone, one of the three major naturally occurring estrogens, has a significant correlation with the incidence of post-menopausal breast cancer. However, it is challenging to quantitatively monitor it owing to its low abundance. Here, we develop a robust and highly sensitive mass-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based quantitative platform to identify the absolute quantities of endogenous estrones in a variety of clinical specimens. The one-step modification of endogenous estrone provided good linearity (R2 > 0.99) and significantly increased the sensitivity of the platform (limit of quantitation: 11 fmol). In addition, we could identify the absolute amount of endogenous estrones in cells of the breast cancer cell line MCF-7 (34 fmol/106 cells) by using a deuterated estrone as an internal standard. Finally, by applying the MALDI-MS-based quantitative method to endogenous estrones, we successfully monitored changes in the metabolic expression level of estrones (17.7 fmol/106 letrozole-treated cells) in MCF-7 cells resulting from treatment with an aromatase inhibitor. Taken together, these results suggest that this MALDI-MS-based quantitative approach may be a general method for the targeted metabolomics of ketone-containing metabolites, which can reflect clinical conditions and pathogenic mechanisms. PMID:27091422

  4. Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and human embryonic stem cells.

    PubMed

    Wissing, Silke; Montano, Mauricio; Garcia-Perez, Jose Luis; Moran, John V; Greene, Warner C

    2011-10-21

    Members of the APOBEC3 (A3) family of cytidine deaminase enzymes act as host defense mechanisms limiting both infections by exogenous retroviruses and mobilization of endogenous retrotransposons. Previous studies revealed that the overexpression of some A3 proteins could restrict engineered human Long INterspersed Element-1 (LINE-1 or L1) retrotransposition in HeLa cells. However, whether endogenous A3 proteins play a role in restricting L1 retrotransposition remains largely unexplored. Here, we show that HeLa cells express endogenous A3B and A3C, whereas human embryonic stem cells (hESCs) express A3B, A3C, A3DE, A3F, and A3G. To study the relative contribution of endogenous A3 proteins in restricting L1 retrotransposition, we first generated small hairpin RNAs (shRNAs) to suppress endogenous A3 mRNA expression, and then assessed L1 mobility using a cell-based L1 retrotransposition assay. We demonstrate that in both HeLa and hESCs, shRNA-based knockdown of A3B promotes a ∼2-3.7-fold increase in the retrotransposition efficiency of an engineered human L1. Knockdown of the other A3s produced no significant increase in L1 activity. Thus, A3B appears to restrict engineered L1 retrotransposition in a broad range of cell types, including pluripotent cells.

  5. Floral Scent Diversity is Differently Expressed in Emitted and Endogenous Components in Petunia axillaris Lines

    PubMed Central

    KONDO, M.; OYAMA-OKUBO, N.; ANDO, T.; MARCHESI, E.; NAKAYAMA, M.

    2006-01-01

    • Background and Aims Among the subspecies of Petunia axillaris are various lines emitting sensorially different scents. Analysis of variations in floral scent among genetically close individuals is a powerful approach to understanding the mechanisms for generating scent diversity. • Methods Emitted and endogenous components were analysed independently to gain information about evaporation and endogenous production in 13 wild lines of P. axillaris. A dynamic headspace method was used to collect emitted components. Endogenous components were extracted with solvent. Both of these sample types were subjected to quantitative and qualitative analysis by gas chromatography (GC)–flame ionization detector (FID) and GC–mass spectrometry (MS). • Key Results and Conclusions Whereas the profiles of emitted compounds showed qualitative homogeneity, being mainly composed of methyl benzoate with quantitative variation, the profiles of endogenous compounds showed both qualitative and quantitative variation. A negative correlation was found between the evaporation ratio and boiling point of each compound examined. Lower boiling point compounds were strongly represented in the emitted component, resulting in the reduction of qualitative variation in floral scent. In conclusion, floral scent diversity results from variation in both the endogenous production and the evaporation rate of the individual volatile compounds. PMID:17060364

  6. A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca).

    PubMed

    Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix; Avila-Arcos, María; Stenglein, Mark D; Chen, Wei; Sun, Wei; Mazzoni, Camila J; Osterrieder, Nikolaus; Greenwood, Alex D

    2013-08-15

    Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs. Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant panda sequences U. maritimus endogenous retrovirus (UmaERV) and A. melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary history within the HERV-K group. All individual remnants of proviral sequences contain numerous frameshifts and stop codons and thus, the virus is likely non-infectious. PMID:23725819

  7. A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca)

    PubMed Central

    Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix; Ávila-Arcos, Maria; Stenglein, Mark D.; Chen, Wei; Sun, Wei; Mazzoni, Camila; Osterrieder, Nikolaus; Greenwood, Alex D.

    2013-01-01

    Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs. Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant panda sequences Ursus maritimus endogenous retrovirus (UmaERV) and Ailuropoda melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary history within the HERV-K group. All individual remnants of proviral sequences contain numerous frameshifts and stop codons and thus, the virus is likely non-infectious. PMID:23725819

  8. Arterial Calcium Stimulation with Hepatic Venous Sampling in the Localization Diagnosis of Endogenous Hyperinsulinism

    PubMed Central

    Moreno-Moreno, Paloma; Alhambra-Expósito, María Rosa; Palomares-Ortega, Rafel; Zurera-Tendero, Luis; Espejo Herrero, Juan José; Gálvez-Moreno, María Angeles

    2016-01-01

    Objective. The aim of this study was to assess the utility of arterial calcium stimulation with hepatic venous sampling (ASVS) in the localization diagnosis of endogenous hyperinsulinism. Patients and Methods. A retrospective descriptive study was performed including patients with endogenous hyperinsulinism who underwent ASVS. The histopathological diagnosis in patients who underwent a surgical procedure was used as the reference for the statistical study of the accuracy of this technique. Results. 30 patients were included with endogenous hyperinsulinism and nonconclusive imaging diagnosis was included. ASVS was performed in all cases. Surgery was performed in 20 cases. Insulinoma was removed in 19 patients; the location of all cases was detected in the ASVS. All cases of endogenous hyperinsulinism had a positive result for the ASVS, with this association being statistically significant (χ2 = 15.771; p < 0.001). A good and statistically significant agreement was obtained between histopathologic diagnosis and ASVS results (K = 0.518, p < 0.001). Conclusions. ASVS is a useful procedure in the localization diagnosis of endogenous hyperinsulinism undetected by other imaging tests. This technique allows the localization of intrapancreatic insulinomas and represents useful tool for the diagnosis and surgical management of these tumors. PMID:27795707

  9. Chromatin-modifying agents for epigenetic reprogramming and endogenous neural stem cell-mediated repair in stroke.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2011-03-01

    The recent explosion of interest in epigenetics and chromatin biology has made a significant impact on our understanding of the pathophysiology of cerebral ischemia and led to the identification of new treatment strategies for stroke, such as those that employ histone deacetylase inhibitors. These are key advances; however, the rapid pace of discovery in chromatin biology and innovation in the development of chromatin-modifying agents implies there are emerging classes of drugs that may also have potential benefits in stroke. Herein, we discuss how various chromatin regulatory factors and their recently identified inhibitors may serve as drug targets and therapeutic agents for stroke, respectively. These factors primarily include members of the repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor macromolecular complex, polycomb group (PcG) proteins, and associated chromatin remodeling factors, which have been linked to the pathophysiology of cerebral ischemia. Further, we suggest that, because of the key roles played by REST, PcG proteins and other chromatin remodeling factors in neural stem and progenitor cell (NSPC) biology, chromatin-modifying agents can be utilized not only to mitigate ischemic injury directly but also potentially to promote endogenous NSPC-mediated brain repair mechanisms. PMID:24014083

  10. Porcine endogenous retrovirus (PERV) and its transmission characteristics: a study of the New Zealand designated pathogen-free herd.

    PubMed

    Garkavenko, O; Wynyard, S; Nathu, D; Simond, D; Muzina, M; Muzina, Z; Scobie, L; Hector, R D; Croxson, M C; Tan, P; Elliott, B R

    2008-01-01

    Previously a strategy for monitoring of pigs intended for cell transplantation was developed and successfully applied to several representative herds in New Zealand. A designated pathogen-free (DPF) herd has been chosen as a good candidate for xenotransplantation. This herd has previously tested free of infectious agents relevant to xenotransplantation and we present here an in depth study of porcine endogenous retrovirus (PERV) transmission. A panel of assays that describes the constraints for the transmission of PERV has been suggested. It includes a) infectivity test in coculture of DPF pig primary cells with both human and pig target cell lines; b) RT activity in supernatant of stimulated primary cells from DPF pigs; c) viral load in donor's blood plasma; d) PERV proviral copy number in DPF pig genome; e) PERV class C prevalence in the herd and its recombination potential. There was no evidence of PERV transmission from DPF pig tissue to either pig or human cells. Additionally, there was no evidence of PERV RNA present in pig blood plasma. PERV copy number differs in individual pigs from as low as 3 copies to 30 copies and the presence of PERV-C varied between animals and breeds. In all DPF pigs tested, a specific locus for PERV-C potentially associated with the recombination of PERV in miniature swine was absent. Presented data on the PERV transmission allows us to classify the DPF potential donors as "null" or noninfectious pigs.

  11. The rib1 Mutant Is Resistant to Indole-3-Butyric Acid, an Endogenous Auxin in Arabidopsis1

    PubMed Central

    Poupart, Julie; Waddell, Candace S.

    2000-01-01

    The presence of indole-3-butyric acid (IBA) as an endogenous auxin in Arabidopsis has been recently demonstrated. However, the in vivo role of IBA remains to be elucidated. We present the characterization of a semi-dominant mutant that is affected in its response to IBA, but shows a wild-type response to indole-3-acetic acid (IAA), the predominant and most studied form of auxin. We have named this mutant rib1 for resistant to IBA. Root elongation assays show that rib1 is specifically resistant to IBA, to the synthetic auxin 2,4-dichlorophenoxyacetic acid, and to auxin transport inhibitors. rib1 does not display increased resistance to IAA, to the synthetic auxin naphthalene acetic acid, or to other classes of plant hormones. rib1 individuals also have other root specific phenotypes including a shortened primary root, an increased number of lateral roots, and a more variable response than wild type to a change in gravitational vector. Adult rib1 plants are morphologically indistinguishable from wild-type plants. These phenotypes suggest that rib1 alters IBA activity in the root, thereby affecting root development and response to environmental stimuli. We propose models in which RIB1 has a function in either IBA transport or response. Our experiments also suggest that IBA does not use the same mechanism to exit cells as does IAA and we propose a model for IBA transport. PMID:11115890

  12. Cutting Edge: DNase II deficiency prevents activation of autoreactive B cells by double-stranded DNA endogenous ligands.

    PubMed

    Pawaria, Sudesh; Moody, Krishna; Busto, Patricia; Nündel, Kerstin; Choi, Chee-Ho; Ghayur, Tariq; Marshak-Rothstein, Ann

    2015-02-15

    In mice that fail to express the phagolysosomal endonuclease DNase II and the type I IFN receptor, excessive accrual of undegraded DNA results in a STING-dependent, TLR-independent inflammatory arthritis. These double-knockout (DKO) mice develop additional indications of systemic autoimmunity, including anti-nuclear autoantibodies and splenomegaly, that are not found in Unc93b1(3d/3d) DKO mice and, therefore, are TLR dependent. The DKO autoantibodies predominantly detect RNA-associated autoantigens, which are commonly targeted in TLR7-dominated systemic erythematosus lupus-prone mice. To determine whether an inability of TLR9 to detect endogenous DNA could explain the absence of dsDNA-reactive autoantibodies in DKO mice, we used a novel class of bifunctional autoantibodies, IgM/DNA dual variable domain Ig molecules, to activate B cells through a BCR/TLR9-dependent mechanism. DKO B cells could not respond to the IgM/DNA dual variable domain Ig molecule, despite a normal response to both anti-IgM and CpG ODN 1826. Thus, DKO B cells only respond to RNA-associated ligands because DNase II-mediated degradation of self-DNA is required for TLR9 activation.

  13. The anthocyanidin delphinidin mobilizes endogenous copper ions from human lymphocytes leading to oxidative degradation of cellular DNA.

    PubMed

    Hanif, Sarmad; Shamim, Uzma; Ullah, M F; Azmi, Asfar S; Bhat, Showket H; Hadi, S M

    2008-07-10

    Epidemiological and experimental evidence exists to suggest that pomegranate and its juice possess chemopreventive and anticancer properties. The anthocyanidin delphinidin is a major polyphenol present in pomegranates and has been shown to be responsible for these effects. Plant polyphenols are recognized as naturally occurring antioxidants but also catalyze oxidative DNA degradation of cellular DNA either alone or in the presence of transition metal ions such as copper. In this paper we show that similar to various other classes of polyphenols, delphinidin is also capable of causing oxidative degradation of cellular DNA. Lymphocytes were exposed to various concentrations of delphinidin (10, 20, 50 microM) for 1h and the DNA breakage was assessed using single cell alkaline gel electrophoresis (Comet assay). Inhibition of DNA breakage by several scavengers of reactive oxygen species (ROS) indicated that it is caused by the formation of ROS. Incubation of lymphocytes with neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation in intact lymphocytes in a dose dependent manner. Bathocuproine, which is unable to permeate through the cell membrane, did not cause such inhibition. We have further shown that delphinidin is able to degrade DNA in cell nuclei and that such DNA degradation is also inhibited by neocuproine suggesting that nuclear copper is mobilized in this reaction. These results indicate that the generation of ROS possibly occurs through mobilization of endogenous copper ions. The results are in support of our hypothesis that the prooxidant activity of plant polyphenols may be an important mechanism for their anticancer properties.

  14. Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions

    PubMed Central

    Mendenhall, Eric M.; Williamson, Kaylyn E.; Reyon, Deepak; Zou, James Y.; Ram, Oren; Joung, J. Keith; Bernstein, Bradley E.

    2013-01-01

    Mammalian gene regulation is dependent on tissue-specific enhancers that can act across large distances to influence transcriptional activity1-3. Mapping experiments have identified hundreds of thousands of putative enhancers whose functionality is supported by cell type–specific chromatin signatures and striking enrichments for disease-associated sequence variants4-11. However, these studies did not address the in vivo functions of the putative elements or their chromatin states and could not determine which genes, if any, a given enhancer regulates. Here we present a strategy to investigate endogenous regulatory elements by selectively altering their chromatin state using programmable reagents. Transcription activator–like (TAL) effector repeat domains fused to the LSD1 histone demethylase efficiently remove enhancer-associated chromatin modifications from target loci, without affecting control regions. We find that inactivation of enhancer chromatin by these fusion proteins frequently causes down-regulation of proximal genes, revealing enhancer target genes. Our study demonstrates the potential of ‘epigenome editing’ tools to characterize an important class of functional genomic elements. PMID:24013198

  15. Relative age of proviral porcine endogenous retrovirus sequences in Sus scrofa based on the molecular clock hypothesis.

    PubMed

    Tönjes, Ralf R; Niebert, Marcus

    2003-11-01

    Porcine endogenous retroviruses (PERV) are discussed as putative infectious agents in xenotransplantation. PERV classes A, B, and C harbor different envelope proteins. Two different types of long terminal repeat (LTR) structures exist, of which both are present only in PERV-A. One type of LTR contains a distinct repeat structure in U3, while the other is repeatless, conferring a lower level of transcriptional activity. Since the different LTR structures are distributed unequally among the proviruses and, apparently, PERV is the only virus harboring two different LTR structures, we were interested in determining which LTR is the ancestor. Replication-competent viruses can still be found today, suggesting an evolutionary recent origin. Our studies revealed that the age of PERV is at most 7.6 x 10(6) years, whereas the repeatless LTR type evolved approximately 3.4 x 10(6) years ago, being the phylogenetically younger structure. The age determined for PERV correlates with the time of separation between pigs (Suidae, Sus scrofa) and their closest relatives, American-born peccaries (Tayassuidae, Pecari tajacu), 7.4 x 10(6) years ago.

  16. Relative Age of Proviral Porcine Endogenous Retrovirus Sequences in Sus scrofa Based on the Molecular Clock Hypothesis

    PubMed Central

    Tönjes, Ralf R.; Niebert, Marcus

    2003-01-01

    Porcine endogenous retroviruses (PERV) are discussed as putative infectious agents in xenotransplantation. PERV classes A, B, and C harbor different envelope proteins. Two different types of long terminal repeat (LTR) structures exist, of which both are present only in PERV-A. One type of LTR contains a distinct repeat structure in U3, while the other is repeatless, conferring a lower level of transcriptional activity. Since the different LTR structures are distributed unequally among the proviruses and, apparently, PERV is the only virus harboring two different LTR structures, we were interested in determining which LTR is the ancestor. Replication-competent viruses can still be found today, suggesting an evolutionary recent origin. Our studies revealed that the age of PERV is at most 7.6 × 106 years, whereas the repeatless LTR type evolved approximately 3.4 × 106 years ago, being the phylogenetically younger structure. The age determined for PERV correlates with the time of separation between pigs (Suidae, Sus scrofa) and their closest relatives, American-born peccaries (Tayassuidae, Pecari tajacu), 7.4 × 106 years ago. PMID:14581574

  17. Safety assessment considerations for food and feed derived from plants with genetic modifications that modulate endogenous gene expression and pathways.

    PubMed

    Kier, Larry D; Petrick, Jay S

    2008-08-01

    The current globally recognized comparative food and feed safety assessment paradigm for biotechnology-derived crops is a robust and comprehensive approach for evaluating the safety of both the inserted gene product and the resulting crop. Incorporating many basic concepts from food safety, toxicology, nutrition, molecular biology, and plant breeding, this approach has been used effectively by scientists and regulatory agencies for 10-15 years. Current and future challenges in agriculture include the need for improved yields, tolerance to biotic and abiotic stresses, and improved nutrition. The next generation of biotechnology-derived crops may utilize regulatory proteins, such as transcription factors that modulate gene expression and/or endogenous plant pathways. In this review, we discuss the applicability of the current safety assessment paradigm to biotechnology-derived crops developed using modifications involving regulatory proteins. The growing literature describing the molecular biology underlying plant domestication and conventional breeding demonstrates the naturally occurring genetic variation found in plants, including significant variation in the classes, expression, and activity of regulatory proteins. Specific examples of plant modifications involving insertion or altered expression of regulatory proteins are discussed as illustrative case studies supporting the conclusion that the current comparative safety assessment process is appropriate for these types of biotechnology-developed crops.

  18. Chromatin-Modifying Agents for Epigenetic Reprogramming and Endogenous Neural Stem Cell-Mediated Repair in Stroke

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2013-01-01

    The recent explosion of interest in epigenetics and chromatin biology has made a significant impact on our understanding of the pathophysiology of cerebral ischemia and led to the identification of new treatment strategies for stroke, such as those that employ histone deacetylase inhibitors. These are key advances; however, the rapid pace of discovery in chromatin biology and innovation in the development of chromatin-modifying agents implies there are emerging classes of drugs that may also have potential benefits in stroke. Herein, we discuss how various chromatin regulatory factors and their recently identified inhibitors may serve as drug targets and therapeutic agents for stroke, respectively. These factors primarily include members of the repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor macromolecular complex, polycomb group (PcG) proteins, and associated chromatin remodeling factors, which have been linked to the pathophysiology of cerebral ischemia. Further, we suggest that, because of the key roles played by REST, PcG proteins and other chromatin remodeling factors in neural stem and progenitor cell (NSPC) biology, chromatin-modifying agents can be utilized not only to mitigate ischemic injury directly but also potentially to promote endogenous NSPC-mediated brain repair mechanisms. PMID:24014083

  19. Consumer Education in Any Class

    ERIC Educational Resources Information Center

    Wingo, Rosetta F.

    1977-01-01

    Examples are offered of how the classroom teacher can blend consumer education into typewriting, business English, business math, and other classes by intentionally focusing on principles and concepts or by including it incidentally when the opportunity arises. (TA)

  20. Integrals of the Ising Class

    SciTech Connect

    Bailey, David H.; Borwein, Jonathan M.; Crandall, Richard E.

    2006-06-01

    From an experimental-mathematical perspective we analyze"Ising-class" integrals. Our experimental results involvedextreme-precision, multidimensional quadrature on intricate integrands;thus, highly parallel computation was required.

  1. Wildflower Collecting: A Class Project

    ERIC Educational Resources Information Center

    Moore, Sheila V.

    1976-01-01

    Advocates wildflower collecting as a class project, citing instances of interest in studies of soil composition, growing wildflowers, and increased student motivation toward the subject of botany as basis for the activity. (CP)

  2. Class Sizes and Dissadvantaged Schools.

    ERIC Educational Resources Information Center

    Warner, David

    1978-01-01

    Describes a program in which smaller class groups for socially and culturally deprived children resulted in enhanced social attitudes and more responsive, mature behavior in interaction with both adults and peers. (Author/IRT)

  3. Statistical Descriptors of School Classes

    ERIC Educational Resources Information Center

    Lohnes, Paul R.

    1972-01-01

    It may be useful in evaluation research to employ the class as the unit of analysis, assessing its syntality by a vector of distribution cumulants or indices for each of several input tests administered. (Author)

  4. Inhibition of leukocyte function and interleukin-2 gene expression by 2-methylarachidonyl-(2'-fluoroethyl)amide, a stable congener of the endogenous cannabinoid receptor ligand anandamide

    SciTech Connect

    Kaplan, Barbara L.F.; Ouyang Yanli; Herring, Amy; Yea, Sung Su; Razdan, Raj; Kaminski, Norbert E. . E-mail: kamins11@msu.edu

    2005-06-01

    Arachidonylethanolamide (anandamide, AEA) has been identified as an endogenous ligand for cannabinoid receptors CB1 and CB2. Characterization of the direct cannabimimetic actions of anandamide has been hampered by its short duration of action and rapid degradation in in vivo and in vitro systems to arachidonic acid, a precursor in the biosynthesis of a broad range of biologically active molecules. In the present studies, we utilized 2-methylarachidonyl-(2'-fluoroethyl)amide (F-Me-AEA), an analog of anandamide resistant to enzymatic degradation, to determine whether F-Me-AEA modulated T cell function similar to that of plant-derived cannabinoids. Indeed, F-Me-AEA at low micromolar concentrations exhibited a marked inhibition of phorbol ester plus calcium ionophore (PMA/Io)-induced IL-2 protein secretion and steady state mRNA expression. Likewise, a modest suppression of the mixed lymphocyte response was observed in the presence of F-Me-AEA indicating an alteration in T cell responsiveness to allogeneic MHC class II antigens. F-Me-AEA was also found to modestly inhibit forskolin-stimulated adenylate cyclase activity in thymocytes and splenocytes, a hallmark of cannabinoid receptor agonists. Further characterization of the influence of F-Me-AEA on the cAMP signaling cascade revealed an inhibition of CREB-1/ATF-1 phosphorylation and subsequently, an inhibition of CRE DNA binding activity. Characterization of nuclear binding proteins further revealed that NF-AT and, to a lesser extent, NF-{kappa}B DNA binding activities were also suppressed. These studies demonstrate that F-Me-AEA modulates T cell function in a similar manner to plant-derived and endogenous cannabinoids and therefore can be utilized as an amidase- and hydrolysis-resistant endogenous cannabinoid.

  5. Whole Class Laboratories: More Examples

    NASA Astrophysics Data System (ADS)

    Kouh, Minjoon

    2016-03-01

    Typically, introductory physics courses are taught with a combination of lectures and laboratories in which students have opportunities to discover the natural laws through hands-on activities in small groups. This article reports the use of Google Drive, a free online document-sharing tool, in physics laboratories for pooling experimental data from the whole class. This pedagogical method was reported earlier, and the present article offers a few more examples of such "whole class" laboratories.

  6. Less than a Class Set

    ERIC Educational Resources Information Center

    Bennett, Kristin Redington

    2012-01-01

    The iPad holds amazing potential for classroom use. Just a few--or even only one--is enough to get results. Having a class set promotes traditional, whole-class instruction, but fewer iPads facilitate individualized and tailored instruction. In this article, the author discusses the potential of the iPad and suggests ways to put the iPad to use in…

  7. Two classes of speculative peaks

    NASA Astrophysics Data System (ADS)

    Roehner, Bertrand M.

    2001-10-01

    Speculation not only occurs in financial markets but also in numerous other markets, e.g. commodities, real estate, collectibles, and so on. Such speculative movements result in price peaks which share many common characteristics: same order of magnitude of duration with respect to amplitude, same shape (the so-called sharp-peak pattern). Such similarities suggest (at least as a first approximation) a common speculative behavior. However, a closer examination shows that in fact there are (at least) two distinct classes of speculative peaks. For the first, referred to as class U, (i) the amplitude of the peak is negatively correlated with the price at the start of the peak (ii) the ensemble coefficient of variation exhibits a trough. Opposite results are observed for the second class that we refer to as class S. Once these empirical observations have been made we try to understand how they should be interpreted. First, we show that the two properties are in fact related in the sense that the second is a consequence of the first. Secondly, by listing a number of cases belonging to each class we observe that the markets in the S-class offer collection of items from which investors can select those they prefer. On the contrary, U-markets consist of undifferentiated products for which a selection cannot be made in the same way. All prices considered in the paper are real (i.e., deflated) prices.

  8. School Class Size: Research and Policy

    ERIC Educational Resources Information Center

    Glass, Gene V.; And Others

    This book synthesizes research evidence to demonstrate that 1) class size is strongly related to pupil achievement; 2) smaller classes are more conducive to improved pupil performance than larger classes; 3) smaller classes provide more opportunities to adapt learning programs to individual needs; 4) pupils in smaller classes have more interest in…

  9. Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.

    PubMed

    Fernandez, A; Mills, E N C; Lovik, M; Spoek, A; Germini, A; Mikalsen, A; Wal, J M

    2013-12-01

    Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured.

  10. Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion.

    PubMed

    Mattijssen, Frits; Alex, Sheril; Swarts, Hans J; Groen, Albert K; van Schothorst, Evert M; Kersten, Sander

    2014-04-01

    Dietary triglycerides are hydrolyzed in the small intestine principally by pancreatic lipase. Following uptake by enterocytes and secretion as chylomicrons, dietary lipids are cleared from the bloodstream via lipoprotein lipase. Whereas lipoprotein lipase is inhibited by several proteins including Angiopoietin-like 4 (Angptl4), no endogenous regulator of pancreatic lipase has yet been identified. Here we present evidence that Angptl4 is an endogenous inhibitor of dietary lipid digestion. Angptl4-/- mice were heavier compared to their wild-type counterparts without any difference in food intake, energy expenditure or locomotor activity. However, Angptl4-/- mice showed decreased lipid content in the stools and increased accumulation of dietary triglycerides in the small intestine, which coincided with elevated luminal lipase activity in Angptl4-/- mice. Furthermore, recombinant Angptl4 reduced the activity of pancreatic lipase as well as the lipase activity in human ileostomy output. In conclusion, our data suggest that Angptl4 is an endogenous inhibitor of intestinal lipase activity. PMID:24634819

  11. A shared inhibitory circuit for both exogenous and endogenous control of stimulus selection.

    PubMed

    Mysore, Shreesh P; Knudsen, Eric I

    2013-04-01

    The mechanisms by which the brain suppresses distracting stimuli to control the locus of attention are unknown. We found that focal, reversible inactivation of a single inhibitory circuit in the barn owl midbrain tegmentum, the nucleus isthmi pars magnocellularis (Imc), abolished both stimulus-driven (exogenous) and internally driven (endogenous) competitive interactions in the optic tectum (superior colliculus in mammals), which are vital to the selection of a target among distractors in behaving animals. Imc neurons transformed spatially precise multisensory and endogenous input into powerful inhibitory output that suppressed competing representations across the entire tectal space map. We identified a small, but highly potent, circuit that is employed by both exogenous and endogenous signals to exert competitive suppression in the midbrain selection network. Our findings reveal, to the best of our knowledge, for the first time, a neural mechanism for the construction of a priority map that is critical for the selection of the most important stimulus for gaze and attention. PMID:23475112

  12. Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen.

    PubMed

    Pontel, Lucas B; Rosado, Ivan V; Burgos-Barragan, Guillermo; Garaycoechea, Juan I; Yu, Rui; Arends, Mark J; Chandrasekaran, Gayathri; Broecker, Verena; Wei, Wei; Liu, Limin; Swenberg, James A; Crossan, Gerry P; Patel, Ketan J

    2015-10-01

    Endogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5(-/-) mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5(-/-)Fancd2(-/-) mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism.

  13. The biological effect of endogenous sulfur dioxide in the cardiovascular system.

    PubMed

    Wang, Xin-Bao; Jin, Hong-Fang; Tang, Chao-Shu; Du, Jun-Bao

    2011-11-16

    Sulfur dioxide is considered a toxic gas in air pollution and detrimental to many organs, however, it can be generated endogenously in the cardiovascular system in vivo. Gaseous sulfur dioxide has an endothelium-dependent vasorelaxing effect at low concentrations, but is endothelium-independent at high concentrations and has a negative inotropic effect on cardiac function. This vasorelaxing effect is mediated by adenosine triphosphate-sensitive calcium channels and L-type calcium channels. Under pathophysiological conditions, sulfur dioxide increases anti-inflammatory response and antioxidant capacities in pulmonary hypertensive rats. Sulfur dioxide also attenuates increased blood pressure and vascular remodeling in spontaneously hypertensive and hypoxic pulmonary hypertensive rats. Recent studies suggest that endogenous sulfur dioxide is also involved in the process of myocardial ischemia-reperfusion injury and lipid metabolism. Therefore, the evidence suggests that endogenous sulfur dioxide may be a novel gasotransmitter in the cardiovascular system. The significance of sulfur dioxide on the cardiovascular system is intriguing and appealing.

  14. Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen.

    PubMed

    Pontel, Lucas B; Rosado, Ivan V; Burgos-Barragan, Guillermo; Garaycoechea, Juan I; Yu, Rui; Arends, Mark J; Chandrasekaran, Gayathri; Broecker, Verena; Wei, Wei; Liu, Limin; Swenberg, James A; Crossan, Gerry P; Patel, Ketan J

    2015-10-01

    Endogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5(-/-) mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5(-/-)Fancd2(-/-) mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism. PMID:26412304

  15. Synthetic Biology Platform for Sensing and Integrating Endogenous Transcriptional Inputs in Mammalian Cells.

    PubMed

    Angelici, Bartolomeo; Mailand, Erik; Haefliger, Benjamin; Benenson, Yaakov

    2016-08-30

    One of the goals of synthetic biology is to develop programmable artificial gene networks that can transduce multiple endogenous molecular cues to precisely control cell behavior. Realizing this vision requires interfacing natural molecular inputs with synthetic components that generate functional molecular outputs. Interfacing synthetic circuits with endogenous mammalian transcription factors has been particularly difficult. Here, we describe a systematic approach that enables integration and transduction of multiple mammalian transcription factor inputs by a synthetic network. The approach is facilitated by a proportional amplifier sensor based on synergistic positive autoregulation. The circuits efficiently transduce endogenous transcription factor levels into RNAi, transcriptional transactivation, and site-specific recombination. They also enable AND logic between pairs of arbitrary transcription factors. The results establish a framework for developing synthetic gene networks that interface with cellular processes through transcriptional regulators. PMID:27545896

  16. Endogenous florendoviruses are major components of plant genomes and hallmarks of virus evolution

    PubMed Central

    Geering, Andrew D. W.; Maumus, Florian; Copetti, Dario; Choisne, Nathalie; Zwickl, Derrick J.; Zytnicki, Matthias; McTaggart, Alistair R.; Scalabrin, Simone; Vezzulli, Silvia; Wing, Rod A.; Quesneville, Hadi; Teycheney, Pierre-Yves

    2014-01-01

    The extent and importance of endogenous viral elements have been extensively described in animals but are much less well understood in plants. Here we describe a new genus of Caulimoviridae called ‘Florendovirus’, members of which have colonized the genomes of a large diversity of flowering plants, sometimes at very high copy numbers (>0.5% total genome content). The genome invasion of Oryza is dated to over 1.8 million years ago (MYA) but phylogeographic evidence points to an even older age of 20–34 MYA for this virus group. Some appear to have had a bipartite genome organization, a unique characteristic among viral retroelements. In Vitis vinifera, 9% of the endogenous florendovirus loci are located within introns and therefore may influence host gene expression. The frequent colocation of endogenous florendovirus loci with TA simple sequence repeats, which are associated with chromosome fragility, suggests sequence capture during repair of double-stranded DNA breaks. PMID:25381880

  17. Study of mango endogenous pectinases as a tool to engineer mango purée consistency.

    PubMed

    Jamsazzadeh Kermani, Zahra; Shpigelman, Avi; Houben, Ken; ten Geuzendam, Belinda; Van Loey, Ann M; Hendrickx, Marc E

    2015-04-01

    The objective of this work was to evaluate the possibility of using mango endogenous pectinases to change the viscosity of mango purée. Hereto, the structure of pectic polysaccharide and the presence of sufficiently active endogenous enzymes of ripe mango were determined. Pectin of mango flesh had a high molecular weight and was highly methoxylated. Pectin methylesterase showed a negligible activity which is related to the confirmed presence of a pectin methylesterase inhibitor. Pectin contained relatively high amounts of galactose and considerable β-galactosidase (β-Gal) activity was observed. The possibility of stimulating β-Gal activity during processing (temperature/pressure, time) was investigated. β-Gal of mango was rather temperature labile but pressure stable relatively to the temperature and pressure levels used to inactivate destructive enzymes in industry. Creating processing conditions allowing endogenous β-Gal activity did not substantially change the consistency of mango purée.

  18. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: involvement of endogenous copper and a putative mechanism for anticancer properties.

    PubMed

    Bhat, S H; Azmi, A S; Hadi, S M

    2007-02-01

    Plant-derived dietary material contains several classes of polyphenols such as flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing cellular DNA degradation in the presence of transition metal ions such as copper. Earlier we have shown that the stilbene resveratrol is able to mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major constituent of coffee, is also capable of DNA breakage in human peripheral lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that caffeic acid generates oxidative stress in lymphocytes, which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action.

  19. Examining the role of endogenous orexins in hypothalamus-pituitary-adrenal axis endocrine function using transient dual orexin receptor antagonism in the rat.

    PubMed

    Steiner, Michel A; Sciarretta, Carla; Brisbare-Roch, Catherine; Strasser, Daniel S; Studer, Rolf; Jenck, Francois

    2013-04-01

    The orexin neuropeptide system regulates wakefulness and contributes to physiological and behavioral stress responses. Moreover, a role for orexins in modulating hypothalamus-pituitary-adrenal (HPA) axis activity has been proposed. Brain penetrating dual orexin receptor (OXR) antagonists such as almorexant decrease vigilance and have emerged as a novel therapeutic class for the treatment of insomnia. Almorexant was used here as a pharmacological tool to examine the role of endogenous orexin signaling in HPA axis endocrine function under natural conditions. After confirming the expression of prepro-orexin and OXR-1 and OXR-2 mRNA in hypothalamus, pituitary and adrenal glands, the effects of systemic almorexant were investigated on peripheral HPA axis hormone release in the rat under baseline, stress and pharmacological challenge conditions. Almorexant did not alter basal or stress-induced corticosterone release despite affecting wake and sleep stages (detected by radiotelemetric electroencephalography/electromyography) during the stress exposure. Moreover, almorexant did not affect the release of adrenocorticotropin (ACTH) and corticosterone at different time points along the diurnal rhythm, nor corticotrophin-releasing hormone (CRH)- and ACTH-stimulated neuroendocrine responses, measured in vivo under stress-free conditions. These results illustrate that dual OXR antagonists, despite modulating stress-induced wakefulness, do not interfere with endocrine HPA axis function in the rat. They converge to suggest that endogenous orexin signaling plays a minor role in stress hormone release under basal conditions and under challenge.

  20. Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties

    SciTech Connect

    Bhat, S.H.; Azmi, A.S.; Hadi, S.M. . E-mail: smhadi@vsnl.com

    2007-02-01

    Plant-derived dietary material contains several classes of polyphenols such as flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing cellular DNA degradation in the presence of transition metal ions such as copper. Earlier we have shown that the stilbene resveratrol is able to mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major constituent of coffee, is also capable of DNA breakage in human peripheral lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that caffeic acid generates oxidative stress in lymphocytes, which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action.