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Sample records for abrogates son binding

  1. Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

    Science.gov (United States)

    Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

    1993-06-25

    Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

  2. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress.

    Science.gov (United States)

    Annarapu, Gowtham K; Singhal, Rashi; Peng, Yuandong; Guchhait, Prasenjit

    2016-01-01

    Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions.

  3. NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

    2013-11-29

    Highlights: •NS1 induced excessive phosphorylation of ERK and elevated cell viability. •NS1-BP expression and CRKL knockdown abolished survival effect of NS1. •NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

  4. A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis.

    Science.gov (United States)

    Mumford, Andrew D; Dawood, Ban B; Daly, Martina E; Murden, Sherina L; Williams, Michael D; Protty, Majd B; Spalton, Jennifer C; Wheatley, Mark; Mundell, Stuart J; Watson, Steve P

    2010-01-14

    We investigated the cause of mild mucocutaneous bleeding in a 14-year-old male patient (P1). Platelet aggregation and ATP secretion induced by arachidonic acid and the thromboxane A(2) receptor (TxA(2)R) agonist U46619 were reduced in P1 compared with controls, whereas the responses to other platelet agonists were retained. P1 was heterozygous for a transversion within the TBXA2R gene predictive of a D304N substitution in the TxA(2)R. In Chinese hamster ovary-K1 cells expressing the variant D304N TxA(2)R, U46619 did not increase cytosolic free Ca(2+) concentration, indicating loss of receptor function. The TxA(2)R antagonist [(3)H]-SQ29548 showed an approximate 50% decrease in binding to platelets from P1 but absent binding to Chinese hamster ovary-K1 cells expressing variant D304N TxA(2)R. This is the second naturally occurring TxA(2)R variant to be associated with platelet dysfunction and the first in which loss of receptor function is associated with reduced ligand binding. D304 lies within a conserved NPXXY motif in transmembrane domain 7 of the TxA(2)R that is a key structural element in family A G protein-coupled receptors. Our demonstration that the D304N substitution causes clinically significant platelet dysfunction by reducing ligand binding establishes the importance of the NPXXY motif for TxA(2)R function in vivo.

  5. An interaction study in mammalian cells demonstrates weak binding of HSPB2 to BAG3, which is regulated by HSPB3 and abrogated by HSPB8.

    Science.gov (United States)

    Morelli, Federica F; Mediani, Laura; Heldens, Lonneke; Bertacchini, Jessika; Bigi, Ilaria; Carrà, Arianna Dorotea; Vinet, Jonathan; Carra, Serena

    2017-07-01

    The ten mammalian small heat shock proteins (sHSPs/HSPBs) show a different expression profile, although the majority of them are abundant in skeletal and cardiac muscles. HSPBs form hetero-oligomers and homo-oligomers by interacting together and complexes containing, e.g., HSPB2/HSPB3 or HSPB1/HSPB5 have been documented in mammalian cells and muscles. Moreover, HSPB8 associates with the Hsc70/Hsp70 co-chaperone BAG3, in mammalian, skeletal, and cardiac muscle cells. Interaction of HSPB8 with BAG3 regulates its stability and function. Weak association of HSPB5 and HSPB6 with BAG3 has been also reported upon overexpression in cells, supporting the idea that BAG3 might indirectly modulate the function of several HSPBs. However, it is yet unknown whether other HSPBs highly expressed in muscles such as HSPB2 and HSPB3 also bind to BAG3. Here, we report that in mammalian cells, upon overexpression, HSPB2 binds to BAG3 with an affinity weaker than HSPB8. HSPB2 competes with HSPB8 for binding to BAG3. In contrast, HSPB3 negatively regulates HSPB2 association with BAG3. In human myoblasts that express HSPB2, HSPB3, HSPB8, and BAG3, the latter interacts selectively with HSPB8. Combining these data, it supports the interpretation that HSPB8-BAG3 is the preferred interaction.

  6. Attenuation of cancer-initiating cells stemness properties by abrogating S100A4 calcium binding ability in head and neck cancers.

    Science.gov (United States)

    Cheng, Li-Hao; Hung, Kai-Feng; Huang, Tung-Fu; Hsieh, Hsin-Pei; Wang, Shu-Ying; Huang, Chih-Yang; Lo, Jeng-Fan

    2016-11-29

    S100A4 is a calcium-binding protein capable of promoting epithelial-mesenchymal transition. Previously, we have demonstrated that S100A4 is required to sustain the head and neck cancer-initiating cells (HN-CICs) subpopulation. In this study, to further investigate the molecular mechanism, we established the head and neck squamous cell carcinoma (HNSCC) cell lines stably expressing mutant S100A4 proteins with defective calcium-binding sites on either N-terminal (NM) or C-terminal (CM), or a deletion of the last 15 amino-acid residues (CD). We showed that the NM, CM and CD harboring sphere cells that were enriched with HN-CICs population exhibited impaired stemness and malignant properties in vitro, as well as reduced tumor growth ability in vivo. Mechanistically, we demonstrated that mutant S100A4 proteins decreased the promoter activity of Nanog, likely through inhibition of p53. Moreover, the biophysical analyses of purified recombinant mutant S100A4 proteins suggest that both NM and CM mutant S100A4 were very similar to the WT S100A4 with subtle difference on the secondary structure, and that the CD mutant protein displayed the unexpected monomeric form in the solution phase.Taken together, our results suggest that both the calcium-binding ability and the C-terminal region of S100A4 are important for HN-CICs to sustain its stemness property and malignancy, and that the mechanism could be mediated by repressing p53 and subsequently activating the Nanog expression.

  7. Son, Sent, and Servant

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    Truls Åkerlund

    2015-11-01

    Full Text Available This study challenges the claim that Jesus is the archetypical servant leader as described in contempo-rary leadership literature. Based on a theological reading of the Fourth Gospel, the paper suggests that, as a servant, Jesus cannot be understood apart from his mission and obedience to God. Consequently, Jesus was not primarily a servant leader but rather the Son who was sent to the world to enact the Fa-ther’s will. In this regard, the Fourth Gospel provides a unique perspective that is barely noted in the current discourse on servant leadership modelled on the example of Christ. Although certain aspects of servant leadership theory correspond to John’s portrayal of Jesus, the study concludes that other de-scriptions of him as a servant leader suffer from a one-sided and reductionist Christology. Implications of this view for Christian ministry are briefly sketched out.

  8. À chacun son puzzle

    Directory of Open Access Journals (Sweden)

    Jean-Noël Ferrié

    2012-05-01

    Full Text Available Le texte soutient que le « tournant naturaliste » que l’on nous invite à négocier ne donne aucun moyen supplémentaire pour parvenir à une description perspicace de ce que les gens font dans des circonstances précises, l’existence humaine pouvant être considérée comme une collection de circonstances précises. Sans doute le naturalisme nous permet-il de comprendre comment certaines actions humaines sont possibles, mais cela ne nous dit pas pourquoi et comment elles font sens pour tout un chacun. La méthodologie nécessaire pour éclaircir le premier point obscurcit généralement le second. Le mieux est donc de considérer que les deux approches ne vont pas de pair. Ce point de vue est soutenu à partir d’exemple tirés de l’anthropologie de la religion.To each one his puzzle. For a serene methodological pluralismThe text argues that the « naturalistic turn » that we are invited to negotiate does not give any additional means to achieve an insightful description of what people do in specific circumstances, and human existence can be considered as a collection of specific circumstances. Probably naturalism allows us to understand how some human actions are possible, but that does not tell us why and how they make sense for everyone. The methodology needed to clarify the first point usually obscures the second one. The best way is to consider that the two approaches do not go together. The text supports this view from an example drawn from the anthropology of religion.A cada uno su rompecabezas. En favor de un pluralismo metodológico serenoEl texto argumenta que la inflexión naturalista a la que se nos invita a participar no proporciona ningún medio suplementario que desemboque en una descripción perspicaz de lo que la gente hace en circunstancias concretas ya que la existencia humana puede ser considerada como una concatenación de circunstancias concretas. Sin duda el naturalismo nos permite comprender como son

  9. THE LAWFUL CONSEQUENCES OF BIRTH CERTIFICATE ON CHILDREN ABROGATION

    Directory of Open Access Journals (Sweden)

    Natasya Immanuela Sandjojo

    2017-12-01

    Full Text Available Research due to the law on the abrogation of birth certificates against children aims to know the effect of law affecting the child, as well as review of the determination and judgment in court that play a role in the birth certificate abrogation. This research describes the importance of birth certificate because of the low public awareness to perform birth registration. The study uses normative juridical research, which faces legal issues with the process of discovering legal rules, principles, and legal doctrines, with deductive methods, starting from the general thing and then generating specific and legitimate answers. Based on the results of the study, that the abrogation of birth certificate brings great lawful consequences for the child, especially the status and position of the child, as well as the right of alimentation,  which in this study included some examples of determination and court decision about the birth certificate abrogation.

  10. Ebselen abrogates TNFα induced pro‐inflammatory response in glioblastoma

    OpenAIRE

    Tewari, Richa; Sharma, Vivek; Koul, Nitin; Ghosh, Abhishek; Joseph, Christy; Hossain Sk, Ugir; Sen, Ellora

    2008-01-01

    We investigated the pro‐inflammatory response mediated by TNFα in glioblastoma and whether treatment with organoselenium Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3[2H]one) can affect TNFα induced inflammatory response. Exposure to TNFα increased the expression of pro‐inflammatory mediator interleukin IL‐6, IL‐8, monocyte chemoattractant protein‐1 (MCP‐1) and cyclooxygenase (COX‐2). Treatment with Ebselen abrogated TNFα induced increase in pro‐inflammatory mediators. Ebselen not only abrogated T...

  11. Review on Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    顾燕君

    2013-01-01

    This essay centralizes on the analysis of the writing skills, the theme and my personal insights of Sons and Lovers, as well as my interpretation of the mother-son relationship in terms of feminism. Overall, hope it will provide a specific perspective of this renowned novel and arouse the readers’attention to interpret the novel themselves.

  12. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik

    2010-01-01

    the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  13. Travailler loin de son domicile

    OpenAIRE

    Bonnet, Estelle; Verley, Elise; Ries, Tammy

    2017-01-01

    Résumé : La mobilité géographique liée à un lieu de travail éloigné du domicile – supposant soit de longs trajets quotidiens, soit de dormir en dehors du domicile – s’inscrit à l’articulation de la sphère professionnelle et de la sphère privée. Elle met à l’épreuve le couple et la distribution des rôles sexués en son sein. Cet article interroge les divisions sexuées inhérentes à cette articulation selon que l’on se place du point de vue d’une mobilité féminine ou masculine. Il examine en quoi...

  14. Son huasteco e identidad regional

    Directory of Open Access Journals (Sweden)

    Rosa María Bonilla Burgos

    2013-04-01

    Full Text Available La población de la región Huasteca es partícipe de manifestaciones musicales en diferentes ámbitos, lo cual permite reconocer que entre todos los géneros utilizados destaca el son huasteco y su correspondiente bailable llamado huapango. Dichas expresiones musicales se impregnan de los ambientes tanto físico como social que viven constantemente. Es a través de las letras de los sones huastecos que se desarrolla el mecanismo para reflejar el mundo natural que perciben, y los acontecimientos que les suceden, cobrando una importancia que deriva en una identificación que trasciende. Conciben su entorno y lo refieren con sentido de pertenencia-apropiación, que les permite recrear su vida y fundirse en una identificación cultural a la que se le llamará “identidad regional”. La relevancia de considerar una expresión musical de estas características radica en que se preserva y enriquece constantemente unificando un área de México que no necesariamente corresponde a límites políticos establecidos en las diferentes etapas históricas.

  15. ...And Kronos Ate His Sons

    Science.gov (United States)

    Vitiello, Giuseppe

    In closed systems, energy is conserved. The origin of the time axis is completely arbitrary due to the invariance under continuous time-translations. The flowing of time swallows those fictitious origins one might assign on its axis, as Kronos ate his sons. Dissipation breaks such a scenario. It implies a non-forgettable origin of time. Open systems need their complement (their "double") in order to become, together, a closed system. Time emerges as an observable measured by the evolution of the open system complement, which acts as a clock. The conservation of the energy-momentum tensor in electrodynamics is considered and its relation with dissipative systems and self-similar fractal structures is discussed. The isomorphism with coherent states in quantum field theory (QFT) is established and the generator of transitions among unitarily inequivalent representations of the canonical commutation relations (CCR) is shown to provide sequences in time of phases, which defines the arrow of time. Merging properties of electrodynamics, fractal self-similarity, dissipation and coherent states point to an integrated vision of Nature.

  16. The experience of sons caring for a parent with dementia.

    Science.gov (United States)

    McDonnell, Eilis; Ryan, Assumpta A

    2014-11-01

    This study explored the experiences of sons caring for a parent with dementia. Individual, semi-structured interviews were conducted with a purposeful sample of sons (n = 13) in a rural part of Ireland. Interviews were audiotaped, transcribed verbatim and analysed for common themes. The key themes that emerged were 'the parental bond', 'a binding role', 'coordinating care and support' and a 'getting on with it' approach to care. The study highlighted the commitment of sons to their caregiving role and the strong sense of duty that motivated them to provide care. The findings suggested that while many aspects of the caregiving experience such as lack of information and support are gender neutral, there are differences in the caregiving experiences of men and women in how they view their relationship with their parent and in the management of their caregiving role that merit further investigation. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. TSH Receptor Signaling Abrogation by a Novel Small Molecule.

    Science.gov (United States)

    Latif, Rauf; Realubit, Ronald B; Karan, Charles; Mezei, Mihaly; Davies, Terry F

    2016-01-01

    Pathological activation of the thyroid-stimulating hormone receptor (TSHR) is caused by thyroid-stimulating antibodies in patients with Graves' disease (GD) or by somatic and rare genomic mutations that enhance constitutive activation of the receptor influencing both G protein and non-G protein signaling. Potential selective small molecule antagonists represent novel therapeutic compounds for abrogation of such abnormal TSHR signaling. In this study, we describe the identification and in vitro characterization of a novel small molecule antagonist by high-throughput screening (HTS). The identification of the TSHR antagonist was performed using a transcription-based TSH-inhibition bioassay. TSHR-expressing CHO cells, which also expressed a luciferase-tagged CRE response element, were optimized using bovine TSH as the activator, in a 384 well plate format, which had a Z score of 0.3-0.6. Using this HTS assay, we screened a diverse library of ~80,000 compounds at a final concentration of 16.7 μM. The selection criteria for a positive hit were based on a mean signal threshold of ≥50% inhibition of control TSH stimulation. The screening resulted in 450 positive hits giving a hit ratio of 0.56%. A secondary confirmation screen against TSH and forskolin - a post receptor activator of adenylyl cyclase - confirmed one TSHR-specific candidate antagonist molecule (named VA-K-14). This lead molecule had an IC 50 of 12.3 μM and a unique chemical structure. A parallel analysis for cell viability indicated that the lead inhibitor was non-cytotoxic at its effective concentrations. In silico docking studies performed using a TSHR transmembrane model showed the hydrophobic contact locations and the possible mode of inhibition of TSHR signaling. Furthermore, this molecule was capable of inhibiting TSHR stimulation by GD patient sera and monoclonal-stimulating TSHR antibodies. In conclusion, we report the identification of a novel small molecule TSHR inhibitor, which has the

  18. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    Science.gov (United States)

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  19. Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation.

    Science.gov (United States)

    Tesco, G; Kim, T W; Diehlmann, A; Beyreuther, K; Tanzi, R E

    1998-12-18

    beta-Catenin has previously been shown to interact with presenilin 1 (PS1) in transfected cells. Here we report that beta-catenin co-immunoprecipitates with the endogenous C-terminal fragment of presenilin 1 (PS1-CTF) but not with the endogenous CTF of presenilin 2 (PS2-CTF) in H4 human neuroglioma cells. During staurosporine (STS)-induced cell death, beta-catenin and PS1-CTF undergo a caspase-mediated cleavage. After 12 h of STS treatment, the beta-catenin.PS1-CTF interaction is abrogated. While PS1-CTF immunoprecipitated with all caspase-cleaved species of beta-catenin, beta-catenin holoprotein did not co-immunoprecipitate with the "alternative" caspase-derived PS1-CTF (PS1-aCTF). Thus, the abrogation of the beta-catenin.PS1-CTF complex was due to caspase cleavage of PS1-CTF. beta-Catenin co-immunoprecipitated with PS1-NTF, but only when PS1-NTF was associated with PS1-CTF. Even though PS1-NTF.CTF complex stability was not altered by caspase cleavage, its ability to bind beta-catenin was abolished. Thus, while the PS1-NTF.CTF complex is preserved after caspase cleavage, it may no longer be fully functional.

  20. A bioavailable cathepsin S nitrile inhibitor abrogates tumor development.

    Science.gov (United States)

    Wilkinson, Richard D A; Young, Andrew; Burden, Roberta E; Williams, Rich; Scott, Christopher J

    2016-04-21

    Cathepsin S has been implicated in a variety of malignancies with genetic ablation studies demonstrating a key role in tumor invasion and neo-angiogenesis. Thus, the application of cathepsin S inhibitors may have clinical utility in the treatment of cancer. In this investigation, we applied a cell-permeable dipeptidyl nitrile inhibitor of cathepsin S, originally developed to target cathepsin S in inflammatory diseases, in both in vitro and in vivo tumor models. Validation of cathepsin S selectivity was carried out by assaying fluorogenic substrate turnover using recombinant cathepsin protease. Complete kinetic analysis was carried out and true K i values calculated. Abrogation of tumour invasion using murine MC38 and human MCF7 cell lines were carried out in vitro using a transwell migration assay. Effect on endothelial tube formation was evaluated using primary HUVEC cells. The effect of inhibitor in vivo on MC38 and MCF7 tumor progression was evaluated using cells propagated in C57BL/6 and BALB/c mice respectively. Subsequent immunohistochemical staining of proliferation (Ki67) and apoptosis (TUNEL) was carried out on MCF7 tumors. We confirmed that this inhibitor was able to selectively target cathepsin S over family members K, V, L and B. The inhibitor also significantly reduced MC38 and MCF7 cell invasion and furthermore, significantly reduced HUVEC endothelial tubule formation in vitro. In vivo analysis revealed that the compound could significantly reduce tumor volume in murine MC38 syngeneic and MCF7 xenograft models. Immunohistochemical analysis of MCF7 tumors revealed cathepsin S inhibitor treatment significantly reduced proliferation and increased apoptosis. In summary, these results highlight the characterisation of this nitrile cathepsin S inhibitor using in vitro and in vivo tumor models, presenting a compound which may be used to further dissect the role of cathepsin S in cancer progression and may hold therapeutic potential.

  1. Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

    Energy Technology Data Exchange (ETDEWEB)

    Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F. (CNRS-INSERM); (Mount Sinai Hospital); (LB-Ecuador); (Iowa State)

    2010-10-11

    Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.

  2. Natural Mutations in Streptococcus agalactiae Resulting in Abrogation of β Antigen Production.

    Science.gov (United States)

    Vasilyeva, Anastasia; Santos Sanches, Ilda; Florindo, Carlos; Dmitriev, Alexander

    2015-01-01

    Streptococcus agalactiae genome encodes 21 two-component systems (TCS) and a variety of regulatory proteins in order to control gene expression. One of the TCS, BgrRS, comprising the BgrR DNA-binding regulatory protein and BgrS sensor histidine kinase, was discovered within a putative virulence island. BgrRS influences cell metabolism and positively control the expression of bac gene, coding for β antigen at transcriptional level. Inactivation of bgrR abrogated bac gene expression and increased virulence properties of S. agalactiae. In this study, a total of 140 strains were screened for the presence of bac gene, and the TCS bgrR and bgrS genes. A total of 53 strains carried the bac, bgrR and bgrS genes. Most of them (48 strains) expressed β antigen, while five strains did not express β antigen. Three strains, in which bac gene sequence was intact, while bgrR and/or bgrS genes had mutations, and expression of β antigen was absent, were complemented with a constructed plasmid pBgrRS(P) encoding functionally active bgrR and bgrS gene alleles. This procedure restored expression of β antigen indicating the crucial regulatory role of TCS BgrRS. The complemented strain A49V/BgrRS demonstrated attenuated virulence in intraperitoneal mice model of S. agalactiae infection compared to parental strain A49V. In conclusion we showed that disruption of β antigen expression is associated with: i) insertion of ISSa4 upstream the bac gene just after the ribosomal binding site; ii) point mutation G342A resulting a stop codon TGA within the bac gene and a truncated form of β antigen; iii) single deletion (G) in position 439 of the bgrR gene resulting in a frameshift and the loss of DNA-binding domain of the BgrR protein, and iv) single base substitutions in bgrR and bgrS genes causing single amino acid substitutions in BgrR (Arg187Lys) and BgrS (Arg252Gln). The fact that BgrRS negatively controls virulent properties of S. agalactiae gives a novel clue for understanding of S

  3. Cuidados invisibles: ¿son suficientemente reconocidos?

    Directory of Open Access Journals (Sweden)

    Rosanna de la Rosa Eduardo

    Full Text Available Los cuidados invisibles son un elemento central y fundamental de la práctica de la Enfermería y son la base de su identidad profesional. La Enfermería ha sufrido un importante y positivo proceso de profesionalización en los últimos 150 años, sin embargo, los cuidados invisibles siguen siendo poco reconocidos, a pesar de su importancia en la recuperación y en la calidad de vida de los usuarios. En este trabajo se analizan brevemente las grandes transformaciones sociales actuales que obligan a replantearse la necesidad de visibilizar los cuidados invisibles, se plantean interrogantes clave para abordar esta discusión y se proponen una serie de acciones concretas para avanzar en este reconocimiento.

  4. SON68 glass alteration enhanced by magnetite

    Energy Technology Data Exchange (ETDEWEB)

    Godon, Nicole; Gin, Stephane; Rebiscoul, Diane; Frugier, Pierre [CEA, DEN-Marcoule, F30207, Bagnols-sur-Ceze (France)

    2013-07-01

    This paper reports experimental and modeling results of SON68 glass / magnetite interactions while in contact with synthetic groundwater from a clay environment. It is shown that magnetite enhances glass alteration, first by the sorption of Si released from the glass onto magnetite surfaces, then by a second process that could be the precipitation of an iron silicate mineral or the transformation of magnetite into a more reactive phase like hematite or goethite. This study globally suggests a detrimental effect of magnetite on the long-term durability of nuclear glass in geological disposal conditions. (authors)

  5. ?Cuales son las amenazas o peligros volcanicos?

    Science.gov (United States)

    Myers, Bobbie; Brantley, Steven R.; Stauffer, Peter; Hendley, James W.

    2000-01-01

    Los volcanes son capaces de producir numerosos peligros geologicos e hidrologicos. Los cientificos del Servicio Geologico de los EE. UU. (USGS, por sus siglas en ingles) y de otras instituciones alrededor del mundo estan estudiando los peligros de muchos de los centenares de volcanes activos y potencialmente activos del mundo. Estos cientificos vigilan muy de cerca la actividad de algunos de los volcanes mas peligrosos, por lo que estan preparados para alertar a las autoridades y/o a la poblacion en caso de que aumente sustancialmente la probabilidad de que ocurra una erupcion u otro evento peligroso.

  6. My Son 22.10.11

    Directory of Open Access Journals (Sweden)

    Rebecca Baillie

    2013-01-01

    Full Text Available 'My Son 22.10.11' was made immediately following a miscarriage 8 weeks into pregnancy. After bleeding lightly for a couple of hours, I went to the toilet and a large bloody mass fell from within me. I knew that I could not flush this away, and that to retrieve the mass was my only chance to connect with the unborn foetus. I fished the contents from the bottom of the toilet bowl using my hands and carried them into my small studio. I found some paper and began to dissect the mass. At the centre, I found the tiny, cold, hard foetus. I kissed it and then began to use it as a kind of painting tool, drawing the outline of the lost child using its very own flesh and blood. I knew that to create a lasting and tangible portrait of 'my son' was the best way to understand the somewhat unreal and fleeting experience of miscarriage. I thought of Frida Kahlo while making the work, thinking 'thank God' that I had a reference to miscarriage before it happened to me. I also thought of my childhood days spent on our family pig farm, and of all the dead pig foetuses that I had seen at various stages of development. Before the miscarriage, I thought little about the subject; afterwards, I recognise the profundity of the creation of a life that is never born. The experience is so common, yet so very rarely discussed or depicted.

  7. Combinational chelation therapy abrogates lead-induced neurodegeneration in rats

    International Nuclear Information System (INIS)

    Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J.S.

    2009-01-01

    Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril + DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

  8. Selecting sex: the effect of preferring sons.

    Science.gov (United States)

    Hesketh, Therese

    2011-11-01

    Son preference remains common in countries from East Asia through South Asia to the Middle East and North Africa. Where sex selective technology and abortion are readily available, such as in China, South Korea and India, this has led to a marked excess in male births. Worst excesses are seen in parts of rural China where there are 140 male births for every 100 female. This leads to large numbers of unmarriageable men. Concerns about the consequences centre around the propensity to aggression and violence of these men with increased levels of crime and antisocial behaviour, threatening societal stability and security. But recent studies do not support these assumptions, but rather suggest that these men are marginalised, lonely, withdrawn and prone to psychological problems. Measures to reduce sex selection should include enforcement of existing legislation on sex-selection, and public awareness campaigns about the dangers of late abortion and gender imbalance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. L'astronomie et son histoire

    CERN Document Server

    Roy, Jean-René

    1982-01-01

    Le livre de Jean-René Roy nous présente une vaste synthèse des connaissances présentes en astronomie. Le grand mérite du livre est de dérouler son sujet en parallèle avec une histoire de l'astronomie. Le côté historique est ici beaucoup plus qu'un luxe. Il redonne leurs dimensions vraies aux réponses qu'apporte l'astronomie. Pour bien sentir la nature d'une étape franchie, il faut aussi avoir vécu la situation telle qu'elle se présentait avant. Et les fiches personnelles incluses dans le livre ont l'intérêt de nous rapprocher encore plus du "" feu de l'action "". Écrit dans un style direct et

  10. Lo que son mujeres en los escenarios

    Directory of Open Access Journals (Sweden)

    González Cañal, Rafael

    2007-06-01

    Full Text Available In this article I review the publishing and stage trajectory of one of Rojas Zorrilla’s most significant plays: Lo que son mujeres. As well as collecting a list of the different editions, I emphasize the 1822 version by the Mexican Manuel Eduardo de Gorostiza, which started a new renaissance period for this play on stage. I also analyze the 1899 one-act version by Emilio Bobadilla. Finally, I include all the different productions between the 17th and the 19th centuries, and address the little interest aroused in the 20th century–suffice to say that it has not been staged even during these early years of the 21st century when the centenary of Rojas Zorrilla is being celebrated.En este artículo se hace un repaso detallado de la fortuna editorial y escénica de una de las obras más significativas de Rojas Zorrilla: Lo que son mujeres. Aparte de recoger las diferentes ediciones de la misma, se hace hincapié en la refundición del mexicano Manuel Eduardo de Gorostiza, estrenada en 1822, que abrió un período de cierta recuperación de este texto dramático en los escenarios. Se analiza también la refundición que llevó a cabo en un solo acto Emilio Bobadilla en 1899. Finalmente, se registran todas las representaciones conocidas de la obra desde el siglo XVII hasta el siglo XIX y se constata el poco interés que ha despertado en los escenarios del siglo XX. Incluso en los últimos años, en los que los montajes de obras de Rojas comienzan a ser más frecuentes, esta obra no ha sido todavía llevada a escena.

  11. G2 checkpoint abrogator abates the antagonistic interaction between antimicrotubule drugs and radiation therapy

    International Nuclear Information System (INIS)

    Sui Meihua; Zhang Hongfang; Di Xiaoyun; Chang Jinjia; Shen Youqing; Fan Weimin

    2012-01-01

    Background and purpose: We previously demonstrated that radiation may arrest tumor cells at G2 phase, which in turn prevents the cytotoxicity of antimicrotubule drugs and results in antagonistic interaction between these two modalities. Herein we tested whether G2 abrogators would attenuate the above antagonistic interaction and improve the therapeutic efficacy of combination therapy between radiation and antimicrotubule drugs. Materials and methods: Breast cancer BCap37 and epidermoid carcinoma KB cell lines were administered with radiation, UCN-01 (a model drug of G2 abrogator), paclitaxel or vincristine, alone or in combinations. The antitumor activities of single and combined treatments were analyzed by a series of cytotoxic, apoptotic, cell cycle, morphological and biochemical assays. Results: UCN-01 significantly enhanced the cytotoxicity of radiation, antimitotic drugs, and their combined treatments in vitro. Further investigations demonstrated that UCN-01 attenuated radiation-induced G2 arrest, and subsequently repressed the inhibitory effect of radiation on drug-induced mitotic arrest and apoptosis. Conclusions: This is the first report demonstrating that G2 checkpoint abrogation represses the inhibitory effect of radiation on antimicrotubule drugs, which may be implicated in cancer combination therapy. Considering that G2 abrogators are under extensive evaluation for cancer treatment, our findings provide valuable information for this class of promising compounds.

  12. Mutations that abrogate transactivational activity of the feline leukemia virus long terminal repeat do not affect virus replication

    International Nuclear Information System (INIS)

    Abujamra, Ana L.; Faller, Douglas V.; Ghosh, Sajal K.

    2003-01-01

    The U3 region of the LTR of oncogenic Moloney murine leukemia virus (Mo-MuLV) and feline leukemia viruses (FeLV) have been previously reported to activate expression of specific cellular genes in trans, such as MHC class I, collagenase IV, and MCP-1, in an integration-independent manner. It has been suggested that transactivation of these specific cellular genes by leukemia virus U3-LTR may contribute to the multistage process of leukemogenesis. The U3-LTR region, necessary for gene transactivational activity, also contains multiple transcription factor-binding sites that are essential for normal virus replication. To dissect the promoter activity and the gene transactivational activity of the U3-LTR, we conducted mutational analysis of the U3-LTR region of FeLV-A molecular clone 61E. We identified minimal nucleotide substitution mutants on the U3 LTR that did not disturb transcription factor-binding sites but abrogated its ability to transactivate the collagenase gene promoter. To determine if these mutations actually have altered any uncharacterized important transcription factor-binding site, we introduced these U3-LTR mutations into the full-length infectious molecular clone 61E. We demonstrate that the mutant virus was replication competent but could not transactivate cellular gene expression. These results thus suggest that the gene transactivational activity is a distinct property of the LTR and possibly not related to its promoter activity. The cellular gene transactivational activity-deficient mutant FeLV generated in this study may also serve as a valuable reagent for testing the biological significance of LTR-mediated cellular gene activation in the tumorigenesis caused by leukemia viruses

  13. Sons fricativos surdos Voiceless fricatives sounds

    Directory of Open Access Journals (Sweden)

    Carla Aparecida Cielo

    2008-01-01

    Full Text Available TEMA: características dos sons fricativos surdos. OBJETIVO: propor uma revisão da literatura pertinente às características acústicas, fonéticas e fonológicas dos fonemas fricativos surdos que integram o sistema fonológico do Português. Além disso, são descritas suas aplicações na terapia vocal. CONCLUSÕES: os fricativos são fonemas agudos, abrangendo de 2500 a 8000Hz; são plenamente adquiridos até os 3:7 anos de idade; o /s/ que também é o mais afetado em casos de frênulo lingual curto; a omissão do /s/ é uma das ocorrências mais freqüentes na alfabetização; sendo que, no desvio fonológico e na fissura lábio-palatina, freqüentemente ocorre comprometimento de toda a classe de fricativos. Na avaliação de voz, os fricativos são mencionados com as medidas de TMF e relação s/z, bem como seu uso como sons de apoio na fonoterapia.BACKGROUND: characteristics of voiceless fricative sounds PURPOSE: to review the literature related to acoustic, phonetics and phonological characteristics of voiceless fricative sounds that are part of the phonological system of the Portuguese Language. Furthermore, it describes the use of these sounds in voice therapy. CONCLUSIONS: fricatives are acute phonemes comprised between 2500 and 8000 Hz; they are fully acquired up to the age of 3:7 years; the /s/, which is the most affected in cases of short lingual frenum; omission of the /s/ is one of the most frequent occurrences during literacy education; and in the phonological deviation and labial-palatine fissure the entire class of fricatives is frequently affected. In voice assessment, fricative sounds are mentioned as TMF measurements and s/z relationship, and their use as support sounds in speech therapy.

  14. Dombey and Son: An Inverted Maid's Tragedy

    Directory of Open Access Journals (Sweden)

    Taher Badinjki

    2015-06-01

    Full Text Available Ross Dabney, J. Butt & K. Tillotson, and others think that Dickens revised the role of Edith in the original plan of Dombey and Son upon the advice of a friend. I tend to believe that Dickens's swerve from his course was prompted by two motives, his relish for grand scenes, and his endeavour to engage the reader's sympathies for a character who was a victim of a social practice which he was trying to condemn. Dickens's humanitarian attitude sought to redeem the sinner and condemn the sin. In engaging the reader's sympathies,  Dickens  had entrapped his own.  Both Edith and Alice are shown as victims of rapacious mothers who sell anything, or anybody for money. While Good Mrs Brown sells Alice's virtue and innocence for cash, Mrs Skewton trades on Edith's beauty in the marriage market to secure fortune and a good establishment. Edith and Alice's maturity and moral growth and their scorn and anger at their mothers' false teaching come in line with public prudery. Moreover, their educators in the principles of Mammonism have not succeeded altogether in stifling their innate feminine tenderness and capacity for affection, the thing that draws them near their reader's heart and wins them love and sympathy. Keywords: Money,  transaction,  victims,  saleable,  Mormonism,  greedy, rapacious

  15. Mate-sampling costs and sexy sons.

    Science.gov (United States)

    Kokko, H; Booksmythe, I; Jennions, M D

    2015-01-01

    Costly female mating preferences for purely Fisherian male traits (i.e. sexual ornaments that are genetically uncorrelated with inherent viability) are not expected to persist at equilibrium. The indirect benefit of producing 'sexy sons' (Fisher process) disappears: in some models, the male trait becomes fixed; in others, a range of male trait values persist, but a larger trait confers no net fitness advantage because it lowers survival. Insufficient indirect selection to counter the direct cost of producing fewer offspring means that preferences are lost. The only well-cited exception assumes biased mutation on male traits. The above findings generally assume constant direct selection against female preferences (i.e. fixed costs). We show that if mate-sampling costs are instead derived based on an explicit account of how females acquire mates, an initially costly mating preference can coevolve with a male trait so that both persist in the presence or absence of biased mutation. Our models predict that empirically detecting selection at equilibrium will be difficult, even if selection was responsible for the location of the current equilibrium. In general, it appears useful to integrate mate sampling theory with models of genetic consequences of mating preferences: being explicit about the process by which individuals select mates can alter equilibria. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  16. Son Preference and Its Consequences (A Review) | Shah | Gender ...

    African Journals Online (AJOL)

    Cultural preference for sons was evident from that fact that in Hindu\\'s traditions, ... A common perception of son\\'s preference on daughter was the ascribed ability of ... against females in the allocation of food and health care within the household. ... their-self in most of the south Asian countries preferred sons to daughters.

  17. Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.

    Directory of Open Access Journals (Sweden)

    Abhirami A Ananth

    Full Text Available Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA-dopachrome tautomerase (AdDCT and resection resulting in major surgical stress (abdominal nephrectomy, we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients.

  18. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

    Science.gov (United States)

    Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

    2013-08-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. SON is a spliceosome-associated factor required for mitotic progression.

    Science.gov (United States)

    Huen, Michael S Y; Sy, Shirley M H; Leung, Ka Man; Ching, Yick-Pang; Tipoe, George L; Man, Cornelia; Dong, Shuo; Chen, Junjie

    2010-07-01

    The eukaryotic RNA splicing machinery is dedicated to the daunting task of excising intronic sequences on the many nascent RNA transcripts in a cell, and in doing so facilitates proper translation of its transcriptome. Notably, emerging evidence suggests that RNA splicing may also play direct roles in maintaining genome stability. Here we report the identification of the RNA/DNA-binding protein SON as a component of spliceosome that plays pleiotropic roles during mitotic progression. We found that SON is essential for cell proliferation, and that its inactivation triggers a MAD2-dependent mitotic delay. Moreover, SON deficiency is accompanied by defective chromosome congression, compromised chromosome segregation and cytokinesis, which in turn contributes to cellular aneuploidy and cell death. In summary, our study uncovers a specific link between SON and mitosis, and highlights the potential of RNA processing as additional regulatory mechanisms that govern cell proliferation and division. © 2010 Landes Bioscience

  20. Having a Son Promotes Clean Cooking Fuel Use in Urban India: Women's Status and Son Preference

    OpenAIRE

    Avinash Kishore; Dean Spears

    2014-01-01

    Urban Indian households with a male first child are approximately 2 percentage points more likely to use clean cooking fuel than comparable households with a female first child. Given Indian son preference, there are at least two mechanisms by which child sex could affect fuel choice: by improving the intrahousehold status of women, who bear more of the costs of traditional fuels, or by presenting an opportunity to invest in children's health, in the context of a preference for healthier boys...

  1. Sexual Orientation of Adult Sons of Gay Fathers.

    Science.gov (United States)

    Bailey, J. Michael; And Others

    1995-01-01

    Examined the sexual orientation of 82 adult sons of 55 gay men. Found that more than 90% of the sons whose sexual orientation could be rated were heterosexual. Gay and heterosexual sons did not differ on potentially relevant variables such as length of time they had lived with their fathers. (MDM)

  2. Son Preference in Pakistan; A Myth or Reality.

    Science.gov (United States)

    Atif, Khaula; Ullah, Muhammad Zia; Afsheen, Afeera; Naqvi, Syed Abid Hassan; Raja, Zulqarnain Ashraf; Niazi, Saleem Asif

    2016-01-01

    To analyze desire for sons/daughters among ladies of Peshawar, Pakistan, with a view to rule out son preference and to study impact of various demographic characteristics on the subject. Cross-sectional descriptive study conducted at Combined Military Hospital, Peshawar, from August 2015 - January 2016; sampling technique was random/probability/non-purposive. Self-designed questionnaire was utilized; carrying questions pertinent to desire for sons/daughters during marital life, and demographic details. Data analyzed via descriptive analysis (SPSS-21), expressed as frequencies/percentages and mean ± standard deviation(minimum/maximum). Sons and daughters desired (dependent variables) were cross-tabulated with independent variables. Response rate was 63.25% (n-506). Data revealed following: Sons desired 3.05±2.061(1/12); Daughters desired 1.15±0.767(0/4); 6.1%(n-31) and 0.6%(n-3) desired infinite number of sons and daughters respectively, 18.2%(n-92) did not desire to have even one daughter, while 2.2%(n-11) considered it immaterial to have daughters or sons. There was a significant relation between sons desired and client's education (pGender discrimination can be attenuated by adequately addressing son preference at all tiers.

  3. The culture of referendum in Albania: Technical and theoritecal reflections on the abrogative referendum

    Directory of Open Access Journals (Sweden)

    Valbona Pajo Bala

    2014-01-01

    Full Text Available The aim of this paper is to analyse the Albanian constitutional and legal framework on referenda, in general, focusing special attention to the abrogative referenda of a law or part thereof. Given the absence of any concrete case of an abrogative referenda held in Albania, which does not creates very much room for discussion in that regard, the paper, through a comparative approach on the referenda culture in other european states, aims at offering to the reader a more complete view on the mechanisms and guarantees enjoyed by voters and the effective way of their use, in order to give life to the direct democracy, but without replacing the representative one. In addition, part of the analyses will be the powers of the Constitutional Court for the ex ante constitutional review of the issue subject to a referendum, the review of constitutionality of the referndum and of its results. In this context, the paper will focus on the constitutional case-law as a tool for increasing the referenda culture and shaping the constitional order, as well as a source of standards and values. Another objective of the paper is to open a discussion on the need for the reception of referenda-related standards elaborated in those European countries, where the culture of helding a referenda and the case-law on the regard is enriched and may serve as a qualitative basis for further reference.

  4. A test of the "sexy son" hypothesis: sons of polygynous collared flycatchers do not inherit their fathers' mating status.

    Science.gov (United States)

    Gustafsson, Lars; Qvarnström, Anna

    2006-02-01

    According to the original "sexy son" hypothesis, a female may benefit from pairing with an already-mated male despite a reduction in fecundity because her sons inherit their father's attractiveness. We used data from a long-term study of collared flycatchers (Ficedula albicollis) collected during 24 years to test this prediction. Our results show that the sons of polygynously mated females fledged in poor condition and therefore did not inherit their father's large forehead patch (a condition-dependent display trait) or mating status. From the female's perspective, polygynous pairing resulted in fewer recruited grandchildren than did a monogamous pairing. The reproductive value of sons did not outweigh the fecundity costs of polygyny because the low paternal care reduced the attractiveness of sons. When there are long-lasting parental effects on offspring attractiveness, costs of polygyny may include the production of nonsexy sons.

  5. A Letter from a Black Mom to Her Son

    Science.gov (United States)

    Watson, Dyan

    2012-01-01

    An African American mother and teacher educator uses examples from her own childhood to describe how she hopes her child will be treated by teachers, and what she fears. In her letter to her son, the African American mom expresses how she want teachers to know her son's journey to school--metaphorically and physically. She wants them to know that…

  6. Son preference in rural China: patrilineal families and socioeconomic change.

    Science.gov (United States)

    Murphy, Rachel; Tao, Ran; Lu, Xi

    2011-01-01

    This article draws on a survey conducted in six provinces in summer 2008 to investigate the determinants of son preference in rural China. The analysis confirms the conventional wisdom that son preference is embedded within patrilineal family structures and practices. We extend our analysis by exploring specific aspects of variation within patrilineal family culture. We find that the patrilineal group (clan) composition of villages and family participation in practices such as building ancestral halls and updating genealogies significantly influence son preference. Yet even though son preference is embedded within patrilineal family culture, our analysis suggests that over time the attenuation of son preference is likely. This is because determinants associated with socioeconomic change—for instance, higher levels of education, direct exposure to official policy education materials, higher income (a proxy for rural industrialization), and agricultural mechanization—all attenuate son preference. Being younger and female are also associated with weaker son preference, and both characteristics are likely to interact with education and industrialization to further dilute son preference in the longer term. Nevertheless, our findings suggest that concerted efforts are needed to ameliorate institutional discrimination against rural people in welfare provisioning and in labor markets, and to promote multiple dimensions of gender equality, including in land rights, wage rates, and education.

  7. Son preference in a rural village in North Vietnam.

    Science.gov (United States)

    Bélanger, Danièle

    2002-12-01

    This article explores the continuing preference for sons in the context of low fertility in Vietnam. Although the total fertility rate for Vietnam declined from 6.0 children per woman of reproductive age in 1979 to 2.2 children in 1998, demographic evidence shows that son preference remains strong and influences contraceptive and fertility behavior. This study examines the underlying factors for son preference in a rural village in North Vietnam. The methodology includes focus-group discussions, an in-depth study of 25 families, and ethnographic observation. Results indicate that sons are highly desired for their social, symbolic, and economic value. In spite of four decades of socialist policies aimed at reducing gender-based inequalities and at weakening the patriarchal kinship system, the desire for sons continues to drive the family-building process. The article also indicates a gap between discourse and social practice with respect to roles assigned to children on the basis of their sex.

  8. Abrogation of cisplatin-induced hepatotoxicity in mice by xanthorrhizol is related to its effect on the regulation of gene transcription

    International Nuclear Information System (INIS)

    Hwan Kim, Seong; Ok Hong, Kyoung; Chung, Won-Yoon; Kwan Hwang, Jae; Park, Kwang-Kyun

    2004-01-01

    Cisplatin is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because Curcuma xanthorrhiza Roxb. (Zingiberaceae) has been traditionally used to treat liver disorders, the protective effect of xanthorrhizol, which is isolated from C. xanthorrhiza, on cisplatin-induced hepatotoxicity was evaluated in mice. The pretreatment of xanthorrhizol (200 mg/kg/day, po) for 4 days prevented the hepatotoxicity induced by cisplatin (45 mg/kg, ip) with statistical significance. Interestingly, it abrogated cisplatin-induced DNA-binding activity of nuclear factor-kappaB (NF-κB), which consequently affected mRNA expression levels of NF-κB-dependent genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), even in part. It also attenuated the cisplatin-suppressed DNA-binding activity of activator protein 1 (AP-1). Using differential display reverse transcription-polymerase chain reaction (DDRT-PCR), seven upregulated genes including S100 calcium binding protein A9 (S100A9) mRNA and antigenic determinant for rec-A protein mRNA and five downregulated genes including caseinolytic protease X (ClpX) mRNA and ceruloplasmin (CP) mRNA by cisplatin were identified. Although these mRNA expression patterns were not totally consistent with gel shift patterns, altered expression levels by cisplatin were reversed by the pretreatment of xanthorrhizol. In conclusion, the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factors, NF-κB and AP-1, could be one possible mechanism to elucidate the preventive effect of xanthorrhizol on cisplatin-induced hepatotoxicity. Furthermore, genes identified in this study could be helpful to understand the mechanism of cisplatin-induced hepatotoxicity. Finally, the combination treatment of xanthorrhizol and cisplatin may provide more advantage than single treatment of cisplatin in cancer therapy

  9. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

    International Nuclear Information System (INIS)

    Li Yuqing; Aubert, Isabelle; Wong, C. Shun

    2010-01-01

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

  10. Chromosomal instability and the abrogated G2/M arrest in x-irradiated myelodysplastic syndrome cells

    International Nuclear Information System (INIS)

    Ban, S.; Sudo, H.; Saegusa, K.; Sagara, M.; Imai, T.; Kimura, A.

    2003-01-01

    A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors in Hiroshima. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the karyotypes of bone marrow cells and the micronucleus (MN) frequency in peripheral T lymphocytes of twenty- three atomic bomb survivors with MDS and five normal individuals. Aneuploidy was observed in 10 of 23 patients. Chromosome aberrations were observed in 3 of 12 patients with mild symptoms, and six of 11 patients of severe symptoms. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation- therapy, their unusual radiosensitivity may be related to their chromosomal or genomic instability. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrest was observed in 10 of 12 MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that the abrogated G2/M arrest may be involved in the pathophysiology of disease progression and the high radiation sensitivity of patients

  11. The Telephone Connection: An Interview with Ernest Hemingway's Son.

    Science.gov (United States)

    Workman, Brooke

    1979-01-01

    Relates how a conference call to Ernest Hemingway's son, Gregory, resolved questions and brought understanding and excitement to a group of Iowa high school students enrolled in a 12-week Hemingway seminar. (FL)

  12. The discovery and exploration of Hang Son Doong

    Energy Technology Data Exchange (ETDEWEB)

    Limbert, H.; Limbert, D.; Hieu, N.; Phai, V. V.; Kinh Bac, D.; Phuong, T. H.; Granger, D.

    2016-08-01

    Hang Son Doong is located in the Phong Nha Ke Bang Limestone Massif in Quang Binh Province, Central Vietnam. Cave exploration by British cavers has been continuous in this area since 1990. Hang Son Doong is part of the Phong Nha Cave system which runs from the southern end of the National Park near the Lao border to the final resurgence at Phong Nha Cave. (Author)

  13. Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Singh, Kanhaiya; Agrawal, Neeraj K; Gupta, Sanjeev K; Mohan, Gyanendra; Chaturvedi, Sunanda; Singh, Kiran

    2016-10-01

    The inflammatory phase of wound healing cascade is an important determinant of the fate of the wound. Acute inflammation is necessary to initiate proper wound healing, while chronic inflammation abrogates wound healing. Different endosomal members of toll-like receptor (TLR) family initiate inflammatory signalling via a range of different inflammatory mediators such as interferons, internal tissue damaged-associated molecular patterns (DAMPs) and hyperactive effector T cells. Sustained signalling of TLR9 and TLR7 contributes to chronic inflammation by activating the plasmacytoid dendritic cells. Diabetic wounds are also characterised by sustained inflammatory phase. The objective of this study was to analyse the differential expression of endosomal TLRs in human diabetic wounds compared with control wounds. We analysed the differential expression of TLR7 and TLR9 both at transcriptional and translational levels in wounds of 84 patients with type 2 diabetes mellitus (T2DM) and 6 control subjects without diabetes using quantitative real-time polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. TLR7 and TLR9 were significantly up-regulated in wounds of the patients with T2DM compared with the controls and were dependent on the infection status of the diabetic wounds, and wounds with microbial infection exhibited lower expression levels of endosomal TLRs. Altered endosomal TLR expression in T2DM subjects might be associated with wound healing impairment. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  14. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    Science.gov (United States)

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic PreconditioningCraig...

  15. THE MOTIF OF THE PRODIGAL SON IN IVAN TURGENEV'S NOVELS

    Directory of Open Access Journals (Sweden)

    Valentina Ivanovna Gabdullina

    2013-11-01

    Full Text Available The author questions the perception of Ivan Turgenev as a “non- Christian writer” and studies the problem of the prodigal son motif functioning in a series of his novels. In his novels, Turgenev pictured different phases of the archetypal story, originating from the Gospel parable of the prodigal son. In the novel Rudin he depicted the phase of spiritual wanderings of the hero who had lost touch with his native land — Russia. In his next novels (Home of the Gentry, Fathers and Sons and Smoke, after leading his hero in circles and sending him back to his paternal home, Turgenev reconstructs the model of human behavior, represented in the parable, thereby recognizing the immutability of the idea formalized in the Gospel. The motif of the return to Russian land gets its completion in Turgenev's last novel Virgin Soil, in which the author paradoxically connects the Westernist idea with the Gospel imperative. Solomin, the son of a deacon, sent by his wise father out to Europe “to get education”, studies in England, masters the European knowledge and returns back “to his native land” to establish his own business in inland Russia. Thus, a series of Turgenev's novels, in which he portrayed different phases of social life, are interlinked with the motif of the prodigal son, who is represented by novels' main characters.

  16. Herpesvirus telomerase RNA (vTR with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis.

    Directory of Open Access Journals (Sweden)

    Benedikt B Kaufer

    2011-10-01

    Full Text Available Telomerase reverse transcriptase (TERT and telomerase RNA (TR represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5 by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1 that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2 that this strategy could be used to generate novel vaccine candidates

  17. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

    International Nuclear Information System (INIS)

    Santra, Amal; Chowdhury, Abhijit; Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna

    2007-01-01

    Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects

  18. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    Directory of Open Access Journals (Sweden)

    Stephanie Puukila

    Full Text Available Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG, a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  19. Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.

    Science.gov (United States)

    Minemoto, Yuzuru; Uchida, Sanae; Ohtsubo, Motoaki; Shimura, Mari; Sasagawa, Toshiyuki; Hirata, Masato; Nakagama, Hitoshi; Ishizaka, Yukihito; Yamashita, Katsumi

    2003-04-01

    Most cell lines that lack functional p53 protein are arrested in the G2 phase of the cell cycle due to DNA damage. When the G2 checkpoint is abrogated, these cells are forced into mitotic catastrophe. A549 lung adenocarcinoma cells, in which p53 was eliminated with the HPV16 E6 gene, exhibited efficient arrest in the G2 phase when treated with adriamycin. Administration of caffeine to G2-arrested cells induced a drastic change in cell phenotype, the nature of which depended on the status of p53. Flow cytometric and microscopic observations revealed that cells that either contained or lacked p53 resumed their cell cycles and entered mitosis upon caffeine treatment. However, transit to the M phase was slower in p53-negative cells than in p53-positive cells. Consistent with these observations, CDK1 activity was maintained at high levels, along with stable cyclin B1, in p53-negative cells. The addition of butyrolactone I, which is an inhibitor of CDK1 and CDK2, to the p53-negative cells reduced the floating round cell population and induced the disappearance of cyclin B1. These results suggest a relationship between the p53 pathway and the ubiquitin-mediated degradation of mitotic cyclins and possible cross-talk between the G2-DNA damage checkpoint and the mitotic checkpoint.

  20. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin

    International Nuclear Information System (INIS)

    Chang, Seung-Hee; Minai-Tehrani, Arash; Shin, Ji-Young

    2012-01-01

    Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy. (author)

  1. Types of sons/siblings, fraternal function and peers

    Directory of Open Access Journals (Sweden)

    Luisa Brunori

    2013-12-01

    Full Text Available In this article, the author starts by exploring family dynamics using the psychodynamic-groupanalytic paradigm to explore the intertwined relationships amongst the family figures like son, daughter, parents and sibling. The work focuses on the analysis of the psychological aspects related to siblings in the family, birth order and their consequences.

  2. Understanding Motherhood as Maturation: Maternity Scripts in Lois Lowry's "Son"

    Science.gov (United States)

    Deszcz-Tryhubczak, Justyna; Marecki, Mateusz

    2015-01-01

    When put together with the other parts of The Giver Quartet, "Son" (2012), Lowry's recently published concluding book, emerges as an odd exception to the focus on young adult protagonists since it foregrounds the mother's perspective and addresses the issue of motherhood. It presents the reader with at least three conceptual models of…

  3. Supersymmetric vector multiplets in nonadjoint representations of SO(N)

    International Nuclear Information System (INIS)

    Nishino, Hitoshi; Rajpoot, Subhash

    2007-01-01

    In the conventional formulation of N=1 supersymmetry, a vector multiplet is supposed to be in the adjoint representation of a given gauge group. We present a new formulation with a vector multiplet in the nonadjoint representation of SO(N) gauge group. Our basic algebra is [T I ,T J ]=f IJK T K , [T I ,U i ]=-(T I ) ij U j , [U i ,U j ]=-(T I ) ij T I , where T I are the generators of SO(N), while U i are the new ''generators'' in certain nonadjoint real representation R of SO(N). We use here the word generator in the broader sense of the word. Such a representation can be any real representation of SO(N) with the positive definite metric, satisfying (T I ) ij =-(T I ) ji and (T I ) [ij| (T I ) |k]l ≡0. The first nontrivial examples are the spinorial 8 S and conjugate spinorial 8 C representations of SO(8) consistent with supersymmetry. We further couple the system to chiral multiplets and show that a Higgs mechanism can give positive definite (mass) 2 to the new gauge fields for U i . We show an analogous system working with N=1 supersymmetry in 10D, and thereby N=4 system in 4D interacting with extra multiplets in the representation R. We also perform superspace reformulation as an independent confirmation

  4. A case of aneurysmal bone cyst in father and son

    International Nuclear Information System (INIS)

    Leithner, A.; Windhager, R.; Kainberger, F.; Lang, S.

    1998-01-01

    The authors report a familial case of primary aneurysmal bone cyst in father and son, affecting both at the same location at nearly the same age. This fact again raises the speculation of a genetic link as another factor in the pathogenesis of aneurysmal bone cyst

  5. La croissance demographique et son impact sur le developpement ...

    African Journals Online (AJOL)

    La croissance demographique et son impact sur le developpement des grandes villes au ... La ville de Porto-Novo au Bénin n'est pas en marge de cette réalité que ... and the need for improving its framework of life through its development.

  6. ¿Son los obreros idiotas e irracionales?

    Directory of Open Access Journals (Sweden)

    Francisco José León

    2010-01-01

    Full Text Available En este artículo presentamos un análisis crítico de la aproximación posmoderna y posestructuralista a la cuestión de la subjetividad obrera. El examen evidencia que: a algunas de sus proposiciones explicativas son internamente contradictorias o lógicamente inconsistentes; b en otras ocasiones la contradicción se produce entre las distintas proposiciones que la teoría ofrece para explicar un mismo fenómeno; c son frecuentes las contradicciones entre las proposiciones explicativas y los principios teóricos de los que se derivan; d es común la falta de inteligibilidad de las proposiciones; e abundan los "agujeros negros" en las cadenas de acontecimientos que se presentan como previos a la producción del efecto que pretenden explicar, y f muchas de sus proposiciones o bien no son plausibles empíricamente o simplemente no son empíricamente testables. Atribuimos a estas deficiencias la responsabilidad del fracaso de los autores posmodernos en su intento por recuperar la agencia obrera en los estudios del proceso de trabajo.

  7. SO(N) reformulated link invariants from topological strings

    International Nuclear Information System (INIS)

    Borhade, Pravina; Ramadevi, P.

    2005-01-01

    Large N duality conjecture between U(N) Chern-Simons gauge theory on S 3 and A-model topological string theory on the resolved conifold was verified at the level of partition function and Wilson loop observables. As a consequence, the conjectured form for the expectation value of the topological operators in A-model string theory led to a reformulation of link invariants in U(N) Chern-Simons theory giving new polynomial invariants whose integer coefficients could be given a topological meaning. We show that the A-model topological operator involving SO(N) holonomy leads to a reformulation of link invariants in SO(N) Chern-Simons theory. Surprisingly, the SO(N) reformulated invariants also has a similar form with integer coefficients. The topological meaning of the integer coefficients needs to be explored from the duality conjecture relating SO(N) Chern-Simons theory to A-model closed string theory on orientifold of the resolved conifold background

  8. The Transmission of Parenting from Fathers to Sons

    Science.gov (United States)

    Hofferth, Sandra L.; Pleck, Joseph H.; Vesely, Colleen K.

    2012-01-01

    SYNOPSIS Objective We address the extent to which parenting practices of fathers and mothers are associated with their sons’ parenting behaviors as young adults and whether adolescent behavior explains this association. Design Data come from 409 young men interviewed in the 2006 Young Adult study of the 1979 National Longitudinal Survey of Youth. Results Men whose fathers were positively involved with them when growing up report more positive parenting of their own children, a direct effect. Less harsh mothering and more positive fathering are associated with reduced adolescent behavior problems, and positive mothering is associated with positive adjustment of these young men as adolescents. However, neither adolescent problem behavior nor positive adjustment is associated with young men’s fathering of their own children, and thus does not explain the association between the fathering young men received and their own fathering behavior. Conclusions Men’s parenting of their sons can have a long-term direct effect on how their sons parent their own children. Although parenting is associated with both positive and negative behaviors of sons during adolescence, these adolescent behaviors are not directly linked to later parenting behavior when sons have their own children. More research is needed to examine mediation mechanisms for the intergenerational transmission of parenting. PMID:23284271

  9. Major ion chemistry of the Son River, India: Weathering processes ...

    Indian Academy of Sciences (India)

    solute flux and CDR values. The water chemistry indicates that the Son River water is good to excellent .... to separate suspended sediments and preserved at. 4◦C for further ...... and waste water, 20th edn; American Public Health. Association ...

  10. Major ion chemistry of the Son River, India: Weathering processes ...

    Indian Academy of Sciences (India)

    Major ion chemistry of the Son River, India: Weathering processes, dissolved fluxes and water quality assessment. Chinmaya Maharana, Sandeep Kumar Gautam,. Abhay Kumar Singh and Jayant K Tripathi. J. Earth Syst. Sci. 124(6) cO Indian Academy of Sciences. Supplementary data ...

  11. Major ion chemistry of the Son River, India

    Indian Academy of Sciences (India)

    The chemistry of major ions in the surface water of the Son River was studied in detail to determine various source(s) and processes controlling its water chemistry, seasonal and spatial variations in water chemistry, dissolved fluxes and chemical denudation rate (CDR). The study shows that Ca2+, Mg2+ and HCO 3 − are ...

  12. Reproductive Rights and Son Preference in India : Mobilizing ...

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

    This project is concerned with two overlapping manifestations of gender inequality in India : limited access to reproductive rights on the one hand, and practices associated with son preference on the other. Work that brings together these two issues is urgently needed, particularly in the context of declining funding for ...

  13. Benefits of Self-Organizing Networks (SON for Mobile Operators

    Directory of Open Access Journals (Sweden)

    Olav Østerbø

    2012-01-01

    Full Text Available Self-Organizing Networks (SON is a collection of functions for automatic configuration, optimization, diagnostisation and healing of cellular networks. It is considered to be a necessity in future mobile networks and operations due to the increased cost pressure. The main drivers are essentially to reduce CAPEX and OPEX, which would otherwise increase dramatically due to increased number of network parameters that has to be monitored and set, the rapidly increasing numbers of base stations in the network and parallel operation of 2G, 3G and Evolved Packet Core (EPC infrastructures. This paper presents evaluations on the use of some of the most important SON components. Mobile networks are getting more complex to configure, optimize and maintain. Many SON functions will give cost savings and performance benefits from the very beginning of a network deployment and these should be prioritized now. But even if many functions are already available and can give large benefits, the field is still in its infancy and more advanced functions are either not yet implemented or have immature implementations. It is therefore necessary to have a strategy for how and when different SON functions should be introduced in mobile networks.

  14. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

    2014-08-15

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

  15. Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer

    International Nuclear Information System (INIS)

    Choi, Yoon Pyo; Kim, Baek Gil; Gao, Ming-Qing; Kang, Suki; Cho, Nam Hoon

    2012-01-01

    Highlights: ► The potential of targeting ILK and integrins for highly aggressive ovarian cancer. ► Unanticipated synergistic effect for the combination of ILK/β4 integrin. ► Combination of ILK/β4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. ► Targeting of β4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  16. Targeting ILK and {beta}4 integrin abrogates the invasive potential of ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Pyo; Kim, Baek Gil [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Gao, Ming-Qing; Kang, Suki [Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Nam Hoon, E-mail: cho1988@yuhs.ac [BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.

  17. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

    Science.gov (United States)

    Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

    2014-12-24

    TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

  18. Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab.

    Directory of Open Access Journals (Sweden)

    Chaonan Sun

    Full Text Available The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER homeostatic state and result in ER stress (ERS, subsequently causing resistance to radiation and drugs. Whether the ERS pathway is involved in radioresistance after administration of cetuximab has not been reported. Herein, we show that cetuximab could increase the radiosensitivity of FaDu cells but not Detroit562 cells. In addition, cetuximab inhibited the radiation-induced activation of the ERS signalling pathway IRE1α/ATF6-GRP78 in FaDu cells, while this effect was absent in Detroit562 cells. Silencing GRP78 increased the radiosensitivity of oropharyngeal carcinoma cells and inhibited radiation-induced DNA double-strand-break (DSB repair and autophagy. More interestingly, silencing GRP78 abrogated resistance to cetuximab and radiation in Detroit562 cells and had a synergistic effect with cetuximab in increasing the radiosensitivity of FaDu cells. Immunohistochemistry showed that overexpression of both GRP78 and EGFR was associated with a poor prognosis in oropharyngeal carcinoma patients (P<0.05. Overall, the results of this study show that radioresistance after EGFR inhibition by cetuximab is mediated by the ERS signalling pathway IRE1α/ATF6-GRP78. This suppression was consequently unable to inhibit radiation-induced DSB repair and autophagy in oropharyngeal carcinoma cells, which conferred resistance to radiotherapy and cetuximab. These results suggest that the cooperative effects of radiotherapy and cetuximab could be further improved by inhibiting GRP78 in non-responsive oropharyngeal carcinoma patients.

  19. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2014-01-01

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway

  20. Selective induction of cyclin B protein abrogates the G2 delay after irradiation

    International Nuclear Information System (INIS)

    Kao, G.; Muschel, R.J.; Maity, A.; Kunig, A.; McKenna, W.G.

    1996-01-01

    Purpose/Objective: Irradiation of tumor cells commonly results in G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is also often marked in some cell lines by delayed expression of cyclin B protein, suggesting a role for cyclin B regulation. Investigations of these hypotheses however has been hampered by the inability to selectively perturb the G2 delay in a physiologic manner. Materials and Methods: We have devised a system, with which we are able to selectively induce cyclin B protein expression in vivo at specific points in the cell cycle, by transfecting Hela cells with an expression vector under control of a dexamethasone-inducible promoter. Experiments were subsequently performed by synchronizing, releasing, irradiating, inducing, and harvesting these cells through the cell cycle. Results: Irradiation with 5 Gy led to a pronounced G2 delay, reflected by markedly slowed progression into mitosis, concomitant with reduced expression of cyclin B protein. Induction of cyclin B after radiation in these cells abrogated the G2 delay by approximately doubling the rate at which the cells re-enter mitosis. Treatment of irradiated untransfected control cells with dexamethasone, in which cyclin B is not induced, led to minimal changes. Studies of effects of cyclin B induction on cyclin B localization (using immunofluorescence), cdc2 phosphorylation and activation will also be presented. Conclusion: This system should allow further investigations into fundamental mechanisms of cell cycle regulation after irradiation and DNA damage. This also provides direct evidence for the first time that cyclin B protein regulation may play a role in the G2 delay following irradiation in Hela cells, perhaps complementing phosphorylation events

  1. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways

    International Nuclear Information System (INIS)

    Oommen, Deepu; Prise, Kevin M.

    2012-01-01

    Highlights: ► KNK437, a benzylidene lactam compound, is a novel radiosensitizer. ► KNK437 inhibits AKT signaling and abrogates the accumulation of HIF-1α under hypoxia. ► KNK437 abrogates hypoxia induced resistance to radiation. -- Abstract: KNK437 is a benzylidene lactam compound known to inhibit stress-induced synthesis of heat shock proteins (HSPs). HSPs promote radioresistance and play a major role in stabilizing hypoxia inducible factor-1α (HIF-1α). HIF-1α is widely responsible for tumor resistance to radiation under hypoxic conditions. We hypothesized that KNK437 sensitizes cancer cells to radiation and overrides hypoxia-induced radioresistance via destabilizing HIF-1α. Treatment of human cancer cells MDA-MB-231 and T98G with KNK437 sensitized them to ionizing radiation (IR). Surprisingly, IR did not induce HSPs in these cell lines. As hypothesized, KNK437 abrogated the accumulation of HIF-1α in hypoxic cells. However, there was no induction of HSPs under hypoxic conditions. Moreover, the proteosome inhibitor MG132 did not restore HIF-1α levels in KNK437-treated cells. This suggested that the absence of HIF-1α in hypoxic cells was not due to the enhanced protein degradation. HIF-1α is mainly regulated at the level of post-transcription and AKT is known to modulate the translation of HIF-1α mRNA. Interestingly, pre-treatment of cells with KNK437 inhibited AKT signaling. Furthermore, down regulation of AKT by siRNA abrogated HIF-1α levels under hypoxia. Interestingly, KNK437 reduced cell survival in hypoxic conditions and inhibited hypoxia-induced resistance to radiation. Taken together, these data suggest that KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways.

  2. 'SON-GO-KU' : a dream of automated library

    Science.gov (United States)

    Sato, Mamoru; Kishimoto, Juji

    In the process of automating libraries, the retrieval of books through the browsing of shelves is being overlooked. The telematic library is a document based DBMS which can deliver the content of books by simulating the browsing process. The retrieval actually simulates the process a person would use in selecting a book in a real library, where a visual presentation using a graphic display is substituted. The characteristics of prototype system "Son-Go-Ku" for such retrieval implemented in 1988 are mentioned.

  3. Integrating Equality - Globalization, Women's Rights, Son Preference and Human Trafficking

    OpenAIRE

    Cho, Seo-Young

    2011-01-01

    Employing economic and social globalization indicators, we empirically analyze whether globalization affects women’s rights in the economic and social dimensions. Using panel data from 150 countries over the 1981-2008 period, we find that social globalization positively affects both women’s economic and social rights, while the impact of economic globalization disappears when controlling for social globalization. Furthermore, we find that social globalization also reduces ‘son preference’ pro...

  4. Por qué todas las cuentas son falsas

    OpenAIRE

    Aerde, Michel van

    1994-01-01

    Los principales criterios para evaluación y decisión, en la sociedad actual, son inspirados por cálculos económicos. Mucho nos preocupamos de cuentas pero muy poco nos preguntamos de lo que es el dinero. Muy poco reflexionamos filosóficamente, ontológicamente, sobre la naturaleza misma del dinero. ¿Qué es esto que pretende ser la base de nuestra sociedad? El dinero es mentiroso por naturaleza. Es una representación de mucha vida, que no puede ser representada. El dinero es peligroso, se convi...

  5. Cryptorchidism and hypospadias in sons of gardeners and farmers

    DEFF Research Database (Denmark)

    Weidner, I S; Møller, H; Jensen, Tina Kold

    1998-01-01

    Cryptorchidism and hypospadias have been related to prenatal estrogen exposure in animal models. Some chemicals used in farming and gardening have been shown to possess estrogenic and other hormone-disrupting effects. Earlier studies have indicated increased risks of urogenital malformations...... in the sons of pesticide appliers. In the present study, parental occupation in the farming and gardening industry among 6,177 cases of cryptorchidism, 1,345 cases of hypospadias, and 23,273 controls, born live from 1983 to 1992 in Denmark, was investigated in a register-based case-control study...... of female gardeners could suggest an association with prenatal exposure to occupationally related chemicals....

  6. Like father, like son: the intergenerational cycle of adolescent fatherhood.

    Science.gov (United States)

    Sipsma, Heather; Biello, Katie Brooks; Cole-Lewis, Heather; Kershaw, Trace

    2010-03-01

    Strong evidence exists to support an intergenerational cycle of adolescent fatherhood, yet such a cycle has not been studied. We examined whether paternal adolescent fatherhood (i.e., father of study participant was age 19 years or younger when his first child was born) and other factors derived from the ecological systems theory predicted participant adolescent fatherhood. Data included 1496 young males who were interviewed annually from the National Longitudinal Survey of Youth 1997. Cox regression survival analysis was used to determine the effect of paternal adolescent fatherhood on participant adolescent fatherhood. Sons of adolescent fathers were 1.8 times more likely to become adolescent fathers than were sons of older fathers, after other risk factors were accounted for. Additionally, factors from each ecological domain-individual (delinquency), family (maternal education), peer (early adolescent dating), and environment (race/ethnicity, physical risk environment)-were independent predictors of adolescent fatherhood. These findings support the need for pregnancy prevention interventions specifically designed for young males who may be at high risk for continuing this cycle. Interventions that address multiple levels of risk will likely be most successful at reducing pregnancies among partners of young men.

  7. Sexy sons: a dead end for cytoplasmic genes.

    Science.gov (United States)

    Zeh, Jeanne A

    2004-08-07

    Critics of sexual conflict theory argue that females may gain a net reproductive benefit from mating with manipulative males because the direct costs that they suffer may be offset by the production of sexy, i.e. manipulative, sons. However, this exclusive focus on nuclear gene effects represents an incomplete view of female fitness. Females differ fundamentally from males in transmitting not only nuclear genes but also a wide range of cytoplasmic genetic elements (CGEs) that can have profound effects, from male killing to influencing development of the nervous system and cognitive ability. Maternal transmission of CGEs has two major implications for sexual selection. First, the evolution of male fitness traits, such as sperm competitive ability, may be constrained because response to selection on mitochondrial genomes can occur only through the female line. Second, CGEs bear the direct costs of male manipulation but gain no indirect benefits when females produce sexy sons. This should result in perpetual antagonistic coevolution between nuclear genes involved in male manipulation and CGEs that promote female resistance to male sexually selected traits. Explicit consideration of the consequences of selection acting on CGEs is therefore necessary for a better understanding of the relationship between sexual selection and sexual conflict.

  8. Artonin E and Structural Analogs from Artocarpus Species Abrogates Estrogen Receptor Signaling in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Imaobong Etti

    2016-06-01

    Full Text Available The increasing rate of mortality ensued from breast cancer has encouraged research into safer and efficient therapy. The human Estrogen receptor α has been implicated in the majority of reported breast cancer cases. Molecular docking employing Glide, Schrodinger suite 2015, was used to study the binding affinities of small molecules from the Artocarpus species after their drug-like properties were ascertained. The structure of the ligand-binding domain of human Estrogen receptor α was retrieved from Protein Data Bank while the structures of compounds were collected from PubChem database. The binding interactions of the studied compounds were reported as well as their glide scores. The best glide scored ligand, was Artonin E with a score of −12.72 Kcal when compared to other studied phytomolecules and it evoked growth inhibition of an estrogen receptor positive breast cancer cells in submicromolar concentration (3.8–6.9 µM in comparison to a reference standard Tamoxifen (18.9–24.1 µM within the tested time point (24–72 h. The studied ligands, which had good interactions with the target receptor, were also drug-like when compared with 95% of orally available drugs with the exception of Artoelastin, whose predicted physicochemical properties rendered it less drug-like. The in silico physicochemical properties, docking interactions and growth inhibition of the best glide scorer are indications of the anti-breast cancer relevance of the studied molecules.

  9. Meaning of becoming mother and son/daughter through massage

    Directory of Open Access Journals (Sweden)

    Francisca Márquez Doren

    2014-06-01

    Full Text Available Objective: Revealing the experience of mothers when massaging their children to know the phenomenon in the context of a mother-child healthy development. Method: This is a qualitative study with a phenomenological approach carried out with 11 women who massaged their children and answered the guiding question: What did the experience of massaging your child mean to you? Results: The experience of massaging their children meant the development of their being a mother and of being a son/daughter, in addition to developing the attachment relationship between them. The massage can operationalize this integrality, become a tool of communication, stimulation and promotion of secure attachment, by promoting the loving interaction between mother and child. Conclusion: This practice should be considered as an option in the programs that promote the comprehensive health of the mother and child.

  10. Transgenerational effects of nutrition are different for sons and daughters.

    Science.gov (United States)

    Zizzari, Z V; van Straalen, N M; Ellers, J

    2016-07-01

    Food shortage is an important selective factor shaping animal life-history trajectories. Yet, despite its role, many aspects of the interaction between parental and offspring food environments remain unclear. In this study, we measured developmental plasticity in response to food availability over two generations and tested the relative contribution of paternal and maternal food availability to the performance of offspring reared under matched and mismatched food environments. We applied a cross-generational split-brood design using the springtail Orchesella cincta, which is found in the litter layer of temperate forests. The results show adverse effects of food limitation on several life-history traits and reproductive performance of both parental sexes. Food conditions of both parents contributed to the offspring phenotypic variation, providing evidence for transgenerational effects of diet. Parental diet influenced sons' age at maturity and daughters' weight at maturity. Specifically, being born to food-restricted parents allowed offspring to alleviate the adverse effects of food limitation, without reducing their performance under well-fed conditions. Thus, parents raised on a poor diet primed their offspring for a more efficient resource use. However, a mismatch between maternal and offspring food environments generated sex-specific adverse effects: female offspring born to well-fed mothers showed a decreased flexibility to deal with low-food conditions. Notably, these maternal effects of food availability were not observed in the sons. Finally, we found that the relationship between age and size at maturity differed between males and females and showed that offspring life-history strategies in O. cincta are primed differently by the parents. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  11. Les Ilenti ou maudire son prochain en turc

    Directory of Open Access Journals (Sweden)

    Altan Gokalp

    2009-05-01

    Full Text Available La langue turque contemporaine dispopse d’un nombre important de formules d’invective et de malédiction qui relèvent d’un genre appelé ilenç ou ilenti, forme qui est connue depuis les premières inscriptions turques runiques de la Haute Asie. Bien que l’islam réprouve le fait de maudire son prochain, le genre issu d’une grande tradition turque ancienne est d’un usage commun chez les Turcs. Plus encore, la manière de maudire relève d’une tradition savante, d’un « Grand Parler » qui s’apparente aux genres littéraires les plus classiques comme l’épopée, le conte ou la poésie lyrique : la métrique, les rimes, l’usage des assonances obéissent aux mêmes règles que la grande tradition littéraire turque. En cela, le fait d’user de l’invective et de la malédiction est d’une certaine manière une prétention à la distinction et à la domination de l’autre. Les cibles de l’invective éclairent bien cette volonté de dominer et de détruire son ennemi (le corps, la famille, la maladie, une mort peu digne, etc..

  12. Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2011-01-01

    Full Text Available Abstract Background The surface glycoprotein (SU, gp120 of the human immunodeficiency virus (HIV must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP to bind the Duffy Antigen Receptor for Chemokines (DARC and invade reticulocytes. Results Variable loop 3 (V3 of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins. Conclusion A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.

  13. BAKUNIN'S SON, A DIALOGIC NOVEL BY SERGIO ATZENI

    Directory of Open Access Journals (Sweden)

    Masina Depperu (Universidade de Lisboa

    2013-10-01

    Full Text Available Bakunin’s Son, a short novel by Sergio Atzeni, is the perfect embodiment of Bakhtin’s theory of the dialogic novel. The author sets his stories and characters - mostly humble outcast defeated people - in his own homeland, Sardinia. The accurately planned structure as an interview to thirty-two people reflects a multifarious reality with its complex rules and mentality expressed through different points of view, languages and ideologies. The protagonist’s story may result contradictory according to the different opinions of people who met him. Also the choice of a hybrid language contributes to create a highly connoted cultural context. In Bakunin’s Son, in fact, the Italian and the Sardinian overlap in a manner that cannot be distinguished or graphically marked, since form and meaning are fused together.Key words: dialogic novel, hybrid language.O filho de Bakunin, um romance polifónico de Sergio AtzeniO romance breve de Sergio Atzeni, O filho de Bakunin, è a perfeita exemplificação da teoria bachtininana do romance polifónico. O autor insere as histórias e as persona gens, geralmente abatidas, pessoas humildes e marginalizadas, na sua terra natal, a Sardenha. A história è estruturada na forma de entrevista a trinta e duas persona gens que com os seus pontos de vista criam una realidade multi-facetada e subjectiva. A vida de Tullio Saba, o protagonista, está narrada às vezes em modo contraditório e, por isso, os factos podem ser divergentes nas opiniões de quem esteve mais ou menos em contacto directo com ele. O uso característico de um instrumento linguístico híbrido, a meio caminho entre o italiano e o sardo, conota não somente o léxico mas também a estruturação inteira do discurso que atinge o efeito final pretendido pelo autor de descrever uma diversa ealidade antropológico-cultural.Palavras chave: romance polifónico, instrumento linguístico híbrido

  14. The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints

    International Nuclear Information System (INIS)

    Zhang Weifang; Li Jing; Kanginakudru, Sriramana; Zhao Weiming; Yu Xiuping; Chen, Jason J.

    2010-01-01

    HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.

  15. Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom.

    Science.gov (United States)

    Arias, Ana Silvia; Rucavado, Alexandra; Gutiérrez, José María

    2017-06-15

    The ability of two peptidomimetic hydroxamate metalloproteinase inhibitors, Batimastat and Marimastat, to abrogate toxic and proteinase activities of the venom of Echis ocellatus from Cameroon and Ghana was assessed. Since this venom largely relies for its toxicity on the action of zinc-dependent metalloproteinases (SVMPs), the hypothesis was raised that toxicity could be largely eliminated by using SVMP inhibitors. Both hydroxamate molecules inhibited local and pulmonary hemorrhagic, in vitro coagulant, defibrinogenating, and proteinase activities of the venoms in conditions in which venom and inhibitors were incubated prior to the test. In addition, the inhibitors prolonged the time of death of mice receiving 4 LD 50 s of venom by the intravenous route. Lower values of IC 50 were observed for in vitro and local hemorrhagic activities than for systemic effects. When experiments were performed in conditions that simulated the actual circumstances of snakebite, i.e. by administering the inhibitor after envenoming, Batimastat completely abrogated local hemorrhage if injected immediately after venom. Moreover, it was also effective at inhibiting lethality and defibrinogenation when venom and inhibitor were injected by the intraperitoneal route. Results suggest that these, and possibly other, metalloproteinase inhibitors may become an effective adjunct therapy in envenomings by E. ocellatus when administered at the anatomic site of venom injection rapidly after the bite. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Dietary chlorophyllin abrogates TGFβ signaling to modulate the hallmark capabilities of cancer in an animal model of forestomach carcinogenesis.

    Science.gov (United States)

    Thiyagarajan, Paranthaman; Kavitha, Krishnamurthy; Thautam, Avaneesh; Dixit, Madhulika; Nagini, Siddavaram

    2014-07-01

    Transforming growth factor (TGF) β signaling pathway plays a central role in the regulation of a wide range of cellular processes involved in the acquisition of the malignant phenotype. The objective of the present study was to examine the effect of chlorophyllin, a semisynthetic derivative of chlorophyll on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)--induced rat forestomach carcinogenesis based on the modulation of TGFβ signaling and the downstream target genes associated with cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis. We determined the effect of dietary chlorophyllin on TGFβ signaling and the downstream events-cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis by semiquantitative and quantitative reverse transcription (RT)-PCR, Western blot, and immunohistochemical analyses. We further validated the inhibition of TGFβ signaling by chlorophyllin by performing molecular docking studies. We found that dietary supplementation of chlorophyllin at 4-mg/kg bw inhibits the development of MNNG-induced forestomach carcinomas by downregulating the expression of TGFβ RI, TGFβ RII, and Smad 2 and 4 and upregulating Smad 7, thereby abrogating canonical TGFβ signaling. Docking interactions also confirmed the inhibition of TGFβ signaling by chlorophyllin via inactivating TGFβ RI. Furthermore, attenuation of TGFβ signaling by chlorophyllin also blocked cell proliferation, angiogenesis, invasion, and metastasis, and induced mitochondria-mediated cell death. Dietary chlorophyllin that simultaneously abrogates TGFβ signaling pathway and the key hallmark events of cancer appear to be an ideal candidate for cancer chemoprevention.

  17. The global tantalum industry and Sons of Gwalia Ltd

    International Nuclear Information System (INIS)

    Paull, D.

    2002-01-01

    Sons of Gwalia Ltd., in Perth Australia is a long-term supplier of tantalum (Ta), a valuable rare metal with adequate supply. Tantalum is soft and ductile with high melting and boiling points and a low co-efficient of thermal expansion. It has excellent capacity to store and release electrical charge and offers exceptional resistance to corrosion. Its' main use is in consumer electronics such as mobile phones, laptop computers, DVD players, personal video recorders and MP-3 players. For automotive electronics, tantalum is used for air-bags, audio systems, navigation systems, anti-lock break systems and under the hood vehicle management systems. The super alloy is also in demand by the aerospace industry and for turbine blades for power stations. The total demand of Tantalum in 2000 was 5 million lbs. Demand growth has increased steadily since 1993 with perhaps a slight increase in the past 5 years. Resources are estimated at a 125 year supply based on year 2000 production rates. 41 per cent of the world supply of tantalum is obtained from Australia, 13 per cent from Africa, 16 per cent from America, 22 per cent from Asia. The Greenbushes mine in Australia is the world's largest tantalum mine with 80 million lbs Ta, followed by Australia's Wodgina Mine with 50 million lbs Ta. Both mines are expected to be operational for the next 25 years. 12 figs

  18. Jean Alesi and his son Giuliano visited CERN

    CERN Multimedia

    Emma Jones

    2010-01-01

    Jean Alesi, former F1 racing driver, and his kids visited CERN on Monday 1st February 2010. The Bulletin and the Video productions team had the opportunity to meet him. The video interview is transcribed for your convenience. What attracted you to CERN, what was it that made you want to come? We talked at home with the children about places to see close to us, like CERN, where they are seeking to reproduce the origins of the world. These things are so far removed from what we ordinarily think and talk about, that they captured our imagination and made us want to come see for ourselves. We know that your son (Giuliano, 9 years) is interested in what is happening at CERN, so we'd like to ask him: how did he find out about it? Giuliano: I am very interested in the technologies used in laboratories, and the exploration of the Universe. Plus, I wanted to see some of the incredible machines. I enjoyed my visit a lot. I found out about CERN from my mother. She showed me a video that I really liked, so I wanted to...

  19. ¿Son las mujeres una minoría?

    Directory of Open Access Journals (Sweden)

    Osborne, Raquel

    1996-10-01

    Full Text Available Not available.

    El clásico tratamiento de las mujeres como minoría desde la sociología se halla contemporáneamente interrelacionado con las políticas de igualdad tejidas en torno a las mujeres. Pasado y presente, teoría y práctica se unen para mostrar que las teorías no son accidentales ni fortuitas sino que acarrean importantes consecuencias en la acción, pudiendo dar lugar a intervenciones en la vida pública, que es lo que, a mi entender, confiere su sentido a la. sociología y, en particular, a la sociología del género. El título alude a la existencia de un importante desarrollo en sociología de la temática de las minorías, que traemos a colación por cuanto desde muy temprano dicha ciencia refirió este tema a las mujeres, desarrollo que seguiremos en este artículo. La conceptualización de las mujeres como minoría se traducirá, en términos de políticas públicas, en lo que se conoce como medidas de acción o discriminación positiva impulsadas, en lo que a las mujeres atañe, por el movimiento feminista.

  20. State supervision of SONS in the mammographic departments

    International Nuclear Information System (INIS)

    Jursikova, E.; Kodl, O.

    2008-01-01

    State Office for Nuclear Safety has been performed the state supervision over radiation protection at all mammographic centres in the Czech Republic. Inspections are carried out on the basis of requirements of: Act No. 18/1997 Coll., Atomic Act, subsequently amended; Act No. 552/1991 Coll., Supervision Act, subsequently amended; Decree No. 307 /2002 Coll., On radiation protection, as amended by Decree No. 499/2005 Coll. 137 mammography X-ray units have been used actively by 108 independent licensees since 1 September 2008. The mammography screening program started in September 2002. The screening program was carried out at 59 working places last year and already at 66 workplaces with accreditation from 1 up to 3 years this year. The activity of the centres is monitored and inspected continuously (not only by SONS). Inspections at 35 workplaces were carried out last year .The doses are significantly below guidance levels at major part of working places. Most of detected defects were eliminated after inspections. The quality of mammographic workplaces in the Czech Republic has been gradually increased and improved. (authors)

  1. Views of Astronaut (Col.) Joe Engle and son Jon with L-5 Piper Cub

    Science.gov (United States)

    1981-01-01

    Views of Astronaut (Col.) Joe Engle and son Jon with L-5 Piper Cub at Clover Airport. Photos include Engle turning propeller while his son sits in the cockpit (34323); both Engle and son examine propeller (34324); Engle works on engine while his son sits in cockpit (34325).

  2. Male-mediated infertility in sons of building painters and gardeners

    DEFF Research Database (Denmark)

    Ramlau-Hansen, C H; Stoltenberg, C D G; Hougaard, K S

    2012-01-01

    To investigate whether sons of gardeners and building painters have increased risk of infertility in comparison with sons of bricklayers, carpenters and electricians.......To investigate whether sons of gardeners and building painters have increased risk of infertility in comparison with sons of bricklayers, carpenters and electricians....

  3. ¿Son los MOOC una alternativa de aprendizaje?

    Directory of Open Access Journals (Sweden)

    Antonio Ramón Bartolomé Pina

    2015-01-01

    Full Text Available Este trabajo reflexiona sobre los MOOC como entornos de aprendizaje. El número de cursos masivos abiertos y en línea (MOOC ha crecido exponencialmente en pocos años desde que fueron introducidos. Los MOOC son considerados una nueva forma de entornos virtuales de aprendizaje potenciados por la tecnología. Se consideran dos tipos de MOOC: unos los organizados por Siemens y Downes (cMOOC y otros los desarrollados en lugares como Stanford, con muchos estudiantes y loables objetivos (xMOOC; estos tienen también sus debilidades. Aunque han sido recibidos con altas expectativas, también han encontrado una fuerte oposición que está aumentando con el tiempo, lo que nos permite estudiar este fenómeno en profundidad. Aunque todavía hay pocas investigaciones empíricas sobre los efectos de los MOOC en el aprendizaje, este estudio trata de arrojar luz sobre el tema desde un punto de vista teórico. En primer lugar exploraremos las expectativas positivas y negativas generadas. Los MOOC pueden constituir una buena propuesta a gran escala, lo que solo es posible para unas pocas grandes instituciones. No hay estudio de mercado, ni modelo de negocio, ni investigaciones empíricas que permitan confirmar los anuncios de sus efectos positivos. Revisaremos las teorías del aprendizaje recientes y clásicas respecto a su capacidad para explicar el proceso de aprendizaje y compararemos los cursos en línea tradicionales, los xMOOC y los cMOOC en relación a su potencial para apoyar el aprendizaje y su auto-regulación.

  4. Increase of CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells.

    Science.gov (United States)

    Kunzmann, Steffen; Krempl, Christine; Seidenspinner, Silvia; Glaser, Kirsten; Speer, Christian P; Fehrholz, Markus

    2018-04-16

    Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase of CTGF mRNA. RSV may be involved in airway remodeling processes by increasing CTGF mRNA expression. Caffeine might abrogate these negative effects and thereby help to restore lung homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice.

    Directory of Open Access Journals (Sweden)

    Lea-Maxie Haag

    Full Text Available BACKGROUND: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. METHODOLOGY/PRINCIPAL FINDINGS: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. CONCLUSION/SIGNIFICANCE: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiota composition towards elevated E. coli loads during intestinal inflammation as well as in infant mice. Intestinal inflammation and microbiota shifts thus represent potential risk factors for C. jejuni infection. Corresponding interplays between C. jejuni and microbiota might

  6. Vorinostat synergizes with ridaforolimus and abrogates the ridaforolimus-induced activation of AKT in synovial sarcoma cells.

    Science.gov (United States)

    Morgan, Sherif S; Cranmer, Lee D

    2014-11-18

    Curative treatments for patients with metastatic synovial sarcoma (SS) do not exist, and such patients have a poor prognosis. We explored combinations of molecularly-targeted and cytotoxic agents to identify synergistic treatment combinations in SS cells. Two SS cell lines (HS-SY-II and SYO-I) were treated with single agents or combinations of molecularly targeted therapies (HDAC inhibitor, vorinostat; mTOR inhibitor, ridaforolimus) and cytotoxic agents. After 72 hours, cell viability was measured using the MTS cell proliferation assay. Combination Indices (CI) were calculated to determine whether each combination was synergistic, additive, or antagonistic. Western Blot analysis assessed alterations in total and phospho-AKT protein levels in response to drug treatment. We determined the single-agent IC50 for ridaforolimus, vorinostat, doxorubicin, and melphalan in HS-SY-II and SYO-I. Synergism was apparent in cells co-treated with ridaforolimus and vorinostat: CI was 0.28 and 0.63 in HS-SY-II and SYO-I, respectively. Ridaforolimus/doxorubicin and ridaforolimus/melphalan exhibited synergism in both cell lines. An additive effect was observed with combination of vorinostat/doxorubicin in both cell lines. Vorinostat/melphalan was synergistic in HS-SY-II and additive in SYO-I. Western blot analysis demonstrated that ridaforolimus increased pAKT-ser473 levels; this effect was abrogated by vorinostat co-treatment. The combination of ridaforolimus and vorinostat demonstrates in vitro synergism in SS. Addition of vorinostat abrogated ridaforolimus-induced AKT activation. Since AKT activation is a possible mechanism of resistance to mTOR inhibitors, adding vorinostat (or another HDAC inhibitor) may be a route to circumvent AKT-mediated resistance to mTOR inhibitors.

  7. An interaction study in mammalian cells demonstrates weak binding of HSPB2 to BAG3, which is regulated by HSPB3 and abrogated by HSPB8

    NARCIS (Netherlands)

    Morelli, Federica F; Mediani, Laura; Heldens, Lonneke; Bertacchini, Jessika; Bigi, Ilaria; Carra, Arianna Dorotea; Vinet, Jonathan; Carra, Serena

    The ten mammalian small heat shock proteins (sHSPs/HSPBs) show a different expression profile, although the majority of them are abundant in skeletal and cardiac muscles. HSPBs form hetero-oligomers and homo-oligomers by interacting together and complexes containing, e.g., HSPB2/HSPB3 or HSPB1/HSPB5

  8. The Power of a Single Mother: The Influence of Black Women on Their Sons' Academic Performance

    Science.gov (United States)

    Robinson, Quintin L.; Werblow, Jacob

    2013-01-01

    This study examines the ways single Black mothers contribute to the educational success of their 11th-grade sons, despite the fact that their sons are enrolled in "failing schools." Data from five interviews and one focus group reveal common characteristics of how single-Black mothers help their sons beat the odds.

  9. Mothers' Predictions of Their Son's Executive Functioning Skills: Relations to Child Behavior Problems

    Science.gov (United States)

    Johnston, Charlotte

    2011-01-01

    This study examined mothers' ability to accurately predict their sons' performance on executive functioning tasks in relation to the child's behavior problems. One-hundred thirteen mothers and their 4-7 year old sons participated. From behind a one-way mirror, mothers watched their sons perform tasks assessing inhibition and planning skills.…

  10. HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice

    International Nuclear Information System (INIS)

    Hanna, Zaher; Priceputu, Elena; Hu, Chunyan; Vincent, Patrick; Jolicoeur, Paul

    2006-01-01

    HIV-1 Nef has the ability to downmodulate CD4 cell surface expression. Several studies have shown that CD4 downregulation is required for efficient virus replication and high infectivity. However, the pathophysiological relevance of this phenomenon in vivo, independently of its role in sustaining high virus loads, remains unclear. We studied the impact of the CD4 downregulation function of Nef on its pathogenesis in vivo, in the absence of viral replication, in the CD4C/HIV transgenic (Tg) mouse model. Two independent Nef mutants (RD35/36AA and D174K), known to abrogate CD4 downregulation, were tested in Tg mice. Flow cytometry analysis showed that downregulation of murine CD4 was severely decreased or abrogated on Tg T cells expressing respectively Nef RD35/36AA and Nef D174K . Similarly, the severe depletion of double-positive CD4 + CD8 + and of single-positive CD4 + CD8 - thymocytes, usually observed with Nef Wt , was not detected in Nef RD35/36AA and Nef D174K Tg mice. However, both mutant Tg mice showed a partial depletion of peripheral CD4 + T cells. This was accompanied, as previously reported for Net Wt Tg mice, by the presence of an activated/memory-like phenotype (CD69 + , CD25 + , CD44 + , CD45RB Low , CD62 Low ) of CD4 + T cells expressing Nef RD35/36AA and to a lesser extent Nef D174K . In addition, both mutants retained the ability to block CD4 + T cell proliferation in vitro after anti-CD3 stimulation, but not to enhance apoptosis/death of CD4 + T cells. Therefore, it appears that Nef-mediated CD4 downregulation is associated with thymic defects, but segregates independently of the activated/memory-like phenotype, of the partial depletion and of the impaired in vitro proliferation of peripheral CD4 + T cells. Histopathological assessment revealed the total absence of or decrease severity and frequency of organ AIDS-like diseases (lung, heart and kidney pathologies) in respectively Nef RD35/36AA and Nef D174K Tg mice, relative to those developing in

  11. De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive.

    Science.gov (United States)

    Tokita, Mari J; Braxton, Alicia A; Shao, Yunru; Lewis, Andrea M; Vincent, Marie; Küry, Sébastien; Besnard, Thomas; Isidor, Bertrand; Latypova, Xénia; Bézieau, Stéphane; Liu, Pengfei; Motter, Connie S; Melver, Catherine Ward; Robin, Nathaniel H; Infante, Elena M; McGuire, Marianne; El-Gharbawy, Areeg; Littlejohn, Rebecca O; McLean, Scott D; Bi, Weimin; Bacino, Carlos A; Lalani, Seema R; Scott, Daryl A; Eng, Christine M; Yang, Yaping; Schaaf, Christian P; Walkiewicz, Magdalena A

    2016-09-01

    SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development. However, the phenotypic effects of deleterious germline variants in SON have not been clearly defined. Herein, we describe seven unrelated individuals with de novo variants in SON and propose that deleterious variants in SON are associated with a severe multisystem disorder characterized by developmental delay, persistent feeding difficulties, and congenital malformations, including brain anomalies. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Point mutations in EBV gH that abrogate or differentially affect B cell and epithelial cell fusion

    International Nuclear Information System (INIS)

    Wu Liguo; Hutt-Fletcher, Lindsey M.

    2007-01-01

    Cell fusion mediated by Epstein-Barr virus requires three conserved glycoproteins, gB and gHgL, but activation is cell type specific. B cell fusion requires interaction between MHC class II and a fourth virus glycoprotein, gp42, which complexes non-covalently with gHgL. Epithelial cell fusion requires interaction between gHgL and a novel epithelial cell coreceptor and is blocked by excess gp42. We show here that gp42 interacts directly with gH and that point mutations in the region of gH recognized by an antibody that differentially inhibits epithelial and B cell fusion significantly impact both the core fusion machinery and cell-specific events. Substitution of alanine for glycine at residue 594 completely abrogates fusion with either B cells or epithelial cells. Substitution of alanine for glutamic acid at residue 595 reduces fusion with epithelial cells, greatly enhances fusion with B cells and allows low levels of B cell fusion even in the absence of gL

  13. Dexamethasone abrogates the antimicrobial and antibiofilm activities of different drugs against clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Aquila Rodrigues

    2017-01-01

    Full Text Available Staphylococcus aureus and Pseudomonas aeruginosa are part of the human microbiota and are also important bacterial pathogens, for which therapeutic options are lacking nowadays. The combined administration of corticosteroids and antimicrobials is commonly used in the treatment of infectious diseases to control inflammatory processes and to minimize potential toxicity of antimicrobials, avoiding sequelae. Although different pharmaceutical dosage forms of antimicrobials combined to corticosteroids are available, studies on the interference of corticosteroids on the pharmacological activity of antimicrobials are scarce and controversial. Here, we provide evidence of the interference of dexamethasone on the pharmacological activity of clinically important antimicrobial drugs against biofilms and planktonic cells of S. aureus and P. aeruginosa. Broth microdilution assays of minimal inhibitory concentration (MIC, minimum bactericidal concentration (MBC, and minimum biofilm eradication concentration (MBEC of gentamicin, chloramphenicol, oxacillin, ceftriaxone and meropenem were conducted with and without the addition of dexamethasone. The effect of all drugs was abrogated by dexamethasone in their MIC, MBC, and MBEC, except gentamicin and meropenem, for which the MBC was not affected in some strains. The present study opens doors for more investigations on in vitro and in vivo effects and safety of the combination of antimicrobials and glucocorticoids.

  14. Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.

    Directory of Open Access Journals (Sweden)

    Damián Pérez-Mazliah

    2015-03-01

    Full Text Available Interleukin-21 signaling is important for germinal center B-cell responses, isotype switching and generation of memory B cells. However, a role for IL-21 in antibody-mediated protection against pathogens has not been demonstrated. Here we show that IL-21 is produced by T follicular helper cells and co-expressed with IFN-γ during an erythrocytic-stage malaria infection of Plasmodium chabaudi in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the chronic phase of P. chabaudi infection and P. yoelii infection resulting in sustained high parasitemias, and are not immune to re-infection. This is associated with abrogated P. chabaudi-specific IgG responses, including memory B cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on B cells is necessary to control chronic P. chabaudi infection. Our data uncover a mechanism by which CD4+ T cells and B cells control parasitemia during chronic erythrocytic-stage malaria through a single gene, Il21, and demonstrate the importance of this cytokine in the control of pathogens by humoral immune responses. These data are highly pertinent for designing malaria vaccines requiring long-lasting protective B-cell responses.

  15. Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation.

    Science.gov (United States)

    Mahmoud, Ayman M

    2014-09-01

    The most important reason for the non-approval and withdrawal of drugs by the Food and Drug Administration is hepatotoxicity. Therefore, this study was undertaken to evaluate the protective effects of hesperidin against cyclophosphamide (CYP)-induced hepatotoxicity in Wistar rats. The rats received a single intraperitoneal dose of CYP of 200 mg/kg body mass, followed by treatment with hesperidin, orally, at doses of 25 and 50 mg/kg for 11 consecutive days. CYP induced hepatic damage, as evidenced by the significantly elevated levels of serum pro-inflammatory cytokines, serum transaminases, liver lipid peroxidation, and nitric oxide. As a consequence, there was reduced glutathione content, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were markedly reduced. In addition, CYP administration induced a considerable downregulation of peroxisome proliferator activated receptor gamma (PPARγ) and upregulation of nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) mRNA expression. Hesperidin, in a dose-dependent manner, rejuvenated the altered markers to an almost normal state. In conclusion, hesperidin showed a potent protective effect against CYP-induced oxidative stress and inflammation leading to hepatotoxicity. The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

  16. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  17. HPV vaccine for teen boys: Dyadic analysis of parents' and sons' beliefs and willingness.

    Science.gov (United States)

    Moss, Jennifer L; Reiter, Paul L; Brewer, Noel T

    2015-09-01

    Parents and adolescents often decide together whether the child should receive human papillomavirus (HPV) vaccine. However, few studies have investigated the dyadic nature of beliefs that affect this process. Data came from the 2010 HPV Immunization in Sons (HIS) Study, a national sample of 412 parents and their adolescent sons. We conducted dyadic multivariate logistic regression to examine the relationships between parents' and sons' HPV vaccine beliefs and their willingness to have the son receive the vaccine. Less than half of parents and sons were willing to have the sons receive HPV vaccine (43% and 29%, respectively). Willing parents and sons anticipated greater regret if the son did not receive HPV vaccine but later contracted an HPV infection (parent odds ratio [OR]=1.72, 95% confidence interval [CI]=1.24-2.40; son OR=1.51, 95% CI=1.04-2.19) (both pCommunication campaigns may be able to target these beliefs to increase parents' and sons' willingness to seek HPV vaccination. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Son Preference and Family Limitation in Pakistan: A Parity- and Contraceptive Method-Specific Analysis.

    Science.gov (United States)

    Channon, Melanie Dawn

    2017-09-01

    Son preference exerts a strong influence over contraceptive and fertility decisions in many South Asian countries. In Pakistan, where fertility remains high and contraceptive use low, research on son preference has been limited. Data from Pakistan Demographic and Health Surveys conducted in 1990-1991, 2006-2007 and 2012-2013 were used to examine potential indicators and outcomes of son preference. Descriptive analyses looked at sex composition preferences of men and women, as well as the sex ratio at last birth. Multivariate logistic regression analyses examined parity progression by birth order, while multinomial logistic regression was used to identify associations between sex composition and use of permanent, temporary and traditional contraceptive methods. Parity progression and choice of contraceptive method are increasingly associated with the sex composition of children. Many respondents wanted at least two sons, though most also wanted at least one daughter. Analyses suggest that the prevalence of modern contraceptive use among parous women would have been 19% higher in 2012-2013 in the absence of son preference. Permanent method use was extremely low among women with no sons and increased significantly with number of sons. The association between number of sons and use of temporary methods was weaker, while son preference had little relationship with traditional method use. The association of son preference with parity progression and modern contraceptive use has become stronger in Pakistan. Continuation of the fertility transition may be difficult unless the degrees of differential stopping behavior and differential contraceptive use decline.

  19. Maternal pre-pregnancy body mass index and pubertal development among sons

    DEFF Research Database (Denmark)

    Hounsgaard, M L; Håkonsen, L B; Vested, A

    2014-01-01

    Maternal overweight and obesity in pregnancy has been associated with earlier age of menarche in daughters as well as reduced semen quality in sons. We aimed at investigating pubertal development in sons born by mothers with a high body mass index (BMI). The study included 2522 sons of mothers...... indicators of pubertal development, results also indicated earlier pubertal development among sons of obese mothers. After excluding sons of underweight mothers in a subanalysis, we observed an inverse trend between maternal pre-pregnancy BMI and age at regular shaving, acne and first nocturnal emission....... In conclusion, maternal pre-pregnant obesity may be related to earlier timing of pubertal milestones among sons. More research, preferably based on prospectively collected information about pubertal development, is needed to draw firm conclusions....

  20. In the Pursuit of Sons: Additional Births or Sex-Selective Abortion in Pakistan?

    Science.gov (United States)

    Zaidi, Batool; Morgan, S Philip

    2016-12-01

    Even though Pakistan is a highly patriarchal society, it has not featured prominently in studies focusing on sex-selective abortion and sex ratios at birth. But with fertility declining and existing strong son preference-Pakistan has one of the highest desired sex ratios in the world-how will Pakistani families respond? In the pursuit of sons, will they have additional children or resort to sex-selective abortions? Or is there evidence that the pursuit of sons is weakening? Using data from three rounds of the demographic and health survey, we show clear evidence of son preference in fertility intentions, patterns of contraceptive use and parity progression ratios. More specifically, we find pervasive evidence that Pakistanis continue childbearing to have a son, to have more than one son and to have at least one daughter. We do not find consistent and convincing evidence that sex ratios at birth (which indicate sex-selective abortion) are increasing.

  1. Allogeneic hematopoietic cell transplantation in first remission abrogates poor outcomes associated with high-risk pediatric acute myeloid leukemia.

    Science.gov (United States)

    Burke, Michael J; Wagner, John E; Cao, Qing; Ustun, Celalettin; Verneris, Michael R

    2013-07-01

    Despite remission rates of approximately 85% for children diagnosed with acute myeloid leukemia (AML), greater than 40% will die from relapsed disease. Patients with poor-risk molecular/cytogenetics and/or inadequate response to up-front therapy are typically considered high-risk (HR) and historically have poor outcomes with chemotherapy alone. We investigated whether allogeneic hematopoietic cell transplantation (allo-HCT) with best available donor in first remission (CR1) would abrogate the poor outcomes associated with HR AML in children and young adults treated with chemotherapy. We reviewed the outcomes of 50 consecutive children and young adults (ages 0 to 30 years) with AML who received a myeloablative allo-HCT between 2001 and 2010. Thirty-six patients (72%) were HR, defined as having FLT3-ITD mutations, 11q23 MLL rearrangements, chromosome 5 or 7 abnormalities, induction failure, and/or having persistent disease. The majority of patients received cyclophosphamide and total body irradiation conditioning, and graft-versus-host-disease (GVHD) prophylaxis was cyclosporine based. Transplantation outcomes for HR patients were compared to standard-risk patients, with no significant differences observed in overall survival (72% versus 78%, P = .72), leukemia-free survival (69% versus 79%, P = .62), relapse (11% versus 7%, P = .71), or treatment-related mortality (17% versus 14%, P = .89). Children and young adults with HR-AML have comparable outcomes to standard-risk patients following allo-HCT in CR1. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Combined inhibition of p38 and Akt signaling pathways abrogates cyclosporine A-mediated pathogenesis of aggressive skin SCCs

    Energy Technology Data Exchange (ETDEWEB)

    Arumugam, Aadithya; Walsh, Stephanie B.; Xu, Jianmin; Afaq, Farrukh [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer p38 and Akt are the crucial molecular targets in the pathogenesis of SCCs in OTRs. Black-Right-Pointing-Pointer Combined inhibition of these targets diminished tumor growth by 90%. Black-Right-Pointing-Pointer Inhibition of these targets act through downregulating mTOR signaling pathway. -- Abstract: Non-melanoma skin cancers (NMSCs) are the most common neoplasm in organ transplant recipients (OTRs). These cancers are more invasive and metastatic as compared to those developed in normal cohorts. Previously, we have shown that immunosuppressive drug, cyclosporine A (CsA) directly alters tumor phenotype of cutaneous squamous cell carcinomas (SCCs) by activating TGF-{beta} and TAK1/TAB1 signaling pathways. Here, we identified novel molecular targets for the therapeutic intervention of these SCCs. We observed that combined blockade of Akt and p38 kinases-dependent signaling pathways in CsA-promoted human epidermoid carcinoma A431 xenograft tumors abrogated their growth by more than 90%. This diminution in tumor growth was accompanied by a significant decrease in proliferation and an increase in apoptosis. The residual tumors following the combined treatment with Akt inhibitor triciribine and p38 inhibitors SB-203580 showed significantly diminished expression of phosphorylated Akt and p38 and these tumors were less invasive and highly differentiated. Diminished tumor invasiveness was associated with the reduced epithelial-mesenchymal transition as ascertained by the enhanced E-cadherin and reduced vimentin and N-cadherin expression. Consistently, these tumors also manifested reduced MMP-2/9. The decreased p-Akt expression was accompanied by a significant reduction in p-mTOR. These data provide first important combinatorial pharmacological approach to block the pathogenesis of CsA-induced highly aggressive cutaneous neoplasm in OTRs.

  3. The institutionalization of Jesus' charismatic authority: "Son of Man" as case study1

    OpenAIRE

    Yolanda Dreyer

    2000-01-01

    This article argues that Jesus used the expression "son of man" not in a titular way, but genetically, meaning "humankind". This use of "son of man" developed into a titular usage in which Jesus is identified with "Son of Man". The study shows that Jesus' use of the expression "son of man" should be understood in the context of the "little tradition" which was reinterpreted in terms of the "great tradition" in a titular way. It is argued that this transition from "litle tradition" to "great t...

  4. Serum and plasma fibronectin binds to complement reacted immune complexes primarily via Clq

    DEFF Research Database (Denmark)

    Baatrup, G; Svehag, S E

    1986-01-01

    The binding of fibronectin to human Clq, C3b, and complement-reacted immune complexes (IC) was investigated by enzyme-linked immunosorbent assays. Microplates were coated with BSA followed by incubation with rabbit-anti-BSA IgG or F(ab')2 fragments of rabbit anti-BSA. Incubation of the solid phase...... with serum at 37 degrees C caused attachment of Clq and C3b. Addition of EDTA to the serum inhibited the binding of C3b, but not Clq, whereas substitution of the anti-BSA IgG on the solid phase with the F(ab')2 fragments abrogated the Clq, but not the C3b binding. Fibronectin binding was observed after...

  5. Further characterization of loss of heterozygosity enhanced by p53 abrogation in human lymphoblastoid TK6 cells: disappearance of endpoint hotspots.

    Science.gov (United States)

    Yatagai, Fumio; Morimoto, Shigeko; Kato, Takesi; Honma, Masamitsu

    2004-06-13

    Loss of heterozygosity (LOH) is the predominant mechanism of spontaneous mutagenesis at the heterozygous thymindine kinase locus (tk) in TK6 cells. LOH events detected in spontaneous TK(-) mutants (110 clones from p53 wild-type cells TK6-20C and 117 clones from p53-abrogated cells TK6-E6) were analyzed using 13 microsatellite markers spanning the whole of chromosome 17. Our analysis indicated an approximately 60-fold higher frequency of terminal deletions in p53-abrogated cells TK6-E6 compared to p53 wild-type cells TK6-20C whereas frequencies of point mutations (non-LOH events), interstitial deletions, and crossing over events were found to increase only less than twofold by such p53 abrogation. We then made use of an additional 17 microsatellite markers which provided an average map-interval of 1.6Mb to map various LOH endpoints on the 45Mb portion of chromosome 17q corresponding to the maximum length of LOH tracts (i.e. from the distal marker D17S932 to the terminal end). There appeared to be four prominent peaks (I-IV) in the distribution of LOH endpoints/Mb of Tk6-20C cells that were not evident in p53-abrogated cells TK6-E6, where they appeared to be rather broadly distributed along the 15-20Mb length (D17S1807 to D17S1607) surrounding two of the peaks that we detected in TK6-20C cells (peaks II and III). We suggest that the chromosomal instability that is so evident in TK6-E6 cells may be due to DNA double-strand break repair occurring through non homologous end-joining rather than allelic recombination.

  6. HDAC6 inhibition enhances 17-AAG--mediated abrogation of hsp90 chaperone function in human leukemia cells.

    Science.gov (United States)

    Rao, Rekha; Fiskus, Warren; Yang, Yonghua; Lee, Pearl; Joshi, Rajeshree; Fernandez, Pravina; Mandawat, Aditya; Atadja, Peter; Bradner, James E; Bhalla, Kapil

    2008-09-01

    Histone deacetylase 6 (HDAC6) is a heat shock protein 90 (hsp90) deacetylase. Treatment with pan-HDAC inhibitors or depletion of HDAC6 by siRNA induces hyperacetylation and inhibits ATP binding and chaperone function of hsp90. Treatment with 17-allylamino-demothoxy geldanamycin (17-AAG) also inhibits ATP binding and chaperone function of hsp90, resulting in polyubiquitylation and proteasomal degradation of hsp90 client proteins. In this study, we determined the effect of hsp90 hyperacetylation on the anti-hsp90 and antileukemia activity of 17-AAG. Hyperacetylation of hsp90 increased its binding to 17-AAG, as well as enhanced 17-AAG-mediated attenuation of ATP and the cochaperone p23 binding to hsp90. Notably, treatment with 17-AAG alone also reduced HDAC6 binding to hsp90 and induced hyperacetylation of hsp90. This promoted the proteasomal degradation of HDAC6. Cotreatment with 17-AAG and siRNA to HDAC6 induced more inhibition of hsp90 chaperone function and depletion of BCR-ABL and c-Raf than treatment with either agent alone. In addition, cotreatment with 17-AAG and tubacin augmented the loss of survival of K562 cells and viability of primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) samples. These findings demonstrate that HDAC6 is an hsp90 client protein and hyperacetylation of hsp90 augments the anti-hsp90 and antileukemia effects of 17-AAG.

  7. Antihelminthic benzimidazoles are novel HIF activators that prevent oxidative neuronal death via binding to tubulin.

    Science.gov (United States)

    Aleyasin, Hossein; Karuppagounder, Saravanan S; Kumar, Amit; Sleiman, Sama; Basso, Manuela; Ma, Thong; Siddiq, Ambreena; Chinta, Shankar J; Brochier, Camille; Langley, Brett; Haskew-Layton, Renee; Bane, Susan L; Riggins, Gregory J; Gazaryan, Irina; Starkov, Anatoly A; Andersen, Julie K; Ratan, Rajiv R

    2015-01-10

    Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter of hypoxia-inducible factor (HIF)-dependent transcription. Our screen identified more than 40 compounds with the ability to induce hypoxia response element-driven luciferase activity as well or better than deferoxamine, a canonical activator of hypoxic adaptation. Among the chemical entities identified, the antihelminthic benzimidazoles represented one pharmacophore that appeared multiple times in our screen. Secondary assays confirmed that antihelminthics stabilized the transcriptional activator HIF-1α and induced expression of a known HIF target gene, p21(cip1/waf1), in post-mitotic cortical neurons. The on-target effect of these agents in stimulating hypoxic signaling was binding to free tubulin. Moreover, antihelminthic benzimidazoles also abrogated oxidative stress-induced death in vitro, and this on-target effect also involves binding to free tubulin. These studies demonstrate that tubulin-binding drugs can activate a component of the hypoxic adaptive response, specifically the stabilization of HIF-1α and its downstream targets. Tubulin-binding drugs, including antihelminthic benzimidazoles, also abrogate oxidative neuronal death in primary neurons. Given their safety in humans and known ability to penetrate into the central nervous system, antihelminthic benzimidazoles may be considered viable candidates for treating diseases associated with oxidative neuronal death, including stroke.

  8. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

    Science.gov (United States)

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

    2016-01-01

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

  9. The rise of the daughter-in-law: Why son preference is weakening in ...

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

    2012-11-13

    Nov 13, 2012 ... Millions of women are 'missing' because they die in much larger ... This means that the population of Bangladesh, along with that of India and Pakistan, ... Sons, on the other hand, were considered insurance against poverty in old age. ... sons would defy child mortality rates to look after their aged parents.

  10. Crustal thickness mapping in Raipur–Katni area of Narmada–Son ...

    Indian Academy of Sciences (India)

    The Narmada–Son lineament (NSL) is one of the most prominent tectonic features which divides the .... fault at Red Sea area (Bhattacharjee and Koide. 1978). The Son and .... relationship between SI and number of infinite dimension of the ...

  11. Disability in the Family: John and Alice Dewey Raising Their Son Sabino

    Science.gov (United States)

    Danforth, Scot

    2018-01-01

    Background/Context: The current biographic understanding of John Dewey's experience adopting and raising an Italian boy named Sabino emphasizes the theme of finding an emotional replacement for Morris and Gordon, two young sons who had tragically died on family trips to Europe. Lacking is substantive attention to the fact that John Dewey's son had…

  12. African-American Fathers' Perspectives on Facilitators and Barriers to Father-Son Sexual Health Communication.

    Science.gov (United States)

    Randolph, Schenita D; Coakley, Tanya; Shears, Jeffrey; Thorpe, Roland J

    2017-06-01

    African-American males ages 13 through 24 are disproportionately affected by sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), accounting for over half of all HIV infections in this age group in the United States. Clear communication between African-American parents and their youth about sexual health is associated with higher rates of sexual abstinence, condom use, and intent to delay initiation of sexual intercourse. However, little is known about African-American fathers' perceptions of what facilitates and inhibits sexual health communication with their preadolescent and adolescent sons. We conducted focus groups with 29 African-American fathers of sons ages 10-15 to explore perceived facilitators and barriers for father-son communication about sexual health. Participants were recruited from barbershops in metropolitan and rural North Carolina communities highly affected by STIs and HIV, and data were analyzed using content analysis. Three factors facilitated father-son communication: (a) fathers' acceptance of their roles and responsibilities; (b) a positive father-son relationship; and (c) fathers' ability to speak directly to their sons about sex. We also identified three barriers: (a) fathers' difficulty in initiating sexual health discussions with their sons; (b) sons' developmental readiness for sexual health information; and (c) fathers' lack of experience in talking with their own fathers about sex. These findings have implications for father-focused prevention interventions aimed at reducing risky sexual behaviors in adolescent African-American males. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Older parents enjoy better filial piety and care from daughters than sons in China

    DEFF Research Database (Denmark)

    Zeng, Yi; George, Linda; Sereny, Melanie

    2016-01-01

    OBJECTIVE: To examine whether older parents in China would benefit more from daughters' care than from sons' emotional care. METHOD: Analysis of the unique data sets of the Chinese Longitudinal Healthy Longevity Survey conducted in 2002, 2005, and 2008-2009 in 22 provinces. RESULTS: As compared......' health outcome could help promote gender equality and reduce traditional son preference, especially in rural China....

  14. Father-Son Inter-Generational Transmission of Authoritarian Paternal Attitudes.

    Science.gov (United States)

    Peretti, Peter O.; Statum, Jo Ann

    1984-01-01

    Attempted to determine authoritarian paternal attitude inter-generational transmission in fathers and sons (N=75). Results suggested that authoritarian paternal attitudes could be indicated in terms of five factors: Dominant, Rigidity, Conformity, Intolerant, and Uncreative; and that the sons expressed strongly the authoritarian attitudes of their…

  15. Older Parents Benefit More in Health Outcome From Daughters' Than Sons' Emotional Care in China.

    Science.gov (United States)

    Zeng, Yi; Brasher, Melanie Sereny; Gu, Danan; Vaupel, James W

    2016-12-01

    To examine whether older parents in China would benefit more from daughters' care than from sons' emotional care. Analysis of the unique data sets of the Chinese Longitudinal Healthy Longevity Survey conducted in 2002, 2005, and 2008-2009 in 22 provinces. As compared with having son(s), having daughter(s) is significantly more beneficial at older ages in China, with regard to maintaining higher cognitive capacity and reducing mortality risk. Such daughter advantages in providing emotional care to older parents are more profound among the oldest-old aged 80+ as compared with the young-old aged 65 to 79 and surprisingly more profound in rural areas as compared with urban areas, even though son preference is much more common among rural residents. We describe how educational campaigns aimed at informing the public about the benefits of daughter(s) for older parents' health outcome could help promote gender equality and reduce traditional son preference, especially in rural China.

  16. Coupling coefficients of SO(n) and integrals involving Jacobi and Gegenbauer polynomials

    International Nuclear Information System (INIS)

    Alisauskas, Sigitas

    2002-01-01

    The expressions for the coupling coefficients (3j-symbols) for most degenerate (symmetric) representations of orthogonal groups SO(n) in a canonical basis (with SO(n) restricted to SO(n-1) and different semicanonical or tree bases (with SO(n) restricted to SO(n')xSO(n''), n'+n''=n) are considered, respectively, in context of integrals involving triplets of the Gegenbauer and the Jacobi polynomials. Since the directly derived triple-hypergeometric series do not reveal the apparent triangle conditions of the 3j-symbols, they are rearranged, using their relation with semistretched isofactors of the second kind for the complementary chain Sp(4) contains SU(2)xSU(2) and analogy with the stretched 9j coefficients of SU(2), into formulae with more rich limits for summation intervals and obvious triangle conditions. The isofactors of class-one representations of orthogonal groups or class-two representations of unitary groups (and, of course, the related integrals involving triplets of the Gegenbauer and the Jacobi polynomials) turn into double sums in the cases of canonical SO(n) contains SO(n-1) or U(n) contains U(n-1) and semicanonical SO(n) contains SO(n-2)xSO(2) chains, as well as into the 4 F 3 (1) series under more specific conditions. Some ambiguities of the phase choice of the complementary group approach are adjusted, as well as problems with an alternating sign parameter of SO(2) representations in the SO(3) contains SO(2) and SO(n) contains SO(n-2)xSO(2) chains. (author)

  17. Breaking the ice! Predictors about communication between nonresident African American fathers and sons about sex.

    Science.gov (United States)

    Burns, Jade C; Caldwell, Cleopatra H

    2016-02-01

    Research on communication between resident and nonresident African American fathers and their sons about sex has been understudied. The purpose of this study is to determine the influence of parenting variables, specifically, racial socialization and father involvement on nonresident African American father-son communication about sex. Data for this study are from the Fathers and Sons Project. This intervention study is designed to enhance relationships between nonresident African American fathers and their 8-12 year old sons and to prevent risky health behaviors among sons. The present study is based on 345 African American boys who completed baseline face-to-face interviews. The average age of the sons was 10.2 years old (SD = 1.4), with an average of two siblings (SD = 1.53). Age and sons' perceptions of more parental monitoring by their fathers were predictive of increased communication about sex. Racial socialization messages explained additional variance in communication about sex above other parenting variables and controls. Findings suggest when working with African American families, providers who counsel parents, and in particular provide outreach to fathers regarding communication about sex, are in a unique position to enhance parenting communication skills about sexuality. ©2015 American Association of Nurse Practitioners.

  18. The UNG2 Arg88Cys variant abrogates RPA-mediated recruitment of UNG2 to single-stranded DNA.

    Science.gov (United States)

    Torseth, Kathrin; Doseth, Berit; Hagen, Lars; Olaisen, Camilla; Liabakk, Nina-Beate; Græsmann, Heidi; Durandy, Anne; Otterlei, Marit; Krokan, Hans E; Kavli, Bodil; Slupphaug, Geir

    2012-06-01

    In human cell nuclei, UNG2 is the major uracil-DNA glycosylase initiating DNA base excision repair of uracil. In activated B cells it has an additional role in facilitating mutagenic processing of AID-induced uracil at Ig loci and UNG-deficient patients develop hyper-IgM syndrome characterized by impaired class-switch recombination and disturbed somatic hypermutation. How UNG2 is recruited to either error-free or mutagenic uracil processing remains obscure, but likely involves regulated interactions with other proteins. The UNG2 N-terminal domain contains binding motifs for both proliferating cell nuclear antigen (PCNA) and replication protein A (RPA), but the relative contribution of these interactions to genomic uracil processing is not understood. Interestingly, a heterozygous germline single-nucleotide variant leading to Arg88Cys (R88C) substitution in the RPA-interaction motif of UNG2 has been observed in humans, but with unknown functional relevance. Here we demonstrate that UNG2-R88C protein is expressed from the variant allele in a lymphoblastoid cell line derived from a heterozygous germ line carrier. Enzyme activity as well as localization in replication foci of UNG2-R88C was similar to that of WT. However, binding to RPA was essentially abolished by the R88C substitution, whereas binding to PCNA was unaffected. Moreover, we show that disruption of the PCNA-binding motif impaired recruitment of UNG2 to S-phase replication foci, demonstrating that PCNA is a major factor for recruitment of UNG2 to unperturbed replication forks. Conversely, in cells treated with hydroxyurea, RPA mediated recruitment of UNG2 to stalled replication forks independently of functional PCNA binding. Modulation of PCNA- versus RPA-binding may thus constitute a functional switch for UNG2 in cells subsequent to genotoxic stress and potentially also during the processing of uracil at the immunoglobulin locus in antigen-stimulated B cells. Copyright © 2012 Elsevier B.V. All rights

  19. Impaired Reproductive Development in Sons of Women Occupationally Exposed to Pesticides during Pregnancy

    DEFF Research Database (Denmark)

    Andersen, Helle Raun; Schmidt, Ida M.; Grandjean, Philippe

    2008-01-01

    OBJECTIVES: The aim of this prospective study was to investigate whether occupational pesticide exposure during pregnancy causes adverse effects on the reproductive development in the male infants. DESIGN AND MEASUREMENTS: Pregnant women employed in greenhouses in Denmark were consecutively...... recruited, and 113 mother-son pairs were included. The mothers were categorized as occupationally exposed (91 sons) or unexposed (22 sons) to pesticides during pregnancy. Testicular position and volume, penile length, and position of urethral opening were determined at 3 months of age using standardized...

  20. Some relevant properties of SO(n) representations for Grand unified theories

    International Nuclear Information System (INIS)

    Girardi, G.; Sorba, P.; Sciarrino, A.

    1980-05-01

    General properties of the SO(n) groups are examined, with emphasis on the usefulness of the Gel'fand-Zetlin basis for explicit calculations. The SO(n) representations containing a vector stabilized by subgroups of the type S[O(n-p) x O(p)], SU(k) x U(1) or SU(k) if n=2k, are characterized in view of selecting Higgs representations in SO(n) gauge models. Some useful properties of the SU(n) Gel'fand-Zetlin basis are given in the appendices

  1. Reliability of P mode event classification using contemporaneous BiSON and GOLF observations

    International Nuclear Information System (INIS)

    Simoniello, R; Chaplin, W J; Elsworth, Y P; Garcia, R A

    2008-01-01

    We carried out a comparison of the signals seen in contemporaneous BiSON and GOLF data sets. Both instruments perform Doppler shift velocity measurements in integrated sunlight, although BiSON perform measurements from the two wings of potassium absorption line and GOLF from one wing of the NaD1 line. Discrepancies between the two datasets have been observed. We show,in fact, that the relative power depends on the wing in which GOLF data observes. During the blue wing period, the relative power is mugh higher than in BiSON datasets, while a good agreement has been observed during the red period.

  2. Influência das vogais na estimulabilidade dos sons líquidos

    OpenAIRE

    Castro,Márcia Mathias de; Wertzner,Haydée Fizbein

    2009-01-01

    OBJETIVO: verificar o número de crianças, entre 5:0 e 11:6 anos, com e sem Transtorno Fonológico, falantes do Português Brasileiro que imitaram corretamente os sons líquidos no teste de estimulabilidade considerando cada uma das vogais subsequentes. MÉTODOS: a estimulabilidade foi medida por uma prova de imitação de 63 sílabas com os sons com as sete vogais orais, em três repetições. Foi analisada a porcentagem de sujeitos que produziu corretamente os sons em função da vogal subsequente. RESU...

  3. Parent-son decision-making about human papillomavirus vaccination: a qualitative analysis

    Directory of Open Access Journals (Sweden)

    Alexander Andreia B

    2012-12-01

    Full Text Available Abstract Background Licensed for use in males in 2009, Human Papillomavirus (HPV vaccination rates in adolescent males are extremely low. Literature on HPV vaccination focuses on females, adult males, or parents of adolescent males, without including adolescent males or the dynamics of the parent-son interaction that may influence vaccine decision-making. The purpose of this paper is to examine the decision-making process of parent-son dyads when deciding whether or not to get vaccinated against HPV. Methods Twenty-one adolescent males (ages 13–17, with no previous HPV vaccination, and their parents/guardians were recruited from adolescent primary care clinics serving low to middle income families in a large Midwestern city. Dyad members participated in separate semi-structured interviews assessing the relative role of the parent and son in the decision regarding HPV vaccination. Interviews were recorded, transcribed, and coded using inductive content analysis. Results Parents and sons focused on protection as a reason for vaccination; parents felt a need to protect their child, while sons wanted to protect their own health. Parents and sons commonly misinterpreted the information about the vaccine. Sons were concerned about an injection in the penis, while some parents and sons thought the vaccine would protect them against other sexually transmitted infections including Herpes, Gonorrhea, and HIV. Parents and sons recalled that the vaccine prevented genital warts rather than cancer. The vaccine decision-making process was rapid and dynamic, including an initial reaction to the recommendation for HPV vaccine, discussion between parent and son, and the final vaccine decision. Provider input was weighed in instances of initial disagreement. Many boys felt that this was the first health care decision that they had been involved in. Dyads which reported shared decision-making were more likely to openly communicate about sexual issues than those

  4. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yueyang [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

  5. RhoA Activation Sensitizes Cells to Proteotoxic Stimuli by Abrogating the HSF1-Dependent Heat Shock Response.

    Directory of Open Access Journals (Sweden)

    Roelien A M Meijering

    Full Text Available The heat shock response (HSR is an ancient and highly conserved program of stress-induced gene expression, aimed at reestablishing protein homeostasis to preserve cellular fitness. Cells that fail to activate or maintain this protective response are hypersensitive to proteotoxic stress. The HSR is mediated by the heat shock transcription factor 1 (HSF1, which binds to conserved heat shock elements (HSE in the promoter region of heat shock genes, resulting in the expression of heat shock proteins (HSP. Recently, we observed that hyperactivation of RhoA conditions cardiomyocytes for the cardiac arrhythmia atrial fibrillation. Also, the HSR is annihilated in atrial fibrillation, and induction of HSR mitigates sensitization of cells to this disease. Therefore, we hypothesized active RhoA to suppress the HSR resulting in sensitization of cells for proteotoxic stimuli.Stimulation of RhoA activity significantly suppressed the proteotoxic stress-induced HSR in HL-1 atrial cardiomyocytes as determined with a luciferase reporter construct driven by the HSF1 regulated human HSP70 (HSPA1A promoter and HSP protein expression by Western Blot analysis. Inversely, RhoA inhibition boosted the proteotoxic stress-induced HSR. While active RhoA did not preclude HSF1 nuclear accumulation, phosphorylation, acetylation, or sumoylation, it did impair binding of HSF1 to the hsp genes promoter element HSE. Impaired binding results in suppression of HSP expression and sensitized cells to proteotoxic stress.These results reveal that active RhoA negatively regulates the HSR via attenuation of the HSF1-HSE binding and thus may play a role in sensitizing cells to proteotoxic stimuli.

  6. Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Kristian Tore; Jensen, Morten Søndergaard; Toft, Gunnar Vase

    2014-01-01

    on occupation and cryptorchidism. METHODS: The cohort consisted of >600 000 boys born in Denmark from 1980-2007 with a parent in employment during pregnancy. These boys were followed for cryptorchidism from 1980-2009 comparing risks among sons of horticultural workers and farmers with sons of parents in other...... occupations. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox regression adjusting for parental age, birth years, parity, and geographical region. RESULTS: Sons of maternal farmers were at increased risk of cryptorchidism (157 cases; HR 1.31, 95% CI 1.12-1.53) compared to boys...... of mothers in other occupations (15 511 cases). Paternal occupation as farmer was unrelated to the risk among sons. Maternal occupation as a horticultural worker was associated with a non-significantly increased risk (72 cases; HR 1.20, 95% CI 0.95-1.52). A similar association was found for paternal...

  7. Que son las Cochinillas de los Cotrus (Naranjos, Limoneros, Mandarinos, etc. y como se Combaten.

    Directory of Open Access Journals (Sweden)

    Posada Sinisterra. Belisario

    1942-04-01

    Full Text Available Las cochinillas son insectos de aspecto variado. Son llamados también insectos-escamas porque la mayoría de ellos viven protegidos por una concha o escama de forma y coloración diversa. Las especies que en seguida se describen tienen un ciclo biológico muy similar. Se reproducen por medio de huevos que depositan las hembras bajo la escama.

  8. Associations Between Fathers' and Sons' Sexual Risk in Rural Kenya: The Potential for Intergenerational Transmission.

    Science.gov (United States)

    Giusto, Ali M; Green, Eric P; Puffer, Eve S

    2017-08-01

    Despite high rates of HIV in areas of Sub-Saharan Africa and men's role in driving the epidemic, little is known about whether or how sexual risk-both behaviors and beliefs-may be passed down through generations of males. This study examined associations between sexual risk behaviors and sex-related beliefs of adolescent males and those of their male caregivers in Kenya, as well as the potential moderating effects of parenting characteristics and father-son relationship quality. Cross-sectional linear regression analysis was applied to baseline data from a trial of a family- and church-based intervention for families in rural Kenya that followed a stepped-wedge cluster randomized design. Our subsample consisted of 79 male caregiver and son (aged 10-16 years) dyads. Results demonstrated a direct relationship between fathers' and sons' sex-related beliefs that was not moderated by parenting or quality of father-son relationship. Parenting/relationship characteristics did moderate the relationship between fathers' and sons' sexual behavior; if fathers did not engage in high-risk sex and exhibited more positive parenting/higher relationship quality, their sons were less likely to be sexually active. Among fathers having high-risk sex, parenting was unrelated to sons' behavior except at very high levels of positive parenting/relationship quality; at these levels, sons were actually more likely to have had sex. Findings support recommendations to include male caregivers in youth HIV prevention efforts, potentially by targeting fathers' parenting strategies and their individual risk. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  9. Short-lived radiopharmaceutical development at E.R. Squibb and Sons, Inc

    International Nuclear Information System (INIS)

    Loberg, M.D.

    1985-01-01

    This paper describes the present status and future plans of E.R. Squibb and Sons, Inc. as they relate to the development of short-lived radiopharmaceuticals. The advantages of short-lived radiopharmaceuticals are summarized as are the problems inherent in their manufacture, quality control, and distribution. The nuclear generator is advocated as the best means of distributing short-lived radiopharmaceuticals. The E.R. Squibb and Sons work with the 82 Sr → 82 Rb generator is summarized

  10. The institutionalization of Jesus' charismatic authority: "Son of Man" as case study1

    Directory of Open Access Journals (Sweden)

    Yolanda Dreyer

    2000-12-01

    Full Text Available This article argues that Jesus used the expression "son of man" not in a titular way, but genetically, meaning "humankind". This use of "son of man" developed into a titular usage in which Jesus is identified with "Son of Man". The study shows that Jesus' use of the expression "son of man" should be understood in the context of the "little tradition" which was reinterpreted in terms of the "great tradition" in a titular way. It is argued that this transition from "litle tradition" to "great tradition"can be seen as "false attribution". After Jesus' death when his followers reorganized themselves into a cultic community, they gave Jesus the position "founder of the cult". They did this by making use of honorary titles. The use of the title "Son of Man" for Jesus is interpreted in terms of the social theory of the institutionalization of charismatic authority. The focus is on the title "Son of Man" as it appears in legal sayings or church rules, wisdom sayings and prophetic and apocalyptic sayings.

  11. Like daughter, like son? Fertility decline and the transformation of gender systems in the family

    Directory of Open Access Journals (Sweden)

    Keera Allendorf

    2012-10-01

    Full Text Available BACKGROUND An important question for population research is whether fertility decline transforms gender systems. OBJECTIVE This paper contributes to answering this broad question by examining how fertility decline may change the relative value and roles of daughters versus sons in families. First, I outline theoretical pathways, suggesting that a key factor is the gender composition of families. As fertility declines, the proportion of families with children of only one gender increases, which may facilitate greater gender symmetry between daughters and sons. Second, I explore how fertility decline may be transforming the relative value and roles of sons and daughters in practice in one place. METHODS The analysis draws primarily on semi-structured interviews with 30 respondents living in one Indian village. RESULTS In recent decades, fertility has declined to at least replacement levels. Respondents also perceive changes in the gender system, including less son preference, more equal schooling for sons and daughters, more freedom in marriage and pre-marital relationships, and perhaps greater daughter support of parents in old age. CONCLUSIONS The results describe changes in the relative value, treatment, and behavior of sons and daughters that are consistent with the theorized effects of fertility decline. Future research is needed, however, to determine whether fertility decline makes a unique causal contribution to changes in the gender system.

  12. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory

    International Nuclear Information System (INIS)

    2011-01-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  13. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  14. Has Their Son Been Vaccinated? Beliefs About Other Parents Matter for Human Papillomavirus Vaccine.

    Science.gov (United States)

    Schuler, Christine L; Coyne-Beasley, Tamera

    2016-07-01

    The goal of this study was to determine if parents' beliefs about social norms of human papillomavirus (HPV) vaccination for sons were associated with knowledge of HPV, intention to vaccinate sons, or beliefs about side effects. A cross-sectional, survey-based study of parents with sons was performed in 2010. Fisher's exact tests were used to examine associations between demographics and responses about social norms. Multivariate logistic regression models examined beliefs about social norms of male HPV vaccination and primary outcomes. Few parents agreed that others were vaccinating sons (n = 31/267, 12%), including 1% responding strongly agree and 11% responding agree. Most parents, 52%, disagreed that others were vaccinating (40% disagree, 11% strongly disagree), and 37% chose prefer not to answer regarding others' vaccination practices. Hispanic parents and those with a high school education or less were significantly more likely to choose prefer not to answer than their respective counterparts regarding vaccination norms. In multivariate models, parents agreeing others were vaccinating sons had greater odds of having high knowledge of HPV (adjusted odds ratio [aOR] high vs low knowledge 3.15, 95% confidence interval [CI] 1.13, 8.77) and increased intention to vaccinate sons (n = 243, aOR = 4.41, 95% CI = 1.51, 12.89). Beliefs about side effects were not significantly associated with beliefs about social norms. Parents' beliefs about others' vaccination practices are important with regard to knowledge of HPV and intention to vaccinate sons. Studying how various public messages about HPV vaccine may influence normative beliefs could be relevant to improving vaccination coverage. © The Author(s) 2015.

  15. Aditivos alimentarios: ¿qué son, cómo actúan, por qué son tan necesarios?

    OpenAIRE

    Blanco de Alvarado-Ortiz, Teresa

    2014-01-01

    Para John M. deMan, en su obra PrincipIes of Food Chemistry a los aditivos alimentarios con frecuencia se les asocia a algo químico, otorgándose erradamente a lo quimico características de artificial, no siempre bueno para la salud.Dicen bien erradamente, porque hombres, animales, plantas, microorganismos, alimentos, aire, cerros, minas y todo lo que nos rodea en la maravillosa naturaleza, es químico. Los aditivos alimentarios,todos químicos, naturales o artificiales son extraordinarias susta...

  16. Sensitization of Tumor to {sup 212}Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    Energy Technology Data Exchange (ETDEWEB)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E. [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Brechbiel, Martin W., E-mail: martinwb@mail.nih.gov [Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-15

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using {sup 212}Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by {sup 212}Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with {sup 212}Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. {sup 212}Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of {sup 212}Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling.

  17. Sensitization of Tumor to 212Pb Radioimmunotherapy by Gemcitabine Involves Initial Abrogation of G2 Arrest and Blocked DNA Damage Repair by Interference With Rad51

    International Nuclear Information System (INIS)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2013-01-01

    Purpose: To elucidate the mechanism of the therapeutic efficacy of targeted α-particle radiation therapy using 212 Pb-TCMC-trastuzumab together with gemcitabine for treatment of disseminated peritoneal cancers. Methods and Materials: Mice bearing human colon cancer LS-174T intraperitoneal xenografts were pretreated with gemcitabine, followed by 212 Pb-TCMC-trastuzumab and compared with controls. Results: Treatment with 212 Pb-TCMC-trastuzumab increased the apoptotic rate in the S-phase-arrested tumors induced by gemcitabine at earlier time points (6 to 24 hours). 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment abrogated G2/M arrest at the same time points, which may be associated with the inhibition of Chk1 phosphorylation and, in turn, cell cycle perturbation, resulting in apoptosis. 212 Pb-TCMC-trastuzumab treatment after gemcitabine pretreatment caused depression of DNA synthesis, DNA double-strand breaks, accumulation of unrepaired DNA, and down-regulation of Rad51 protein, indicating that DNA damage repair was blocked. In addition, modification in the chromatin structure of p21 may be associated with transcriptionally repressed chromatin states, indicating that the open structure was delayed at earlier time points. Conclusion: These findings suggest that the cell-killing efficacy of 212 Pb-TCMC-trastuzumab after gemcitabine pretreatment may be associated with abrogation of the G2/M checkpoint, inhibition of DNA damage repair, and chromatin remodeling

  18. SON connects the splicing-regulatory network with pluripotency in human embryonic stem cells.

    Science.gov (United States)

    Lu, Xinyi; Göke, Jonathan; Sachs, Friedrich; Jacques, Pierre-Étienne; Liang, Hongqing; Feng, Bo; Bourque, Guillaume; Bubulya, Paula A; Ng, Huck-Hui

    2013-10-01

    Human embryonic stem cells (hESCs) harbour the ability to undergo lineage-specific differentiation into clinically relevant cell types. Transcription factors and epigenetic modifiers are known to play important roles in the maintenance of pluripotency of hESCs. However, little is known about regulation of pluripotency through splicing. In this study, we identify the spliceosome-associated factor SON as a factor essential for the maintenance of hESCs. Depletion of SON in hESCs results in the loss of pluripotency and cell death. Using genome-wide RNA profiling, we identified transcripts that are regulated by SON. Importantly, we confirmed that SON regulates the proper splicing of transcripts encoding for pluripotency regulators such as OCT4, PRDM14, E4F1 and MED24. Furthermore, we show that SON is bound to these transcripts in vivo. In summary, we connect a splicing-regulatory network for accurate transcript production to the maintenance of pluripotency and self-renewal of hESCs.

  19. Independent Contributions of Early Positive Parenting and Mother-Son Coercion on Emerging Social Development.

    Science.gov (United States)

    Akcinar, Berna; Shaw, Daniel S

    2018-06-01

    In the current study, we explored associations between parent-child coercion and positive parenting in the toddler period in relation to children's social-behavioral development during the school-age period. The data were drawn from the Pitt Mother & Child Project, a sample of 310 low-income, ethnically diverse boys. Drawing on tenets of both attachment and social learning theory, it was hypothesized that coercive mother-son interaction would lead to reductions in positive maternal parenting in the toddler period, and that both positive parenting and mother-son coercion in the toddler period would contribute to children's conduct problems at school entry and lower social skills and peer rejection in middle childhood. The results were largely confirmed, such that mother-son coercive interaction at 18 months was related to decreases in positive parenting at 24 months. Additionally, mother-son coercive interaction and positive parenting at 24 months were linked to child conduct problems at age 5, which in turn predicted child social skills and peer rejection during middle childhood. In addition to indirect effects through child conduct problems, mother-son coercion continued to be independently related to school-age peer rejection. The findings are discussed with respect to the importance of early coercive interactions in the growth of child social-behavioral development from early to middle childhood.

  20. Herpes Simplex Virus 1 UL24 Abrogates the DNA Sensing Signal Pathway by Inhibiting NF-κB Activation.

    Science.gov (United States)

    Xu, Haiyan; Su, Chenhe; Pearson, Angela; Mody, Christopher H; Zheng, Chunfu

    2017-04-01

    Cyclic GMP-AMP synthase (cGAS) is a newly identified DNA sensor that recognizes foreign DNA, including the genome of herpes simplex virus 1 (HSV-1). Upon binding of viral DNA, cGAS produces cyclic GMP-AMP, which interacts with and activates stimulator of interferon genes (STING) to trigger the transcription of antiviral genes such as type I interferons (IFNs), and the production of inflammatory cytokines. HSV-1 UL24 is widely conserved among members of the herpesviruses family and is essential for efficient viral replication. In this study, we found that ectopically expressed UL24 could inhibit cGAS-STING-mediated promoter activation of IFN-β and interleukin-6 (IL-6), and UL24 also inhibited interferon-stimulatory DNA-mediated IFN-β and IL-6 production during HSV-1 infection. Furthermore, UL24 selectively blocked nuclear factor κB (NF-κB) but not IFN-regulatory factor 3 promoter activation. Coimmunoprecipitation analysis demonstrated that UL24 bound to the endogenous NF-κB subunits p65 and p50 in HSV-1-infected cells, and UL24 was also found to bind the Rel homology domains (RHDs) of these subunits. Furthermore, UL24 reduced the tumor necrosis factor alpha (TNF-α)-mediated nuclear translocation of p65 and p50. Finally, mutational analysis revealed that the region spanning amino acids (aa) 74 to 134 of UL24 [UL24(74-134)] is responsible for inhibiting cGAS-STING-mediated NF-κB promoter activity. For the first time, UL24 was shown to play an important role in immune evasion during HSV-1 infection. IMPORTANCE NF-κB is a critical component of the innate immune response and is strongly induced downstream of most pattern recognition receptors (PRRs), leading to the production of IFN-β as well as a number of inflammatory chemokines and interleukins. To establish persistent infection, viruses have evolved various mechanisms to counteract the host NF-κB pathway. In the present study, for the first time, HSV-1 UL24 was demonstrated to inhibit the activation of NF

  1. Having a son or daughter with Down syndrome: perspectives from mothers and fathers.

    Science.gov (United States)

    Skotko, Brian G; Levine, Susan P; Goldstein, Richard

    2011-10-01

    This study asks parents who have children with Down syndrome (DS) how they feel about their lives so that such information could be shared with expectant couples during prenatal counseling sessions. A valid and reliable survey instrument was mailed to 4,924 households on the mailing lists of six non-profit DS organizations. Of the 2,044 respondents, 99% reported that they love their son or daughter; 97% were proud of them; 79% felt their outlook on life was more positive because of them; 5% felt embarrassed by them; and 4% regretted having them. The parents report that 95% of their sons or daughters without DS have good relationships with their siblings with DS. The overwhelming majority of parents surveyed report that they are happy with their decision to have their child with DS and indicate that their sons and daughters are great sources of love and pride. Copyright © 2011 Wiley-Liss, Inc.

  2. Binding of tissue plasminogen activator to human umbilical vein endothelial cells

    International Nuclear Information System (INIS)

    Beebe, D.P.

    1987-01-01

    The binding of purified, recombinant tissue plasminogen activator (tPA) to human umbilical vein endothelial cells (HUVEC) was studied in vitro using immunofluorescence as well as radiolabeled tPA. Immunofluorescence was performed on HUVEC grown on round glass coverslips using rabbit anti-human tPA and fluorescein-conjugated anti-rabbit immunoglobulin. Positive fluorescence was observed only after incubation of HUVEC with tPA. HUVEC were grown to confluence in 24-well tissue culture plates, washed, and incubated with a constant amount of 125 I-tPA and various concentrations of unlabeled tPA. The binding of tPA to HUVEC was found to be specific, saturable, and reversible. Scatchard analysis yielded as equilibrium constant (K/sub eq/) of 4.2 x 10 6 M -1 and 1.2 x 10 7 binding sites per cell. Binding was inhibited by positively charged amino acids and by D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone but not by carbohydrates including mannose, galactose, N-acetyl glucosamine and N-acetyl galactosamine. Neat human plasma abrogates but does not totally inhibit binding of tPA to HUVEC. Binding was neither enhanced nor inhibited by fibronectin. Although the affinity of binding of tPA to HUVEC is low, the endothelial cell may be involved in regulating plasma levels of tPA in vivo which may have therapeutic significance

  3. The relation of son preference and religion to induced abortion: the case of South Korea.

    Science.gov (United States)

    Chung, Woojin

    2007-09-01

    This paper explores the factors that influence the practice of induced abortion in a very low fertility society, with particular emphasis on son preference and three distinct religions: Confucianism, Buddhism and Christianity. Using multivariate logistic regression models fitted by the generalized estimating equation (GEE) method, this paper analysed the data collected by the 2000 Korea National Fertility and Family Health Survey of 6348 married women aged 15-49 years with a total of 1217 pregnancy outcomes. The results showed that the likelihood of induced abortions in women with two or more children, compared with those with one child, was significantly influenced by the sex composition of the previous children: odds ratio (OR)=12.71 (95% CI=5.49, 29.42) for women with only son(s), and OR=3.91 (95% CI=1.67, 9.14) for women with only daughter(s). At parity two, women with two sons were much more likely to have induced abortions than women with two daughters (OR=5.88, 95% CI=2.70, 12.85). Although Buddhist women were not significantly different from Confucian women in induced abortion practice, Christian women were much less likely than Confucian women to have an induced abortion (OR=0.39, 95% CI=0.18, 0.88 for women with only sons and OR=0.44, 95% CI=0.24, 0.81 for women with two children). This suggests that even in this very low fertility society, son preference and religious affiliation are significant predictors of women's practice of induced abortion.

  4. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

    Science.gov (United States)

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

    2016-01-22

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. The risk of cryptorchidism among sons of women working in horticulture in Denmark

    DEFF Research Database (Denmark)

    Gabel, Pernille; Jensen, Morten Søndergaard; Andersen, Helle Raun

    2011-01-01

    Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate wheth...... pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism....

  6. "Fathers and Sons" in Xenophon's Teaching of the Man Taking Care of Himself

    Science.gov (United States)

    Pichugina, Victoria; Bezrogov, Vitaly

    2017-01-01

    This article considers the oeuvre of Xenophon (c.430-354 bc) as providing an insight into the concept of "care of the self" in Greek education. In many of his works the leading characters are men who take care of themselves through education. Addressing the theme of "fathers and sons," Xenophon aimed to show that "care of…

  7. Poetics of Narrative: A Study on the "Sons of the Wind" by Laila Al Atrash

    Science.gov (United States)

    Al Zuraigat, Asma M.; Zeidanin, Hussein Hasan

    2015-01-01

    This study aims at identifying the poetic devices overlapping with the genre of fiction in Laila Al Atrash's novel "The Sons of the Wind". The devices the study explores are the poetics of the title, poetics of the prologue and poetics of the language upon which the writer relies to support her point of view about the topics and issues…

  8. Mother-son discrepant reporting on parenting practices: The contribution of temperament and depression.

    Science.gov (United States)

    Shishido, Yuri; Latzman, Robert D

    2017-06-01

    Despite low to moderate convergent correlations, assessment of youth typically relies on multiple informants for information across a range of psychosocial domains including parenting practices. Although parent-youth informant discrepancies have been found to predict adverse youth outcomes, few studies have examined contributing factors to the explanation of informant disagreements on parenting practices. The current study represents the first investigation to concurrently examine the role of mother and son's self-reported affective dimensions of temperament and depression as pathways to informant discrepancies on parenting practices. Within a community sample of 174 mother-son dyads, results suggest that whereas mother's self-reported temperament evidenced no direct effects on discrepancies, the association between the product term of mother's negative and positive temperament and discrepancies on positive parenting was fully mediated by mother's depression (a mediated moderation). In contrast, son's self-reported temperament evidenced both direct and indirect effects, partially mediated by depression, on rating discrepancies for positive parenting. All told, both son's self-reported affective dimensions of temperament and depression contributed to the explanation of discrepant reporting on parenting practices; only mother's self-reported depression, but not temperament, uniquely contributed. Results highlight the importance of considering both parent and youth's report in the investigation of informant discrepancies on parenting practices. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. When the Least Restrictive Environment is Residential: Meeting the Needs of Our Son

    Science.gov (United States)

    Morris, Djenne-Amal

    2013-01-01

    In this article, the author, a parent of Malik, a special needs child with CHARGE Syndrome, describes the difficulties she encountered with her local educational agency (LEA) in transitioning her son from the Perkins School for the Blind in Watertown, Massachusetts to the Eastern North Carolina School for the Deaf (ENCSD). At ENCSD, Malik now…

  10. Andrew Wyeth and N.C. Wyeth: a psychodynamic perspective on father and son.

    Science.gov (United States)

    Shaw, Jon A

    2013-01-01

    This paper examines the relationship between two extraordinary artists, father and son--N.C. Wyeth (1882-1945) and Andrew Wyeth (1917-2009)--and their art. N.C. Wyeth, the father, the most famous illustrator of his day, painted scenes full of drama and action, often of men engaged in violent life and death struggles. N.C. was unable to separate from his powerful mother and yearned for his iconic father. He thought himself an artistic failure and dedicated himself to raising his children to be geniuses. The youngest son, Andrew Wyeth, who lived a "secret life," painted scenes often characterized by pathos: bleak and barren landscapes, leaden skies, tire tracks, gray framed houses, desiccated fields, and circling buzzards. In the father-son relationship, we often seen three themes perpetuated developmentally: (1) the son's identification with the innermost conflicts of his father; (2) the yearning for the iconic father of his youth; and (3) a continuation and disavowal of his father's life. These themes are played out in the relationship between Andrew Wyeth and his father.

  11. Compte rendu critique du livre Voir son steak comme un animal mort, de Martin Gibert

    Directory of Open Access Journals (Sweden)

    Drolet, Marie-Josée

    2016-10-01

    Full Text Available This critical review provides, first, a step-by-step synthesis of the arguments presented in each chapter of Martin Gibert’s bookVoir son steak comme un animal mort (Seeing your steak as a dead animal. Second, a critical perspective of the book and a personal reflection are presented.

  12. The (un) making of a man: fathers and sons in the African novel

    African Journals Online (AJOL)

    Lipenga

    Things Fall Apart (1958), Zakes Mda's The Sculptors of. Mapungubwe ... The important thing to note in his analysis is his highlighting of the various ... to this discussion – of a farmer (strong, hard-working, strict) who is contrasted with his son ...

  13. Ahn and Son Afr J Tradit Complement Altern Med. (2014) 11(1):28 ...

    African Journals Online (AJOL)

    cadewumi

    Ahn and Son Afr J Tradit Complement Altern Med. (2014) 11(1):28-29 ... The comparisons of the frequency and choice of functional supplements were analysed using Chi-square test with. SPSS (SPSSs 18.0K for ... Significant difference of choice for functional supplements was observed between male and female (p < 0.01) ...

  14. The Putative Son's Attractiveness Alters the Perceived Attractiveness of the Putative Father.

    Science.gov (United States)

    Prokop, Pavol

    2015-08-01

    A body of literature has investigated female mate choice in the pre-mating context (pre-mating sexual selection). Humans, however, are long-living mammals forming pair-bonds which sequentially produce offspring. Post-mating evaluations of a partner's attractiveness may thus significantly influence the reproductive success of men and women. I tested herein the theory that the attractiveness of putative sons provides extra information about the genetic quality of fathers, thereby influencing fathers' attractiveness across three studies. As predicted, facially attractive boys were more frequently attributed to attractive putative fathers and vice versa (Study 1). Furthermore, priming with an attractive putative son increased the attractiveness of the putative father with the reverse being true for unattractive putative sons. When putative fathers were presented as stepfathers, the effect of the boy's attractiveness on the stepfather's attractiveness was lower and less consistent (Study 2). This suggests that the presence of an attractive boy has the strongest effect on the perceived attractiveness of putative fathers rather than on non-fathers. The generalized effect of priming with beautiful non-human objects also exists, but its effect is much weaker compared with the effects of putative biological sons (Study 3). Overall, this study highlighted the importance of post-mating sexual selection in humans and suggests that the heritable attractive traits of men are also evaluated by females after mating and/or may be used by females in mate poaching.

  15. The (un) making of a man: fathers and sons in the African novel

    African Journals Online (AJOL)

    Lipenga

    This perspective enables a reading of the texts as not merely depicting ... level, these texts reveal a structural trend where the relationship between the .... recipient of the teaching of masculinity, as Okonkwo's adopted son. .... from a feminist point of view, but in Mapungubwe, the norm is that a woman ..... critical dualism.

  16. Fathers Are Important People: A Study of Father-Son Sexual Communication

    Science.gov (United States)

    DiIorio, Colleen; Lehr, Sally; Wasserman, Jill L.; Eichler, Michelle; Cherry, Chauncey; Denzmore, Pamela

    2006-01-01

    The purpose of this study was to examine the perceived role of African-American fathers in educating their sons about sex and HIV prevention. Given that some studies have shown a relationship between parent-adolescent sexual communication and adolescent sexual behavior, and the disproportionately high rates of teen pregnancy and HIV (and other…

  17. Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

    OpenAIRE

    Morton, Daniel J.; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

    1999-01-01

    Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

  18. Mechanisms of zinc binding to the solute-binding protein AztC and transfer from the metallochaperone AztD.

    Science.gov (United States)

    Neupane, Durga P; Avalos, Dante; Fullam, Stephanie; Roychowdhury, Hridindu; Yukl, Erik T

    2017-10-20

    Bacteria can acquire the essential metal zinc from extremely zinc-limited environments by using ATP-binding cassette (ABC) transporters. These transporters are critical virulence factors, relying on specific and high-affinity binding of zinc by a periplasmic solute-binding protein (SBP). As such, the mechanisms of zinc binding and release among bacterial SBPs are of considerable interest as antibacterial drug targets. Zinc SBPs are characterized by a flexible loop near the high-affinity zinc-binding site. The function of this structure is not always clear, and its flexibility has thus far prevented structural characterization by X-ray crystallography. Here, we present intact structures for the zinc-specific SBP AztC from the bacterium Paracoccus denitrificans in the zinc-bound and apo-states. A comparison of these structures revealed that zinc loss prompts significant structural rearrangements, mediated by the formation of a sodium-binding site in the apo-structure. We further show that the AztC flexible loop has no impact on zinc-binding affinity, stoichiometry, or protein structure, yet is essential for zinc transfer from the metallochaperone AztD. We also found that 3 His residues in the loop appear to temporarily coordinate zinc and then convey it to the high-affinity binding site. Thus, mutation of any of these residues to Ala abrogated zinc transfer from AztD. Our structural and mechanistic findings conclusively identify a role for the AztC flexible loop in zinc acquisition from the metallochaperone AztD, yielding critical insights into metal binding by AztC from both solution and AztD. These proteins are highly conserved in human pathogens, making this work potentially useful for the development of novel antibiotics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Feature Binding in Zebrafish

    Directory of Open Access Journals (Sweden)

    P Neri

    2012-07-01

    Full Text Available Binding operations are primarily ascribed to cortex or similarly complex avian structures. My experiments show that the zebrafish, a lower vertebrate lacking cortex, supports visual feature binding of form and motion for the purpose of social behavior. These results challenge the notion that feature binding may require highly evolved neural structures and demonstrate that the nervous system of lower vertebrates can afford unexpectedly complex computations.

  20. DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells.

    Science.gov (United States)

    Singh, Kamaleshwar P; Treas, Justin; Tyagi, Tulika; Gao, Weimin

    2012-03-01

    Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA hypermethylation is known to inactivate DNA repair genes and apoptotic response in cancer cells. Therefore, the objective of this study was to determine the role of DNA hypermethylation in estrogen-induced cell growth and regulation of DNA repair genes expression in breast cancer cells. To achieve this objective, the estrogen-responsive MCF-7 cells either pretreated with 5-aza-2-deoxycytidine (5-aza-dC) or untreated (as control) were exposed to 17 beta-estradiol (E2), and its effect on cell growth and expression of DNA repair genes were measured. The result revealed that 5-aza-dC abrogates the E2-induced growth in MCF-7 cells. An increased expression of OGG1, MSH4, and MLH1 by 5-aza-dC treatment alone, suggest the DNA hypermethylation as a potential cause for decreased expression of these genes in MCF-7 cells. The decreased expression of ERCC1, XPC, OGG1, and MLH1 by E2 alone and its restoration by co-treatment with 5-aza-dC further suggest that E2 reduces the expression of these DNA repair genes potentially through promoter hypermethylation. Reactivation of mismatch repair (MMR) gene MLH1 and abrogation of E2-induced cell growth by 5-aza-dC treatment suggest that estrogen causes increased growth in breast cancer cells potentially through the inhibition of MMR-mediated apoptotic response. In summary, this study suggests that estrogen increases cell growth and decreases the DNA repair capacity in breast cancer cells, at least in part, through epigenetic mechanism. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications.

    Directory of Open Access Journals (Sweden)

    Jose L Ortega Roldan

    Full Text Available SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination.

  2. DOLOR Y SUFRIMIENTO NO SON SINÓNIMOS PERO SON INTRÍNSECOS A LA NATURALEZA HUMANA:UNA VISIÓN DEL DOLOR Y EL SUFRIMIENTO HUMANO

    Directory of Open Access Journals (Sweden)

    Rubén Darío Camargo

    2012-01-01

    Full Text Available El dolor y el sufrimiento no tienen un referente histórico en el hombre. Solo desde que el hombre es consciente de su humanidad se presenta el dolor y el sufrimiento. El hombre y el dolor siempre han existido, se sufre cuando se nace y se siente dolor, proceso que se repite en cada respiración celular, en cada reacción de oxireducción. Bioló-gicamente en Latín PATIOR = SUFRIR-PADECER es el esfuerzo energético de todo ser vivo para su integración factorial celular.En la medicina el dolor tiene su explicación anatómica y fisiológica, el dolor hace referencia a lo somático y a lo fisiológico. El Dolor agudo es la consecuencia inmediata de la activación del siste-ma nociceptivo, generalmente por un daño tisular somático o visceral, desapareciendo habitualmente con la lesión que lo originó. El Dolor crónico es aquel que persiste en ausencia de la lesión perifé-rica inicial. En la esencia de la filosofía el dolor es impensable e inteligible, se siente, se maneja se tolera pero no se piensa en dolor. Dolor y sufrimiento no son sinónimos pero son intrínsecos a la naturaleza humana. El hombre cuando experimenta el dolor se encuentra con su propio límite, con su propia impotencia de no poder cambiar un hecho real. El sufrimiento humano en la atención diaria del paciente enfermo no lo maneja-mos por ser este algo intangible no monitorizable y mucho menos medible y cuantificable.El dolor del enfermo no es libre ni voluntario, es producto de la fragilidad de su materia, el dolor del que sufre despierta en sus familiares la solidaridad y Tolerancia.

  3. Why Are Indian Children So Short? The Role of Birth Order and Son Preference.

    Science.gov (United States)

    Jayachandran, Seema; Pandi, Rohini

    2017-09-01

    Child stunting in India exceeds that in poorer regions like sub-Saharan Africa. Data on over 168,000 children show that, relative to Africa, India's height disadvantage increases sharply with birth order. We posit that India’s steep birth order gradient is due to favoritism toward eldest sons, which affects parents' fertility decisions and resource allocation across children. We show that, within India, the gradient is steeper for high-son-preference regions and religions. The gradient also varies with sibling gender as predicted. A back-of-the-envelope calculation suggests that India's steeper birth order gradient can explain over one-half of the India-Africa gap in average child height.

  4. Experiences of parents whose sons or daughters have (had) attempted suicide

    DEFF Research Database (Denmark)

    Buus, Niels; Caspersen, Jimmy; Hansen, Rasmus

    2014-01-01

    problem and relatives are understood as playing an important role in suicide prevention; however, suicide and suicidal behaviour affect the relatives' lives profoundly, both emotionally and socially, and the psychosocial impact on families is underresearched. DESIGN: Focus groups with parents of sons......AIM: The aim of this exploratory study was to gain further insights into the experiences of parents of sons or daughters who have attempted suicide and how these parents respond to the increased psychosocial burden following the suicide attempt(s). BACKGROUND: Suicide is a major public health...... or daughters who have attempted suicide. METHODS: In January and February 2012, we interviewed two groups of parents recruited at a counselling programme for relatives of persons who have attempted suicide. The analysis combined a thematic analysis with a subsequent analysis of how the themes were negotiated...

  5. Parents' perceptions of their adolescent sons' recovery in a therapeutic community for addicted clients.

    Science.gov (United States)

    Chen, Gila; Elisha, Ety; Timor, Uri; Ronel, Natti

    2013-11-01

    A qualitative phenomenological study of parents of addicted male adolescents who were residents of a Jewish therapeutic community (TC) describes and interprets the parents' perceptions of the recovery process. Deep, semistructured interviews with 14 parents provided the data. The parents' perceptions were clustered into three main themes of meaning: (a) the process of change, (b) the experiences of family members in the course of the son's recovery process, and (c) the parents' perception of the treatment at Retorno. According to the parents, the admission of their sons into the TC brought notable relief to the family life, which enabled the whole family to begin a recovery process. The findings support the positive criminology perspective that emphasizes the disintegration-integration vector as significant in the recovery process. Recommendations for intervention planning are provided.

  6. 6j-symbols for symmetric representations of SO(n) as the double series

    International Nuclear Information System (INIS)

    Alisauskas, Sigitas

    2002-01-01

    The corrected triple sum expression of Alisauskas (1987 J. Phys. A: Math. Gen. 20 35) for the recoupling (Racah) coefficients (6j-symbols) of the symmetric (most degenerate) representations of the orthogonal groups SO(n) (previously derived from the fourfold sum expression of Alisauskas also related to the result of Hormess and Junker (1999 J. Phys. A: Math. Gen. 32 4249) is rearranged into three new different double sum expressions (related to the hypergeometric Kampe de Feriet type series) and a new triple sum expression with preferable summation condition. The Regge type symmetry of special 6j-symbols of the orthogonal groups SO(n) in terms of special Kampe de Feriet F 1:4 1:3 series is revealed. The recoupling coefficients for antisymmetric representations of symplectic group Sp(2n) are derived using their relation with the recoupling coefficients of the formal orthogonal group SO(-2n)

  7. O campo magnético e a massa dos mésons

    OpenAIRE

    Camila Sampaio Machado

    2013-01-01

    Neste trabalho buscamos explorar os efeitos do campo magnético, criado em colisões de íons pesados não-centrais, em estados ligados. Motivados pelo caso do átomo de hidrogênio, onde a presença do campo magnético deixa o estado mais ligado,estudamos o caso dos mésons B e D. Inicialmente trabalhamos com a equação de Schrödinger e utilizamos o modelo de potencial de Cornell que faz uma boa descrição da espectroscopoia de mésons pesados. Em seguida, utilizando as regras de soma da QCD, procuram...

  8. The Son's Fault: Martin Luther King, Jr.'s Search for and Recovery of Sonship.

    Science.gov (United States)

    Hinds, Jay-Paul

    2018-04-01

    This article examines the role of sonship in the psychological and spiritual development of men. In using the methodology of psychobiography, I explore the life history of Martin Luther King, Jr. to analyze his search for and recovery of sonship. I propose that sonship helps men rebel against and, in the end, overcome the feelings of inadequacy that are experienced in their struggles to achieve manhood, particularly within the father-son dyad. The scholarship of pastoral theologian Donald Capps is instructive in this regard, in that he suggests that sons should be allowed to search for a male figure, a father-substitute, who can affirm, not disdain or reject, this state of sonship. In the end, what is often viewed as a negative act of regression-i.e., the recovery of and return to sonship-is recognized instead as a positive one that assists a man in his journey toward wholeness.

  9. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    Packer, S.; Fairchild, R.G.; Watts, K.P.; Greenberg, D.; Hannon, S.J.

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  10. Competitive protein binding assay

    International Nuclear Information System (INIS)

    Kaneko, Toshio; Oka, Hiroshi

    1975-01-01

    The measurement of cyclic GMP (cGMP) by competitive protein binding assay was described and discussed. The principle of binding assay was represented briefly. Procedures of our method by binding protein consisted of preparation of cGMP binding protein, selection of 3 H-cyclic GMP on market, and measurement procedures. In our method, binding protein was isolated from the chrysalis of silk worm. This method was discussed from the points of incubation medium, specificity of binding protein, the separation of bound cGMP from free cGMP, and treatment of tissue from which cGMP was extracted. cGMP existing in the tissue was only one tenth or one scores of cGMP, and in addition, cGMP competed with cGMP in binding with binding protein. Therefore, Murad's technique was applied to the isolation of cGMP. This method provided the measurement with sufficient accuracy; the contamination by cAMP was within several per cent. (Kanao, N.)

  11. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory; Proposition de Loi visant a abroger les permis exclusifs de recherches d'hydrocarbures non conventionnels et a interdire leur exploration et leur exploitation sur le territoire national

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  12. Bill project aiming at abrogating exclusive search permits for unconventional hydrocarbon searches, and at prohibiting their exploration and exploitation of the national territory; Proposition de Loi visant a abroger les permis exclusifs de recherches d'hydrocarbures non conventionnels et a interdire leur exploration et leur exploitation sur le territoire national

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    After having briefly recalled the origin of shale gases, their extraction process and the evolution of their production in the USA, the authors outline the extremely negative environmental impacts of the fracking technique (hydraulic fracturing): water pollution, air pollution, soil pollution, existence of numerous drilling sites which would degrade landscapes, water and soil contamination risks. As some search permits have already been awarded, and while taking these negative consequences into account, the authors propose a bill project to prohibit these explorations, to abrogate the existing permits, and to ensure public information before bestowing such search permits and exploitation concessions

  13. Borgring sæson 1 - Vold, brand og ødelæggelse

    DEFF Research Database (Denmark)

    Ulriksen, Jens; Christensen, Jonas; Holm, Nanna

    2017-01-01

    son 1 af Borgringprojektet er overstået – i hvert fald i marken. Efter måneders planlægning, både blandt arkæologer og formidlingsfolk, kunne Hendes Majestæt Dronningen officielt åbne den publikumsorienterede del af forskningsprojektet den sidste dag i maj 2016. Gennem de følgende tre måneder bl...

  14. Las computadoras ¿son buenas o malas para los niños?

    Directory of Open Access Journals (Sweden)

    Revista Chasqui

    2015-01-01

    Full Text Available Se trabaja sobre un estudio del Instituo Argentino de Computación. Sobre las computadoras hay criterios opuestos unos las defienden y otros las atacan, pero lo cierto es que éstas no son ni buenas ni malas para los niños. Da a los padres y maestros advertencias sobre los riesgos. Informa sobre el programa Kidkey que ayuda a fijar el tiempo de conexión a Internet.

  15. The iron swords from the necropolis of Son Pellisser; preliminary advance

    Directory of Open Access Journals (Sweden)

    Agustín Fernández Mártinez

    2016-11-01

    Full Text Available This paper submits the iron swords from the necropolis of Son Pellisser (Calvià-Majorca. Although the materials that we find are numerous and still under research offer a preliminary study about three imported swords, found in burial objects, also their possible origin and way of introduction on the island. These weapons could be the first archaeological evidence that the Balearic mercenaries participated in the Wars of Sicily, between Carthaginians and Greeks, from the fifth century BC.

  16. ¡Son notables… los desaciertos y los vacíos!

    Directory of Open Access Journals (Sweden)

    Manuel Argüello Rodríguez

    2007-10-01

    Full Text Available Son notables las ausencias y los equilibrios forzados en el informe de los cinco ciudadanos costarricenses sobre el TLC. Ausencias y seudoequilibrios que han sido ya utilizados para fortalecer la campaña de propaganda arrebatadora contra la oposición al TLC indicando que ‘los notables’ desnudaron los fantasmas (con lo cual, a decir verdad no se vería nada, sería la total transparencia.

  17. Values that Fathers Communicate to Sons about Sex, Sexuality, Relationships, and Marriage.

    Science.gov (United States)

    Coakley, Tanya M; Randolph, Schenita D; Shears, Jeffrey; Collins, Patrick

    2017-01-01

    African American males between ages 13 and 24 are disproportionately affected by unintended pregnancy and sexually transmitted infections (STIs) such as chlamydia, gonorrhea, syphilis, and HIV/AIDS; indeed, they account for 50% of HIV infections among all youth. Clear communication between parents and their youth about sex is associated with higher rates of sexual abstinence, condom use, and intent to delay initiation of sexual intercourse, which can prevent STIs and unintended pregnancy. However, barriers exist for parents to educate their youth about sexual health. The purpose of this article is to explore the values fathers communicate to their sons to prevent their risky sexual behaviors that lead to STIs, HIV, and adolescent parenthood. This was a qualitative study conducted from May and June 2015. African American fathers (N = 29) who had sons, ages 10 to 15 years, participated in five focus groups across metropolitan and rural North Carolina communities in barbershops. A qualitative content analysis revealed four themes regarding areas that fathers imparted their values onto their sons to protect them from sexual health risks: (a) sex, (b) sexuality, (c) relationships, and (d) marriage. The findings have implications for social work and public health practice.

  18. Multivariate Multiple Regression Models for a Big Data-Empowered SON Framework in Mobile Wireless Networks

    Directory of Open Access Journals (Sweden)

    Yoonsu Shin

    2016-01-01

    Full Text Available In the 5G era, the operational cost of mobile wireless networks will significantly increase. Further, massive network capacity and zero latency will be needed because everything will be connected to mobile networks. Thus, self-organizing networks (SON are needed, which expedite automatic operation of mobile wireless networks, but have challenges to satisfy the 5G requirements. Therefore, researchers have proposed a framework to empower SON using big data. The recent framework of a big data-empowered SON analyzes the relationship between key performance indicators (KPIs and related network parameters (NPs using machine-learning tools, and it develops regression models using a Gaussian process with those parameters. The problem, however, is that the methods of finding the NPs related to the KPIs differ individually. Moreover, the Gaussian process regression model cannot determine the relationship between a KPI and its various related NPs. In this paper, to solve these problems, we proposed multivariate multiple regression models to determine the relationship between various KPIs and NPs. If we assume one KPI and multiple NPs as one set, the proposed models help us process multiple sets at one time. Also, we can find out whether some KPIs are conflicting or not. We implement the proposed models using MapReduce.

  19. Girl adoption in China-A less-known side of son preference.

    Science.gov (United States)

    Chen, Yuyu; Ebenstein, Avraham; Edlund, Lena; Li, Hongbin

    2015-01-01

    In 1987, 4 per cent of girls were adopted within China. Why? Unlike infanticide, abandonment rids parents of daughters while preserving the supply of potential brides. In fact, an erstwhile tradition common in Fujian and Jiangxi provinces had parents of sons adopting an infant girl to serve as a future daughter-in-law and household help. Analysing a nationally representative 1992 survey of children, we found that: (1) girl adoptions were concentrated in the above-mentioned provinces; (2) girls were predominantly adopted by families with sons; (3) adopted girls faced substantial disadvantage as measured by school attendance at ages 8-13. In the 1990s, as the sex ratio at birth climbed, were girls aborted rather than abandoned? Observing that in the 2000 census too many girls appear in families with older sons, we estimated that at least 1/25 girls were abandoned in the 1990s, a proportion that in Fujian and Jiangxi may have peaked at 1/10 in 1994.

  20. Paternal antisocial behavior and sons' cognitive ability: a population-based quasiexperimental study.

    Science.gov (United States)

    Latvala, Antti; Kuja-Halkola, Ralf; Långström, Niklas; Lichtenstein, Paul

    2015-01-01

    Parents' antisocial behavior is associated with developmental risks for their offspring, but its effects on their children's cognitive ability are unknown. We used linked Swedish register data for a large sample of adolescent men (N = 1,177,173) and their parents to estimate associations between fathers' criminal-conviction status and sons' cognitive ability assessed at compulsory military conscription. Mechanisms behind the association were tested in children-of-siblings models across three types of sibling fathers with increasing genetic relatedness (half-siblings, full siblings, and monozygotic twins) and in quantitative genetic models. Sons whose fathers had a criminal conviction had lower cognitive ability than sons whose fathers had no conviction (any crime: Cohen's d = -0.28; violent crime: Cohen's d = -0.49). As models adjusted for more genetic factors, the association was gradually reduced and eventually eliminated. Nuclear-family environmental factors did not contribute to the association. Our results suggest that the association between men's antisocial behavior and their children's cognitive ability is not causal but is due mostly to underlying genetic factors. © The Author(s) 2014.

  1. Mutational definition of binding requirements of an hnRNP-like protein in Arabidopsis using fluorescence correlation spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Leder, Verena [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Lummer, Martina [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Tegeler, Kathrin [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Humpert, Fabian [Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Lewinski, Martin [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany); Schüttpelz, Mark [Biomolecular Photonics, Faculty of Physics, Bielefeld University (Germany); Staiger, Dorothee, E-mail: dorothee.staiger@uni-bielefeld.de [Molecular Cell Physiology, Faculty of Biology, Bielefeld University (Germany)

    2014-10-10

    Highlights: • We use FCS to investigate binding site requirements for the hnRNP-like protein AtGRP7. • We identify three nucleotides critical for AtGRP7 binding to its own intron. • Mutation of the conserved R{sup 49} abolishes binding altogether. • The paralogue AtGRP8 binds to an overlapping motif with different sequence requirement. • The glycine-rich stretch of a plant hnRNP-like protein contributes to binding. - Abstract: Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased K{sub d} value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R{sup 49} that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding.

  2. Mutational definition of binding requirements of an hnRNP-like protein in Arabidopsis using fluorescence correlation spectroscopy

    International Nuclear Information System (INIS)

    Leder, Verena; Lummer, Martina; Tegeler, Kathrin; Humpert, Fabian; Lewinski, Martin; Schüttpelz, Mark; Staiger, Dorothee

    2014-01-01

    Highlights: • We use FCS to investigate binding site requirements for the hnRNP-like protein AtGRP7. • We identify three nucleotides critical for AtGRP7 binding to its own intron. • Mutation of the conserved R 49 abolishes binding altogether. • The paralogue AtGRP8 binds to an overlapping motif with different sequence requirement. • The glycine-rich stretch of a plant hnRNP-like protein contributes to binding. - Abstract: Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased K d value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R 49 that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding

  3. The Son Jarocho and Fandango Amidst Struggle and Social Movements: Migratory Transformation and Reinterpretation of the Son Jarocho in La Nueva Espa�a, M�xico, and the United States

    OpenAIRE

    Hern�ndez, Alexandro David

    2014-01-01

    This dissertation is a study on the son jarocho and its fandango as a migratory and transformative musical culture between nations and social circumstances. The son jarocho embodies tradition in many cultural practices of society, such as its presence at social rites and at fandangos. However, there exist hidden histories, transcripts of resistance not accounted for in M�xico's official history, of the son jarocho as music of struggle and protest. From censorship, punishment, and imprisonme...

  4. Complicated grief and manic comorbidity in the aftermath of the loss of a son.

    Science.gov (United States)

    Carmassi, Claudia; Shear, M Katherine; Socci, Chiara; Corsi, Martina; Dell'osso, Liliana; First, Michael B

    2013-09-01

    Based on the recommendations of the sub-workgroup on trauma and dissociative disorders, the American Psychiatric Association (APA) removed the "bereavement exclusion" from the criteria for major depression in DSM-5. In addition, proposed DSM-5 research criteria for persistent complex bereavement disorder (PCBD) were included in the new manual in a section for conditions and criteria needing further research. We describe a case that warranted such a diagnosis. The patient was a 52- year-old woman who was admitted to the inpatient unit of our clinic on the birthday of her son who had died 18 months earlier. She was diagnosed with a manic episode with psychotic symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and was treated accordingly. Three months after discharge, she made a suicide attempt and was admitted and re-assessed. During this admission, she completed the Inventory of Complicated Grief (ICG), the Mood-Spectrum Rating Scale (MOODS-SR), and the Trauma and Loss Spectrum questionnaire (TALS-SR). She endorsed symptoms of intense yearning for her son, feelings of shock and disbelief, anger and bitterness related to his death, estrangement from others, auditory, tactile and visual hallucinations of the deceased, and intense emotional reactivity to memories of her son. These symptoms were sufficiently prolonged and severe to meet criteria for complicated grief. While complicated grief appeared to be the primary diagnosis for this patient, when she was diagnosed using only DSMIV-TR criteria, her treatment failed to address herprimary problem. This case draws attention to the occurrence of manic-like symptoms as well as depression-like manifestations following bereavement and highlights the importance of including the syndrome of complicated grief in the diagnostic nomenclature.

  5. The risk of cryptorchidism among sons of women working in horticulture in Denmark: a cohort study.

    Science.gov (United States)

    Gabel, Pernille; Jensen, Morten Søndergaard; Andersen, Helle Raun; Baelum, Jesper; Thulstrup, Ane Marie; Bonde, Jens Peter; Toft, Gunnar

    2011-11-14

    Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate whether pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism. We conducted a cohort study of pregnant women working in horticulture using four cohorts including one cohort established with data from the departments of occupational medicine in Jutland and Funen and three existing mother-child cohorts (n=1,468). A reference group was established from the entire Danish population of boys born in the period of 1986-2007 (n=783,817). Nationwide Danish health registers provided information on birth outcome, cryptorchidism diagnosis and orchiopexy. The level of occupational exposure to pesticides was assessed by expert judgment blinded towards outcome status. Risk of cryptorchidism among exposed horticulture workers compared to the background population and to unexposed horticulture workers was assessed by Cox regression models. Pesticide exposed women employed in horticulture had a hazard ratio (HR) of having cryptorchid sons of 1.39 (95% CI 0.84; 2.31) and a HR of orchiopexy of 1.34 (0.72; 2.49) compared to the background population. Analysis divided into separate cohorts revealed a significantly increased risk of cryptorchidism in cohort 2: HR 2.58 (1.07;6.20) and increased risk of orchiopexy in cohort 4: HR 2.76 (1.03;7.35), but no significant associations in the other cohorts. Compared to unexposed women working in horticulture, pesticide exposed women had a risk of having sons with cryptorchidism of 1.34 (0.30; 5.96) and of orchiopexy of 1.93 (0.24;15.4). The data are compatible with a slightly increased risk of cryptorchidism in sons of women exposed to pesticides by working in horticulture.

  6. Representations of the algebra Uq'(son) related to quantum gravity

    International Nuclear Information System (INIS)

    Klimyk, A.U.

    2002-01-01

    The aim of this paper is to review our results on finite dimensional irreducible representations of the nonstandard q-deformation U q ' (so n ) of the universal enveloping algebra U(so(n)) of the Lie algebra so(n) which does not coincide with the Drinfeld-Jimbo quantum algebra U q (so n ).This algebra is related to algebras of observables in quantum gravity and to algebraic geometry.Irreducible finite dimensional representations of the algebra U q ' (so n ) for q not a root of unity and for q a root of unity are given

  7. ¿Son Fiables las Estimaciones de Pobreza en América Latina?

    OpenAIRE

    Sanjay G. Reddy

    2008-01-01

    ¿Cuál es el nivel de pobreza de ingresos en América Latina? ¿Ha estado disminuyendo? ¿Son fiables las estimaciones actuales? El enfoque más influyente para medir la pobreza de ingresos a nivel regional y mundial es él utilizado por el Banco Mundial, que establece líneas internacionales de pobreza de ?un dólar al día? y ?dos dólares al día? por persona. El banco utiliza factores de ?paridad del poder adquisitivo? (PPA) para transformar estas líneas internacionales en monedas locales. (...)...

  8. Failed Mothers, Monster Sons. Reading Shakespeare’S Richard Iii as a Fairy Tale

    Directory of Open Access Journals (Sweden)

    Percec Dana

    2014-03-01

    Full Text Available The paper looks at Shakespeare’s historical play Richard III and its fairy tale-like character given by the configuration of the main character as an arch-villain and the presence of motifs and patterns typically associated with the fairy tale genre. More specifically, it considers the mother-son relationship between the Duchess of York and Richard in the light of the motif of monstrous birth. It is not a coincidence that the emergence of such motifs coincides with the historical contexts of the early modern period. Reading Richard III in this key is related to the revisionist approach to chronicle plays.

  9. THE EPITHESIS IN THE LOAN WORDS ALINTI KELİMELERDE SON TÜREME

    Directory of Open Access Journals (Sweden)

    Gülden SAĞOL YÜKSEKKAYA

    2010-01-01

    Full Text Available Anaptyxis is a sound appearing that is not found in the original structure of the word. There are three types of anaptyxis: prothesis, epenthesis and epithesis. Epithesis is a vowel or consonant appearing at the end of a word which is not found in the original structure of it. Although, there isn’t not so much example, both vowel and consonant reproduction is seen even in the last sound of the word; but the derivative sound isn’t the same, standard in the whole dialects and accents. Nevertheless some derivative sounds have an intense in a specific region, they aren’t seen in the other areas or has rare example. In this study, the epithesis in the loan words in Turkish will be emphasized. Bir kelimede aslında bulunmayan bir sesin sonradan ortaya çıkmasına ses türemesi denir. Ses türemesinin üç çeşidi vardır: ön türeme, iç türeme, son türeme. Son türeme, kelimenin aslında bulunmayan bir ünlü veya ünsüzün kelime sonunda belirmesidir. Örneği fazla olmamakla birlikte son seste de hem ünlü hem de ünsüz türemesi görülür. Ancak türeyen sesler standart olarak bütün lehçe ve ağızlarda ortak değildir. Türeyen bazı sesler belli bir bölge içerisinde yoğunlaşırken, bazı bölgelerde görülmemekte veya sadece birkaç, hatta bir örnekle sınırlı kalabilmektedir. Bu çalışmada Türkçede alıntı kelimelerdeki son türeme örnekleri üzerinde durulacaktır.

  10. THE APOCOPE IN THE LOAN WORDS ALINTI KELİMELERDE SON SES DÜŞMESİ

    Directory of Open Access Journals (Sweden)

    Aylin KOÇ

    2010-10-01

    Full Text Available Disappearance is the loss of a sound in structure of the word with some reasons. There are three types of disappearance: apheresis, syncope and apocope. The apocope is disappearance of a vowel or consonant at the end of a word. This situation isn’t standard in whole dialects and accents. Some dropping sounds, have an intense in a spesific region, they aren’t seen in the other areas or have rare examples. This is rather common in the dialects. In this study will be handled the apocope in the loan words with the examples in Turkey Turkish and contemporary Turkish dialects. Bir kelimedeki seslerden birinin, çeşitli nedenlerle düşmesine ses düşmesi denir. Ses düşmesi üç çeşittir: ön ses düşmesi, iç ses düşmesi ve son ses düşmesi. Son ses düşmesi, kelimede son ses durumunda olan ünlü veya ünsüzün düşmesidir. Bu durum, bütün lehçelerde ve ağızlarda standart değildir. Düşen bazı sesler, belli bir bölge içinde yoğunlaşırken, bazı bölgelerde görülmemekte ve hatta birkaç ya da bir örnekle sınırlı kalabilmektedir. Bu daha çok ağızlarda görülür. Çalışmada, Türkiye Türkçesinde ve Çağdaş Türk Lehçelerinde alıntı kelimelerde son ses düşmesi bahsi örnekleriyle ele alınacaktır.

  11. LA SABIDURIA DEL SILENCIO. HACIA EL DIÁLOGO... ¡OTROS MUNDOS SON POSIBLES!

    Directory of Open Access Journals (Sweden)

    Juan Carlos Valverde Campos

    2012-05-01

    Full Text Available A Occidentales y Orientales nos cobija un mismo techo. Sin embargo, la manera de concebir el mundo y, por ende, de actuar, es diferente. La sociedad globalizada en la que vivimos quiere hacer de este mundo uno solo, con un solo corazón y una sola manera de actuar y pensar. Occidente ha impuesto su mundo cuando en realidad son muchos y debemos conocerlos. El pensamiento oriental tiene mucho qué decirnos a los occidentales. En todo caso, el silencio que impone la escucha es fundamental en eso que tantos llaman hoy el diálogo.

  12. Son preference, number of children, education and occupational choice in rural Nepal

    OpenAIRE

    Hatlebakk, Magnus

    2012-01-01

    A unique family survey was conducted in Nepal to investigate the economic consequences of having a first-born girl. Women get more children, but we find no causal effect of number of children on economic outcomes. But independently of the number of children there is a positive effect on boys' education of having a first born sister, who presumably takes care of household work so the boys can focus on school. This indicates a stronger son-preference in Nepal than what is found in studies from ...

  13. The Tragedy of Hamlet, Son of an Organic Chemist of Denmark

    Science.gov (United States)

    Brisbois, Ronald G.

    2004-04-01

    Once faced with structure reactivity relationships in the context of nucleophilic substitution at sp 3 carbon, introductory organic chemistry students must compare and contrast the various attributes and ramifications of S N 2 versus S N 1 reaction pathways. The dramatic (even melodramatic) way in which some students ask such comparative questions inspired a parody of Hamlet's famous to be or not to be soliloquy. Herein, Hamlet (the son of an organic chemist of Denmark) is the surrogate of any and every student as he uses a thoroughly Shakespearian approach to sorting out some of the key distinguishing features of S N 2 versus S N 1 reactions.

  14. ¿Son efectivas las intervenciones para reducir el consumo de sodio en la dieta?

    Directory of Open Access Journals (Sweden)

    Gabriel Rada

    2015-09-01

    Full Text Available Las personas que consumen más sodio tienen cifras de presión arterial más alta, lo cual aumenta su morbimortalidad cardiovascular. El consumo de sodio en países latinoamericanos duplica o triplica lo recomendado, lo que ha llevado a redoblar los esfuerzos por abordar este problema. Los cambios de conducta y modificación de estilos de vida son difíciles de conseguir y mantener en el tiempo, por lo que las intervenciones a este nivel suelen precisar un abordaje desde múltiples perspectivas.

  15. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  16. Knockdown of platinum-induced growth differentiation factor 15 abrogates p27-mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis

    International Nuclear Information System (INIS)

    Meier, Julia C; Haendler, Bernard; Seidel, Henrik; Groth, Philip; Adams, Robert; Ziegelbauer, Karl; Kreft, Bertolt; Beckmann, Georg; Sommer, Anette; Kopitz, Charlotte

    2015-01-01

    Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer

  17. EGFR-targeted plasmonic magnetic nanoparticles suppress lung tumor growth by abrogating G2/M cell-cycle arrest and inducing DNA damage

    Directory of Open Access Journals (Sweden)

    Kuroda S

    2014-08-01

    Full Text Available Shinji Kuroda,1 Justina Tam,2 Jack A Roth,1 Konstantin Sokolov,2 Rajagopal Ramesh3–5 1Department of Thoracic and Cardiovascular Surgery, 2Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Pathology, 4Graduate Program in Biomedical Sciences, 5Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Background: We have previously demonstrated the epidermal growth factor receptor (EGFR-targeted hybrid plasmonic magnetic nanoparticles (225-NP produce a therapeutic effect in human lung cancer cell lines in vitro. In the present study, we investigated the molecular mechanism of 225-NP-mediated antitumor activity both in vitro and in vivo using the EGFR-mutant HCC827 cell line. Methods: The growth inhibitory effect of 225-NP on lung tumor cells was determined by cell viability and cell-cycle analysis. Protein expression related to autophagy, apoptosis, and DNA-damage were determined by Western blotting and immunofluorescence. An in vivo efficacy study was conducted using a human lung tumor xenograft mouse model. Results: The 225-NP treatment markedly reduced tumor cell viability at 72 hours compared with the cell viability in control treatment groups. Cell-cycle analysis showed the percentage of cells in the G2/M phase was reduced when treated with 225-NP, with a concomitant increase in the number of cells in Sub-G1 phase, indicative of cell death. Western blotting showed LC3B and PARP cleavage, indicating 225-NP-treatment activated both autophagy- and apoptosis-mediated cell death. The 225-NP strongly induced γH2AX and phosphorylated histone H3, markers indicative of DNA damage and mitosis, respectively. Additionally, significant γH2AX foci formation was observed in 225-NP-treated cells compared with control treatment groups, suggesting 225-NP induced cell death by triggering DNA damage. The 225-NP-mediated DNA damage involved abrogation of the

  18. Léon Bardalès: Sa vie et son œuvre

    Directory of Open Access Journals (Sweden)

    Ilias Taxidis

    2011-07-01

    Full Text Available Cette étude comprend la présentation et l’édition critique de deux lettres et six poèmes de Léon Bardalès qui fut l’un des dignitaires impériaux byzantins de la fin du XIIIe et du début du XIVe siècle. Pour l’occasion, toutes les données concernant l’auteur et son activité politique et littéraire sont réévaluées conformément aux informations fournies par les lettres que Bardalès a reçues d’épistoliers connus de son époque, comme Maxime Planude, Nicéphore Choumnos et Nicéphore Grégoras. Dans l’édition, les erreurs et fautes d’inattention des éditeurs précédents sont corrigées, et un apparat des sources est ajouté.

  19. A Stylistic Analysis of D.H. Lawrence’s ‘Sons and Lovers’

    Directory of Open Access Journals (Sweden)

    Nozar Niazi

    2013-05-01

    Full Text Available This paper aims at analyzing D.H. Lawrence’s ‘Sons and Lovers’ using a stylistic approach. Stylistics is a study of the amalgamation of form with content. The stylistic analysis of a novel goes beyond the traditional, intuitive interpretation, because it combines intuition and detailed linguistic analysis of the text. The defining elements of modern language are within the text itself, not prescribed from outside. With modernist texts, usually understanding comes from close study of the language system defined within the text itself. Form, technique and style are considered not as a mere vehicle of the content of the story, but an integral part of the work’s meaning and value. In our analysis of ‘Sons and Lovers’ the resources of language: lexis, syntax, phonology, figurative language, cohesion and coherence, are discussed in relation to the style of discourse in order to explore hidden meanings in the text. The resources of language are shown to be an essential part of the meaning of the novel.

  20. Cinematic narratives of Sonderkommando: Son of saul or narrating the victim, perpetrator, trauma and death

    Directory of Open Access Journals (Sweden)

    Daković Nevena

    2016-01-01

    Full Text Available The aim of this paper is to map out - by analysing the film Son of Saul, but also by its comparison with two other films dealing with the topic, Himmelkommando and The Grey Zone, the narrative mechanism that satisfies the complex ethical and aesthetical demands imposed by the theme of Sonderkommando as the particular episode of the Holocaust. The key element of the narrative structure is the construction of the Levi’s “dead and drowned” witness who “resurrected” through the narrative intervention becomes the only reliable and credible narrator of the historical trauma. The prerequisite for his emergence is the narration and representation of the death which makes but also solves the traumatised - understood as multiple, fragmented, opposed - identities of the members of the special squad. Their entangled identity involves the simultaneous presence of a victim, perpetrator, witness and the authentic narrator of the trauma of the death camp. The death of the perpetrator is the condition sina qua non for the emergence of the figure of the victim-witness narrator but also for making of narrative which overcomes the initial trauma of the Holocaust. The detailed analysis of the film Son of Saul confirms and identifies these narratives as the modernist narration of the post-traumatic film.

  1. Seismic Interpretation of the Nam Con Son Basin and its Implication for the Tectonic Evolution

    Directory of Open Access Journals (Sweden)

    Nguyen Quang Tuan

    2016-06-01

    Full Text Available DOI:10.17014/ijog.3.2.127-137The Nam Con Son Basin covering an area of circa 110,000 km2 is characterized by complex tectonic settings of the basin which has not fully been understood. Multiple faults allowed favourable migration passageways for hydrocarbons to go in and out of traps. Despite a large amount of newly acquired seismic and well data there is no significant update on the tectonic evolution and history of the basin development. In this study, the vast amount of seismic and well data were integrated and reinterpreted to define the key structural events in the Nam Con Son Basin. The results show that the basin has undergone two extentional phases. The first N - S extensional phase terminated at around 30 M.a. forming E - W trending grabens which are complicated by multiple half grabens filled by Lower Oligocene sediments. These grabens were reactivated during the second NW - SE extension (Middle Miocene, that resulted from the progressive propagation of NE-SW listric fault from the middle part of the grabens to the margins, and the large scale building up of roll-over structure. Further to the SW, the faults of the second extentional phase turn to NNE-SSW and ultimately N - S in the SW edge of the basin. Most of the fault systems were inactive by Upper Miocene except for the N - S fault system which is still active until recent time.

  2. Thermodynamic and structural models compared with the initial dissolution rates of SON glass samples

    International Nuclear Information System (INIS)

    Tovena, I.; Advocat, T.; Ghaleb, D.; Vernaz, E.

    1993-01-01

    The experimentally determined initial dissolution rate R 0 of nuclear glass was correlated with thermodynamic parameters and structural parameters. The initial corrosion rates of six ''R7T7'' glass samples measured at 100 deg C in a Soxhlet device were correlated with the glass free hydration energy and the glass formation enthalpy. These correlations were then tested with a group of 26 SON glasses selected for their wide diversity of compositions. The thermodynamic models provided a satisfactory approximation of the initial dissolution rate determined under Soxhlet conditions for SON glass samples that include up to 15 wt% of boron and some alumina. Conversely, these models are inaccurate if the boron concentration exceeds 15 wt% and the glass contains no alumina. Possible correlations between R 0 and structural parameters, such as the boron coordination number and the number of nonbridging oxygen atoms, were also investigated. The authors show that R 0 varies inversely with the number of 4-coordinate boron atoms; conversely, the results do not substantiate published reports of a correlation between R 0 and the number of nonbridging oxygen atoms. (authors). 13 refs., 2 figs., 4 tabs

  3. The Quest for the Whole in D. H. Lawrence’s Sons and Lovers

    Directory of Open Access Journals (Sweden)

    Nesar Uddin

    2013-10-01

    Full Text Available David Herbert Lawrence portrays a complex husband-wife, mother-son, and man-woman relationship in his novel Sons and Lovers. This article studied the relational motifs of the major character Paul Morel with other characters and the dire upshot resulting from this relation. The study found that Paul strove for happiness through the concerted entertainment of body and soul with his beloved people, but he failed because his mother’s unusual attachment to him negatively impacted on his building up a normal relation with others. Mother’s failure to find happiness in her conjugal life led her to pouring her love into Paul, exploiting him, making him sub-serve her own need and denying him the right to his own independent life. As a result, the son’s relation with other women proved a disastrous failure. The women with whom Paul had relation underwent part of the sufferings somehow or other. Finally, Mother’s death made him hopeless and left his life in nothingness.

  4. Blueberry and malvidin inhibit cell cycle progression and induce mitochondrial-mediated apoptosis by abrogating the JAK/STAT-3 signalling pathway.

    Science.gov (United States)

    Baba, Abdul Basit; Nivetha, Ramesh; Chattopadhyay, Indranil; Nagini, Siddavaram

    2017-11-01

    Blueberries, a rich source of anthocyanins have attracted considerable attention as functional foods that confer immense health benefits including anticancer properties. Herein, we assessed the potential of blueberry and its major constituent malvidin to target STAT-3, a potentially druggable oncogenic transcription factor with high therapeutic index. We demonstrate that blueberry abrogates the JAK/STAT-3 pathway and modulates downstream targets that influence cell proliferation and apoptosis in a hamster model of oral oncogenesis. Further, we provide mechanistic evidence that blueberry and malvidin function as STAT-3 inhibitors in the oral cancer cell line SCC131. Blueberry and malvidin suppressed STAT-3 phosphorylation and nuclear translocation thereby inducing cell cycle arrest and mitochondrial-mediated apoptosis. However, the combination of blueberry and malvidin with the STAT-3 inhibitor S3I-201 was more efficacious in STAT-3 inhibition relative to single agents. The present study has provided leads for the development of novel combinations of compounds that can serve as inhibitors of STAT-mediated oncogenic signalling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Proteasome Inhibitor YSY01A Abrogates Constitutive STAT3 Signaling via Down-regulation of Gp130 and JAK2 in Human A549 Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2017-08-01

    Full Text Available Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells. The reduction in gp130 and JAK2 can be restored by co-treatment with 3-methyladenine, an early-stage autophagy lysosome and type I/III PI3K inhibitor. YSY01A also effectively inhibits cancer cell migration and lung xenograft tumor growth with little adverse effect on animals. Thus, our findings suggest that YSY01A represents a promising candidate for further development of novel anticancer therapeutics targeting the proteasome.

  6. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  7. Linking objects in the process of mourning for sons disappeared in war: Croatia 2001.

    Science.gov (United States)

    Jurcević, Slavica; Urlić, Ivan

    2002-04-01

    Mothers use linking object to externalize the complex aspects of their relationship to the loss of their child. We analyzed the linking objects that mothers kept in memory of their sons who disappeared in the 1991-1995 war in Croatia or whose remains were uncovered and identified long time after they had gone missing. The case study of disturbed mourning included 26 mothers of Croatian soldiers from Croatian Osijek-Baranja County who went missing in war or whose remains were recovered and identified long after they had gone missing. The mothers were selected independently by the president of the Association of Families of Missing and Detained Croatian Soldiers and agreed to participate in the study in 2001. They were interviewed in their homes, their testimonies were recorded, and photographs of the linking objects taken. Linking objects were classified according to the Volkan's four-group classification. Out of four Volkan's groups of linking objects, we identified the objects belonging to the first three. Those were 1) objects that had been worn by the deceased (clothes, wrist-watch, ring, or glasses), (6/26); 2) objects that could be viewed in the psychoanalytic sense as an extension of the body of the disappeared or dead person, such as a camera (4/26); and 3) objects with realistic or symbolic resemblance to the deceased, usually a photograph (8/26). None of the examined objects belonged to the fourth Volkan's group (objects at hand when the news of the death came or objects present at the funeral, things that could be considered last-minute objects, ie, related to the moment when the deceased was last seen alive). However, 8/26 objects formed a new hitherto undescribed group. Mothers used such objects to create a memorial shrine to their sons. A photograph of the missing person or person whose remains were identified long after he had gone missing occupied a central place at the shrine, and was surrounded by other symbols of the Catholic iconography (Virgin

  8. The Impact of Birth Order on Intergenerational Transmission of Attitudes from Parents to Adolescent Sons: The Israeli Case

    Science.gov (United States)

    Kulik, Liat

    2004-01-01

    This study deals with birth order and its impact on intergenerational transmission of parental attitudes to adolescent sons in Israeli society. The sample included 294 participants (including 98 mothers, 98 fathers, and 98 sons). The attitudes chosen were key issues of concern in Israeli society: gender role attitudes, ethnic stereotypes, and…

  9. From Here to There and Back Again: The Story of a Mother, Her Son, Disability, and School Choice

    Science.gov (United States)

    Mann, Glenys

    2016-01-01

    Nelly and her children live in Queensland, Australia. When it came time for her second youngest son to start school, Nelly was not prepared for the difficulty that she had enrolling him at the school of her choice. In spite of her son's disability, Nelly thought that it was natural that he would go to his local school with his sister. It is not…

  10. HIGHER PARENTAL PERCEPTIONS OF WEALTH ASSOCIATED WITH THE BIRTH OF MORE SONS IN AN AUSTRALIAN POPULATION.

    Science.gov (United States)

    Behie, A M; O'Donnell, M H

    2017-09-20

    Many industrialized nations are currently experiencing a decline in average secondary sex ratio (SSR) resulting in fewer boys being born relative to girls. While many potential factors may explain the decline in the birth of males relative to females, it seems most studies support the idea that male offspring are produced less often when environmental conditions are poor owing to males being more susceptible to loss in harsh environments. This study investigates the maternal factors that are associated with the sex of offspring in a cohort of the Australian population. It found that greater parental perceptions of wealth were significantly associated with an increase in the number of sons produced. These results suggest that male offspring are born at increased numbers to women with higher available resources, which may reflect the fact that male offspring are more vulnerable in poor environments.

  11. CUENTOS QUE NO SON CUENTOS...UN RECORRIDO POR SAN ZENÓN (MAGDALENA

    Directory of Open Access Journals (Sweden)

    Tania Ximena Salcedo Goméz

    2013-07-01

    Full Text Available Es de tarde y el sol inclemente de febrero se refleja sobre Las cálidas aguas del río Magdalena; sus visos en naranja y rojo se inmortalizan en el tapiz del cielo, mientras en tierra, esta gama de luz iridescente se forja en la piel de los hombres y mujeres de San Zenón. Los árboles desnudos han sido bañados por el frío invierno. Las ciénagas y el río han dejado sus marcas a través del marrón 330 de sus cortezas. Las pocas hojas que quedan son solo un breve recuerdo de un amanecer con sombra. El asfalto y la pasividad del viento, quienes amenazan la lucidez.

  12. Bad Mothers and Monstrous Sons: Autistic Adults, Lifelong Dependency, and Sensationalized Narratives of Care.

    Science.gov (United States)

    Allen, Holly

    2017-03-01

    Sensationalized representations of autistic families in film and other media frequently feature violent encounters between mothers and sons. This essay analyzes two media stories and three films that suggest how limited-and therefore misleading-popular representations of the autism family are. Except for one of the films, these representations blame the problem of adult autistic dependency on either monstrous autism or bad mothering. Doing so elides collective social responsibility for autism care and denies the reality that autistic adults continue to have complex dependency needs that families cannot always meet. Narratives that sensationalize youth and adults with autism or scapegoat their maternal caregivers also diminish opportunities for social inclusion and for autistic people to live fully and dependently.

  13. The prodigal son: some psychological aspects of Augustine's conversion to Christianity.

    Science.gov (United States)

    Nauta, Rein

    2008-03-01

    Augustine's conversion is considered exemplary for its Christian testimony. However, the psychological aspects are also relevant, for Augustine's conversion to Christianity was as much inspired by personal and cultural ambitions as by religious convictions. For Augustine, the conversion to the Christian faith spelled a life of asceticism--a life of celibacy, a virtuous and chaste existence, which also offered him a means of escape from the threatening ambiguity of parental relations and a chance to realize the cultural ideal of the civilized philosopher who has subjugated the passions of the flesh. In this paper we explore the psychological dynamics of the absent father, the suffering mother and the prodigal son and the role they played in Augustine's conversion to Christianity.

  14. Evolution of the uranium local environment during alteration of SON68 glass

    International Nuclear Information System (INIS)

    Jollivet, Patrick; Auwer, Christophe Den; Simoni, Eric

    2002-01-01

    The speciation of uranium in SON68 glass specimens doped with 0.75-3.5 wt% uranium and in the gels formed by alteration of the specimens was investigated by X-ray absorption spectroscopy. In the glasses, uranium is present at oxidation state VI and coordination number 6 with the same average distances than those found in a UO 3 type environment. The U-O distances and uranium coordination numbers are identical throughout the uranium concentration range. During glass alteration the uranium remains at oxidation state VI in the gels, but was found in the uranyl form. An increase in the equatorial distances (from 2.20 and 2.32 A in the glass to respectively 2.22 and 2.39 A in the gel) and coordination numbers (to about 7 and 8, respectively) was observed

  15. Using BiSON to detect solar internal g-modes

    Directory of Open Access Journals (Sweden)

    Kuszlewicz J.

    2015-01-01

    Full Text Available The unambiguous detection of individual solar internal g modes continues to elude us. With the aid of new additions to calibration procedures, as well as updated methods to combine multi-site time series more effectively, the noise and signal detection threshold levels in the low-frequency domain (where the g modes are expected to be found have been greatly improved. In the BiSON 23-year dataset these levels now rival those of GOLF, and with much greater frequency resolution available, due to the long time series, there is an opportunity to place more constraints on the upper limits of individual g mode amplitudes. Here we detail recent work dedicated to the challenges of observing low-frequency oscillations using a ground-based network, including the role of the window function as well as the effect of calibration on the low frequency domain.

  16. Like father, like son: periventricular nodular heterotopia and nonverbal learning disorder.

    Science.gov (United States)

    McCann, Marcia V; Pongonis, Stephen J; Golomb, Meredith R; Edwards-Brown, Mary; Christensen, Celanie K; Sokol, Deborah K

    2008-08-01

    Periventricular nodular heterotopia is a common malformation of cortical development in which the migration of developing neurons destined for the cerebral cortex is abbreviated. Bilateral periventricular nodular heterotopia is most commonly an X-linked disorder that involves mutations in the filamin A (FLNA) gene, but an autosomal recessive form and sporadic forms have been identified. To our knowledge, autosomal dominant transmission of isolated periventricular nodular heterotopia has not been reported. Periventricular nodular heterotopia has a heterogeneous phenotype, associated commonly with seizure disorder, and more recently with reading deficits and visual-spatial deficits in some patients. We present a father and son with bilateral periventricular nodular heterotopia and similar visual-spatial learning deficits, consistent with nonverbal learning disability.

  17. J. M. W. Turner's painting "The unpaid bill, or the dentist reproving his son's prodigality".

    Science.gov (United States)

    Bishop, M; Gelbier, S; King, J

    2004-12-25

    In November 2002, the BDA News carried an item, illustrated with a colour reproduction, describing a painting of a Georgian dentist's rooms by Joseph Mallord William Turner (1775-1851), one of the most respected of English artists, which was shortly to come up for auction at Christies' Rooms in London. This work, first exhibited in 1808, was entitled "The unpaid bill, or the dentist reproving his son's prodigality", and had originally been commissioned by the connoisseur Richard Payne Knight (1750-1824). "The examiner", a contemporary London journal, identifies the 'cradle-piece' for the commission as being a Rembrandt which Payne Knight owned, and the journalist Robert Hunt said that Turner had more than come up to the task of showing that a modern could handle light as well as the old master, 'for a picture of colouring and effect, it is ... inestimable'.

  18. The death of a young son in violent circumstance: understanding the experience of the mother.

    Science.gov (United States)

    Alarcão, Ana Carolina Jacinto; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa

    2008-01-01

    This study was aimed at understanding the life of a mother who lost their child in violent circumstances. The methodological proceedings were supported on phenomenology. The study population was constituted by five mothers who had lost its young children for homicide. These homicides occurred different times ranging from 50 days to 10 years. I used as instrument of collection of data open interview the phenomenological method guided by a orienting question. The analysis phenomenology in their discourses showed the comprehension of essential meanings which were systematized in categories: the child's mummification in the memory; the two ways followed by the publicity concerning the death; fondness to spirituality to endure the pain from the child's death; maternal complicity and impunity. The results of this study can contribute to elaboration of intervention proposals close to the mothers in the sense of helping them in the reorganization of their lives after son's death.

  19. ABRAM ET LA MAISON DE SON PÈRE (GN 11,26-32)

    OpenAIRE

    Misenga Dituanya, Marie-Anne; Abram et la maison de son père (Gn 11,26-32)

    2015-01-01

    L’élection et l’alliance sont des concepts fondamentaux dans l’Ancien Testament. Cette initiative divine commence avec Abraham par qui Dieu promet de bénir tous les clans de la terre (Gn 12,1-4; 15; 17). Cependant, on néglige souvent le point de départ d’Abraham qui n’est pas l’appel de Dieu, mais la situation de la famille de son père que Dieu demande à Abraham de quitter (Gn 11,26-32). Il est donc important d’étudier cette partie de plus près pour voir s’il est possible de préciser ce qu’es...

  20. Like father, Like Son? Collective decisions taking into account family relations

    Directory of Open Access Journals (Sweden)

    Ariádne Scalfoni Rigo

    2018-01-01

    Full Text Available This teaching case aims to promote reflection on other possible economic actions and alternative management models based on proximity relations. It presents a real situation in a community in the interior of Bahia, experienced by a Community Development Bank, which is an innovative experience on solidarity financing in Brazil and worldwide, related to a credit request by a certain Mr. Francisco. In order to protect his son, Pedro, Francisco created a dilemma that Ms. Marta, the credit agent of the Community Development Bank, sought to solve within the Credit Analysis Committee, a collective decision-making structure based on neighborhood relations.  The decision was not easy and involved many variables. This case allows to discuss the influence of community relations on solidarity finances, in collective management structures, and in the dynamics of Community Development Banks.

  1. [Suh Yang Park, who became a doctor as a son of a butcher].

    Science.gov (United States)

    Park, Hyoung Woo; Hong, Jung Wan

    2006-12-01

    Dr. Suh Yang Park was born in 1885 as a son of a butcher, which was the lowest class at that time in Korea. However, contact with western missionaries, including Dr. 0. R. Avison, provided him with an understanding of western civilization. After entering Chejungwon Medical School in 1900, Dr. Park learned basic sciences, basic medical sciences like anatomy and physiology, and other Western medical specialties such as internal medicine and surgery. He graduated from medical school in 1908 and received Government Certificate from Home Office, the first in Korea in this field, which granted the right to practice medicine. His certificate number was 4th overall. As both a doctor and a talented musician, Dr. Park actively participated in the social enlightenment movement. He was quite progressive in his time, having surpassed the social limitations as a son of a butcher, as well as actively propagating his knowledge of Western civilization onto others. After graduation, he had served as a professor at the school he graduated from, until he went into exile in Manchuria in 1917 due to the annexation of Korea by Japan in 1910. There, he opened a hospital and provided medical treatment for Koreans. He also established a school for young Koreans, inspiring them with a sense of nationalism. Also, Dr. Park was an active member of various Independence Movement Organizations in Manchuria. Then in 1932, at the time when Japan took control of Manchuria, his school was closed down. As a result, Dr. Park couldn't help but stop his anti-Japanese activities. In 1936, he returned to his homeland and passed away in 1940, just five years before the liberation of Korea from Japanese occupation.

  2. Bidirectional Associations Between Externalizing Behavior Problems and Maladaptive Parenting Within Parent-Son Dyads Across Childhood.

    Science.gov (United States)

    Besemer, Sytske; Loeber, Rolf; Hinshaw, Stephen P; Pardini, Dustin A

    2016-10-01

    Coercive parent-child interaction models posit that an escalating cycle of negative, bidirectional interchanges influences the development of boys' externalizing problems and caregivers' maladaptive parenting over time. However, longitudinal studies examining this hypothesis have been unable to rule out the possibility that between-individual factors account for bidirectional associations between child externalizing problems and maladaptive parenting. Using a longitudinal sample of boys (N = 503) repeatedly assessed eight times across 6-month intervals in childhood (in a range between 6 and 13 years), the current study is the first to use novel within-individual change (fixed effects) models to examine whether parents tend to increase their use of maladaptive parenting strategies following an increase in their son's externalizing problems, or vice versa. These bidirectional associations were examined using multiple facets of externalizing problems (i.e., interpersonal callousness, conduct and oppositional defiant problems, hyperactivity/impulsivity) and parenting behaviors (i.e., physical punishment, involvement, parent-child communication). Analyses failed to support the notion that when boys increase their typical level of problem behaviors, their parents show an increase in their typical level of maladaptive parenting across the subsequent 6 month period, and vice versa. Instead, across 6-month intervals, within parent-son dyads, changes in maladaptive parenting and child externalizing problems waxed and waned in concert. Fixed effects models to address the topic of bidirectional relations between parent and child behavior are severely underrepresented. We recommend that other researchers who have found significant bidirectional parent-child associations using rank-order change models reexamine their data to determine whether these findings hold when examining changes within parent-child dyads.

  3. Suh Yang Park, who Became a Doctor as a Son of a Butcher

    Directory of Open Access Journals (Sweden)

    PARK Hyoung Woo

    2006-12-01

    Full Text Available Dr. Suh Yang Park was born in 1885 as a son of a butcher, which was the lowest class at that time in Korea. However, contact with western missionaries, including Dr. O. R. Avison, provided him with an understanding of western civilization. After entering Chejungwon Medical School in 1900, Dr. Park learned basic sciences, basic medical sciences like anatomy and physiology, and other Western medical specialties such as internal medicine and surgery. He graduated from medical school in 1908 and received Government Certificate from Home Office, the first in Korea in this field, which granted the right to practice medicine. His certificate number was 4th overall. As both a doctor and a talented musician, Dr. Park actively participated in the social enlightenment movement. He was quite progressive in his time, having surpassed the social limitations as a son of a butcher, as well as actively propagating his knowledge of Western civilization onto others. After graduation, he had served as a professor at the school he graduated from, until he went into exile in Manchuria in 1917 due to the annexation of Korea by Japan in 1910. There, he opened a hospital and provided medical treatment for Koreans. He also established a school for young Koreans, inspiring them with a sense of nationalism. Also, Dr. Park was an active member of various Independence Movement Organizations in Manchuria. Then in 1932, at the time when Japan took control of Manchuria, his school was closed down. As a result, Dr. Park couldn't help but stop his anti-Japanese activities. In 1936, he returned to his homeland and passed away in 1940, just five years before the liberation of Korea from Japanese occupation.

  4. Detection de la fin de la compaction des anodes par le son

    Science.gov (United States)

    Sanogo, Bazoumana

    L'objectif de ce projet etait de developper un outil de controle en temps reel du temps de compaction en se servant du son genere par le vibrocompacteur pendant le formage des anodes crues. Ainsi, une application a ete developpee pour l'analyse des sons enregistres. Des essais ont ete realises avec differents microphones pour une meilleure qualite des mesures et un a ete choisi pour la suite du projet. De meme, differents tests ont ete realises sur des anodes de laboratoire ainsi que des anodes a l'echelle industrielle afin de mettre en place une methode pour la detection du temps optimal necessaire au formage des anodes. Les travaux au laboratoire de carbone a l'Universite du Quebec a Chicoutimi (UQAC) ont consiste a l'enregistrement de son des anodes fabriquees sur place avec differentes configurations; et a la caracterisation de certaines anodes de l'usine. Les anodes fabriquees au laboratoire sont reparties en deux groupes. Le premier regroupe les anodes pour la validation de notre methode. Ce sont des anodes produites avec des temps de compaction differents. Le laboratoire de carbone a l'UQAC est unique et il est possible de produire des anodes avec les memes proprietes que celles des anodes industrielles. Par consequent, la validation initialement prevue a l'usine a ete effectuee avec les anodes de laboratoire. Le deuxieme groupe a servi a etudier les effets des matieres premieres sur le temps de compaction. Le type de coke et le type de brai ont constitue les differentes variations dans ce deuxieme groupe. Quant aux tests et mesures a l'usine, ils ont ete realises en trois campagnes de mesure. La premiere campagne en juin 2014 a servi a standardiser et a trouver le meilleur positionnement des appareils pour les mesures, a regler le logiciel et a faire les premieres mesures. Une deuxieme campagne en mai 2015 a fait l'objet d'enregistrement de son en classant les anodes selon differents temps de compaction. La troisieme et derniere campagne en decembre 2015 a

  5. Thiazolidinediones abrogate cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Wuertz, Beverly R., E-mail: knier003@umn.edu; Darrah, Lindsay, E-mail: ldarrah@obgynmn.com; Wudel, Justin, E-mail: drwudel@drwudel.com; Ondrey, Frank G., E-mail: ondre002@umn.edu

    2017-04-15

    Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100 mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions. - Highlights: • Thiazolidinediones decreases cervical cancer proliferation. • Pioglitazone increases cervical cancer differentiation. • Pioglitazone decreases tumor growth in mice. • Pioglitazone may be a useful treatment adjunct.

  6. E-selectin ligand-1 (ESL-1) is a novel adiponectin binding protein on cell adhesion.

    Science.gov (United States)

    Yamamoto, Hiroyasu; Kuroda, Nana; Uekita, Hiromi; Kochi, Ikoi; Matsumoto, Akane; Niinaga, Ryu; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

    2016-02-05

    Adiponectin (APN) is an adipocyte-derived bioactive molecule with anti-diabetic and anti-atherogenic properties. Although anti-diabetic effects are mostly mediated by the adiponectin receptors AdipoR1 and AdipoR2, the anti-atherogenic mechanisms have not been fully elucidated. In this study, we identified E-selectin ligand (ESL)-1 as a novel APN-binding protein by mass spectrometry analysis of HepG2 cell-derived immunoprecipitant with an anti-APN antibody. Cell adhesion assays using fluorescence-labelled monocyte cell line THP-1 cells and human umbilical vein endothelial cells (HUVECs) revealed that APN-pre-treated THP-1 cells had reduced binding ability to HUVECs. This APN-mediated suppressive effect on monocyte binding to endothelial cells was partially abrogated by targeting ESL-1 with shRNA in THP-1 cells. In addition, serial mutagenesis analysis disclosed that five extracellular amino acids close to the N-terminus of ESL-1 were essential for binding with APN. Our results highlight the fact that interaction between APN and ESL-1 could provide a fundamental mechanism underlying the anti-atherogenic properties of APN. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  8. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  9. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova

    2003-01-01

    In haar proefschrift analyseert Lilia Schürcks de anaforische verschijnselen in de Bulgaarse taal. Het gaat dan om wederkerende aspecten, uitgedrukt bij woorden als ‘zich’ en ‘elkaar’. De situatie in het Bulgaars blijkt moeilijk in te passen in de klassieke Binding Theory van Noam Chomsky. Bron: RUG

  10. DNA Binding by the Ribosomal DNA Transcription Factor Rrn3 Is Essential for Ribosomal DNA Transcription*

    Science.gov (United States)

    Stepanchick, Ann; Zhi, Huijun; Cavanaugh, Alice H.; Rothblum, Katrina; Schneider, David A.; Rothblum, Lawrence I.

    2013-01-01

    The human homologue of yeast Rrn3 is an RNA polymerase I-associated transcription factor that is essential for ribosomal DNA (rDNA) transcription. The generally accepted model is that Rrn3 functions as a bridge between RNA polymerase I and the transcription factors bound to the committed template. In this model Rrn3 would mediate an interaction between the mammalian Rrn3-polymerase I complex and SL1, the rDNA transcription factor that binds to the core promoter element of the rDNA. In the course of studying the role of Rrn3 in recruitment, we found that Rrn3 was in fact a DNA-binding protein. Analysis of the sequence of Rrn3 identified a domain with sequence similarity to the DNA binding domain of heat shock transcription factor 2. Randomization, or deletion, of the amino acids in this region in Rrn3, amino acids 382–400, abrogated its ability to bind DNA, indicating that this domain was an important contributor to DNA binding by Rrn3. Control experiments demonstrated that these mutant Rrn3 constructs were capable of interacting with both rpa43 and SL1, two other activities demonstrated to be essential for Rrn3 function. However, neither of these Rrn3 mutants was capable of functioning in transcription in vitro. Moreover, although wild-type human Rrn3 complemented a yeast rrn3-ts mutant, the DNA-binding site mutant did not. These results demonstrate that DNA binding by Rrn3 is essential for transcription by RNA polymerase I. PMID:23393135

  11. DNA binding by the ribosomal DNA transcription factor rrn3 is essential for ribosomal DNA transcription.

    Science.gov (United States)

    Stepanchick, Ann; Zhi, Huijun; Cavanaugh, Alice H; Rothblum, Katrina; Schneider, David A; Rothblum, Lawrence I

    2013-03-29

    The human homologue of yeast Rrn3 is an RNA polymerase I-associated transcription factor that is essential for ribosomal DNA (rDNA) transcription. The generally accepted model is that Rrn3 functions as a bridge between RNA polymerase I and the transcription factors bound to the committed template. In this model Rrn3 would mediate an interaction between the mammalian Rrn3-polymerase I complex and SL1, the rDNA transcription factor that binds to the core promoter element of the rDNA. In the course of studying the role of Rrn3 in recruitment, we found that Rrn3 was in fact a DNA-binding protein. Analysis of the sequence of Rrn3 identified a domain with sequence similarity to the DNA binding domain of heat shock transcription factor 2. Randomization, or deletion, of the amino acids in this region in Rrn3, amino acids 382-400, abrogated its ability to bind DNA, indicating that this domain was an important contributor to DNA binding by Rrn3. Control experiments demonstrated that these mutant Rrn3 constructs were capable of interacting with both rpa43 and SL1, two other activities demonstrated to be essential for Rrn3 function. However, neither of these Rrn3 mutants was capable of functioning in transcription in vitro. Moreover, although wild-type human Rrn3 complemented a yeast rrn3-ts mutant, the DNA-binding site mutant did not. These results demonstrate that DNA binding by Rrn3 is essential for transcription by RNA polymerase I.

  12. Sodium phenylbutyrate abrogates African swine fever virus replication by disrupting the virus-induced hypoacetylation status of histone H3K9/K14.

    Science.gov (United States)

    Frouco, Gonçalo; Freitas, Ferdinando B; Martins, Carlos; Ferreira, Fernando

    2017-10-15

    African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study. Results showed that the sodium phenylbutyrate fully abrogates the ASFV replication, whereas the valproic acid leads to a significant reduction of viral progeny at 48h post-infection (-73.9%, p=0.046), as the two pan-HDAC inhibitors tested (Trichostatin A: -82.2%, p=0.043; Vorinostat: 73.9%, p=0.043). Further evaluation showed that protective effects of NaPB are dose-dependent, interfering with the expression of late viral genes and reversing the ASFV-induced histone H3 lysine 9 and 14 (H3K9K14) hypoacetylation status, compatible to an open chromatin state and possibly enabling the expression of host genes non-beneficial to infection progression. Additionally, a synergic antiviral effect was detected when NaPB is combined with an ASFV-topoisomerase II poison (Enrofloxacin). Altogether, our results strongly suggest that cellular HDACs are involved in the establishment of ASFV infection and emphasize that further in vivo studies are needed to better understand the antiviral activity of HDAC inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

    International Nuclear Information System (INIS)

    Khadjavi, Amina; Magnetto, Chiara; Panariti, Alice; Argenziano, Monica; Gulino, Giulia Rossana; Rivolta, Ilaria; Cavalli, Roberta; Giribaldi, Giuliana; Guiot, Caterina; Prato, Mauro

    2015-01-01

    Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. - Highlights: • Hypoxia impairs MMP9/TIMP1 and MMP2/TIMP2 balances in HaCaT human keratinocytes. • Chitosan-shelled oxygen-loaded nanodroplets (OLNs) are internalised by HaCaT cells. • OLNs are not toxic to HaCaT cells. • OLNs effectively counteract hypoxia effects on MMP/TIMP balances in HaCaT cells. • OLNs appear as promising and cost-effective therapeutic tools for hypoxic

  14. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  15. Defective TCR stimulation in anergized type 2 T helper cells correlates with abrogated p56(lck) and ZAP-70 tyrosine kinase activities.

    Science.gov (United States)

    Faith, A; Akdis, C A; Akdis, M; Simon, H U; Blaser, K

    1997-07-01

    Development of IgE-mediated allergic conditions is dependent on the secretion of a Th2 cytokine pattern, including IL-4, IL-5, and IL-13. The induction of anergy would be one mechanism to abrogate cytokine secretion by Th2 cells, which may be pivotal to the allergic response. We demonstrate here that incubation of cloned human CD4+ phospholipase A2 (PLA)-specific Th2 cells with antigenic peptide, in the absence of professional APC, results in a state of nonresponsiveness. The anergic T cells failed to proliferate or secrete IL-4 in response to optimal stimulation with PLA and autologous, professional APC. Secretion of IL-5 and IL-13, however, was only partially inhibited. The anergic state of the Th2 cells was not associated with CD3 or CD28 down-regulation. However, anergy did appear to be closely related to alterations in signaling pathways, mediated through the TCR, of the cells. In contrast to untreated Th2 cells, anergized Th2 cells failed to respond to anti-CD3 mAb with either increased tyrosine kinase activity or increased levels of tyrosine phosphorylation of p56(lck) or ZAP70. A strong and sustained intracellular calcium flux, observed in untreated Th2 cells in response to anti-CD3 mAb, was absent in anergic Th2 cells. Furthermore, the induction of anergy seems to represent an active process, associated with increased levels of basal tyrosine kinase activity, cytokine production, and CD25 up-regulation in anergic Th2 cells. Together, our results indicate that anergy in Th2 cells is associated with defective transmembrane signaling through the TCR.

  16. Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates

    Directory of Open Access Journals (Sweden)

    Sharoar Md

    2012-12-01

    Full Text Available Abstract Background Aggregation of soluble, monomeric β- amyloid (Aβ to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD. Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh, was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh. Results K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization. Conclusion K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.

  17. Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Khadjavi, Amina [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Magnetto, Chiara [Istituto Nazionale di Ricerca Metrologica (INRIM), Torino (Italy); Panariti, Alice [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Monza (Italy); Argenziano, Monica [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino (Italy); Gulino, Giulia Rossana [Dipartimento di Oncologia, Università di Torino, Torino (Italy); Rivolta, Ilaria [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Monza (Italy); Cavalli, Roberta [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino (Italy); Giribaldi, Giuliana [Dipartimento di Oncologia, Università di Torino, Torino (Italy); Guiot, Caterina [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Prato, Mauro, E-mail: mauro.prato@unito.it [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università di Torino, Torino (Italy)

    2015-08-01

    Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. - Highlights: • Hypoxia impairs MMP9/TIMP1 and MMP2/TIMP2 balances in HaCaT human keratinocytes. • Chitosan-shelled oxygen-loaded nanodroplets (OLNs) are internalised by HaCaT cells. • OLNs are not toxic to HaCaT cells. • OLNs effectively counteract hypoxia effects on MMP/TIMP balances in HaCaT cells. • OLNs appear as promising and cost-effective therapeutic tools for hypoxic

  18. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

    Science.gov (United States)

    Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

    2013-10-29

    Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

  19. Lifestyle in pregnancy and cryptorchidism in sons: a study within two large Danish birth cohorts

    Directory of Open Access Journals (Sweden)

    Kjersgaard C

    2018-03-01

    Full Text Available Camilla Kjersgaard,1 Linn Håkonsen Arendt,1,2 Andreas Ernst,1 Morten Søndergaard Lindhard,2 Jørn Olsen,1,3 Tine Brink Henriksen,2 Katrine Strandberg-Larsen,4 Cecilia Høst Ramlau-Hansen1 1Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, 2Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Aarhus, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 4Department of Public Health, Section of Social Medicine, Copenhagen University, Copenhagen, Denmark Purpose: Cryptorchidism is the most frequent congenital malformation in boys and is associated with low sperm count, infertility and testicular cancer. Unhealthy maternal lifestyle during pregnancy such as smoking, high prepregnancy body mass index (BMI as well as alcohol and caffeine intake may constitute possible risk factors for cryptorchidism, but results from the few previous studies are conflicting. We aimed to explore the association between maternal lifestyle factors and occurrence of cryptorchidism in sons.Patients and methods: The Danish National Birth Cohort and the Aarhus Birth Cohort provided information on maternal lifestyle from early pregnancy. Data were linked to several Danish health registers, multiple imputation was used to handle missing data and Cox proportional hazards models were used to adjust for potential confounders.Results: In total, 85,923 boys were included, and of them, 2.2% were diagnosed with cryptorchidism. We observed the strongest associations between maternal tobacco smoking and prepregnancy BMI and cryptorchidism. Sons of women who smoked 10–14 cigarettes/day had the highest hazard ratio (HR for cryptorchidism (1.37; 95% CI: 1.06–1.76, and for maternal BMI ≥30 kg/m2, the HR was 1.32 (95% CI: 1.06–1.65. Binge drinking was associated with an HR <1, if the women had one or two episodes in pregnancy (HR: 0.81; 95% CI: 0.67–0.98. Average maternal alcohol intake

  20. Poesía y filosofía son de palabra

    Directory of Open Access Journals (Sweden)

    Santamaría Pargada, Antonio

    2006-04-01

    Full Text Available The imaginary and sinister concentration-camp chief Otto Friedrich Zur Linde was conceived by Jorge-Luis Borges as an example of misunderstanding philosophy and life, by seeing in them only the power of fight. This conception is compared with a dynamic understanding of philosophy. For Mr. Zur Linde Aristotle and Plato represent this confrontation, and each philosophical debate in history could be considered as a moment in it. But now, in the last fight, the will to power of man has gone beyond all the limits, even of morality. However some modern techniques of appropriation of ancient philosophy are completely opposed to this conception, namely Paul Ricoeur’s theory of fiction and Heidegger’s Sein und Schein,. Ultimately, the close relationship between poetry and philosophy since its origins speak against this thesis. A closer analysis of Nietzsche and Hölderlin will help to enlighten how wrong Zur Linde´s conception is..El siniestro jefe de un campo de concentración Otto Friedrich Zur Linde, concebido por Borges como ejemplo de una interpretación de la filosofía y la vida en la que la lucha es el único motor, es confrontado con una concepción de la filosofía dinámica. Zur Linde mantiene que Aristóteles y Platón son el enfrentamiento filosófico paradigmático. En el último momento del enfrentamiento la voluntad de poder de un nuevo superhombre ha rebasado todos los límites, incluso el de la conciencia. A esto se oponen las técnicas de apropiación filosófica del mundo griego por parte de la modernidad, a saber: el poder de la ficción, el Schein y el Sein así como el nacimiento de la filosofía, tan cercano a la poesía. Bajo este prisma cabe un análisis de Nietzsche y Hölderlin, que reniega de la interpretación de Zur Linde y clarifica que ante todo poetas y filósofos son seres de palabra.

  1. Self-Organizing Networks (SON) Self-Planning, Self-Optimization and Self-Healing for GSM, UMTS and LTE

    CERN Document Server

    Ramiro, Juan

    2011-01-01

    With the current explosion in network traffic, and mounting pressure on operators' business case, Self-Organizing Networks (SON) play a crucial role. They are conceived to minimize human intervention in engineering processes and at the same time improve system performance to maximize Return-on-Investment (ROI) and secure customer loyalty. Written by leading experts in the planning and optimization of Multi-Technology and Multi-Vendor wireless networks, this book describes the architecture of Multi-Technology SON for GSM, UMTS and LTE, along with the enabling technologies for SON planning, opti

  2. Violencia cometida por los adolescentes en la familia o cuando son los hijos los que maltratan

    Directory of Open Access Journals (Sweden)

    Helena Morales Ortega

    2011-12-01

    Full Text Available Este estudio de tipo cualitativo, de corte deductivo, se propuso realizar un acercamiento al fenómeno de la violencia ejercida por los jóvenes menores de 18 años en el ámbito familiar, para establecer su ocurrencia en la ciudad de Barranquilla, Colombia, describir las características de los jóvenes implicados, la dinámica familiar y algunos aspectos del entorno social que podrían estar facilitando la ocurrencia de la misma. El estudio fue realizado en el Centro de Reeducación del Adolescente Infractor "Oasis", de esta ciudad; se examinaron expedientes de jóvenes judicializados por los delitos de violencia intrafamiliar, hurto, lesiones personales y daño en bien ajeno, donde la víctima había sido un familiar; igualmente, se realizaron entrevistas semiestructuradas con profundidad a madres de jóvenes que al momento de la investigación se hallaban internos en el centro por violencia en la familia. Los resultados indican que son pocos los estudios criminológicos realizados sobre el tema; se trata de jóvenes con edades promedio de 14 a 17 años, provenientes de familias desintegradas, con carencias tanto materiales como afectivas, con dinámicas y estilos de crianza inadecuados; es frecuente en estos jóvenes el consumo de sustancias alucinógenas o alcohol.

  3. Optimal algorithm switching for the estimation of systole period from cardiac microacceleration signals (SonR).

    Science.gov (United States)

    Giorgis, L; Frogerais, P; Amblard, A; Donal, E; Mabo, P; Senhadji, L; Hernández, A I

    2012-11-01

    Previous studies have shown that cardiac microacceleration signals, recorded either cutaneously, or embedded into the tip of an endocardial pacing lead, provide meaningful information to characterize the cardiac mechanical function. This information may be useful to personalize and optimize the cardiac resynchronization therapy, delivered by a biventricular pacemaker, for patients suffering from chronic heart failure (HF). This paper focuses on the improvement of a previously proposed method for the estimation of the systole period from a signal acquired with a cardiac microaccelerometer (SonR sensor, Sorin CRM SAS, France). We propose an optimal algorithm switching approach, to dynamically select the best configuration of the estimation method, as a function of different control variables, such as the signal-to-noise ratio or heart rate. This method was evaluated on a database containing recordings from 31 patients suffering from chronic HF and implanted with a biventricular pacemaker, for which various cardiac pacing configurations were tested. Ultrasound measurements of the systole period were used as a reference and the improved method was compared with the original estimator. A reduction of 11% on the absolute estimation error was obtained for the systole period with the proposed algorithm switching approach.

  4. The Phenomenology of Trauma. Sound and Haptic Sensuality in Son of Saul

    Directory of Open Access Journals (Sweden)

    Vincze Teréz

    2016-12-01

    Full Text Available The winner of many prestigious prizes (Oscar for the best foreign language film, Grand Prize of the Cannes Film Festival, and the Golden Globe among them, the Hungarian film, Son of Saul – according to most critics – represents the Holocaust trauma in a completely new and intriguing way. The filmmakers have invented a special form in order to tackle the heroic task of showing the unwatchable, representing the unthinkable. In this essay I analyse the representational strategy of the film from a phenomenological point of view, and position it in the theoretical framework of haptic sensuality formulated by Vivian Sobchack and Laura U. Marks, among others. I mainly focus on the use of sound, in particular the role of sound design in the creation of haptic space. With the help of the analysis of the representation and artistic invocation of the different bodily senses in the film, I demonstrate how traditional artistic formal elements (characteristic of highly artistic, even experimental productions are combined with high impact effects often present in popular film forms. I argue that the successful combination of these two factors makes the film an example of artistic immersive cinema.1

  5. Bats (Mammalia: Chiroptera of the southeastern Truong Son Mountains, Quang Ngai Province, Vietnam

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    Nguyen Truong Son

    2016-07-01

    Full Text Available Bat communities of mainland Southeast Asia can be highly diverse. Many are under threat. Despite this, regional faunal composition is not well documented for many areas, including regions of Vietnam.  We assessed the biodiversity of bats in a watershed protection forest in the southeastern Truong Son (Annamite Mountains, southwestern Quang Ngai Province, Vietnam in 2011–2013.  Twenty species of insectivorous bats were documented including a high diversity of Murina species Tube-nosed Bats.  Diversity and abundance indices were compared with that recorded previously in two nature reserves and one national park in Vietnam, and were higher or comparable in several measures despite the lack of a karst substrate for roosts.  Reproduction in the insectivorous bat fauna coincided with the early rainy season.  In the late dry season, pregnant females of several species were observed but volant juveniles were not present, whereas in the early wet season adult females were lactating or post-lactating and volant juveniles of nine species were detected.  We recorded echolocation calls of 14 bat species; for each species, we compared features of calls with those reported previously in other Asian localities.  For some species we found discrepancies in call metrics among studies, perhaps suggesting a greater hidden biodiversity of bats in Southeast Asia.

  6. Superselection sectors of SO(N) Wess-Zumino-Witten models

    International Nuclear Information System (INIS)

    Boeckenhauer, J.

    1996-06-01

    The superselection structure of so(N) WZW models is investigated form the point of view of algebraic quantum field theory. At level 1 it turns out that the observable algebras of the WZW theory can be constructed in terms of even CAR algebras. This fact allows to give a formulation of these models close to the DHR framework. Localized endomorphisms are constructed explicitly in terms of Bogoliubov transformations, and the WZW fusion rules are proven using the DHR sector product. At level 2 it is shown that most of the sectors are realized in H NS =H NS x H NS where H NS is the Neveu-Schwarz sector of the level 1 theory. The level 2 charcters are derived and H NS is decomposed completely into tensor products of the sectors of the WZW chiral algebra and irreducible representation spaces of the coset Virasoro algebra. Crucial for this analysis is the DHR decomposition of H NS into sectors of a gauge invariant fermion algebra since the WZW chiral algebra as well as the coset Virasoro algebra are invariant under the gauge group O(2). (orig.)

  7. Study of the Treatment of the Liquid Radioactive Waste Nong Son Uranium Ore Processing

    International Nuclear Information System (INIS)

    Nguyen Ba Tien; Trinh Giang Huong; Luu Cao Nguyen; Harvey, L.K.; Tran Van Quy

    2011-01-01

    Liquid waste from Nong Son uranium ore processing is treated with concentrated acid, agglomerated, leached, run through ion exchange and then treated with H 2 O 2 to precipitate yellowcake. The liquid radioactive waste has a pH of 1.86 and a high content of radioactive elements, such as: [U] 143.898 ppm and [Th] = 7.967 ppm. In addition, this waste contains many polluted chemical elements with high content, such as arsenic, mercury, aluminum, iron, zinc, magnesium, manganese and nickel. The application of the general method as one stage precipitation or precipitation in coordination with BaCl 2 is not effective. These methods generated a large amount of sludge with poor settling characteristics. The volume of final treated waste was large. This paper introduces the investigation of the treatment of this liquid radioactive waste by the method of two stage of precipitation in association with polyaluminicloride (PAC) and polymer. The impact of factors: pH, neutralizing agents, quantity of PAC and polymer to effect precipitation and improve the settling characteristics during processing was studied. The results showed that the processing of liquid radioactive waste treatment through two stages: first stage at pH = 3 and the second stage at pH = 8.0 with limited PAC and polymer (A 101) resulted in significant reduced volume of the treated waste. The discharged liquid satisfied the requirement of the National Technical Regulation on Industrial Waste Water (QCVN 24:2009). (author)

  8. ¿Qué son los modelos físicos?

    Directory of Open Access Journals (Sweden)

    José Luis Rolleri

    2013-01-01

    Full Text Available En este artículo analizamos los principales conceptos propuestos de modelo con el propósito de resaltar el carácter idealizado y abstracto de los modelos físicos, que generalmente es pasado por alto en la literatura filosófica relevante desde diversas posiciones, como el instrumentalismo y el pragmatismo; el cual, sin embargo tiene importantes implicaciones en problemas filosóficos como el del realismo científico. Desde una posición conceptualista, sostenemos que los modelos desidealizados son los vehículos para conceptualizar los sistemas físicos desde la perspectiva de una teoría. In this paper we analyze the main intended concepts of model in order to underline the idealized and abstract character of physical models, that generally is overpass in the relevant philosophical literature from diverse positions on the scientific knowledge, such as instrumentalism and pragmatism, which however has important implications on philosophical problems such as that of scientific realism. From a conceptualistic position we hold that the de-idealized models are the vehicles to conceptualized physical systems from the perspective of a theory

  9. Complicity to Hegemonic Masculinity in D.H. Lawrence’s Sons and Lovers

    Directory of Open Access Journals (Sweden)

    Angelina Subrayan

    2016-04-01

    Full Text Available Men have long been associated with dominance, strength and confidence and the issue regarding being compliant to the acceptable masculine ideal has always been part of a culture’s social identity. This study focuses on the critical discussion on masculinity studies in the classic fiction of D.H Lawrence.  Drawing on narrative data from his novel Sons and Lovers (1913, the study examines how hegemonic masculinity is conformed by the male protagonist, Walter Morel, in his gendered relationship. More specifically, the analysis focuses on how the male character aligns himself with the hegemonically authoritarian philosophy of ‘tough’ masculinity. The effects of social practices and socio-historical context in which Lawrence wrote these novels are also examined. The study utilises Connell’s theory of hegemonic masculinity to explicate Lawrence’s depiction of dominant masculinity through his character. The findings reveal that Lawrence aligns his male protagonist to the dominant role by sanctioning aggressiveness, autonomy and violence. Keywords: Hegemonic Masculinity, Dominant Masculinity, Patriarchy, Gender, Power

  10. Father and son attachment styles in alcoholic and non-alcoholic families

    Directory of Open Access Journals (Sweden)

    Mythili Hazarika

    2017-12-01

    Full Text Available Background: The theory of attachment is important to understand a lot of human behaviour. Styles of attachment could be important predictors in developing dependence on alcoholism. Insecure attachment patterns could be significant risk factors for future alcohol use. Methods: Participants for this study consist of fathers with alcohol dependence syndrome (ADS from treatment centres and fathers from the community with no dependency on alcohol, and their sons (n=200. The Michigan Alcoholism Screening Test (MAST, socioeconomic status scale were administered, and attachment styles were derived by the Attachment Style Questionnaire (ASQ. We hypothesised a prior concept reflecting theoretical predictions for the association between attachment styles and alcohol in both the generations. Results: Statistics on SPSS-16 was used to test our hypotheses. As predicted, fathers with ADS had insecure attachments styles in comparison to the control group. Substance abuse/dependence and treatment participation were at an all-time low for the secure group. Conclusion: The findings from this study identify attachment styles as an influential factor in understanding the divergence between alcohol dependence in treatment seekers. The findings further imply that differential treatment may need to be provided taking into account one’s attachment representation to promote successful recovery. It also highlights the need to develop secure ties in children of alcoholic parents to protect them from use of substances as a coping and a learned mechanism. Limitations of the study and suggestions for further research are highlighted and implications for diagnosis and treatment are discussed.

  11. Fluidez lectora en niños: cuáles son las habilidades subyacentes

    Directory of Open Access Journals (Sweden)

    Julieta-Carolina Fumagalli

    2017-01-01

    Full Text Available del aprendizaje de la lectura y la comprensión de textos. En español son escasas las herramientas para evaluar este constructo que involucra aspectos relativos a la precisión lectora, la expresividad, la velocidad y la comprensión. A fin de obtener información para el futuro diseño de una batería que evalúe la fluidez a partir de textos en español, este trabajo se propone establecer las habilidades subyacentes a la fluidez. Para tal fin, se evaluó a un total de 172 niños de 3º, 5º y 7º curso de Educación Primaria sin dificultades para el aprendizaje de la lectura. Los participantes respondieron cinco tareas: fluidez verbal fonológica (FVF, conciencia fonoló- gica (CF, velocidad de denominación (RAN, lectura de palabras y no palabras (Lectura de PyNP y lectura en voz alta de un texto (LVA, a partir de la cual se extrajeron medidas de precisión lectora, velocidad y comprensión. Los resultados obtenidos brindan información sobre variables que inciden de manera directa (RAN y Lectura de PyNP e indirecta (CF y FVF sobre la fluidez lectora. Estos datos resultan relevantes para el futuro diseño de una batería que permita medir este constructo.

  12. Factors associated with parents' attitudes to the HPV vaccination of their adolescent sons : A systematic review.

    Science.gov (United States)

    Radisic, Gorjana; Chapman, Janine; Flight, Ingrid; Wilson, Carlene

    2017-02-01

    The objective of the study was to identify factors associated with human papilloma virus (HPV) vaccine acceptability in parents of adolescent boys. This information is critical to the development of approaches to optimise HPV vaccine uptake among this population group. We performed a systematic search of the literature in addressing factors influencing parental attitudes to and beliefs about HPV vaccine and its acceptability for use. The findings were organised within the framework of the Health Belief Model (HBM) and summarised using a semi quantitative method. Eighteen studies met the inclusion criteria. Parental decisions were predominantly shaped by the perceived benefits of the vaccine; perceived risk of sons contracting the HPV infection, and having recommendations from health care providers. Fear of side effects and uncertainty about vaccine effectiveness, as well as cost and lack of healthcare, were barriers to HPV vaccination. Other factors such as knowledge, family characteristics, parent-child dialogue and egalitarian values appeared to be important when deciding whether to vaccinate boys. HPV vaccine uptake among male adolescents is suboptimal. Future programs need to address the predictors of uptake by educating parents about the boys' high susceptibility to infection, the benefits of vaccination, and reduce concerns regarding perceived barriers. Additionally, uptake may be facilitated by encouraging health care provider endorsement, particularly in countries without government-funded immunisation programs. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Familial cardiofaciocutaneous syndrome in a father and a son with a novel MEK2 mutation.

    Science.gov (United States)

    Karaer, Kadri; Lissewski, Christina; Zenker, Martin

    2015-02-01

    Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder belonging to the group of RASopathies. It is typically characterized by congenital heart defects, short stature, dysmorphic craniofacial features, intellectual disability, failure to thrive, and ectodermal abnormalities such as hyperkeratosis and sparse, brittle, curly hair. CFC syndrome is caused by dominant mutations in one of the four genes BRAF, MEK1, MEK2, and KRAS. Only three familial cases of CFC syndrome have been reported to date, whereas the vast majorities are sporadic cases due to de novo mutations. We report on a fourth familial case with transmission of CFC syndrome from father to son due to a novel heterozygous sequence change c.376A>G (p.N126D) in exon 3 of MEK2 gene. This observation further documents the possibility of vertical transmission of CFC syndrome, which appears to be associated with rare mutations and relatively mild intellectual disability in affected individual. The hypomorphic effect of specific mutations particularly regarding neurocognitive issues may be related to the variable fertility of affected individuals. © 2014 Wiley Periodicals, Inc.

  14. Evolution of the local environment of lanthanum during simplified SON68 glass leaching

    International Nuclear Information System (INIS)

    Jollivet, P.; Delaye, J.M.; Den Auwer, C.; Simoni, E.

    2007-01-01

    The evolution of the short- and medium-range local environment of lanthanum was determined by L-III-edge X-ray absorption spectroscopy (XAS) during leaching of simplified SON68-type glasses. In glass without phosphorus, lanthanum is found in a silicate environment, and its first coordination sphere comprises eight oxygen atoms at a mean distance of 2.51 angstrom. When this glass was leached at a high renewal rate, the lanthanum local environment was significantly modified: it was present at hydroxy-carbonate and silicate sites with a mean La-O distance of 2.56 angstrom, and the second neighbors consisted of La atoms instead of Si for the glass. Conversely, in the gel formed at low renewal rates, lanthanum was found in a silicate environment similar to that of the glass. In phosphorus-doped glass, lanthanum is found in a phosphate environment, although the Si/P atomic ratio is 20:1. Lanthanum is surrounded by seven oxygen atoms at a mean distance of 2.37 angstrom. When phosphorus-doped glass is leached, regardless of the leaching solution flow rate, the short- and medium-range lanthanum local environment remains almost constant; the most significant change is a 0.05 angstrom increase in the La-O distance. (authors)

  15. Heightened risk of preterm birth and growth restriction after a first-born son.

    Science.gov (United States)

    Bruckner, Tim A; Mayo, Jonathan A; Gould, Jeffrey B; Stevenson, David K; Lewis, David B; Shaw, Gary M; Carmichael, Suzan L

    2015-10-01

    In Scandinavia, delivery of a first-born son elevates the risk of preterm delivery and intrauterine growth restriction of the next-born infant. External validity of these results remains unclear. We test this hypothesis for preterm delivery and growth restriction using the linked California birth cohort file. We examined the hypothesis separately by race and/or ethnicity. We retrieved data on 2,852,976 births to 1,426,488 mothers with at least two live births. Our within-mother tests applied Cox proportional hazards (preterm delivery, defined as less than 37 weeks gestation) and linear regression models (birth weight for gestational age percentiles). For non-Hispanic whites, Hispanics, Asians, and American Indian and/or Alaska Natives, analyses indicate heightened risk of preterm delivery and growth restriction after a first-born male. The race-specific hazard ratios for preterm delivery range from 1.07 to 1.18. Regression coefficients for birth weight for gestational age percentile range from -0.73 to -1.49. The 95% confidence intervals for all these estimates do not contain the null. By contrast, we could not reject the null for non-Hispanic black mothers. Whereas California findings generally support those from Scandinavia, the null results among non-Hispanic black mothers suggest that we do not detect adverse outcomes after a first-born male in all racial and/or ethnic groups. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Discussing Sensitive Issues through a Partnership Lens: A Conversation with My Teenaged Son

    Directory of Open Access Journals (Sweden)

    Kris Malone Grossman

    2018-02-01

    Full Text Available This article explores parenting and the construction of masculinity through the lens of Partnership. Framed by the author’s conversation with her teenaged son, the paper opens with a definition, exploration, and cultural contextualization of androcracy. Fundamental intersections between the disciplines of the Partnership Model and Women’s Spirituality are then introduced, locating story and storytelling, spirit, and relationship as cornerstones for shifting from the Domination Model to a Partnership Model. Interconnected theories and praxes of feminism, radical feminism, womanism, and the Womanist Idea, as well as the Jewish concept of tikkun olam, are defined and proposed as tools for educating children about the Domination/Control and interlocking systems of oppression we live in, and how to enact Partnership/Respect principles in our relationships. The paper proposes that through sharing and enacting a multiplicity of counter narratives that reflect the tenets of Partnership, parents and care givers not only actively model for children Partnership values, but they also equip children with an explicit understanding of the harmful systems we live in and the means to challenge and shift them. Highlighting a multiplicity of traditions that share the same core values of empathy, compassion, and care for all living beings, the paper concludes with a set of tools for employing foundational precepts of Partnership Parenting, from sharing story to embodying and promoting ways to care for self, community, and the world.  

  17. Meta-analysis suggests choosy females get sexy sons more than "good genes".

    Science.gov (United States)

    Prokop, Zofia M; Michalczyk, Łukasz; Drobniak, Szymon M; Herdegen, Magdalena; Radwan, Jacek

    2012-09-01

    Female preferences for specific male phenotypes have been documented across a wide range of animal taxa, including numerous species where males contribute only gametes to offspring production. Yet, selective pressures maintaining such preferences are among the major unknowns of evolutionary biology. Theoretical studies suggest that preferences can evolve if they confer genetic benefits in terms of increased attractiveness of sons ("Fisherian" models) or overall fitness of offspring ("good genes" models). These two types of models predict, respectively, that male attractiveness is heritable and genetically correlated with fitness. In this meta-analysis, we draw general conclusions from over two decades worth of empirical studies testing these predictions (90 studies on 55 species in total). We found evidence for heritability of male attractiveness. However, attractiveness showed no association with traits directly associated with fitness (life-history traits). Interestingly, it did show a positive correlation with physiological traits, which include immunocompetence and condition. In conclusion, our results support "Fisherian" models of preference evolution, while providing equivocal evidence for "good genes." We pinpoint research directions that should stimulate progress in our understanding of the evolution of female choice. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  18. Binding of Thrombin-Activated Platelets to a Fibrin Scaffold through αIIbβ3 Evokes Phosphatidylserine Exposure on Their Cell Surface

    Science.gov (United States)

    Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei

    2013-01-01

    Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an αIIbβ3 antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment. PMID:23383331

  19. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIb)β₃ evokes phosphatidylserine exposure on their cell surface.

    Science.gov (United States)

    Brzoska, Tomasz; Suzuki, Yuko; Mogami, Hideo; Sano, Hideto; Urano, Tetsumei

    2013-01-01

    Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS) and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIb)β₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  20. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIbβ₃ evokes phosphatidylserine exposure on their cell surface.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIbβ₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  1. Were king Stefan the First-Crowned and his son Radoslav co-rulers?

    Directory of Open Access Journals (Sweden)

    Bubalo Đorđe

    2009-01-01

    Full Text Available The Serbian historiography considers the issue of the co-ruling of King Stefan the First-Crowned and his son Radoslav as the one finally resolved. The suggested solution on the co-rule of Stefan and Radoslav may be most succinctly expressed as following: as early as in the year of 1220, due to the frail health of Stefan the First-Crowned and Radoslav's marriage to Anne the Epirus princess, Radoslav was crowned to be the king and positioned to co-rule with his father after the Byzantine model of governing. Nevertheless this point of view has some loose ends. The notion of co-ruling and the very term of 'co-ruler' are quite freely used in the scholarly works. A general consensus on the precise meaning has not been reached yet. At the point where one author perceives a co-rule, the other categorically denies it. Basically the approach equalizing the heir to the throne and the co-ruler is wrong. Although the co-rulers in most cases were the throne heirs, they cannot be called the co-rulers because of the right to inherit the throne, but for the ruling attributes that formally established that right. The conviction of the co-rule of King Stefan and his son Radoslav is founded on the interpretation of the facts coming from the following sources: entitling charters for the monastery of Žiča, produced by Stefan and Radoslav around 1220; some segments from St. Sava's biographies by Domentian and Theodosius describing the circumstances of Stefan's death-bed leaving the throne to Radoslav; the three acts of the town of Kotor from 1221 and 1227 dated by the rule of king Radoslav, the portraits of Stefan and Radoslav next to the entrance to the Church of the Ascension in the monastery of Žiča and in the nartex of the Mileševa monastery church. In the first Žiča charter, Stefan calls Radoslav his heir, while in the second Žiča charter Stefan points out Radoslav as his first-born son blessed by him to be the king of the whole state. (jegože i

  2. A Female Patient with FMR1 Premutation and Mosaic X Chromosome Aneuploidy and Two Sons with Intellectual Disability.

    Science.gov (United States)

    Galanina, Ekaterina M; Tulupov, Andrey A; Lemskaya, Natalya A; Korostyshevskaya, Aleksandra M; Maksimova, Yuliya V; Shorina, Asia R; Savelov, Andrey A; Sergeeva, Irina G; Isanova, Evgeniya R; Grishchenko, Irina V; Yudkin, Dmitry V

    2017-03-01

    In this report, we describe a molecular cytogenetic study of a family burdened with intellectual disability (ID) and suicide. Our study revealed that the mother has a heterozygous premutation in the FMR1 gene and supernumerary X chromosomes as well as X-derived marker chromosomes. Both of her sons have ID and a normal chromosome number. One of the sons has fragile X syndrome, and the other has ID of an unclear nature.

  3. Son preference among the historical Sandžak Muslim population

    Directory of Open Access Journals (Sweden)

    Čvorović Jelena

    2012-01-01

    Full Text Available This paper attempts to explain parental son preferences among historical Muslim population in the Sandžak region, southwestern Serbia. The paper draws upon data collected in the course of anthropological fieldwork studies in the region. The fieldwork was performed among Muslim and Christian families in Serbian rural area of Sandžak, measuring maternal fitness in relation to several variables. The data set comes from 120 women born between 1880-1924, representing so a historical demographic data based on individual and lineage records. These data were complemented with official records from Archive of Novi Pazar, whenever possible. In this Serbian rural area, land is still considered as an abundant resource, useful in establishing a family, livestock or agriculture. In the past, in spite of yearly fluctuations in production, lands and labor constituted a stable source of wealth from generation to generation. In this study, the data include the socio-economic status of each woman, assigned according to her husband’s family economic status: land-ownership vs. landless. This represents differences in resource availability in terms of nutrition, wealth and workload among these women. As the results show, the Muslim families, on average, left more surviving descendants through sons, in contrast with their Christian counterparts. The basic research question, then, is why? Furthermore, what were the impacts of particular behaviors on reproductive and lineage success, under particular social and ecological conditions? In this sample, regarding the Muslim families, the family structure was/is traditional and stratified, characterized by a large disparity in the status of males and females. Patrilineal inheritance, the concentration of wealth and power in males and the social restriction of women all characterize even today this patriarchal family arrangement. This supports the Trivers-Willard hypothesis, especially in terms of sex-biased parental

  4. Ibrahim, Son of Mahmoudek: Accession to Power and Purses (1 »

    Directory of Open Access Journals (Sweden)

    A.L. Ponomarev

    2014-01-01

    Full Text Available The death of the Crimean khan Haji Giray on 25 August 1466 was followed by two months of the political turmoil. Sons of the late ruler, Mengli Giray and Nur Dawlat, were two pretenders well-known to the historians. But numismatic material and newly found archival documents prove that there was one more claimant khan. He was the protege of the Shirin bek Mamak and the copper puls of Caffa with the forked tamga testify that the Genoeses were inclined to accept his supremacy. The said heraldic symbol didn’t belong to Giray khans and it was never more used for the coins of Caffa or the khanate after 1441, when Tartar beks elected Haji Giray to be their lord. These puls were the fractional currency that became necessary after there had happened the monetary reform in the khanate and those old silver dangs started to circulate side by side with a new silver denomination – aqcha. The author has discovered that these puls have die links with aqche coins of Nur Dawlat and moreover he has found that the third «Emperor» had been mentioned in the unpublished accounts of the Genoese treasury, composed in September and October 1466. The shape of his tamga as well the steady political predilections of the Shirin beks demonstrate his kinship with Ulugh Muhammad. The name of this previously unbeknown Crimean khan, who became next year the khan of the Kazan khanate, was Ibrahim. The name of this khan is written on those coins which were earlier attributed to the Siberian khan Ibrahim (Ibak without real, only on far-fetched and untutored grounds.

  5. Ibrahim, Son of Mahmoudek: Accession to Power and Purses (2 »

    Directory of Open Access Journals (Sweden)

    A.L. Ponomarev

    2014-07-01

    Full Text Available The death of the Crimean khan Haij Garey on 25 August 1466 was followed by two months of the political turmoil. Sons of the late ruler, Mengli Garey and Nur Dawlat, were two pretenders well-known to the historians. But numismatic material and newly found archival documents prove that there was one more claimant khan. He was the protege of the Shirin bek Mamak and the copper puls of Caffa with the forked tamga testify that the Genoeses were inclined to accept his supremacy. The said heraldic symbol didn’t belong to Garey khans and it was never more used for the coins of Caffa or the khanate after 1441, when Tartar beks elected Haji Garey to be their lord. These puls were the fractional currency that became necessary after there had happened the monetary reform in the khanate and those old silver dangs started to circulate side by side with a new silver denomination – aqcha. The author has discovered that these puls have die links with aqcha coins of Nur Dawlat and moreover he has found that the third «Emperor» had been mentioned in the unpublished accounts of the Genoese treasury, composed in September and October 1466. The shape of his tamga as well the steady political predilections of the Shirin beks demonstrate his kinship with Ulugh Muhammad. The name of this previously unbeknown Crimean khan, who became next year the khan of the Kazan khanate, was Ibrahim. The name of this khan is written on those coins which were earlier attributed to the Siberian khan Ibrahim (Ibak without real, only on far-fetched and untutored grounds.

  6. Empirical evidence for son-killing X chromosomes and the operation of SA-zygotic drive.

    Directory of Open Access Journals (Sweden)

    Urban Friberg

    Full Text Available Diploid organisms have two copies of all genes, but only one is carried by each haploid gamete and diploid offspring. This causes a fundamental genetic conflict over transmission rate between alternative alleles. Single genes, or gene clusters, only rarely code for the complex phenotypes needed to give them a transmission advantage (drive phenotype. However, all genes on a male's X and Y chromosomes co-segregate, allowing different sex-linked genes to code for different parts of the drive phenotype. Correspondingly, the well-characterized phenomenon of male gametic drive, occurring during haploid gametogenesis, is especially common on sex chromosomes. The new theory of sexually antagonistic zygotic drive of the sex chromosomes (SA-zygotic drive extends the logic of gametic drive into the diploid phase of the lifecycle, whenever there is competition among siblings or harmful sib-sib mating. The X and Y are predicted to gain a transmission advantage by harming offspring of the sex that does not carry them.Here we analyzed a mutant X-chromosome in Drosophila simulans that produced an excess of daughters when transmitted from males. We developed a series of tests to differentiate between gametic and SA-zygotic drive, and provide multiple lines of evidence that SA-zygotic drive is responsible for the sex ratio bias. Driving sires produce about 50% more surviving daughters than sons.Sex-ratio distortion due to genetic conflict has evolved via gametic drive and maternally transmitted endosymbionts. Our data indicate that sex chromosomes can also drive by harming the non-carrier sex of offspring.

  7. Empirical evidence for son-killing X chromosomes and the operation of SA-zygotic drive.

    Science.gov (United States)

    Friberg, Urban; Stewart, Andrew D; Rice, William R

    2011-01-01

    Diploid organisms have two copies of all genes, but only one is carried by each haploid gamete and diploid offspring. This causes a fundamental genetic conflict over transmission rate between alternative alleles. Single genes, or gene clusters, only rarely code for the complex phenotypes needed to give them a transmission advantage (drive phenotype). However, all genes on a male's X and Y chromosomes co-segregate, allowing different sex-linked genes to code for different parts of the drive phenotype. Correspondingly, the well-characterized phenomenon of male gametic drive, occurring during haploid gametogenesis, is especially common on sex chromosomes. The new theory of sexually antagonistic zygotic drive of the sex chromosomes (SA-zygotic drive) extends the logic of gametic drive into the diploid phase of the lifecycle, whenever there is competition among siblings or harmful sib-sib mating. The X and Y are predicted to gain a transmission advantage by harming offspring of the sex that does not carry them. Here we analyzed a mutant X-chromosome in Drosophila simulans that produced an excess of daughters when transmitted from males. We developed a series of tests to differentiate between gametic and SA-zygotic drive, and provide multiple lines of evidence that SA-zygotic drive is responsible for the sex ratio bias. Driving sires produce about 50% more surviving daughters than sons. Sex-ratio distortion due to genetic conflict has evolved via gametic drive and maternally transmitted endosymbionts. Our data indicate that sex chromosomes can also drive by harming the non-carrier sex of offspring.

  8. Shamgar, son of Anath, in the Josephus Flavius’ “Antiquitates Judaicae”

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    Łukasz Toboła

    2014-03-01

    Full Text Available Although Shamgar is described as deliverer of Israel in Judg 3:31, all the regular elements in the description of the work of Israel’s judges seems to be lacking there (for example, the official titles שפט or מושיע. In this context the tradition of Josephus (Antiquities 5:197 is instructive here: Σανάγαρος ὁ Ἀνάθου παῖς αἱρεθεὶς ἄρχειν ἐν τῷ πρώτῳ τῆς ἀρχῆς ἔτει κατέστρεψε τὸν βίον (“Sanagaros, the Anath’s son, having been chosen to rule, in the first year of his rule lost his life”. If Josephus’ biblical source was basically the same as the Masoretic Text, he seems to understood the lexeme הבקר of Judg 3:31 as a passive verbal form from the root בקר, in the sense attested in the Qumran scrolls, where the term מבקר means “supervisor, inspector.” Therefore, although the standard formula of assuming the rule is missing there, the consonantal Hebrew text permits one to recognize Shamgar as chief and deliverer of Israelites. He “has been appointed” (הֻבְקַר to be a “supervisor, chief” (compare αἱρεθεὶς ἄρχειν in Josephus of Israel.

  9. Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the human papillomavirus type 31 life cycle

    International Nuclear Information System (INIS)

    Lee, Choongho; Wooldridge, Tonia R.; Laimins, Laimonis A.

    2007-01-01

    The E6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. E6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. In this study, we investigated the consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16 E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV 31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not alter binding to another α-helical domain protein, E6AP. When HPV 31 genomes containing mutations at amino acid 128 were transfected into human keratinocytes, the viral DNAs were not stably maintained as episomes indicating the importance of this residue for pathogenesis. Many E6 binding partners including E6TP1 are cytoplasmic proteins, but E6 has been also reported to be localized to the nucleus. We therefore investigated the importance of E6 localization to the nucleus in the viral life cycle. Using a fusion of E6 to Green Fluorescent Protein, we mapped one component of the nuclear localization sequences to residues 121 to 124 of HPV 31 E6. Mutation of these residues in the context of the HPV 31 genome abrogated the ability for episomes to be stably maintained and impaired the ability to extend the life span of cells. These studies identify two activities of HPV 31 E6 that are important for its function in the viral life cycle and for extension of cell life span

  10. The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

    Science.gov (United States)

    Christou, Charita M; Hadjisavvas, Andreas; Kyratzi, Maria; Flouri, Christina; Neophytou, Ioanna; Anastasiadou, Violetta; Loizidou, Maria A; Kyriacou, Kyriacos

    2014-01-01

    The identification of variants of unknown clinical significance (VUS) in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02) in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

  11. The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Charita M Christou

    Full Text Available The identification of variants of unknown clinical significance (VUS in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02 in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

  12. Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

    Science.gov (United States)

    Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

    2001-01-01

    the resistance was abrogated by IL-12 treatment, it is speculated that hLT-alpha treatment may have changed a local cytokine balance protective from beta cell destruction. Copyright 2001 Academic Press.

  13. Salmonella enterica serotype Typhimurium Std fimbriae bind terminal α (1,2)fucose residues in the cecal mucosa

    Science.gov (United States)

    Chessa, Daniela; Winter, Maria G.; Jakomin, Marcello; Bäumler, Andreas J.

    2013-01-01

    SUMMARY The std operon encodes a fimbrial adhesin of Salmonella enterica serotype Typhimurium that is required for attachment to intestinal epithelial cells and for cecal colonization in the mouse. To study the mechanism by which this virulence factor contributes to colonization we characterized its binding specificity. Std-mediated binding to human colonic epithelial (Caco-2) cells could be abrogated by removing N-linked glycans. Adherence of Std fimbriated S. Typhimurium to Caco-2 cells could be blocked by co-incubation with H type 2 oligosaccharide (Fucα1-2Galβ1-4GlcNAc) or by pretreatment of cells with α1-2 fucosidase. In contrast, pretreatment of Caco-2 cells with neuraminidase or co-incubation with the type 2 disaccharide precursor (Galβ1-4GlcNAc) did not reduce adherence of Std fimbriated S. Typhimurium. Binding of purified Std fimbriae to Fucα1-2Galβ1-4GlcNAc in a solid phase binding assay was competitively inhibited by Ulex europaeus agglutinin-I (UEA-I), a lectin specific for Fucα1-2 moieties. Purified Std fimbriae and UEA both bound to a receptor localized in the mucus layer of the murine cecum. These data suggest that the std operon encodes an adhesin that binds an α1-2 fucosylated receptor(s) present in the cecal mucosa. PMID:19183274

  14. My Son The Fanatic, de Hanif Kureishi, ou l’intégration à rebours

    Directory of Open Access Journals (Sweden)

    Jean-Paul Revauger

    2007-11-01

    Full Text Available Utiliser un film, ou toute création culturelle, pour comprendre le social pose un certain nombre de problèmes méthodologiques. Un film n’est pas un « reflet ». Une création, même si elle se place sous le sceau du réalisme, a un rapport très fort mais indirect avec le contexte historique de sa genèse. Elle est le produit de la rencontre d’un contexte, d’un créateur doté d’une idéologie, d’un « habitus », d’un corpus de valeurs, des modes et techniques en vigueur dans le champ de la création au moment de celle-ci et, comme le rappelle Bourdieu, de la stratégie du créateur par rapport à ses collègues/concurrents. Enfin, sans ajouter une note discordante supplémentaire aux théories de la réception, l’œuvre sera perçue de façon différente selon les publics. My Son the Fanatic sera donc perçu comme une œuvre satanique par les fondamentalistes musulmans, mais sans doute aussi chrétiens, comme une bluette charmante par les midinettes au grand cœur qui semblent être le public visé par la présentation publicitaire du film, comme une démonstration de la justesse de leurs thèses par les partisans de l’intégration, mais aussi par les émules de Huntington pour qui le choc des civilisations est inéluctable, enfin comme une manifestation irresponsable d’ « islamophobie » par les nostalgiques des politiques multiculturalistes d’antan. Les aficionados de Hanif Kureishi, auteur de la nouvelle sur laquelle le film est fondé, et scénariste du film lui-même, y retrouveront le plaidoyer pour la liberté individuelle et, en particulier, la liberté sexuelle qu’ils attendent, mais seront un peu surpris par les côtés didactiques, pour employer cet adjectif dans une acception qui déplait aux didacticiens, c'est-à-dire une volonté de démonstration un peu insistante.Using films, or, for that matter, any cultural artefact in order to reach an understanding of social issues raises a number of

  15. "There is such a thing as too many daughters, but not too many sons": A qualitative study of son preference and fetal sex selection among Indian immigrants in the United States.

    Science.gov (United States)

    Puri, Sunita; Adams, Vincanne; Ivey, Susan; Nachtigall, Robert D

    2011-04-01

    In response to concerns from feminists, demographers, bioethicists, journalists, and health care professionals, the Indian government passed legislation in 1994 and 2003 prohibiting the use of sex selection technology and sex-selective abortion. In contrast, South Asian families immigrating to the United States find themselves in an environment where reproductive choice is protected by law and technologies enabling sex selection are readily available. Yet there has been little research exploring immigrant Indian women's narratives about the pressure they face to have sons, the process of deciding to utilize sex selection technologies, and the physical and emotional health implications of both son preference and sex selection. We undertook semi-structured, in-depth interviews with 65 immigrant Indian women in the United States who had pursued fetal sex selection on the East and West coasts of the United States between September 2004 and December 2009. Women spoke of son preference and sex selection as separate though intimately related phenomena, and the major themes that arose during interviews included the sociocultural roots of son preference; women's early socialization around the importance of sons; the different forms of pressure to have sons that women experienced from female in-laws and husbands; the spectrum of verbal and physical abuse that women faced when they did not have male children and/or when they found out they were carrying a female fetus; and the ambivalence with which women regarded their own experience of reproductive "choice." We found that 40% of the women interviewed had terminated prior pregnancies with female fetuses and that 89% of women carrying female fetuses in their current pregnancy pursued an abortion. These narratives highlight the interaction between medical technology and the perpetuation of this specific form of violence against women in an immigrant context where women are both the assumed beneficiaries of reproductive choice

  16. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  17. Optical Binding of Nanowires

    Czech Academy of Sciences Publication Activity Database

    Simpson, Stephen Hugh; Zemánek, Pavel; Marago, O.M.; Jones, P.H.; Hanna, S.

    2017-01-01

    Roč. 17, č. 6 (2017), s. 3485-3492 ISSN 1530-6984 R&D Projects: GA ČR GB14-36681G Grant - others:AV ČR(CZ) CNR-16-12 Program:Bilaterální spolupráce Institutional support: RVO:68081731 Keywords : optical binding nanowires * Brownian motion * self-organization * non-equilibrium thermodynamics * non-equilibrium steady state * spin-orbit coupling * emergent phenomena Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 12.712, year: 2016

  18. The role of God in the father/son relationship during identity formation – a Gestalt theoretical perspective

    Directory of Open Access Journals (Sweden)

    H.B. Grobler

    2010-07-01

    Full Text Available This article is based on research done within the Afrikaansspeaking community in the area of the Drakenstein Municipality, Western Cape province, South Africa. The focus falls specifically on one concept that was outlined during the research, namely the perceptions of fathers and adolescent sons on identity formation within their relationship as well as the role that God plays. Combined qualitative/quantitative research was conducted with emphasis on semi-structured interviews with fathers (n=4 and adolescent boys (n=4 and an auto-ethnography of the author as the dominant component. The lessdominant quantitative component consisted of questionnaires completed by fathers (n=42 and adolescent boys (n=180. Metatheoretical assumptions and theoretical assumptions as grounding for the male identity are discussed as part of the author’s paradigmatic perspective. Furthermore, empirical findings are discussed and recommendations are made. From the discussions with fathers and their sons it was clear that both fathers and sons have a need to stand in close relationship to each other and to God. It is within this relationship where their identities are formed. However, fathers seemed to be resistant of transferring their beliefs to their sons. Adolescent boys also indicated no need to one day transfer learned behaviour from their fathers to their sons.

  19. The ability of AIF-1 to activate human vascular smooth muscle cells is lost by mutations in the EF-hand calcium-binding region

    International Nuclear Information System (INIS)

    Autieri, Michael V.; Chen Xing

    2005-01-01

    Allograft Inflammatory Factor-1 (AIF-1) is a cytoplasmic calcium-binding protein expressed in vascular smooth muscle cells (VSMC) in response to injury or cytokine stimulation. AIF-1 contains a partially conserved EF-hand calcium-binding domain, and participates in VSMC activation by activation of Rac1 and induction of Granulocyte-Colony Stimulating Factor (G-CSF) expression; however, the mechanism whereby AIF-1 mediates these effects is presently uncharacterized. To determine if calcium binding plays a functional role in AIF-1 activity, a single site-specific mutation was made in the EF-hand calcium-binding domain to abrogate binding of calcium (AIF-1ΔA), which was confirmed by calcium overlay. Functionally, similar to wild-type AIF-1, AIF-1ΔA was able to polymerize F-actin in vitro. However, in contrast to wild-type AIF-1, over-expression of AIF-1ΔA was unable to increase migration or proliferation of primary human VSMC. Further, it was unable to activate Rac1, or induce G-CSF expression to the degree as wild-type AIF-1. Taken together, modification of the wild-type EF-hand domain and native calcium-binding activity results in a loss of AIF-1 function. We conclude that appropriate calcium-binding potential is critical in AIF-1-mediated effects on VSMC pathophysiology, and that AIF-1 activity is mediated by Rac1 activation and G-CSF expression

  20. Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.

    Directory of Open Access Journals (Sweden)

    Hyeong-Jun Han

    Full Text Available Peptidyl prolyl isomerase (PIN1 regulates the functional activity of a subset of phosphoproteins through binding to phosphorylated Ser/Thr-Pro motifs and subsequently isomerization of the phosphorylated bonds. Interestingly, PIN1 is overexpressed in many types of malignancies including breast, prostate, lung and colon cancers. However, its oncogenic functions have not been fully elucidated. Here, we report that PIN1 directly interacts with hypoxia-inducible factor (HIF-1α in human colon cancer (HCT116 cells. PIN1 binding to HIF-1α occurred in a phosphorylation-dependent manner. We also found that PIN1 interacted with HIF-1α at both exogenous and endogenous levels. Notably, PIN1 binding stabilized the HIF-1α protein, given that their levels were significantly increased under hypoxic conditions. The stabilization of HIF-1α resulted in increased transcriptional activity, consequently upregulating expression of vascular endothelial growth factor, a major contributor to angiogenesis. Silencing of PIN1 or pharmacologic inhibition of its activity abrogated the angiogenesis. By utilizing a bioluminescence imaging technique, we were able to demonstrate that PIN1 inhibition dramatically reduced the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of HIF-1α. These results suggest that PIN1 interacting with HIF-1α is a potential cancer chemopreventive and therapeutic target.

  1. Nuclear localization signal of ING4 plays a key role in its binding to p53

    International Nuclear Information System (INIS)

    Zhang Xin; Wang Kesheng; Wang Zhiqin; Xu Lusheng; Wang Qingwan; Chen Fei; Wei Dongzhi; Han Zeguang

    2005-01-01

    ING4, a novel member of ING family, is recently reported to interact with tumor suppressor p53 and negatively regulate the cell growth with significant G2/M arrest of cell cycle in HepG2 cells through upregulation of p53-inducible gene p21. However, which region of ING4 could have contributed to the binding to p53 remains largely unclear. Herein, the GST-pulldown experiments revealed that the middle region of ING4, a potential bipartite nuclear localization signal (NLS), could be involved in the binding to p53. Furthermore, the interaction of ING4 to p53 was abrogated in vitro and in vivo when certain mutations or the entire deletion of the NLS domain occurred. More interestingly, the mutations of the NLS domain could alter the ING4 nuclear localization, disrupt the interaction of ING4 with p53, and even, deregulate the p53-inducible gene p21 in MCF-7 cells. All data indicated that the NLS domain of ING4 is essential for the binding of ING4 to p53 and the function of ING4 associated with p53

  2. Collagen-binding proteins of Streptococcus mutans and related streptococci.

    Science.gov (United States)

    Avilés-Reyes, A; Miller, J H; Lemos, J A; Abranches, J

    2017-04-01

    The ability of Streptococcus mutans to interact with collagen through the expression of collagen-binding proteins (CBPs) bestows this oral pathogen with an alternative to the sucrose-dependent mechanism of colonization classically attributed to caries development. Based on the abundance and distribution of collagen throughout the human body, stringent adherence to this molecule grants S. mutans with the opportunity to establish infection at different host sites. Surface proteins, such as SpaP, WapA, Cnm and Cbm, have been shown to bind collagen in vitro, and it has been suggested that these molecules play a role in colonization of oral and extra-oral tissues. However, robust collagen binding is not achieved by all strains of S. mutans, particularly those that lack Cnm or Cbm. These observations merit careful dissection of the contribution from these different CBPs towards tissue colonization and virulence. In this review, we will discuss the current understanding of mechanisms used by S. mutans and related streptococci to colonize collagenous tissues, and the possible contribution of CBPs to infections in different sites of the host. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. ¿Son seres humanos los puentes de fábrica?

    Directory of Open Access Journals (Sweden)

    Bauder, E.

    2006-03-01

    éndole cualidades humanas a lo largo de su ciclo vital, a la vez que desempeña el papel de creador, padre, defensor, médico o psicólogo según las situaciones en que se encuentre o los problemas a que se enfrente su puente-hijo. Además, se quiere poner de manifiesto que la abundante utilización de esta metáfora y las correspondencias terminológicas derivadas de ella no son un fenómeno extraño, sino el resultado lógico de la interdisciplinaridad natural entre la técnica constructiva, la medicina (psicología incluida, la terminología y el lenguaje.

  4. IGF binding proteins.

    Science.gov (United States)

    Bach, Leon A

    2017-12-18

    Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF- and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

  5. Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX Mutation in a Father and Son.

    Science.gov (United States)

    Arcot Sadagopan, Karthikeyan; Battista, Robert; Keep, Rosanne B; Capasso, Jenina E; Levin, Alex V

    2015-06-01

    Leber congenital amaurosis (LCA) is most often an autosomal recessive disorder. We report a father and son with autosomal dominant LCA due to a mutation in the CRX gene. DNA screening using an allele specific assay of 90 of the most common LCA-causing variations in the coding sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene was subsequently performed. Both father and son have a heterozygous single base pair deletion of an adenine at codon 153 in the coding sequence of the CRX gene resulting in a frameshift mutation. Mutations involving the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA.

  6. Alexander Falconer Sr Seamen's missionary in New Zealand, son Alexander Falconer medical superintendent for mentally ill, grandson Murray Falconer neurosurgeon.

    Science.gov (United States)

    Hawgood, Barbara J

    2016-08-01

    Alexander Falconer Sr (1843-1915) came from Scotland to New Zealand. A practical Christian, he set up places of relaxation for miners, sailors and soldiers; he became the Seamen's Missionary. Son, Dr Alexander Falconer (1874-1955) trained at Otago University Medical School. As medical superintendent for the mentally ill, he urged the early introduction of psychotherapy. His son, Murray Falconer (1910-1977) was the first Nuffield Dominions Clinical Fellow, training in neurosurgery in Oxford. He was the first director of the Guy's-Maudsley Neurosurgical Unit in London and was internationally known for the surgical management of temporal lobe epilepsy in adults and children. © The Author(s) 2016.

  7. Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation.

    Science.gov (United States)

    Stefanova, Margarita; Zemke, Katrin; Dimitrov, Boyan; Has, Christina; Kern, Johannes S; Bruckner-Tuderman, Leena; Kutsche, Kerstin

    2005-10-01

    Mutations in the type VII collagen gene (COL7A1) cause autosomal recessive and autosomal dominant inherited dystrophic epidermolysis bullosa (DEB). We report a family with three individuals who present blistering, scarring, hypo- and hyperpigmentation, and nail dystrophy suggestive for DEB. Whereas father and son carry a 5;13 translocation, the daughter shows a normal karyotype. Segregation analysis revealed that all affected family members inherited the same COL7A1 allele. Mutation analysis disclosed a heterozygous missense mutation, c.6227G > A (p.G2076D), in COL7A1 in all affected individuals. Delineation of the translocation breakpoints showed that the ERBB2IP (erbb2 interacting protein or Erbin) gene is disrupted in 5q13.1 and GPC6 in 13q32. GPC6 encodes glypican 6 belonging to a family of cell surface heparan sulfate proteoglycans. The binding partners of Erbin, BP230 (BPAG1) and the integrin beta4 subunit, both involved in hemidesmosome (HD) function, and the presence of Erbin in HD suggested that it plays a role in establishment and maintenance of cell-basement membrane adhesions. However, loss of function of one ERBB2IP copy or expression of a putative novel ERBB2IP fusion protein did not apparently modulate the DEB phenotype in both translocation patients. Nonetheless, one cannot yet exclude that ERBB2IP is a candidate for human blistering disorders such as epidermolysis bullosa.

  8. E-selectin ligand-1 (ESL-1) is a novel adiponectin binding protein on cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Hiroyasu; Kuroda, Nana; Uekita, Hiromi; Kochi, Ikoi; Matsumoto, Akane; Niinaga, Ryu [Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka (Japan); Funahashi, Tohru; Shimomura, Iichiro [Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka (Japan); Kihara, Shinji, E-mail: skihara@sahs.med.osaka-u.ac.jp [Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka (Japan)

    2016-02-05

    Background: Adiponectin (APN) is an adipocyte-derived bioactive molecule with anti-diabetic and anti-atherogenic properties. Although anti-diabetic effects are mostly mediated by the adiponectin receptors AdipoR1 and AdipoR2, the anti-atherogenic mechanisms have not been fully elucidated. Methods and Results: In this study, we identified E-selectin ligand (ESL)-1 as a novel APN-binding protein by mass spectrometry analysis of HepG2 cell-derived immunoprecipitant with an anti-APN antibody. Cell adhesion assays using fluorescence-labelled monocyte cell line THP-1 cells and human umbilical vein endothelial cells (HUVECs) revealed that APN-pre-treated THP-1 cells had reduced binding ability to HUVECs. This APN-mediated suppressive effect on monocyte binding to endothelial cells was partially abrogated by targeting ESL-1 with shRNA in THP-1 cells. In addition, serial mutagenesis analysis disclosed that five extracellular amino acids close to the N-terminus of ESL-1 were essential for binding with APN. Conclusion: Our results highlight the fact that interaction between APN and ESL-1 could provide a fundamental mechanism underlying the anti-atherogenic properties of APN. - Highlights: • E-selectin ligand (ESL)-1 was identified as an adiponectin (APN)-binding protein. • ESL-1 bound to APN at its N-terminal 6th-10th amino acids. • shESL-1 reduced the suppressive effect of APN on adhesion of THP-1 cells to HUVECs. • Interaction with ESL may be involved in the anti-atherogenic effects of APN.

  9. E-selectin ligand-1 (ESL-1) is a novel adiponectin binding protein on cell adhesion

    International Nuclear Information System (INIS)

    Yamamoto, Hiroyasu; Kuroda, Nana; Uekita, Hiromi; Kochi, Ikoi; Matsumoto, Akane; Niinaga, Ryu; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

    2016-01-01

    Background: Adiponectin (APN) is an adipocyte-derived bioactive molecule with anti-diabetic and anti-atherogenic properties. Although anti-diabetic effects are mostly mediated by the adiponectin receptors AdipoR1 and AdipoR2, the anti-atherogenic mechanisms have not been fully elucidated. Methods and Results: In this study, we identified E-selectin ligand (ESL)-1 as a novel APN-binding protein by mass spectrometry analysis of HepG2 cell-derived immunoprecipitant with an anti-APN antibody. Cell adhesion assays using fluorescence-labelled monocyte cell line THP-1 cells and human umbilical vein endothelial cells (HUVECs) revealed that APN-pre-treated THP-1 cells had reduced binding ability to HUVECs. This APN-mediated suppressive effect on monocyte binding to endothelial cells was partially abrogated by targeting ESL-1 with shRNA in THP-1 cells. In addition, serial mutagenesis analysis disclosed that five extracellular amino acids close to the N-terminus of ESL-1 were essential for binding with APN. Conclusion: Our results highlight the fact that interaction between APN and ESL-1 could provide a fundamental mechanism underlying the anti-atherogenic properties of APN. - Highlights: • E-selectin ligand (ESL)-1 was identified as an adiponectin (APN)-binding protein. • ESL-1 bound to APN at its N-terminal 6th-10th amino acids. • shESL-1 reduced the suppressive effect of APN on adhesion of THP-1 cells to HUVECs. • Interaction with ESL may be involved in the anti-atherogenic effects of APN.

  10. 77 FR 72906 - Chessie Logistics Co., LLC-Acquisition and Operation Exemption-J. Emil Anderson & Son, Inc.

    Science.gov (United States)

    2012-12-06

    ... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35700] Chessie Logistics Co., LLC--Acquisition and Operation Exemption-- J. Emil Anderson & Son, Inc. Chessie Logistics Co... served on Ariel A. Erbacher, Legal Counsel, Chessie Logistics Co., LLC, 1001 Green Bay Rd., Unit 204...

  11. The Quest of Father and Son: Illuminating Character Identity, Motivation, and Conflict in Cormac McCarthy's "The Road"

    Science.gov (United States)

    Gilbert, Chris

    2012-01-01

    "The Road" has been an important part of the author's English IV Honors course for several years now. Undeniably bleak, it details a father and son's journey through a seared, post-apocalyptic wasteland. As they travel through the burnt remains of America, they are threatened by starvation, dehydration, and scattered, hostile humans. Although his…

  12. "My Son Is Reliable": Young Drivers' Parents' Optimism and Views on the Norms of Parental Involvement in Youth Driving

    Science.gov (United States)

    Guttman, Nurit

    2013-01-01

    The high crash rates among teenage drivers are of great concern across nations. Parents' involvement is known to help increase their young drivers' driving safety. In particular, parents can place restrictions on their son's/daughter's driving (e.g., restrict night time driving), which can enable the young driver to gain driving experience in…

  13. Literature as an exploration of the phenomenology of schizophrenia: disorder and recovery in Denis Johnson's Jesus' Son.

    Science.gov (United States)

    Hamm, Jay A; Leonhardt, Bethany L; Fogley, Rebecca L; Lysaker, Paul H

    2014-12-01

    When read as a fictional psychosis narrative, Jesus' Son, a collection of short stories by Denis Johnson, reveals important elements of the phenomenology of schizophrenia and recovery. It is possible that Jesus' Son, as a work of fiction, may be able to uniquely add depth and nuance to an understanding of the phenomenology of schizophrenia involving a state of psychological fragmentation, an ever-changing interpersonal field and a loss of personal agency. In addition, by following the protagonist in Jesus' Son as he begins to resolve some of his difficulties, the book also offers an individualised account of recovery. The authors detail how the book reveals these insights about schizophrenia and recovery and suggest that these elements are intertwined in such a manner that leads to a profound disruption of self-experience, characterised by a collapse of metacognitive processes. Jesus' Son may add depth to our understanding of the subjective experience of schizophrenia and recovery, and also may serve as one example in which the study of humanities offers an opportunity to explore the human elements in the most profound forms of suffering. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. La Mycorhize à arbuscules : quels bénéfices pour l'homme et son ...

    African Journals Online (AJOL)

    La Mycorhize à arbuscules : quels bénéfices pour l'homme et son ... et quantitative de la production végétale mais aussi pour une gestion et une remédiation ... Mycorrhizal symbiosis, and specifically arbuscular mycorrhization, which occurs ...

  15. Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case.

    Science.gov (United States)

    Diack, Abigail B; Boyle, Aileen; Ritchie, Diane; Plinston, Chris; Kisielewski, Dorothy; de Pedro-Cuesta, Jesús; Rábano, Alberto; Will, Robert G; Manson, Jean C

    2017-09-01

    We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date.

  16. Examination of the Film "My Father and My Son" According to the Basic Concepts of Multigenerational Family Therapy

    Science.gov (United States)

    Acar, Tulin; Voltan-Acar, Nilufer

    2013-01-01

    The aim of this study was to evaluate the basic concepts of multigenerational Family Therapy and to evaluate the scenes of the film ''My Father and My Son'' according to these concepts. For these purposes firstly basic concepts of Multigenerational Family Therapy such as differentiation of self, triangles/triangulation, nuclear family emotional…

  17. Giving Birth to Life--Again!: Bereaved Parents' Experiences with Children Born Following the Death of an Adult Son

    Science.gov (United States)

    Hamama-Raz, Yaira; Rosenfeld, Sarah; Buchbinder, Eli

    2010-01-01

    This article is based on a qualitative study examining the experiences of parents that lost a son during military service in Israel and consequently choose to give birth to another child. Seven couples and 3 mothers were interviewed for the study, and their interviews were analyzed using a phenomenological-hermeneutic approach. Three main themes…

  18. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

    International Nuclear Information System (INIS)

    Innerarity, T.L.; Weisgraber, K.H.; Arnold, K.S.; Mahley, R.W.; Krauss, R.M.; Vega, G.L.; Grundy, S.M.

    1987-01-01

    Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125 I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

  19. Rif1 Binding and Control of Chromosome-Internal DNA Replication Origins Is Limited by Telomere Sequestration.

    Science.gov (United States)

    Hafner, Lukas; Lezaja, Aleksandra; Zhang, Xu; Lemmens, Laure; Shyian, Maksym; Albert, Benjamin; Follonier, Cindy; Nunes, Jose Manuel; Lopes, Massimo; Shore, David; Mattarocci, Stefano

    2018-04-24

    The Saccharomyces cerevisiae telomere-binding protein Rif1 plays an evolutionarily conserved role in control of DNA replication timing by promoting PP1-dependent dephosphorylation of replication initiation factors. However, ScRif1 binding outside of telomeres has never been detected, and it has thus been unclear whether Rif1 acts directly on the replication origins that it controls. Here, we show that, in unperturbed yeast cells, Rif1 primarily regulates late-replicating origins within 100 kb of a telomere. Using the chromatin endogenous cleavage ChEC-seq technique, we robustly detect Rif1 at late-replicating origins that we show are targets of its inhibitory action. Interestingly, abrogation of Rif1 telomere association by mutation of its Rap1-binding module increases Rif1 binding and origin inhibition elsewhere in the genome. Our results indicate that Rif1 inhibits replication initiation by interacting directly with origins and suggest that Rap1-dependent sequestration of Rif1 increases its effective concentration near telomeres, while limiting its action at chromosome-internal sites. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. In silico analysis reveals sequential interactions and protein conformational changes during the binding of chemokine CXCL-8 to its receptor CXCR1.

    Directory of Open Access Journals (Sweden)

    Je-Wen Liou

    Full Text Available Chemokine CXCL-8 plays a central role in human immune response by binding to and activate its cognate receptor CXCR1, a member of the G-protein coupled receptor (GPCR family. The full-length structure of CXCR1 is modeled by combining the structures of previous NMR experiments with those from homology modeling. Molecular docking is performed to search favorable binding sites of monomeric and dimeric CXCL-8 with CXCR1 and a mutated form of it. The receptor-ligand complex is embedded into a lipid bilayer and used in multi ns molecular dynamics (MD simulations. A multi-steps binding mode is proposed: (i the N-loop of CXCL-8 initially binds to the N-terminal domain of receptor CXCR1 driven predominantly by electrostatic interactions; (ii hydrophobic interactions allow the N-terminal Glu-Leu-Arg (ELR motif of CXCL-8 to move closer to the extracellular loops of CXCR1; (iii electrostatic interactions finally dominate the interaction between the N-terminal ELR motif of CXCL-8 and the EC-loops of CXCR1. Mutation of CXCR1 abrogates this mode of binding. The detailed binding process may help to facilitate the discovery of agonists and antagonists for rational drug design.

  1. Compared study of the local structure of alteration products of SON 68 glass and natural gels; Etude comparee de la structure locale des produits d'alteration du verre SON 68 et de gels naturels

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrin, E

    2000-07-01

    This study is a contribution in the understanding of the long time behavior of alteration products of the glass SON 68, used to simulate the nuclear glass R7T7. The local structure around Zirconium and iron has been probed using X-ray absorption spectroscopy in altered surface layer of glass SON 68. Alteration products of this glass have been prepared for short (3 hours to 7 days) and long (17 months) time, using various indexes of saturation for the leaching solution with respect to the Si content of the glass (from 0 to 90 %). The evolution of the local structure around Fe has also been studied in recent and old natural ferric gels. Zr, Fe- L{sub 2,3} XANES and Zr, Fe-K EXAFS spectroscopies have shown that, in the pristine glass, these elements are connected to the polymeric network. Zr is found in an environment close to that of a zircon-silicate containing Na and Ca. Trivalent Fe is a network former. The leached layer of glass SON 68 is constituted of poorly ordered Zr-and Fe-(oxi-hydr)oxides that may have been formed by a mechanism of dissolution/precipitation; a relict phase with the same Zr local structure as that observed in the pristine glass, probably obtained thanks to in-situ solid condensation. The structural characteristics of the leached layer are observed from the first steps of alteration for Zr and Fe. Conversely to Fe, the structural status of Zr depends on the leaching kinetic as well as the contents of Ca and Si in the solid. Fe-K EXAFS results in recent natural ferri-hydrides present a clear structural similarity with that determined in glass SON 68 leached products. The study of old paleosols (between 1,800 and 200,000 years) has demonstrated the long time stability of ferric gels, although an increase of medium range order around Fe is seen. (author)

  2. Pictorial binding: endeavor to classify

    Directory of Open Access Journals (Sweden)

    Zinchenko S.

    2015-01-01

    Full Text Available The article is devoted to the classification of bindings of the 1-19th centuries with a unique and untypical book binding decoration technique (encaustic, tempera and oil paintings. Analysis of design features, materials and techniques of art decoration made it possible to identify them as a separate type - pictorial bindings and divide them into four groups. The first group consists of Coptic bindings, decorated with icon-painting images in encaustic technique. The second group is made up of leather Western bindings of the 13-14th centuries, which have the decoration and technique of ornamentation close to iconography. The third group involves parchment bindings, ornamentation technique of which is closer to the miniature. The last group comprises bindings of East Slavic origin of the 15-19th centuries, decorated with icon-painting pictures made in the technique of tempera or oil painting. The proposed classification requires further basic research as several specific kinds of bindings have not yet been investigated

  3. Structural and binding studies of SAP-1 protein with heparin.

    Science.gov (United States)

    Yadav, Vikash K; Mandal, Rahul S; Puniya, Bhanwar L; Kumar, Rahul; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2015-03-01

    SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (KD = 158 nm). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity. © 2014 John Wiley & Sons A/S.

  4. ‘To refer, not to characterise’: A synchronic look at the Son-of-Man logia in the Sayings Gospel Q

    Directory of Open Access Journals (Sweden)

    Llewellyn

    2013-03-01

    Full Text Available The article intends to address the Son-of-Man problem by applying Delbert Burkett’s ‘question of reference’ to those Son-of-Man logia that appear in the Sayings Gospel Q. A position is taken that recent philological approaches to the Son-of-Man problem have not been overly convincing, successful or helpful. Similarly, attempting to determine the authenticity of individual Son-of-Man sayings has not led to any form of scholarly consensus. In place of these approaches, a synchronic approach is defended and applied to the Son-of-Man sayings in Q, with interesting results.

  5. Oxidative stress decreases functional airway mannose binding lectin in COPD.

    Directory of Open Access Journals (Sweden)

    Hai B Tran

    Full Text Available We have previously established that a defect in the ability of alveolar macrophages (AM to phagocytose apoptotic cells (efferocytosis and pathogens is a potential therapeutic target in COPD. We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function were reduced in the airways but not circulation of COPD patients. We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances. We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages. Oligomeric structure of plasma derived MBL (pdMBL before and after oxidation (oxMBL with 2,2'-azobis(2-methylpropionamidinedihydrochroride (AAPH was investigated by blue native PAGE. Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi and expression of macrophage scavenger receptors. Oxidation disrupted higher order MBL oligomers. This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively. Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels. Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1 in the presence of pdMBL that was abrogated in the presence of oxMBL. We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease.

  6. Le glaive et la chair : le pouvoir et son incarnation au temps des derniers Valois

    OpenAIRE

    Roux, Nicolas Le

    2014-01-01

    Au xvie siècle, pouvait-on concevoir la monarchie autrement qu’incarnée ? Servir le roi, c’était servir un prince auquel on était lié personnellement, et non une institution abstraite. Le monarque devait apparaître comme un compagnon pour la noblesse militaire. Henri II représentait le modèle du roi chevalier. Contrairement à son père, Charles IX ne faisait pas la guerre, mais il épuisait son corps dans d’interminables chasses. Henri III a tenu dans sa jeunesse le rôle de chef de guerre. Deve...

  7. Mothers’ Academic Gender Stereotypes and Education-Related Beliefs About Sons and Daughters in African American Families

    Science.gov (United States)

    Wood, Dana; Kurtz-Costes, Beth; Okeke-Adeyanju, Ndidi; Rowley, Stephanie J.

    2010-01-01

    The role of African American mothers’ academic gender stereotype endorsement in shaping achievement-related expectations for and perceptions of their own children was examined. Mothers (N = 334) of 7th and 8th graders completed measures of expectations for their children’s future educational attainment, perceptions of their children’s academic competence, and academic gender stereotypes. Consistent with hypotheses, mothers held less favorable expectations for sons and perceived sons to be less academically competent than daughters. In addition, mothers reported stereotypes favoring girls over boys in academic domains; stereotype endorsement, in turn, was related to mothers’ educational expectations for and beliefs about the academic competence of their own children, even with youths’ actual achievement controlled. Negative stereotypes about the academic abilities of African American boys may create a negative feedback loop, thereby contributing to the maintenance of the gender gap in African Americans’ educational outcomes. PMID:20648228

  8. Mitochondrial DNA analysis on remains of a putative son of Louis XVI, King of France and Marie-Antoinette.

    Science.gov (United States)

    Jehaes, E; Decorte, R; Peneau, A; Petrie, J H; Boiry, P A; Gilissen, A; Moisan, J P; Van den Berghe, H; Pascal, O; Cassiman, J J

    1998-01-01

    Carl Wilhelm Naundorff was buried in 1845 in Delft as Louis Charles, Duc de Normandie, 'Louis XVII'. However, the son of Louis XVI and Marie-Antoinette-Louis XVII--officially died in the Temple of Paris in 1795. In order to resolve the identity of Naundorff, mitochondrial DNA (mtDNA) D-loop sequences of his remains were compared with the sequences obtained from the hairs of two sisters of Marie-Antoinette, Marie-Antoinette herself, and with the sequences obtained from DNA samples of two living maternal relatives. The mtDNA sequence of a bone sample from Naundorff showed two nucleotide differences from the sequences of the three sisters and four differences from the sequences of living maternal relatives. Based on this evidence it becomes very unlikely that Naundroff is the son of Marie-Antoinette.

  9. ¿Quién habla de las mujeres en las noticias donde ellas son las protagonistas?

    Directory of Open Access Journals (Sweden)

    Ana Tamarit

    2011-01-01

    Full Text Available Este artículo presenta un análisis de las fuentes que los periodistas utilizan en las informaciones donde las mujeres son protagonistas de las noticias. La investigación -cuantitativa y cualitativa- se ha realizado en los periódicos de ámbito nacional y local de Castilla y León. Con los resultados obtenidos observamos cómo en los periódicos las noticias que hablan de las mujeres en la mayoría de las ocasiones no se firman. Comprobamos cuáles son las fuentes más utilizadas para la elaboración de esas noticias y las diferentes formas de citar a la fuente cuando se trata de un hombre o de una mujer.

  10. Meaning Reconstruction Process After Suicide: Life-Story of a Japanese Woman Who Lost Her Son to Suicide.

    Science.gov (United States)

    Kawashima, Daisuke; Kawano, Kenji

    2017-09-01

    Although Japan has a high suicide rate, there is insufficient research on the experiences of suicide-bereaved individuals. We investigated the qualitative aspects of the meaning reconstruction process after a loss to suicide. We conducted a life-story interview using open-ended questions with one middle-aged Japanese woman who lost her son to suicide. We used a narrative approach to transcribe and code the participant's narratives for analysis. The analysis revealed three meaning groups that structured the participant's reactions to the suicide: making sense of her son's death and life, relationships with other people, and reconstruction of a bond with the deceased. The belief that death is not an eternal split and that there is a connection between the living and the deceased reduced the pain felt by our participant. Furthermore, the narratives worked as scaffolds in the meaning reconstruction process. We discuss our results in the light of cross-cultural differences in the grieving process.

  11. QCD Precision Measurements and Structure Function Extraction at a High Statistics, High Energy Neutrino Scattering Experiment: NuSOnG

    International Nuclear Information System (INIS)

    Adams, T.; Batra, P.; Bugel, Leonard G.; Camilleri, Leslie Loris; Conrad, Janet Marie; Fisher, Peter H.; Formaggio, Joseph Angelo; Karagiorgi, Georgia S.; )

    2009-01-01

    We extend the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering On Glass) to address a variety of issues including precision QCD measurements, extraction of structure functions, and the derived Parton Distribution Functions (PDFs). This experiment uses a Tevatron-based neutrino beam to obtain a sample of Deep Inelastic Scattering (DIS) events which is over two orders of magnitude larger than past samples. We outline an innovative method for fitting the structure functions using a parameterized energy shift which yields reduced systematic uncertainties. High statistics measurements, in combination with improved systematics, will enable NuSOnG to perform discerning tests of fundamental Standard Model parameters as we search for deviations which may hint of 'Beyond the Standard Model' physics

  12. The Dramatic Development of the Parable of the Prodigal Son in the Sacramental Play by Alonso Remón

    Directory of Open Access Journals (Sweden)

    Rafael Massanet Rodríguez

    2017-11-01

    Full Text Available The parable of the prodigal son is circumscribed as a predominant theme for the authors of the Spanish Golden Age to develop the plot of some of his autos sacramentales. However, among all these playwrights, the figure of Alonso Remón and his piece have been largely ignored. This article reviews the sacramental career of this author and highlights its importance and differences compared to other comedies that address the same theme.

  13. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  14. Young Children’s Risk-Taking: Mothers’ Authoritarian Parenting Predicts Risk-Taking by Daughters but Not Sons

    Directory of Open Access Journals (Sweden)

    Erin E. Wood

    2017-01-01

    Full Text Available We investigated how mothers’ parenting behaviors and personal characteristics were related to risk-taking by young children. We tested contrasting predictions from evolutionary and social role theories with the former predicting higher risk-taking by boys compared to girls and the latter predicting that mothers would influence children’s gender role development with risk-taking occurring more in children parented with higher levels of harshness (i.e., authoritarian parenting style. In our study, mothers reported their own gender roles and parenting styles as well as their children’s risk-taking and activities related to gender roles. The results were only partially consistent with the two theories, as the amount of risk-taking by sons and daughters did not differ significantly and risk-taking by daughters, but not sons, was positively related to mothers’ use of the authoritarian parenting style and the girls’ engagement in masculine activities. Risk-taking by sons was not predicted by any combination of mother-related variables. Overall, mothers who were higher in femininity used more authoritative and less authoritarian parenting styles. Theoretical implications as well as implications for predicting and reducing children’s risk-taking are discussed.

  15. Sociosexually unrestricted parents have more sons: a further application of the generalized Trivers-Willard hypothesis (gTWH).

    Science.gov (United States)

    Kanazawa, Satoshi; Apari, Péter

    2009-01-01

    The generalized Trivers-Willard hypothesis (gTWH) proposes that parents who possess any heritable trait which increases male reproductive success at a greater rate than female reproductive success in a given environment will have a higher-than-expected offspring sex ratio, and parents who possess any heritable trait which increases the female reproductive success at a greater rate than male reproductive success in a given environment will have a lower-than-expected offspring sex ratio. One heritable trait which increases the reproductive success of sons much more than that of daughters is unrestricted sociosexual orientation. We therefore predict that parents with unrestricted sociosexual orientation (measured by the number of sexual partners, frequency of sex, and attitudes toward relationship commitment and sexual exclusivity) have a higher-than-expected offspring sex ratio (more sons). We analyse the US General Social Surveys and the National Longitudinal Study of Adolescent Health (Add Health), both with large nationally representative samples. Our analyses support the prediction from the gTWH. One standard deviation increase in unrestrictedness of sociosexual orientation increases the odds of having a son by 12-19% in the representative American samples.

  16. BALTIMORE’S M.S. LEVY AND SONS: Straw Hat Makers to the World, 1870-1960

    Directory of Open Access Journals (Sweden)

    Jessica I. Elfenbein

    2008-01-01

    Full Text Available From 1860 to 1960, Baltimore was an important center of the men’s ready-to- wear clothing industries. German-speaking Jews created many businesses that manufactured and sold underwear, men’s suits, and specialty items like hats and umbrellas. The straw hat making firm started by M.S. Levy is an interesting example of a Baltimore-based, family-owned niche business that existedfor 90 years, through three generations ofa singlefamily. The M.S. Levy and Sons story has two main chapters. The first covers the period from its founding by Michael Simon Levy in the 1870s through his son Julius’ death in 1926. This is the story of ascension. A premonition about the coming popularity of straw hats, together with a small but important technological breakthrough, positioned a family and a small industry for significant expansion. The second period began in 1930 with the introduction of wool felt hats and the death of William, M.S. Levy’s oldest son, and includes the Great Depression, unionization, merger, third generation leadership, and finally, in 1959, the family’s withdrawal from the industry. This later period, as told by grandsons of the founder, is the story of struggle followed by decline.

  17. Parental mental health after the accidental death of a son during military service: 23-year follow-up study.

    Science.gov (United States)

    Kristensen, Pål; Heir, Trond; Herlofsen, Pål H; Langsrud, Øyvind; Weisæth, Lars

    2012-01-01

    We prospectively studied parental mental health after suddenly losing a son in a military training accident. Parents (N = 32) were interviewed at 1, 2 and 23 years after the death of their son. The General Health Questionnaire and Expanded Texas Inventory of Grief were self-reported at 1, 2, 5, and 23 years; the Inventory of Complicated Grief was self-reported at 23 years. We observed a high prevalence of psychiatric disorders at 1- and 2-year follow-ups (57% and 45%, respectively), particularly major depression (43% and 31%, respectively). Only one mental disorder was diagnosed at the 23-year follow-up. Grief and psychological distress were highest at 1- and 2-year follow-ups. Spouses exhibited a high concordance of psychological distress. Mothers reported more intense grief reactions than did fathers. The loss of a son during military service may have a substantial impact on parental mental health particularly during the first 2 years after death. Spouses' grief can be interrelated and may contribute to their psychological distress.

  18. Tentative identification of the second substrate binding site in Arabidopsis phytochelatin synthase.

    Directory of Open Access Journals (Sweden)

    Ju-Chen Chia

    Full Text Available Phytochelatin synthase (PCS uses the substrates glutathione (GSH, γGlu-Cys-Gly and a cadmium (Cd-bound GSH (Cd∙GS2 to produce the shortest phytochelatin product (PC2, (γGlu-Cys2-Gly through a ping-pong mechanism. The binding of the 2 substrates to the active site, particularly the second substrate binding site, is not well-understood. In this study, we generated a structural model of the catalytic domain of Arabidopsis AtPCS1 (residues 12-218 by using the crystal structure of the γGlu-Cys acyl-enzyme complex of the PCS of the cyanobacterium Nostoc (NsPCS as a template. The modeled AtPCS1 revealed a cavity in proximity to the first substrate binding site, consisting of 3 loops containing several conserved amino acids including Arg152, Lys185, and Tyr55. Substitutions of these amino acids (R152K, K185R, or double mutation resulted in the abrogation of enzyme activity, indicating that the arrangement of these 2 positive charges is crucial for the binding of the second substrate. Recombinant AtPCS1s with mutations at Tyr55 showed lower catalytic activities because of reduced affinity (3-fold for Y55W for the Cd∙GS2, further suggesting the role of the cation-π interaction in recognition of the second substrate. Our study results indicate the mechanism for second substrate recognition in PCS. The integrated catalytic mechanism of PCS is further discussed.

  19. Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3-epi-deoxynivalenol

    Directory of Open Access Journals (Sweden)

    Yousef I. Hassan

    2016-09-01

    Full Text Available Deoxynivalenol (DON is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC. In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding.

  20. The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins

    Directory of Open Access Journals (Sweden)

    Ning Li

    2015-12-01

    Full Text Available Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.

  1. Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor

    International Nuclear Information System (INIS)

    Raymond, Marc-Andre; Desormeaux, Anik; Labelle, Andree; Soulez, Mathilde; Soulez, Gilles; Langelier, Yves; Pshezhetsky, Alexey V.; Hebert, Marie-Josee

    2005-01-01

    Endothelial cells (EC) under stress release paracrine mediators that facilitate accumulation of vascular smooth muscle cells (VSCM) at sites of vascular injury. We found that medium conditioned by serum-starved EC increase proliferation and migration of VSCM in vitro. Fractionation of the conditioned medium followed by mass spectral analysis identified one bioactive component as vitamin D-binding protein (DBP). DBP induced both proliferation and migration of VSMC in vitro in association with increased phosphorylation of ERK 1/2. PD 98059, a biochemical inhibitor of ERK 1/2, abrogated these proliferative and migratory responses in VSMC. DBP is an important carrier for the vitamin-D sterols, 25-hydroxyvitamin-D, and 1α,25-dihydroxyvitamin-D. Both sterols inhibited the activity of DBP on VSMC, suggesting that vitamin D binding sites are important for initiating the activities of DBP on VSMC. Release of DBP at sites of endothelial injury represents a novel pathway favoring accumulation of VSMC at sites of vascular injury

  2. Effect of Callovo-Oxfordian clay rock on the dissolution rate of the SON68 simulated nuclear waste glass

    Energy Technology Data Exchange (ETDEWEB)

    Neeway, James J., E-mail: James.Neeway@pnnl.gov [SUBATECH, Unité Mixte de Recherche 6457, École des Mines de Nantes, CNRS/IN2P3, Université de Nantes, BP 20722, 44307 Nantes cedex 3 (France); Abdelouas, Abdesselam; Ribet, Solange; El Mendili, Yassine [SUBATECH, Unité Mixte de Recherche 6457, École des Mines de Nantes, CNRS/IN2P3, Université de Nantes, BP 20722, 44307 Nantes cedex 3 (France); Schumacher, Stéphan [ANDRA, Parc de la Croix Blanche, 1/7 rue Jean Monnet, 92298 Châtenay-Malabry (France); Grambow, Bernd [SUBATECH, Unité Mixte de Recherche 6457, École des Mines de Nantes, CNRS/IN2P3, Université de Nantes, BP 20722, 44307 Nantes cedex 3 (France)

    2015-04-15

    Long-term storage of high-level nuclear waste glass in France is expected to occur in an engineered barrier system (EBS) located in a subsurface Callovo-Oxfordian (COx) clay rock formation in the Paris Basin in northeastern France. Understanding the behavior of glass dissolution in the complex system is critical to be able to reliably model the performance of the glass in this complex environment. To simulate this multi-barrier repository scenario in the laboratory, several tests have been performed to measure glass dissolution rates of the simulated high-level nuclear waste glass, SON68, in the presence of COx claystone at 90 °C. Experiments utilized a High-Performance Liquid Chromatography (HPLC) pump to pass simulated Bure site COx pore water through a reaction cell containing SON68 placed between two COx claystone cores for durations up to 200 days. Silicon concentrations at the outlet were similar in all experiments, even the blank experiment with only the COx claystone (∼4 mg/L at 25 °C and ∼15 mg/L at 90 °C). The steady-state pH of the effluent, measured at room temperature, was roughly 7.1 for the blank and 7.3–7.6 for the glass-containing experiments demonstrating the pH buffering capacity of the COx claystone. Dissolution rates for SON68 in the presence of the claystone were elevated compared to those obtained from flow-through experiments conducted with SON68 without claystone in silica-saturated solutions at the same temperature and similar pH values. Additionally, through surface examination of the monoliths, the side of the monolith in direct contact with the claystone was seen to have a corrosion thickness 2.5× greater than the side in contact with the bulk glass powder. Results from one experiment containing {sup 32}Si-doped SON68 also suggest that the movement of Si through the claystone is controlled by a chemically coupled transport with a Si retention factor, K{sub d}, of 900 mL/g.

  3. Mothers, fathers, sons, and daughters: gender differences in factors associated with parent-child communication about sexual topics.

    Science.gov (United States)

    Wilson, Ellen K; Koo, Helen P

    2010-12-14

    In the United States, nearly half of high school students are sexually active, and adolescents experience high rates of unintended pregnancy and sexually transmitted diseases. Parents can have an important influence on their children's sexual behaviour, but many parents do not talk with their children about sexual topics. Research has shown significant differences in parent-child communication about sexual topics depending on the gender of both the parent and the child. Little is known, however, about the reasons for these gender differences. The purpose of this paper is to describe how factors associated with parent-child communication about sexual topics differ by gender. Data are from a nationwide online survey with 829 fathers and 1,113 mothers of children aged 10 to 14. For each of the four gender groups (fathers of sons, fathers of daughters, mothers of sons, mothers of daughters), we calculated the distribution of responses to questions assessing (1) parent-child communication about sex-related topics, and (2) factors associated with that communication. We used chi-square tests to determine whether the distributions differed and the false discovery rate control to reduce the likelihood of type I errors. With both sons and daughters, fathers communicated less about sexual topics than mothers did. Fathers also had lower levels of many characteristics that facilitate communication about sex (e.g., lower self-efficacy and lower expectations that talking to their children about sex would have positive outcomes). Compared with parents of sons, parents of daughters (both mothers and fathers) talked more about sexual topics, were more concerned about potential harmful consequences of sexual activity, and were more disapproving of their child having sex at an early age. Using a large national sample, this study confirms findings from previous studies showing gender differences in parent-child communication about sexual topics and identifies gender differences in

  4. Mothers, fathers, sons, and daughters: gender differences in factors associated with parent-child communication about sexual topics

    Directory of Open Access Journals (Sweden)

    Koo Helen P

    2010-12-01

    Full Text Available Abstract Background In the United States, nearly half of high school students are sexually active, and adolescents experience high rates of unintended pregnancy and sexually transmitted diseases. Parents can have an important influence on their children's sexual behaviour, but many parents do not talk with their children about sexual topics. Research has shown significant differences in parent-child communication about sexual topics depending on the gender of both the parent and the child. Little is known, however, about the reasons for these gender differences. The purpose of this paper is to describe how factors associated with parent-child communication about sexual topics differ by gender. Methods Data are from a nationwide online survey with 829 fathers and 1,113 mothers of children aged 10 to 14. For each of the four gender groups (fathers of sons, fathers of daughters, mothers of sons, mothers of daughters, we calculated the distribution of responses to questions assessing (1 parent-child communication about sex-related topics, and (2 factors associated with that communication. We used chi-square tests to determine whether the distributions differed and the false discovery rate control to reduce the likelihood of type I errors. Results With both sons and daughters, fathers communicated less about sexual topics than mothers did. Fathers also had lower levels of many characteristics that facilitate communication about sex (e.g., lower self-efficacy and lower expectations that talking to their children about sex would have positive outcomes. Compared with parents of sons, parents of daughters (both mothers and fathers talked more about sexual topics, were more concerned about potential harmful consequences of sexual activity, and were more disapproving of their child having sex at an early age. Conclusions Using a large national sample, this study confirms findings from previous studies showing gender differences in parent

  5. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    Kendall, D.A.; Taylor, D.P.; Enna, S.J.

    1983-01-01

    High (17 nM) and low (603 nM) affinity binding sites for [ 3 ]tetrahydrotrazodone ([ 3 ] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [ 3 ]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [ 3 ] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [ 3 ]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  6. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  7. Superresolution microscopy with transient binding.

    Science.gov (United States)

    Molle, Julia; Raab, Mario; Holzmeister, Susanne; Schmitt-Monreal, Daniel; Grohmann, Dina; He, Zhike; Tinnefeld, Philip

    2016-06-01

    For single-molecule localization based superresolution, the concentration of fluorescent labels has to be thinned out. This is commonly achieved by photophysically or photochemically deactivating subsets of molecules. Alternatively, apparent switching of molecules can be achieved by transient binding of fluorescent labels. Here, a diffusing dye yields bright fluorescent spots when binding to the structure of interest. As the binding interaction is weak, the labeling is reversible and the dye ligand construct diffuses back into solution. This approach of achieving superresolution by transient binding (STB) is reviewed in this manuscript. Different realizations of STB are discussed and compared to other localization-based superresolution modalities. We propose the development of labeling strategies that will make STB a highly versatile tool for superresolution microscopy at highest resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Sons & Lumieres / Ivar Jung

    Index Scriptorium Estoniae

    Jung, Ivar

    2004-01-01

    Näitus "Hääl ja valgus" Pariisi Pompidou keskuses 22. IX 2004-3. I 2005. Väljas on 99 kunstniku (Paul Klee, Frantishek Kupka, Vassili Kandinsky, Laszlo Moholy-Nagy, Raoul Hausmann, Bill Viola, Robert Rauschenberg, Joseph Beuys, Rodney Graham jne.) tööd ajavahemikust 1910-2004. Kuraatorid Sophie Duplaix ja Marcella Lista

  9. Son los latinos estadounidenses?

    OpenAIRE

    Aguirre, Mariano

    2009-01-01

    En el año 2050 la población blanca no latina de Estados Unidos sumará el 46% del total de los ciudadanos de ese país. Para entonces, la población latina, negra y asiática combinada representará el 54%. En ese horizonte que predicen los cálculos oficiales, los latinos habrán crecido en un 15%, pasando de los 47 millones que viven ahora EEUU a 133 millones. Mientras que los latinos y los asiáticos (de 16 millones a 41 millones para entonces) no pararán de crecer, las poblaciones blanca y negra ...

  10. The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23 functions and abrogates IL-23-mediated antitumour effects

    Science.gov (United States)

    Shimozato, Osamu; Ugai, Shin-ichi; Chiyo, Masako; Takenobu, Hisanori; Nagakawa, Hiroyasu; Wada, Akihiko; Kawamura, Kiyoko; Yamamoto, Hiroshi; Tagawa, Masatoshi

    2006-01-01

    Interleukin (IL)-23 is a heterodimeric cytokine consisting of a novel p19 molecule and the p40 subunit of IL-12. Since secreted p40 can act as an antagonist for IL-12, we investigated whether p40 also inhibited IL-23-mediated immunological functions. p40 did not induce interferon (IFN)-γ or IL-17 production from splenocytes but impaired IL-23-induced cytokine production by competitive binding to the IL-23 receptors. Furthermore, a mixed population of murine colon carcinoma Colon 26 cells transduced with the p40 gene and those transduced with the IL-23 gene developed tumours in syngenic mice, whereas the IL-23-expressing Colon 26 cells were completely rejected. p40 also suppressed IFN-γ production of antigen-stimulated splenocytes and IL-23-mediated cytotoxic T-lymphocyte activities in the mice that rejected Colon 26 cells expressing IL-23. p40 can thereby antagonize IL-23 and is a possible therapeutic agent for suppression of IL-23 functions. PMID:16423037

  11. "Daughter and son: a completely different story”? Gender as a moderator of the relationship between sexism and parental attitudes

    Directory of Open Access Journals (Sweden)

    Małgorzata Lipowska

    2016-09-01

    Full Text Available Background During childhood, parents are the first and most important individuals who form the base of the content of gender stereotypes in children. A parent’s expectations about the extent a child’s behaviour should be line with gender stereotypes also depends on the intensity of a parent’s sexism. A parent’s sexism may be exhibited in parental attitudes. Hence, in our study we analysed the relationship between parental ambivalent sexism and parental attitudes within dyads of mothers and fathers with a special focus on the role of the gender of both parents and children. Participants and procedure Two hundred and ninety-four couples of parents of five-year-olds (153 girls, 141 boys participated. The Ambivalent Sexism Inventory (ASI was used to measure levels of sexism, and the Parental Attitudes Scale (SPR was used to assess parental attitudes. Results In terms of the profile of parental attitudes, regardless of the child’s sex, mothers and fathers scored highest for inconsequent and demanding attitudes, and lowest for overprotective and autonomy attitudes. The child’s sex is also not important for the overall levels of parents’ sexism – fathers exhibit higher levels of hostile sexism in comparison to mothers. Only the mothers’ education level is important for levels of sexism – women with higher education exhibited the lowest levels of hostile sexism. The child’s sex moderates relationships between parents’ sexism and parental attitudes. In the case of mothers of sons, the intensity of benevolent sexism is negatively related to overprotective and demanding attitudes. The more educated the mothers of sons, the more demanding they were. For fathers of sons, the inconsequence attitude increases under the influence of both hostile and benevolent sexism. Among fathers of daughters, hostile sexism strengthens the overprotective attitude, while levels of both benevolent and hostile sexism as well as education influence the

  12. Activation and transfer of sulfate in biological systems (1960); Activation biologique du sulfate et son transfert (1960)

    Energy Technology Data Exchange (ETDEWEB)

    Chapeville, F [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1960-07-01

    It examines in this review the successive stages of active sulfate formation and its role in biological synthesis of sulfuric esters. The possible role of active sulfate as intermediary in sulfate reduction is also discussed. (author) [French] On examine dans cette etude les stades successifs de la mise en evidence du sulfate actif, son role dans la formation des esters sulfuriques de natures diverses, ainsi que sa participation eventuelle comme intermediaire au cours de la reduction du sulfate. On decrit aussi un procede de preparation du systeme biologique, generateur du sulfate actif et une methode de synthese chimique. (auteur)

  13. La comprensión del relato periodístico: ¿qué son los hechos?

    OpenAIRE

    Saharrea, Juan Manuel

    2013-01-01

    El objetivo de este trabajo echar luz acerca de la comprensión del relato periodístico planteando el debate filosófico acerca del estatus de los hechos. Tomando algunas distinciones de la filosofía del lenguaje y la epistemología contemporáneas definimos nuestra propia posición en relación con los hechos. De acuerdo con nuestra perspectiva los hechos, no son, bajo ningún aspecto, independientes de descripción. Planteamos las tesis del realismo y el relativismo en torno a los hechos y de cada ...

  14. ¿Mejora la calidad de vida de pacientes con EPOC si son tratados por las enfermeras?

    OpenAIRE

    Vega Ramírez, Francisco Antonio; Quero Fuentes, María del Mar

    2015-01-01

    Cartel presentado en la Segunda Conferencia Internacional de Comunicación en Salud, celebrada el 23 de octubre de 2015 en la Universidad Carlos III de Madrid Introducción: la enfermedad pulmonar obstructiva crónica (EPOC), afecta a la calidad de vida (CV) de las personas y origina la necesidad de acciones adicionales de autocuidado. Objetivo: conocer si existe mejora en la calidad de vida en los pacientes con EPOC que son atendidos por enfermeras. Metodología: este estudio se basa en un di...

  15. Occult knowledge and sacred geometry. A new interpretation of a portrait of Rubens and his son from the Hermitage Museum

    Directory of Open Access Journals (Sweden)

    Teresa Esposito

    2017-02-01

    Full Text Available This paper explores the diversity and complexity of Rubens’s humanist interests and illustrates his appropriation of learned and esoteric knowledge, by discussing the anonymous painting in the Hermitage Museum in St. Petersburg in which Rubens is portrayed together with his son Albert. This portrait also depicts a sculpture from Rubens’s collection, that of Hecate Triformis, who in antiquity was considered to be a goddess of the underworld. By focusing on the books, manuscripts, Gnostic gems, and the Hecate statue from the artist’s collections, this paper will provide a new iconographic analysis of the Hermitage painting.

  16. Indicadores regionales de desarrollo sustentable en Chile: ¿Hasta qué punto son útiles y necesarios?

    Directory of Open Access Journals (Sweden)

    Hernán Blanco

    2001-09-01

    Full Text Available Cada vez más necesitamos maneras de asegurar patrones de desarrollo que sean sustentables, es decir, que sean ambiental, social y económicamente apropiados para nosotros y para las generaciones venideras. Los indicadores de desarrollo sustentable son una herramienta promisoria que permitiría "aterrizar" el concepto de sustentabilidad, apoyando la manera en que se toman las decisiones. En Chile existen pocas experiencias sobre el tema. Este artículo presenta el trabajo realizado para desarrollar indicadores de desarrollo sustentable en cuatro regiones del país. El artículo se centra en las lecciones que han surgido de la experiencia

  17. ¿Son útiles las “métricas espaciales fragstats” para caracterizar entornos de movilidad urbanos?

    OpenAIRE

    Arranz, Aldo; Soria-Lara, Julio Alberto; Aguilera Benavente, Francisco

    2014-01-01

    El objetivo de alcanzar una mayor sostenibilidad ambiental en la planificación del transporte urbano ha sido una de las principales razones del desarrollo de conceptos, métodos y herramientas orientadas a vincular de manera efectiva la estructura urbana y el sistema de transporte. En este contexto, surgen los “entornos de movilidad” como instrumentos integrados de planificación con éxitos notables en diferentes ámbitos escalares y contextuales. Los “entornos de movilidad” son concebidos como ...

  18. Kinematics of semiclassical spin and spin fiber bundle associated with so(n) Lie-Poisson manifold

    International Nuclear Information System (INIS)

    Deriglazov, A A

    2013-01-01

    We describe geometric construction underlying the Lagrangian actions for non-Grassmann spinning particles proposed in our recent works. If we discard the spatial variables (the case of frozen spin), the problem reduces to formulation of a variational problem for Hamiltonian system on a manifold with so(n) Lie-Poisson bracket. To achieve this, we identify dynamical variables of the problem with coordinates of the base of a properly constructed fiber bundle. In turn, the fiber bundle is embedded as a surface into the phase space equipped with canonical Poisson bracket. This allows us to formulate the variational problem using the standard methods of Dirac theory for constrained systems.

  19. Motion Sickness: Significance in Aerospace Operations and Prophylaxis (Le Mal des Transports: Son Importance pour les Operations Aerospatiales et Prophylaxies)

    Science.gov (United States)

    1991-09-01

    a range of complex mental reactions including fatigue, drowsiness, poor motivation for work, and depression. 2-20 AUTONOMIC-STRESS REACTIONS It is... rmotions at. 12 ]I;?, z., - 0.19 aInds. 1 J’( tnlro i’, "- 0.5’t, arid P:. -- 0.81 Yiv irq i (It ’’ti tied IttI’ Intill ltk e’r- I rtr’dc’nc" cit 46...cindtoses modifior son comporteomnt at sm motivation par rapport it lora do IPanirsinamant on Icola do pilotage cat I. taux do tnae situation

  20. Bill project aiming at prohibiting the exploration and exploitation of unconventional hydrocarbons, and at abrogating exclusive search permits for liquid or gaseous hydrocarbon mines, and aiming at ensuring transparency in the issue of search permits and concessions

    International Nuclear Information System (INIS)

    2011-01-01

    As offshore drillings and the search for unconventional gas has faced a strong opposition by part of the French population, this bill project (presented mainly by the Socialist group) aims at prohibiting these practices in France, and notably at abrogating some exclusive search permits which have been recently awarded. The authors outline the main motivations of this bill project: these exploitation and mining techniques are very expensive; they have several negative impacts with respect to environment protection commitments like the Grenelle de l'Environnement and the Grenelle de la Mer; these techniques have also an impact on water resources, and generate pollution which impacts water quality as well as ecosystems and biodiversity; some chemical products used by these techniques are carcinogenic (as it already appeared in the USA and in Canada); and finally, the exploitation of unconventional hydrocarbons has a bad carbon assessment. This presentation if followed by the bill project text

  1. The mosaic of environment involvement in autoimmunity: the abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases.

    Science.gov (United States)

    Temajo, Norbert O; Howard, Neville

    2014-06-01

    An autoimmune disease (AD), organ-specific or systemic, results from an aberrant response in which the protective immune system normally schooled to recognize and destroy invading infectious agents (viruses, etc.) instead fails to distinguish self-antigens and proceeds to attack and destroy the host's organs. There can be familial aggregation in which a single AD may occur in members of a family, or a single family may be afflicted with multiple ADs. Finally, sometimes multiple ADs co-occur in a single individual: the kaleidoscope of autoimmunity. Autoimmunity is a multifactorial process in which genetic, hormonal, immunological and environmental factors act in concert to materialize the mosaic of autoimmunity phenomenon. A genetically primed individual may yet not develop an AD: the contribution by an environmental factor (non-infectious or infectious) is essential for completion of the act. Of the non-infectious factors, stress plays a determinative step in autoimmunity in that it abrogates viral latency and thereby ordains the viruses to qualify as infectious environmental factors that trigger ADs. This is note-worthy as viruses rank first as the most important environmental triggers of ADs. Furthermore, all these viruses experience going through latency. Hence the hypothesis: "The abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases". There is collaboration here between non-infectious- and infectious-agent to achieve the cause of autoimmunity. We say viral latency and stress have a covenant: continued perpetration of autoimmunity is dependent on the intervention by stress to reactivate latent infections. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  2. To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

    Science.gov (United States)

    Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

    2013-01-01

    Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

  3. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

    Directory of Open Access Journals (Sweden)

    Lei Wu

    2016-03-01

    Full Text Available For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA, was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae. MOA modulates cytokine expression in lipopolysaccharide (LPS-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO, prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α, interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2, thus blocking nuclear translocation of activation protein (AP-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs and one of their downstream transcription factors, activator protein-1 (AP-1. Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.

  4. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

    Science.gov (United States)

    Wu, Lei; Li, Xueqin; Wu, Haifeng; Long, Wei; Jiang, Xiaojian; Shen, Ting; Qiang, Qian; Si, Chuanling; Wang, Xinfeng; Jiang, Yunyao; Hu, Weicheng

    2016-01-01

    For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases. PMID:26938526

  5. Sexual imprinting on continuous variation: do female zebra finches prefer or avoid unfamiliar sons of their foster parents?

    Science.gov (United States)

    Schielzeth, H; Burger, C; Bolund, E; Forstmeier, W

    2008-09-01

    Sexual imprinting on discrete variation that serves the identification of species, morphs or sexes is well documented. By contrast, sexual imprinting on continuous variation leading to individual differences in mating preferences within a single species, morph and sex has been studied only once (in humans). We measured female preferences in a captive population of wild-type zebra finches. Individual cross-fostering ensured that all subjects grew up with unrelated foster parents and nest mates. Females from two cohorts (N = 113) were given a simultaneous choice between (two or four) unfamiliar males, one of which was a genetic son of their foster parents (SFP). We found no significant overall preference for the SFP (combined effect size d = 0.14 +/- 0.15). Additionally, we tested if foster parent traits could potentially explain between-female variation in preferences. However, neither the effectiveness of cooperation between the parents nor male contribution to parental care affected female preferences for the son of the foster father. We conclude that at least in zebra finches sexual imprinting is not a major source of between-individual variation in mating preferences.

  6. Application of the GRAAL model to leaching experiments with SON68 nuclear glass in initially pure water

    International Nuclear Information System (INIS)

    Frugier, P.; Chave, T.; Gin, S.; Lartigue, J.-E.

    2009-01-01

    Based on a review of the current state of knowledge concerning the aqueous alteration of SON68 nuclear glass we have proposed a mechanistic model, GRAAL (Glass Reactivity with Allowance for the Alteration Layer) [P. Frugier, S. Gin, Y. Minet, T. Chave, B. Bonin, N. Godon, J.E. Lartigue, P. Jollivet, A. Ayral, L. De Windt, G. Santarini, J. Nucl. Mater. 380 (2008) 8]. This article describes how the GRAAL model hypotheses are solved using a calculation code coupling chemistry and transport. The geochemical solution of this model combines three major phenomena: chemical equilibria in solution, water and ion transport by convection or diffusion, and element diffusion through the passivating reactive interphase. The model results are compared with experimental data for SON68 glass leached in initially pure water both in a closed system and in renewed media. The comparison shows the model very satisfactorily accounts for variations in the pH and the element concentrations in solution as a function of time, the glass surface area in contact with solution, and the solution renewal rate. This success is due to the fact that the diffusion of elements through the alteration gel is taken into account in the model. This mechanism cannot be disregarded under most experimental conditions - if only to predict the solution pH - and must therefore be an integral part of the geochemical model.

  7. Bad Boys Meet the Swan of Avon: A Re-Visioning of Hamlet in Sons of Anarchy

    Directory of Open Access Journals (Sweden)

    Burzyńska Katarzyna

    2017-12-01

    Full Text Available This article investigates the intersections between Shakespeare’s Hamlet and a popular TV series Sons of Anarchy (SOA, loosely based on the Shakespearean original. The crime drama series revolves around an outlaw motorcycle club that literally “rules” a fictional town in California like an old royal family with its own brutal dynastic power squabbles and dark family secrets. The club is governed by an unscrupulous President Clay and an equally violent, though more conflicted, Vice President Jax Teller, the son of the late President, who had died in mysterious circumstances. In the article I argue that the popularity of the series lies not in its graphic scenes of violence, over-the-top Harley chases, and sex intrigues, but rather in its Shakespearean and Renaissance structure. SOA, dubbed as “Hamlet on Harleys”1, is an appropriation rather than an adaptation of Shakespeare’s tragedy, which makes it a truly transmedial phenomenon. The article investigates a fascinating blend of seemingly marginal elements of modern American culture and the canonical British tragedy. It also addresses the connections between the lifestyles of the so called outlaw MC clubs and the early modern family structure as presented in Hamlet, focusing on the issues of power and gender relations.

  8. Acceptability of the human papillomavirus vaccine and reasons for non-vaccination among parents of adolescent sons.

    Science.gov (United States)

    Donahue, Kelly L; Stupiansky, Nathan W; Alexander, Andreia B; Zimet, Gregory D

    2014-06-30

    Routine administration of the quadrivalent human papillomavirus (HPV) vaccine has been recommended for 11-12-year-old males since 2011, but coverage remains low. In a U.S. national sample of parents of 11-17-year-old males (n=779), 78.6% of parents reported their sons had not received the HPV vaccine. The most common reason for non-vaccination (56.7%) was "My doctor or healthcare provider has not recommended it." Parents citing only logistical reasons for non-vaccination (e.g., lack of recommendation, access, or education, n=384) reported significantly higher vaccine acceptability than parents reporting a combination of attitudinal (e.g., concerns about vaccine safety or efficacy) and logistical barriers (n=92), while parents citing only attitudinal barriers (n=73) reported the lowest level of vaccine acceptability. In sum, many parents are willing but have not vaccinated sons due to logistical barriers, most commonly lack of healthcare provider recommendation. These findings have important implications for increasing HPV vaccination coverage among adolescent males. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. ¿Qué hogares colombianos son pobres? una aproximación desde la ECV del 2003

    Directory of Open Access Journals (Sweden)

    Adriana Carolina Silva Arias

    2007-01-01

    Full Text Available Este artículo analizó los conceptos y medidas de pobreza. A partir de esta perspectiva, se estudió quiénes son pobres en Colombia y qué características de los hogares determinan dicha condición para el 2003. A partir de la Encuesta de Calidad de Vida, se realizó un análisis logit para identifi car y medir la incidencia de algunos factores en la probabilidad de que un hogar sea clasifi cado como pobre. Estas estimaciones mostraron que los hogares que tienen más probabilidad de considerarse como pobres son aquellos en los que los jefes de hogar eran analfabetas, mujeres, los que se ocuparon en labores agrícolas o que hacían parte de alguna etnia. Adicionalmente, se encontró que los hogares que tenían menores de 12 años tuvieron más de probabilidad de ser pobres. Finalmente, los hogares cuyo jefe de hogar tenía mayor nivel educativo, tenían menor probabilidad de ser pobres, siendo mayor el efecto educativo de su cónyuge.

  10. Expression of multiple sexual signals by fathers and sons in the East-Mediterranean barn swallow: are advertising strategies heritable?

    Science.gov (United States)

    Vortman, Yoni; Safran, Rebecca J; Reiner Brodetzki, Tali; Dor, Roi; Lotem, Arnon

    2015-01-01

    The level of expression of sexually selected traits is generally determined by genes, environment and their interaction. In species that use multiple sexual signals which may be costly to produce, investing in the expression of one sexual signal may limit the expression of the other, favoring the evolution of a strategy for resource allocation among signals. As a result, even when the expression of sexual signals is condition dependent, the relative level of expression of each signal may be heritable. We tested this hypothesis in the East-Mediterranean barn swallow (Hirundo rustica transitiva), in which males have been shown to express two uncorrelated sexual signals: red-brown ventral coloration, and long tail streamers. We show that variation in both signals may partially be explained by age, as well as by paternal origin (genetic father-son regressions), but that the strongest similarity between fathers and sons is the relative allocation towards one trait or the other (relative expression index), rather than the expression of the traits themselves. These results suggest that the expression of one signal is not independent of the other, and that genetic strategies for resource allocation among sexual signals may be selected for during the evolution of multiple sexual signals.

  11. A novel mutation (C1425Y) in the FBN2 gene in a father and son with congenital contractural arachnodactyly.

    Science.gov (United States)

    Chen, Ying; Lei, Yun-Ping; Zheng, Hong-Xiang; Wang, Wei; Cheng, Hong-Bo; Zhang, Jing; Wang, Hong-Yan; Jin, Li; Li, Hong

    2009-06-01

    Congenital contractural arachnodactyly (Beals syndrome) is a rare autosomal dominantly inherited connective tissue disorder characterized by flexion contractures, arachnodactyly, crumpled ears, and mild muscular hypoplasia. Here, a father and son with congenital contractural arachnodactyly features were identified. After sequencing 15 exons (22 to 36) of the FBN2 gene, a novel mutation (C1425Y) was found in exon 33. This de novo mutation presented first in the father and was transmitted to his son, but not in the other 14 unaffected family members and 365 normal people. The C1425Y mutation occurs at the 19th cbEGF domain. Cysteines in this cbEGF domain are rather conserved in species, from human down to ascidian. The cbEGF12-13 in human FBN1 was employed as the template to perform homology modeling of cbEGF18-19 of human FBN2 protein. The mutation has also been evaluated by further prediction tools, for example, SIFT, Blosum62, biochemical Yu's matrice, and UMD-Predictor tool. In all analysis, the mutation is predicted to be pathogenic. Thus, the structure destabilization by C1425Y might be the cause of the disorder.

  12. (Alpha, gamma) irradiation effect on the alteration of high-level radioactive wastes matrices (UO2, hollandite, glass SON68)

    International Nuclear Information System (INIS)

    Suzuki, T.

    2007-06-01

    The aim of this work is to determine the effect of irradiation on the alteration of high level nuclear waste forms matrices. The matrices investigated are UO 2 to simulate the spent fuel, the hollandite for the specific conditioning of Cs, and the inactive glass SON68 representing the nuclear glass R7T7) The alpha irradiation experiments on UO 2 colloids in aqueous carbonate media have enabled to distinguish between the oxidation of UO 2 matrix as initial and dissolution as subsequent step. The simultaneous presence of carbonate and H 2 O 2 (product resulting from water radiolysis) increased the dissolution rate of UO 2 to its maximum value governed by the oxidation rate. ii) The study of hollandite alteration under gamma irradiation confirmed the good retention capacity for Cs and Ba. Gamma irradiation had brought only a little influence on releasing of Cs and Ba in solution. Electronic irradiation had conducted to the amorphization of the hollandite only for a dose 1000 times higher than the auto-induced dose of Ba over millions of years. iii) The experiences of glass irradiation under alpha beam and of helium implantation in the glass SON68 were analyzed by positon annihilation spectroscopy. No effect has been observed on the solid surface for an irradiation dose equal to 1000 years of storage. (author)

  13. When mothers make sons sexy: maternal effects contribute to the increased sexual attractiveness of extra-pair offspring.

    Science.gov (United States)

    Tschirren, Barbara; Postma, Erik; Rutstein, Alison N; Griffith, Simon C

    2012-03-22

    Quality differences between offspring sired by the social and by an extra-pair partner are usually assumed to have a genetic basis, reflecting genetic benefits of female extra-pair mate choice. In the zebra finch (Taeniopygia guttata), we identified a colour ornament that is under sexual selection and appears to have a heritable basis. Hence, by engaging in extra-pair copulations with highly ornamented males, females could, in theory, obtain genes for increased offspring attractiveness. Indeed, sons sired by extra-pair partners had larger ornaments, seemingly supporting the genetic benefit hypothesis. Yet, when comparing ornament size of the social and extra-pair partners, there was no difference. Hence, the observed differences most likely had an environmental basis, mediated, for example, via differential maternal investment of resources into the eggs fertilized by extra-pair and social partners. Such maternal effects may (at least partly) be mediated by egg size, which we found to be associated with mean ornament expression in sons. Our results are consistent with the idea that maternal effects can shape sexual selection by altering the genotype-phenotype relationship for ornamentation. They also caution against automatically attributing greater offspring attractiveness or viability to an extra-pair mate's superior genetic quality, as without controlling for differential maternal investment we may significantly overestimate the role of genetic benefits in the evolution of extra-pair mating behaviour.

  14. Programming of neurotoxic cofactor CXCL-10 in HIV-1-associated dementia: abrogation of CXCL-10-induced neuro-glial toxicity in vitro by PKC activator

    Directory of Open Access Journals (Sweden)

    Mehla Rajeev

    2012-10-01

    Full Text Available Abstract Background More than 50% of patients undergoing lifelong suppressive antiviral treatment for HIV-1 infection develop minor HIV-1-associated neurocognitive disorders. Neurological complications during HIV-1 infection are the result of direct neuronal damage by proinflammatory products released from HIV-1-infected or -uninfected activated lymphocytes, monocytes, macrophages, microglia and astrocytes. The specific pro-inflammatory products and their roles in neurotoxicity are far from clear. We investigated proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF of HIV-demented (HIV-D and HIV-nondemented (HIV-ND patients and studied their affect on neuroglial toxicity. Methods and results Bioplex array showed elevated levels of signatory chemokines or cytokines (IL-6, IFN-γ, CXCL10, MCP-1 and PDGF in the CSF of HIV-D patients (n = 7 but not in that of HIV-ND patients (n = 7. Among the signatory cytokines and chemokines, CXCL10 was distinctly upregulated in-vitro in HIV-1 (NLENG1-activated human fetal astrocytes, HIV-1 (Ba-L-infected macrophages, and HIV-1 (NLENG1-infected lymphocytes. Virus-infected macrophages also had increased levels of TNF-α. Consistently, human fetal astrocytes treated with HIV-1 and TNF-α induced the signatory molecules. CXCL10 in combination with HIV-1 synergistically enhanced neuronal toxicity and showed chemotactic activity (~ 40 fold for activated peripheral blood mononuclear cells (PBMC, suggesting the intersection of signaling events imparted by HIV-1 and CXCL10 after binding to their respective surface receptors, CXCR4 and CXCR3, on neurons. Blocking CXCR3 and its downstream MAP kinase (MAPK signaling pathway suppressed combined CXCL10 and HIV-1-induced neurotoxicity. Bryostatin, a PKC modulator and suppressor of CXCR4, conferred neuroprotection against combined insult with HIV-1 and CXCL10. Bryostatin also suppressed HIV-1 and CXCL10-induced PBMC chemotaxis. Although, therapeutic targeting

  15. Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior.

    Science.gov (United States)

    Vahid-Ansari, Faranak; Daigle, Mireille; Manzini, M Chiara; Tanaka, Kenji F; Hen, René; Geddes, Sean D; Béïque, Jean-Claude; James, Jonathan; Merali, Zul; Albert, Paul R

    2017-12-06

    Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo , we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons ( cF1ko ). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out ( cF1/1A dko ) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment. SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response. Copyright © 2017 the authors 0270-6474/17/3711967-12$15.00/0.

  16. Binding energies of cluster ions

    International Nuclear Information System (INIS)

    Parajuli, R.; Matt, S.; Scheier, P.; Echt, O.; Stamatovic, A.; Maerk, T.D.

    2002-01-01

    The binding energy of charged clusters may be measured by analyzing the kinetic energy released in the metastable decay of mass selected parent ions. Using finite heat bath theory to determine the binding energies of argon, neon, krypton, oxygen and nitrogen from their respective average kinetic energy released were carried out. A high-resolution double focussing two-sector mass spectrometer of reversed Nier-Johnson type geometry was used. MIKE ( mass-analysed ion kinetic energy) were measured to investigate decay reactions of mass-selected ions. For the inert gases neon (Ne n + ), argon (Ar n + ) and krypton (Kr n + ), it is found that the binding energies initially decrease with increasing size n and then level off at a value above the enthalpy of vaporization of the condensed phase. Oxygen cluster ions shown a characteristic dependence on cluster size (U-shape) indicating a change in the metastable fragmentation mechanism when going from the dimer to the decamer ion. (nevyjel)

  17. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    for zinc binding by the investigated amino acids, peptides and proteins. The thiol group or imidazole group containing amino acids, peptides and proteins which exhibited strong zinc binding ability were further selected for interacting with zinc salts in relation to zinc absorption. The interactions...... between the above selected food components and zinc citrate or zinc phytate will lead to the enhanced solubility of zinc citrate or zinc phytate. The main driving force for this observed solubility enhancement is the complex formation between zinc and investigated food components as revealed by isothermal...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  18. Ehlers-Danlos syndrome type IV : unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile

    NARCIS (Netherlands)

    Kroes, HY; Pals, G; van Essen, AJ

    A mother and son with Ehlers-Danlos syndrome (EDS) type IV and unusual congenital anomalies are described. The congenital anomalies include, in the mother, amniotic band-like constrictions on one hand, a unilateral clubfoot, and macrocephaly owing to normal-pressure hydrocephaly and, in the son, an

  19. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  20. Skyrmions with low binding energies

    International Nuclear Information System (INIS)

    Gillard, Mike; Harland, Derek; Speight, Martin

    2015-01-01

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values

  1. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  2. L'enquista de literatura orala e son contèxte au sègle XX

    OpenAIRE

    Bouvier, Jean-Claude

    2014-01-01

    Après lei folcloristas dau sègle dètz-e-nòu, lo moviment de recèrca sus la literatura orala es contunhat ò puslèu représ a partir deis annadas 1960, dins de condicions que pòdon èstre dichas mai marridas, mai de tot biais nòvas. Dison generalament que la tradicion orala es avanida, çò qu'es verai en partida per lo conte meravilhós. Mai es verai pasmens que de tròç entiers de literatura orala son restats vius (n'en tornarai parlar dins un moment) e es verai tanben que de fòrmas novas de tradic...

  3. Introducing SONS, a tool for operational taxonomic unit-based comparisons of microbial community memberships and structures.

    Science.gov (United States)

    Schloss, Patrick D; Handelsman, Jo

    2006-10-01

    The recent advent of tools enabling statistical inferences to be drawn from comparisons of microbial communities has enabled the focus of microbial ecology to move from characterizing biodiversity to describing the distribution of that biodiversity. Although statistical tools have been developed to compare community structures across a phylogenetic tree, we lack tools to compare the memberships and structures of two communities at a particular operational taxonomic unit (OTU) definition. Furthermore, current tests of community structure do not indicate the similarity of the communities but only report the probability of a statistical hypothesis. Here we present a computer program, SONS, which implements nonparametric estimators for the fraction and richness of OTUs shared between two communities.

  4. SON68 nuclear glass dissolution kinetics: Current state of knowledge and basis of the new GRAAL model

    Energy Technology Data Exchange (ETDEWEB)

    Frugier, P. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze cedex (France)], E-mail: pierre.frugier@cea.fr; Gin, S.; Minet, Y.; Chave, T. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze cedex (France); Bonin, B. [CEA Saclay, DEN/DIR/DS, 91191 Gif-sur-Yvette cedex (France); Godon, N.; Lartigue, J.-E.; Jollivet, P. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze cedex (France); Ayral, A. [IEM/CNRS-ENSCM Universite Montpellier 2, CC 047, Place Eugene Bataillon, 34095 Montpellier cedex 5 (France); De Windt, L. [ENSMP, CG, 35 rue St Honore, 77305 Fontainebleau cedex (France); Santarini, G. [CEA Saclay HC/CAB, 91191 Gif-sur-Yvette cedex (France)

    2008-10-15

    This article summarizes the present state of knowledge concerning aqueous alteration of R7T7-type nuclear containment glasses, represented mainly by the inactive reference glass designated SON68. Based on this review, we propose to describe the glass alteration kinetics up to and including the final residual rate regime by means of a new mechanistic model known as GRAAL (glassreactivitywithallowanceforthealterationlayer). Phenomenological analysis findings are reviewed for the various glass alteration regimes: interdiffusion, initial rate, rate drop, residual rate and, under very particular circumstances, resumption of alteration. These alteration regimes are associated with predominant mechanisms. Published work interpreting and modeling these mechanisms was examined in detail. There is a broad consensus on the general mechanisms of the initial rate and even the interdiffusion regime, whereas the mechanisms controlling the rate drop remain a subject of dispute not only with regard to nuclear glasses but also for the dissolution of silicate minerals. The reaction affinity responsible for the rate drop is expressed differently by different authors and depending on the underlying theories. The disagreement concerns the nature of the phase (glass or gel) or the activated complex controlling the rate drop, which in turn determines the elements that must be taken into account in the overall affinity term. Progress in recent years, especially in identifying the mechanisms responsible for the residual rate, has shed new light on these issues, allowing us to propose new theoretical foundations for modeling the different kinetic regimes of SON68 nuclear glass dissolution. The GRAAL model considers that water diffusion in the passivating reaction zone (the gel formed under saturation conditions) is a rate-limiting step in the overall glass dissolution kinetics. Moreover, this passivation zone is a soluble phase whose stability is directly dependent on the nature of the

  5. The meningococcal vaccine candidate neisserial surface protein A (NspA binds to factor H and enhances meningococcal resistance to complement.

    Directory of Open Access Journals (Sweden)

    Lisa A Lewis

    2010-07-01

    Full Text Available Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH to fH-binding protein (fHbp is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a approximately 17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA, a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep I chain of lipooligosaccharide (LOS, or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6-7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components.

  6. The involvement of coordinative interactions in the binding of dihydrolipoamide dehydrogenase to titanium dioxide-Localization of a putative binding site.

    Science.gov (United States)

    Dayan, Avraham; Babin, Gilad; Ganoth, Assaf; Kayouf, Nivin Samir; Nitoker Eliaz, Neta; Mukkala, Srijana; Tsfadia, Yossi; Fleminger, Gideon

    2017-08-01

    Titanium (Ti) and its alloys are widely used in orthodontic and orthopedic implants by virtue to their high biocompatibility, mechanical strength, and high resistance to corrosion. Biointegration of the implants with the tissue requires strong interactions, which involve biological molecules, proteins in particular, with metal oxide surfaces. An exocellular high-affinity titanium dioxide (TiO 2 )-binding protein (TiBP), purified from Rhodococcus ruber, has been previously studied in our lab. This protein was shown to be homologous with the orthologous cytoplasmic rhodococcal dihydrolipoamide dehydrogenase (rhDLDH). We have found that rhDLDH and its human homolog (hDLDH) share the TiO 2 -binding capabilities with TiBP. Intrigued by the unique TiO 2 -binding properties of hDLDH, we anticipated that it may serve as a molecular bridge between Ti-based medical structures and human tissues. The objective of the current study was to locate the region and the amino acids of the protein that mediate the protein-TiO 2 surface interaction. We demonstrated the role of acidic amino acids in the nonelectrostatic enzyme/dioxide interactions at neutral pH. The observation that the interaction of DLDH with various metal oxides is independent of their isoelectric values strengthens this notion. DLDH does not lose its enzymatic activity upon binding to TiO 2 , indicating that neither the enzyme undergoes major conformational changes nor the TiO 2 binding site is blocked. Docking predictions suggest that both rhDLDH and hDLDH bind TiO 2 through similar regions located far from the active site and the dimerization sites. The putative TiO 2 -binding regions of both the bacterial and human enzymes were found to contain a CHED (Cys, His, Glu, Asp) motif, which has been shown to participate in metal-binding sites in proteins. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Structures of the APC–ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners

    Science.gov (United States)

    Zhang, Zhenyi; Akyildiz, Senem; Xiao, Yafei; Gai, Zhongchao; An, Ying; Behrens, Jürgen; Wu, Geng

    2015-01-01

    The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC–Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC–ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC–ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC–ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC–ARM binding partners. PMID:27462415

  8. Structures of the APC-ARM domain in complexes with discrete Amer1/WTX fragments reveal that it uses a consensus mode to recognize its binding partners.

    Science.gov (United States)

    Zhang, Zhenyi; Akyildiz, Senem; Xiao, Yafei; Gai, Zhongchao; An, Ying; Behrens, Jürgen; Wu, Geng

    2015-01-01

    The tumor suppressor APC employs its conserved armadillo repeat (ARM) domain to recognize many of its binding partners, including Amer1/WTX, which is mutated in Wilms' tumor and bone overgrowth syndrome. The APC-Amer1 complex has important roles in regulating Wnt signaling and cell adhesion. Three sites A1, A2, and A3 of Amer1 have been reported to mediate its interaction with APC-ARM. In this study, crystal structures of APC-ARM in complexes with Amer1-A1, -A2, and -A4, which is newly identified in this work, were determined. Combined with our GST pull-down, yeast two-hybrid, and isothermal titration calorimetry (ITC) assay results using mutants of APC and Amer1 interface residues, our structures demonstrate that Amer1-A1, -A2, and -A4, as well as other APC-binding proteins such as Asef and Sam68, all employ a common recognition pattern to associate with APC-ARM. In contrast, Amer1-A3 binds to the C-terminal side of APC-ARM through a bipartite interaction mode. Composite mutations on either APC or Amer1 disrupting all four interfaces abrogated their association in cultured cells and impaired the membrane recruitment of APC by Amer1. Our study thus comprehensively elucidated the recognition mechanism between APC and Amer1, and revealed a consensus recognition sequence employed by various APC-ARM binding partners.

  9. Cellulose binding domain fusion proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  10. When is protein binding important?

    Science.gov (United States)

    Heuberger, Jules; Schmidt, Stephan; Derendorf, Hartmut

    2013-09-01

    The present paper is an ode to a classic citation by Benet and Hoener (2002. Clin Pharm Ther 71(3):115-121). The now classic paper had a huge impact on drug development and the way the issue of protein binding is perceived and interpreted. Although the authors very clearly pointed out the limitations and underlying assumptions for their delineations, these are too often overlooked and the classic paper's message is misinterpreted by broadening to cases that were not intended. Some members of the scientific community concluded from the paper that protein binding is not important. This was clearly not intended by the authors, as they finished their paper with a paragraph entitled: "When is protein binding important?" Misinterpretation of the underlying assumptions in the classic work can result in major pitfalls in drug development. Therefore, we revisit the topic of protein binding with the intention of clarifying when clinically relevant changes should be considered during drug development. Copyright © 2013 Wiley Periodicals, Inc.

  11. Probing into the binding interaction between medroxyprogesterone acetate and bovine serum albumin (BSA): spectroscopic and molecular docking methods.

    Science.gov (United States)

    Fang, Fang; Pan, Dong-Qi; Qiu, Min-Jie; Liu, Ting-Ting; Jiang, Min; Wang, Qi; Shi, Jie-Hua

    2016-09-01

    To further understand the mechanism of action and pharmacokinetics of medroxyprogesterone acetate (MPA), the binding interaction of MPA with bovine serum albumin (BSA) under simulated physiological conditions (pH 7.4) was studied using fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, circular dichroism and molecular docking methods. The experimental results reveal that the fluorescence of BSA quenches due to the formation of MPA-BSA complex. The number of binding sites (n) and the binding constant for MPA-BSA complex are ~1 and 4.6 × 10(3)  M(-1) at 310 K, respectively. However, it can be concluded that the binding process of MPA with BSA is spontaneous and the main interaction forces between MPA and BSA are van der Waals force and hydrogen bonding interaction due to the negative values of ΔG(0) , ΔH(0) and ΔS(0) in the binding process of MPA with BSA. MPA prefers binding on the hydrophobic cavity in subdomain IIIA (site II'') of BSA resulting in a slight change in the conformation of BSA, but BSA retaining the α-helix structure. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. ‘Unkind and cruel, to deceive your Son | In borrow’d Shapes, and his Embrace to shun’: Mother-son love in T. S. Eliot’s ‘La Figlia Che Piange’

    Directory of Open Access Journals (Sweden)

    Matthew Geary

    2015-01-01

    Full Text Available T. S. Eliot's "La Figlia Che Piange" (1916 is a curious anomaly in his early works. It stands out as a love poem of outstanding grace portraying a more positive relationship to the feminine compared to other poems contemporaneous with its writing such as "The Love Song of St. Sebastian" (1914 and "Hysteria" (1915. This essay shows the import of Eliot's chosen epigraph for "La Figlia" taken from Virgil's Aeneid to have been largely neglected or misread by critics. As a consequence, it argues that critical readings have crucially missed the presence of a shrouded maternal aspect within the poem. Through the lens of Lacanian psychoanalysis and the work of adherents to Lacanian theory — such as Bruce Fink, Shoshana Felman and Slavoj Zizek — this paper newly argues that the poem's meditation on the issues of union and separation between two lovers is in fact a screen for deeper unconscious ambivalent feelings between mother and son. That is to say, Eliot's "La Figlia Che Piange" shows a failed attempt to reconstruct, traverse and separate from the "fundamental fantasy" unconsciously orientating the male speaker of the poem and his desire.

  13. Investigating the binding behaviour of two avidin-based testosterone binders using molecular recognition force spectroscopy.

    Science.gov (United States)

    Rangl, Martina; Leitner, Michael; Riihimäki, Tiina; Lehtonen, Soili; Hytönen, Vesa P; Gruber, Hermann J; Kulomaa, Markku; Hinterdorfer, Peter; Ebner, Andreas

    2014-02-01

    Molecular recognition force spectroscopy, a biosensing atomic force microscopy technique allows to characterise the dissociation of ligand-receptor complexes at the molecular level. Here, we used molecular recognition force spectroscopy to study the binding capability of recently developed testosterone binders. The two avidin-based proteins called sbAvd-1 and sbAvd-2 are expected to bind both testosterone and biotin but differ in their binding behaviour towards these ligands. To explore the ligand binding and dissociation energy landscape of these proteins, we tethered biotin or testosterone to the atomic force microscopy probe while the testosterone-binding protein was immobilized on the surface. Repeated formation and rupture of the ligand-receptor complex at different pulling velocities allowed determination of the loading rate dependence of the complex-rupturing force. In this way, we obtained the molecular dissociation rate (k(off)) and energy landscape distances (x(β)) of the four possible complexes: sbAvd-1-biotin, sbAvd-1-testosterone, sbAvd-2-biotin and sbAvd-2-testosterone. It was found that the kinetic off-rates for both proteins and both ligands are similar. In contrast, the x(β) values, as well as the probability of complex formations, varied considerably. In addition, competitive binding experiments with biotin and testosterone in solution differ significantly for the two testosterone-binding proteins, implying a decreased cross-reactivity of sbAvd-2. Unravelling the binding behaviour of the investigated testosterone-binding proteins is expected to improve their usability for possible sensing applications. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Comparison and analysis on the serum-binding characteristics of aspirin-zinc complex and aspirin.

    Science.gov (United States)

    Zhang, Hua-Xin; Zhang, Qun; Wang, Hong-Lin; Li, Li-Wei

    2017-09-01

    This study was designed to compare the protein-binding characteristics of aspirin-zinc complex (AZN) with those of aspirin itself. AZN was synthesized and interacted with a model transport protein, human serum albumin (HSA). Three-dimensional fluorescence, ultraviolet-visible and circular dichroism (CD) spectra were used to characterize the interaction of AZN with HSA under physiological conditions. The interaction mechanism was explored using a fluorescence quenching method and thermodynamic calculation. The binding site and binding locality of AZN on HSA were demonstrated using a fluorescence probe technique and Förster non-radiation energy transfer theory. Synchronous fluorescence and CD spectra were employed to reveal the effect of AZN on the native conformation of the protein. The HSA-binding results for AZN were compared with those for aspirin under consistent experimental conditions, and indicated that aspirin acts as a guide in AZN when binding to Sudlow's site I, in subdomain IIA of the HSA molecule. Moreover, compared with aspirin, AZN showed greater observed binding constants with, but smaller changes in the α-helicity of, HSA, which proved that AZN might be easier to transport and have less toxicity in vivo. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Caseins from bovine colostrum and milk strongly bind piscidin-1, an antimicrobial peptide from fish.

    Science.gov (United States)

    Kütt, Mary-Liis; Stagsted, Jan

    2014-09-01

    A model system of bovine colostrum and piscidin, a fish-derived antimicrobial peptide, was developed to study potential interactions of antimicrobial peptides in colostrum. We did not detect any antimicrobial activity of colostrum using the radial plate diffusion assay; in fact colostrum completely abrogated activity of added piscidin. This could not be explained by degradation of piscidin by colostrum, which was less than ten percent. We found that colostrum even protected piscidin against degradation by added proteases. We further observed that colostrum and milk rapidly quenched the fluorescence of fluorescein-piscidin but not that of fluorescein. This effect was not seen with BSA and the specific quenching of fluorescein-piscidin by colostrum was saturably inhibited with unlabeled piscidin. Size exclusion chromatography indicated that fluorescein-piscidin bound to casein micelles with no apparent binding to IgG or whey proteins. Further, addition of pure caseins was able to quench fluorescence of fluorescein-piscidin and to inhibit the antimicrobial activity of piscidin. The interaction between caseins and piscidin could be dissociated by guanidine hydrochloride and recovered piscidin had antimicrobial activity against bacteria. Based on our results we propose that caseins could be carriers for antimicrobial peptides in colostrum and milk. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Streptococcus mutans SpaP binds to RadD of Fusobacterium nucleatum ssp. polymorphum.

    Science.gov (United States)

    Guo, Lihong; Shokeen, Bhumika; He, Xuesong; Shi, Wenyuan; Lux, Renate

    2017-10-01

    Adhesin-mediated bacterial interspecies interactions are important elements in oral biofilm formation. They often occur on a species-specific level, which could determine health or disease association of a biofilm community. Among the key players involved in these processes are the ubiquitous fusobacteria that have been recognized for their ability to interact with numerous different binding partners. Fusobacterial interactions with Streptococcus mutans, an important oral cariogenic pathogen, have previously been described but most studies focused on binding to non-mutans streptococci and specific cognate adhesin pairs remain to be identified. Here, we demonstrated differential binding of oral fusobacteria to S. mutans. Screening of existing mutant derivatives indicated SpaP as the major S. mutans adhesin specific for binding to Fusobacterium nucleatum ssp. polymorphum but none of the other oral fusobacteria tested. We inactivated RadD, a known adhesin of F. nucleatum ssp. nucleatum for interaction with a number of gram-positive species, in F. nucleatum ssp. polymorphum and used a Lactococcus lactis heterologous SpaP expression system to demonstrate SpaP interaction with RadD of F. nucleatum ssp. polymorphum. This is a novel function for SpaP, which has mainly been characterized as an adhesin for binding to host proteins including salivary glycoproteins. In conclusion, we describe an additional role for SpaP as adhesin in interspecies adherence with RadD-SpaP as the interacting adhesin pair for binding between S. mutans and F. nucleatum ssp. polymorphum. Furthermore, S. mutans attachment to oral fusobacteria appears to involve species- and subspecies-dependent adhesin interactions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Knowledge of carrier status and barriers to testing among mothers of sons with Duchenne or Becker muscular dystrophy.

    Science.gov (United States)

    Bogue, Lauren; Peay, Holly; Martin, Ann; Lucas, Ann; Ramchandren, Sindhu

    2016-12-01

    Our study objective was to survey female carriers for Duchenne and Becker muscular dystrophy to identify barriers to carrier testing and the impact of carrier risk knowledge on cardiac and reproductive health management. We surveyed women who have or had biological sons with Duchenne or Becker muscular dystrophy and were enrolled in the US DuchenneConnect patient registry, with questions assessing knowledge of carrier status and recurrence risk, knowledge of care standards for carriers, and barriers to testing. Of the 182 eligible respondents, 25% did not know their carrier status and 14% incorrectly classified themselves as not at risk. Cost of testing was the most commonly identified barrier to testing. Women reporting unknown carrier status were 13 times as likely to express uncertainty regarding their recurrence risk compared to women reporting positive carrier status. 37% of women at an increased risk for cardiomyopathy had never had an echocardiogram. Women who were certain of their positive carrier status were twice as likely to have had an echocardiogram in the last five years compared to women with unknown carrier status. Future research on reducing barriers to counseling and carrier testing, such as cost, may improve care standard adherence. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. ¿SON EFECTIVOS LOS CONSEJOS DE ADMINISTRACIÓN? LA EFICACIA DEL CONSEJO Y LOS RESULTADOS DE LA EMPRESA

    Directory of Open Access Journals (Sweden)

    Barroso Castro, C.

    2010-01-01

    Full Text Available Numerosos trabajos han estudiado la influencia del consejo de administración en las decisiones y resultados de sus empresas. No obstante, la enorme popularidad alcanzada en el campo del gobierno corporativo por estos estudios, no viene acompañada por sus resultados, que han sido ambiguos y, a veces, conflictivos En esta investigación proponemos que la efectividad de los consejos depende de las experiencias y conocimientos de los consejeros que lo conforman, así como de la estructura de estos consejos. Entendemos que ambas dimensiones (composición y estructura no son “por si” suficientes para el logro de consejos plenamente efectivos, pero si se definen como elementos necesarios para ello. Desde nuestra perspectiva, constituyen el potencial que permitirá lograr una adecuada capacidad estratégica por parte del consejo. Nuestros resultados muestran la importancia de las variables que conforman la estructura y composición del consejo (tamaño del consejo, permanencia, experiencia de los consejeros a la hora de explicar los resultados empresariales.

  19. Precios de los medicamentos: cómo se establecen y cuáles son sus sistemas de control

    Directory of Open Access Journals (Sweden)

    Joan Rovira Forns

    2015-01-01

    Full Text Available El precio es una de las principales barreras de acceso a los medicamentos. Por ello es importante conocer cómo se forman los precios y qué factores determinan su cuantía y también qué formas de intervención y regulación son las más adecuadas teniendo en cuenta sus efectos, tanto sobre el acceso, como sobre la innovación, la producción local y otros posibles objetivos de la política de medicamentos. El análisis económico ha desarrollado un conjunto de modelos de mercado que permiten explicar el comportamiento de los precios, aunque los mercados reales divergen sustancialmente de los modelos teóricos. La regulación de precios está justificada por los llamados “fallos de mercado”; la regulación de precios basada en el costo de producción, la modalidad de control de precios más tradicional, ha caído en desuso a favor de los sistemas de precios de referencia internacionales y por la fijación del precio basada en el valor.

  20. Indicadores regionales de desarrollo sustentable en Chile: ¿Hasta qué punto son útiles y necesarios?

    Directory of Open Access Journals (Sweden)

    Hernán Blanco

    2001-09-01

    Full Text Available Cada vez más necesitamos maneras de asegurar patrones de desarrollo que sean sustentables, es decir, que sean ambiental, social y económicamente apropiados para nosotros y para las generaciones venideras. Los indicadores de desarrollo sustentable son una herramienta promisoria que permitiría "aterrizar" el concepto de sustentabilidad, apoyando la manera en que se toman las decisiones. En Chile existen pocas experiencias sobre el tema. Este artículo presenta el trabajo realizado para desarrollar indicadores de desarrollo sustentable en cuatro regiones del país. El artículo se centra en las lecciones que han surgido de la experienciaWe are increasingly needing ways to secure patterns of development that be sustainable, that is, environmentally, socially and economically appropriate for us and for future generations. Sustainability indicators are a promising tool that would allow us to "land" the concept, supporting the way in which decisions are made. In Chile there are few experiences on the subject. This paper presents the work carried out to develop sustainability indicators in four regions. The paper focuses on the lessons that have been drawn from the experience

  1. Autosomal dominant inheritance of Williams-Beuren syndrome in a father and son with haploinsufficiency for FKBP6.

    Science.gov (United States)

    Metcalfe, Kay; Simeonov, Emil; Beckett, William; Donnai, Dian; Tassabehji, May

    2005-04-01

    Williams-Beuren syndrome (WBS) is a neurodevelopmental microdeletion disorder that usually occurs sporadically due to its location within a highly repetitive genomic region that is unstable and prone to unequal cross-over during meiosis. The consequential loss of chromosomal material includes approximately 1.5 Mb of DNA at 7q11.23. Whilst cases of dominant inheritance have been described in the literature, there have been few reports of molecular confirmation and none have carried out detailed genotyping. We describe a Bulgarian father and son with WBS detected by fluorescent in situ hybridisation (with an elastin gene probe) and loss of heterozygosity mapping using microsatellite markers located in the critical region. These individuals appear to have a common WBS heterozygous deletion, confirming the expected dominant transmission and adding to the few familial cases reported. The deletion includes the gene FKBP6 which has recently been shown to play a role in homologous chromosome pairing in meiosis and male fertility in mouse models. Homozygous Fkbp6 -/- male mice are infertile and our data suggests that haploinsufficiency for FKBP6 does not appear to preclude male fertility in WBS, although male infertility involving this gene has the potential to follow the mouse model as a human autosomal recessive condition.

  2. Expectations and self-efficacy of African American parents who discuss sexuality with their adolescent sons: an intervention study.

    Science.gov (United States)

    Weekes, Carmon V N; Haas, Barbara K; Gosselin, Kevin P

    2014-01-01

    Despite research that suggests parental communication may help deter high-risk sexual behavior among adolescents, parents report a lack of confidence in their ability to answer sexually related questions. The purpose of this study was to test the effect of a multimedia intervention on outcome expectations and perceived self-efficacy for the sex educator role for parents of African American adolescent males. A pilot study using mixed methods was conducted. A nonprobability sample (N = 61) was obtained from a large urban community using a combination of convenience and snowball recruitment methods. Self-efficacy and outcome expectations were measured using self-reported questionnaires. A multimedia intervention for use at home and incorporating an audio CD and associated activities was implemented over a 3-week time period. Outcome expectations and self-efficacy both significantly improved after the intervention (p parents' outcome expectancy and self-efficacy for talking about sex with adolescent sons. © 2013 Wiley Periodicals, Inc.

  3. Effect of clayey groundwater on the dissolution rate of SON68 simulated nuclear waste glass at 70 °C

    Science.gov (United States)

    De Echave, T.; Tribet, M.; Jollivet, P.; Marques, C.; Gin, S.; Jégou, C.

    2018-05-01

    To predict the long-term behavior of high-level radioactive waste glass, it is necessary to study aqueous dissolution of the glass matrix under geological repository conditions. The present article focuses on SON68 (an inactive surrogate of the R7T7 glass) glass alteration in synthetic clayey groundwater at 70 °C. Experiments in deionized water as reference were also performed in the same conditions. Results are in agreement with those of previous studies showing that magnesium present in the solution is responsible for higher glass alteration. This effect is transient and pH-dependent: Once all the magnesium is consumed, the glass alteration rate diminishes. Precipitation of magnesium silicate of the smectite group seems to be the main factor for the increased glass alteration. A pH threshold of 7.5-7.8 was found, above which precipitation of these magnesium silicates at 70 °C is possible. TEM observations reveal that magnesium silicates grow at the expense of the passivating gel, which partly dissolves, forming large pores which increase mass transfer between the reacting glass surface and the bulk solution.

  4. Household opportunity costs of protecting and developing forest lands in Son La and Hoa Binh Provinces, Vietnam

    Directory of Open Access Journals (Sweden)

    Le Ngoc Lan

    2016-09-01

    Full Text Available Vietnam has pilot-tested a payment for forest environmental services (PFES program in an effort to restore and protect forest areas, some of which have been severely degraded by the excessive cutting of trees by small-scale farmers planting annual crops on steep, sloping lands. The pilot program implemented in southern Vietnam seems to be successful, yet the program in northern Vietnam has not produced the desired rates of planting and maintaining forest areas. The reasons for these mixed results include differences in socio-economic characteristics and also the production and marketing opportunities available to rural households in the project areas. To gain insight regarding program participation, we examine the household-level opportunity costs of planting and ­maintaining small plots of forest trees in northern Vietnam. We find that small-scale farmers in Hoa Binh Province, with limited financial resources, prefer the annual revenue stream provided by crops such as maize and cassava, rather than waiting for 7 years to obtain revenue from a forest planting. Farmers in Son La Province, with limited access to markets, prefer annual crops because they are not able to sell bamboo shoots and other forest products harvested from their small plots. In both provinces, the payments offered for planting and maintaining forest trees are smaller than the opportunity costs of planting and harvesting annual crops. Thus, most households likely would choose not to participate in the PFES program, at current payment rates, if given the opportunity to decline.

  5. How parasitoid females produce sexy sons: a causal link between oviposition preference, dietary lipids and mate choice in Nasonia.

    Science.gov (United States)

    Blaul, Birgit; Ruther, Joachim

    2011-11-07

    Sexual selection theory predicts that phenotypic traits used to choose a mate should reflect honestly the quality of the sender and thus, are often costly. Physiological costs arise if a signal depends on limited nutritional resources. Hence, the nutritional condition of an organism should determine both its quality as a potential mate and its ability to advertise this quality to the choosing sex. In insects, the quality of the offspring's nutrition is often determined by the ovipositing female. A causal connection, however, between the oviposition decisions of the mother and the mating chances of her offspring has never been shown. Here, we demonstrate that females of the parasitic wasp Nasonia vitripennis prefer those hosts for oviposition that have been experimentally enriched in linoleic acid (LA). We show by (13)C-labelling that LA from the host diet is a precursor of the male sex pheromone. Consequently, males from LA-rich hosts produce and release higher amounts of the pheromone and attract more virgin females than males from LA-poor hosts. Finally, males from LA-rich hosts possess three times as many spermatozoa as those from LA-poor hosts. Hence, females making the right oviposition decisions may increase both the fertility and the sexual attractiveness of their sons.

  6. Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

    Science.gov (United States)

    Yang, Long; Bashaw, Greg J

    2006-11-22

    Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

  7. Probing protein phosphatase substrate binding

    DEFF Research Database (Denmark)

    Højlys-Larsen, Kim B.; Sørensen, Kasper Kildegaard; Jensen, Knud Jørgen

    2012-01-01

    Proteomics and high throughput analysis for systems biology can benefit significantly from solid-phase chemical tools for affinity pull-down of proteins from complex mixtures. Here we report the application of solid-phase synthesis of phosphopeptides for pull-down and analysis of the affinity...... profile of the integrin-linked kinase associated phosphatase (ILKAP), a member of the protein phosphatase 2C (PP2C) family. Phosphatases can potentially dephosphorylate these phosphopeptide substrates but, interestingly, performing the binding studies at 4 °C allowed efficient binding to phosphopeptides......, without the need for phosphopeptide mimics or phosphatase inhibitors. As no proven ILKAP substrates were available, we selected phosphopeptide substrates among known PP2Cδ substrates including the protein kinases: p38, ATM, Chk1, Chk2 and RSK2 and synthesized directly on PEGA solid supports through a BAL...

  8. Human plasminogen binding protein tetranectin

    DEFF Research Database (Denmark)

    Kastrup, J S; Rasmussen, H; Nielsen, B B

    1997-01-01

    The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...

  9. Role of LAMP1 Binding and pH Sensing by the Spike Complex of Lassa Virus.

    Science.gov (United States)

    Cohen-Dvashi, Hadas; Israeli, Hadar; Shani, Orly; Katz, Aliza; Diskin, Ron

    2016-11-15

    To effectively infect cells, Lassa virus needs to switch in an endosomal compartment from its primary receptor, α-dystroglycan, to a protein termed LAMP1. A unique histidine triad on the surface of the receptor-binding domain from the glycoprotein spike complex of Lassa virus is important for LAMP1 binding. Here we investigate mutated spikes that have an impaired ability to interact with LAMP1 and show that although LAMP1 is important for efficient infectivity, it is not required for spike-mediated membrane fusion per se Our studies reveal important regulatory roles for histidines from the triad in sensing acidic pH and preventing premature spike triggering. We further show that LAMP1 requires a positively charged His230 residue to engage with the spike complex and that LAMP1 binding promotes membrane fusion. These results elucidate the molecular role of LAMP1 binding during Lassa virus cell entry and provide new insights into how pH is sensed by the spike. Lassa virus is a devastating disease-causing agent in West Africa, with a significant yearly death toll and severe long-term complications associated with its infection in survivors. In recent years, we learned that Lassa virus needs to switch receptors in a pH-dependent manner to efficiently infect cells, but neither the molecular mechanisms that allow switching nor the actual effects of switching were known. Here we investigate the activity of the viral spike complex after abrogation of its ability to switch receptors. These studies inform us about the role of switching receptors and provide new insights into how the spike senses acidic pH. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  11. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    James, W.P.T.; Branch, W.J.; Southgate, D.A.T.

    1978-01-01

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  12. Pietro Filippo Bernini, son of Gianlorenzo, and the mediation of the courts of Madrid and Paris for the concession of his prebend in Santa Maria Maggiore of Rome

    Directory of Open Access Journals (Sweden)

    Margarita de Alfonso Caffarena

    2017-06-01

    Full Text Available The intervention of queen Maria Teresa of Austria at the court of Madrid resulted in the concession of a prebend to Pietro Filippo Bernini, the eldest son of Gianlorenzo and canon of Santa Maria Maggiore in Rome.

  13. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  14. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  15. Anion binding in biological systems

    International Nuclear Information System (INIS)

    Feiters, Martin C; Meyer-Klaucke, Wolfram; Kostenko, Alexander V; Soldatov, Alexander V; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Kuepper, Frithjof C; Hollenstein, Kaspar; Locher, Kaspar P; Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R

    2009-01-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L 3 (2p 3/2 ) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  16. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  17. Clonage de l'IGF-I et de son récepteur chez le turbot (Psetta maxima

    Directory of Open Access Journals (Sweden)

    ELIES G.

    1998-07-01

    Full Text Available Les IGF, leurs récepteurs et leurs protéines de liaison constituent une famille moléculaire qui joue un rôle essentiel dans la régulation de la croissance et du développement. Nous nous sommes intéressés à la caractérisation moléculaire de l'IGF-l et de son récepteur (IGF-1R chez le turbot (Psetta maxima, un poisson plat téléostéen. Par RT-PCR, nous avons clone un ADNc codant pour les quatre domaines de l'IGF-l mature. La protéine présente 70 à 96 % d'identité avec les autres IGF-I de vertébrés. Le clonage de la séquence codante entière du récepteur a nécessité la construction d'une banque d'ADNc d'embryons de turbots. Le récepteur est organisé en domaines dont la taille et les caractéristiques sont semblables à celles des autres récepteurs aux IGF de type 1 décrits chez les mammifères et le poulet. La région catalytique est particulièrement conservée. Dans certains domaines, notamment dans la région C-terminale du précurseur, quelques différences qui pourraient avoir une importance fonctionnelle sont cependant observées. Enfin, par RT-PCR, nous avons mis en évidence une régulation ontogénique du statut de polyadénylation des ARNm IGF-1R.

  18. Comment Hobbes tente de rendre son matérialisme acceptable dans les appendices du Léviathan

    Directory of Open Access Journals (Sweden)

    Anne Staquet

    2011-11-01

    Full Text Available Le Léviathan de Hobbes [1651] a subi de nombreuses attaques, au point qu’il est jugé responsable de la grande peste de 1665 et de l’incendie de Londres l’année suivante et que le parlement ouvre une procédure contre l’ouvrage. Aussi, lorsqu’en 1666, Thomas Hobbes veut publier la traduction latine de ce livre, il y adjoint trois appendices. La version latine de l’œuvre est généralement jugée plus acceptable que le texte originaire anglais. En étudiant la manière dont Hobbes traite de son matérialisme dans ces appendices, je tente de montrer que les addenda latins ne constituent en aucune manière un retour en arrière du texte, mais que le philosophe enrobe simplement davantage des propos que, par ailleurs, il rend plus radicaux.Hobbes’s Leviathan [1651] has been critiqued so much that it was held responsible for the Great Plague of 1665 and the Fire of London during the following year, resulting in the Parliament instituting proceedings against the book. Therefore, when in 1666 Thomas Hobbes wanted to publish a Latin translation of this book, he added three appendices. Generally, the Latin version of the work is considered more acceptable than the English original text. By studying how Hobbes deals with his materialism in these appendices, I try to show that the Latin additions are in no way a reversal of the text, but that the philosopher simply veiled more propositions, while at the same time making them more radical.

  19. Número Expresivo de Suspensos en la Disciplina de Contabilidad de Costes: ¿Cuáles son los Posibles Motivos?

    Directory of Open Access Journals (Sweden)

    Iasmini Turci Borges

    2014-01-01

    Full Text Available El presente artículo tiene por objetivo identificar los posibles motivos del alto índice de suspensos en la disciplina de Contabilidad de Costes ofrecida a los alumnos del curso de graduación en Ciencias Contables de la Universidad Estatal de Maringá (UEM, representando una media de suspensos del 42% en relación al período de 2008 a 2013. Fueron utilizados como técnica de colecta de datos unos cuestionarios con cuestiones abiertas y cerradas y, en lo referente a la estrategia de pesquisa, se utilizó para la tabulación y análisis de los datos obtenidos en las cuestiones abiertas el Discurso del Sujeto Colectivo (DSC. El porcentual referente a los alumnos que suspendieron por nota y los alumnos que suspendieron por falta son, respectivamente, del 16% y 27%. De esta forma, para una tentativa de análisis parcial sobre los alumnos reprobados por nota, se hizo uso de la variable ansiedad, que presentó un porcentual de percepción por parte de los alumnos de, aproximadamente, un 60% de la muestra, a partir del abordaje de la Psicología Cognitiva basada en la Teoría del Procesamiento de la Información. Y, para el análisis parcial sobre los alumnos suspendidos por falta, Se hizo uso de la variable falta de dedicación y desinterés, que presentó un porcentual de percepción por parte de los alumnos del 47% de la muestra, utilizando para fundamentación la Teoría de la Procrastinación.

  20. ¿Son los errores congénitos del metabolismo causa prevenible de muerte súbita?

    Directory of Open Access Journals (Sweden)

    Roberto Álvarez Fumero

    Full Text Available El síndrome de muerte súbita del lactante (SMSL no es un proceso aislado, sino un hecho multifactorial y multicausal, del cual cada día se restan alteraciones potencialmente diagnosticables, para pasar a ser un diagnóstico de exclusión. Algunos errores congénitos del metabolismo (ECM han sido asociados al SMSL y/o a episodios aparentemente letales EAL, aunque la mayoría de ellos suelen tener alguna expresión clínica que los hace potencialmente diagnosticables antes de la muerte, lo que permite ser descartados de entre las causas del SMSL. De ellos, los más estrechamente relacionados con el SMSL son los trastornos de la betaoxidación mitocondrial de ácidos grasos. Solo del 3 al 5 % de los SMSL pueden guardar relación con ECM. El mayor impacto que representa el conocimiento de la asociación de SMSL y estos trastornos, es precisamente la posibilidad de su prevención. El personal médico debe conocer que la más eficiente forma de prevenir el SMSL relacionado con los ECM, es la búsqueda activa de lactantes de riesgo al realizar una exhaustiva anamnesis. Estos casos deben ser objeto de estudios metabólicos especializados, para lo cual es imprescindible conocer los requisitos de obtención, conservación y traslado de muestras al Laboratorio de Referencia.

  1. Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

    Science.gov (United States)

    Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

  2. Nuclear waste glasses of SON68 type and their weathering products, optical spectroscopy of uranium and rare earth elements

    International Nuclear Information System (INIS)

    Ollier, N.

    2002-09-01

    This study concerns the long-term behaviour of high-level waste glasses and more precisely lanthanides and uranium behaviour with weathering. The leaching was performed on glass powder at 90 deg. C in a pseudo-dynamic mode. Two weathering gels were obtained, with different renewal rate and leaching duration. In glass, we demonstrate that U(IV) and U(VI) species coexist. Time-resolved spectroscopy and XPS measurements show that hexavalent uranium is present under uranyl entities and UO 3 type environment. In weathering gels, U(VI) is still present under uranyl form as well as uranyl hydroxide. It means that U behaviour depends on renewal rate, moreover precipitation of crystallized phases like bauranolte BaU 2 O 7 .xH 2 O and uranyl silicate of uranophane type occur. Concerning lanthanides, Eu 3+ was used as a luminescent local probe. Two sites were found in glass and gels. In glass, the sites were attributed to a silicate and a borate one. In gels, the silicate site is conserved whereas the second one is supposed to correspond to an aluminate one. Photoluminescence and Moessbauer measurements show that the rare earth site symmetry increases in gel. This result confirms that order is higher in gels than in glass. The third part of the thesis concerns irradiation effect in glasses. The main result shows some behaviour differences between a 5 oxides borosilicate glass and a more complex one close to the SON68 glass. Presence of mixed alkali (Na, Li and Cs) seems to notably reduce the Na migration. (author)

  3. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.

    Science.gov (United States)

    Wang, Gang G; Song, Jikui; Wang, Zhanxin; Dormann, Holger L; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J; Allis, C David

    2009-06-11

    Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

  4. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Wolverton, C.

    2007-01-01

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  5. Polymeric competitive protein binding adsorbents for radioassay

    International Nuclear Information System (INIS)

    Adams, R.J.

    1976-01-01

    Serum protein comprising specific binding proteins such as antibodies, B 12 intrinsic factor, thyroxin binding globulin and the like may be copolymerized with globulin constituents of serum by the action of ethylchloroformate to form readily packed insoluble precipitates which, following purification as by washing, are eminently suited for employment as competitive binding protein absorbents in radioassay procedures. 10 claims, no drawings

  6. The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

    Energy Technology Data Exchange (ETDEWEB)

    Nemčovičová, Ivana [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States); Slovak Academy of Sciences, Dúbravská cesta 9, SK 84505 Bratislava (Slovakia); Zajonc, Dirk M., E-mail: dzajonc@liai.org [La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037 (United States)

    2014-03-01

    The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X{sub 6}G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host

  7. The structure of cytomegalovirus immune modulator UL141 highlights structural Ig-fold versatility for receptor binding

    International Nuclear Information System (INIS)

    Nemčovičová, Ivana; Zajonc, Dirk M.

    2014-01-01

    The crystal structure of Human cytomegalovirus immune modulator UL141 was solved at 3.25 Å resolution. Here, a detailed analysis of its intimate dimerization interface and the biophysical properties of its receptor (TRAIL-R2 and CD155) binding interactions are presented. Natural killer (NK) cells are critical components of the innate immune system as they rapidly detect and destroy infected cells. To avoid immune recognition and to allow long-term persistence in the host, Human cytomegalovirus (HCMV) has evolved a number of genes to evade or inhibit immune effector pathways. In particular, UL141 can inhibit cell-surface expression of both the NK cell-activating ligand CD155 as well as the TRAIL death receptors (TRAIL-R1 and TRAIL-R2). The crystal structure of unliganded HCMV UL141 refined to 3.25 Å resolution allowed analysis of its head-to-tail dimerization interface. A ‘dimerization-deficient’ mutant of UL141 (ddUL141) was further designed, which retained the ability to bind to TRAIL-R2 or CD155 while losing the ability to cross-link two receptor monomers. Structural comparison of unliganded UL141 with UL141 bound to TRAIL-R2 further identified a mobile loop that makes intimate contacts with TRAIL-R2 upon receptor engagement. Superposition of the Ig-like domain of UL141 on the CD155 ligand T-cell immunoreceptor with Ig and ITIM domains (TIGIT) revealed that UL141 can potentially engage CD155 similar to TIGIT by using the C′C′′ and GF loops. Further mutations in the TIGIT binding site of CD155 (Q63R and F128R) abrogated UL141 binding, suggesting that the Ig-like domain of UL141 is a viral mimic of TIGIT, as it targets the same binding site on CD155 using similar ‘lock-and-key’ interactions. Sequence alignment of the UL141 gene and its orthologues also showed conservation in this highly hydrophobic (L/A)X 6 G ‘lock’ motif for CD155 binding as well as conservation of the TRAIL-R2 binding patches, suggesting that these host–receptor interactions

  8. Le problème du mal dans le Guide des Perplexes et son arrière-plan talmudique

    Directory of Open Access Journals (Sweden)

    Costa, José

    2010-12-01

    Full Text Available At first sight, the question of evil is regarded in the Guide for the Perplexed in a paradoxical manner. Thus, in Guide I, 2, Maimonides examines the notions of good and evil as subjective evaluations possessing neither the rigour not the exactness of the notions of true and false. However, the question of evil occupies an essential place in the Guide, as various modern authors have shown. This question is important to Maimonides because he is, in this respect, the heir of the rabbinic tradition and his conception of evil is largely based on an interaction with the Talmudic and Midrašic texts. Therefore, we would like to review thirty-nine rabbinic ‘quotes’ which appear in chapters 8 to 24 in the third part of the Guide and deal with the origin of evil, the meaning of suffering and the evil inclination. Maimonides reappropriates the midrašim that are susceptible of being in agreement with his rationalist positions and also quotes some rabbinic traditions that are too close to mu ͑tazilism, undoubtedly aware of the more profound resemblance that exists between the rabbinic and mu ͑tazilite doctrines of evil and retribution.A primera vista, el problema del mal es abordado en la Guía de Perplejos de manera paradójica. Para Maimónides, las nociones de bien y mal son subjetivas y no resultan ni rigorosas ni exactas, a la inversa de las nociones de verdad y falsedad (Guía I, 2. Sin embargo, el problema del mal es muy importante en la Guía, como lo demostraran varios autores. Maimónides es el heredero de la tradición rabínica y existe en la Guía una interacción entre la filosofia de Maimónides y los textos talmúdicos y midrásicos. Es particularmente el caso de las treinta y nueve citas rabínicas de la Guía II, 8-24, que tratan del origen del mal, del significado del sufrimiento y de la inclinación al mal. Maimónides cita los midrašim que concuerdan con sus posiciones racionalistas y evoca también algunas tradiciones rab

  9. Profil bactériologique du pied diabétique et son impact sur le choix des antibiotiques

    Science.gov (United States)

    Zemmouri, Adil; Tarchouli, Mohamed; Benbouha, Abdellatif; Lamkinsi, Tarik; Bensghir, Mustapha; Elouennass, Mostafa; Haimeur, Cherqui

    2015-01-01

    Introduction Analyse du profil bactériologique des pieds diabétiques pris en charge à l'hôpital militaire de Rabat et son influence sur l'antibiothérapie de première intention. Méthodes Etude prospective non randomisée étalée sur 18 mois, ayant concerné 105 patients. Après recueil des données et en attente des résultats bactériologiques nos patients ont été divisés en deux groupes: un groupe a été mis sous Amoxicilline + Acide clavulanique + Gentamycine (59 patients) et un groupe sous Ertapénème±Gentamycine (46 patients). Résultats L’étude a regroupé 85 hommes et 20 femmes (sexe ratio = 4.26). L’âge moyen est de 64.4 ans. La gangrène a été observée chez 79% des malades; elle était humide-donc surinfectée en principe- dans 43% des cas. Par ailleurs, 67% des malades ont un chiffre de globules blancs 12000 définissant une infection sévère. L'ostéolyse a été mise en évidence chez 27% de nos patients. Parmi les différentes techniques de prélèvements: 81% ont été profonds dont 21% de biopsie osseuse per opératoire et 14% de prélèvements combinés. 42% de ces prélèvements sont poly microbiens et 21% sont stériles. Les résultats bactériologiques viennent confirmer la prédominance des bactéries aérobies à Gram positif. Le taux de remplacement de l'Ertapénème est de 22% contre un taux de 50% pour l'Amoxiclav. Conclusion L'antibiothérapie ne doit être instaurée qu'en cas d'infection du pied diabétique diagnostiquée sur les critères cliniques établis par les consensus internationaux récents. Le respect des mesures de lutte contre la diffusion de la résistance bactérienne s'avère primordiale. PMID:27386024

  10. A 25-year laboratory experiment on French SON68 nuclear glass leached in a granitic environment - First investigations

    Energy Technology Data Exchange (ETDEWEB)

    Guittonneau, C. [CEA Marcoule DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Gin, S., E-mail: stephane.gin@cea.f [CEA Marcoule DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Godon, N.; Mestre, J.P. [CEA Marcoule DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Dugne, O.; Allegri, P. [CEA Marcoule DTEC/SGCS/LMAC, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France)

    2011-01-01

    We have investigated a 25.75-year old leaching experiment to improve our understanding of the mechanisms controlling glass dissolution in geological disposal conditions. A SON68 glass block was leached in slowly renewed synthetic groundwater (at 90 {sup o}C, 100 bar) in contact with some pieces of granite and Ni-Cr-Mo alloy as environmental storage materials. One hundred and sixty-three samplings were carried out over the entire duration of the experiment and were used to calculate the mean thickness of the altered glass (28 ({+-}9) {mu}m) and the glass dissolution rate. After few months, the rate remained very constant at 6 x 10{sup -3} g m{sup -2} d{sup -1} which is about 20 times higher than the residual rate measured in a batch reactor at the same temperature. At the end of the experiment, mainly SEM analyses were performed on the entire glass block. Surprisingly, the glass alteration layer has neither a homogeneous thickness, nor a homogeneous morphology. The location of the sampling valve (at half height of the glass block) seems to divide the glass block into two parts. In the upper half (above the sampling valve), the general morphology of the alteration layer consists in a relatively simple and uniform gel and some secondary phases which are rare-earth phosphates. The mean measured thickness of this alteration layer is 6.7 ({+-}0.3) {mu}m. However, in the lower half of the glass block, the gel is globally larger and frequently contains rounded shapes which are rare-earth phosphates. This section is edged by secondary phases bearing Mg, Na, Zn and Ni. The mean measured thickness is 81.3 ({+-}1.1) {mu}m in the lower half. In this experiment, the flow rate which leads to the hydrodynamic transport of the soluble species must be a key factor for the local glass alteration process. We have also shown that this unexpected behavior is likely due to heterogeneities of the chemistry of the solution. This conclusion is supported by the behavior of Mg. This element

  11. ¿Son los chilenos igualmente solidarios?la influencia de los recursos personales en las donaciones de dinero

    Directory of Open Access Journals (Sweden)

    Juan Carlos Castillo

    2012-06-01

    Full Text Available En el discurso público comúnmente se asume que Chile es un país solidario, un supuesto que se confunde con la idea de una cierta homogeneidad en lo que respecta a valores solidarios y conductas de ayuda en el país. El presente trabajo apunta a cuestionar esta idea de homogeneidad respecto de solidaridad, proponiendo que las conductas solidarias se relacionan con los recursos que las personas poseen, los que a su vez se asocian al lugar que las personas ocupan en la estructura de estratificación social. Tomando los datos de la Encuesta de Solidaridad realizada en 2009 por el Centro de Medición MIDE UC de la Pontificia Universidad Católica de Chile, el trabajo se centra en un tipo de conducta de ayuda particular: las donaciones en dinero. El análisis se focaliza en la influencia de recursos personales como ingreso, educación y pertenencia a redes sobre este tipo de donaciones. Los resultados indican que los individuos con mayores recursos son más proclives a las donaciones, donde el nivel educacional alcanzado juega un papel preponderante.In the public discourse it is commonly assumed that Chile is a solidary country, an assumption that is mixed with the idea of homogeneity in the country as far as helping behavior and solidarity values is concerned. The present paper is aimed at challenging this homogeneity assumption by proposing that helping behavior is associated to personal resources, which at the same time are linked to the position in the social stratification structure. Using data from the Solidarity Survey implemented by the assessment center MIDE UC of the Pontificia Universidad Católica de Chile in 2009, the paper focuses on a specific type of helping behavior: money donations. The analysis centers on the influence of personal resources such as income, education and networks on this kind of donations. Results indicate that individuals with greater resources are more given to donate, whereby the educational level plays a key

  12. Alternative Constructions of Treason in the Angevin Political World: Traïson in the History of William Marshal

    Directory of Open Access Journals (Sweden)

    Stephen D. WHITE

    2007-05-01

    Full Text Available After some nobles and other fighting men surrendered Rochester castle to King John in 1215, John wanted to hang the nobles but refrained from doing so on the advice of one of his military captains. Would hanging the nobles for making war on the king have been lawful? This question about the law of treason has provoked inconclusive debate among historians who have sought to determine whether, in this period, making war against the English king was legally classified as lèse-majesté (crimen laesae majestatis, proditio or infidelitas. This article, however, asks whether the nobles whom John wanted to hang were guilty of traïson, as this vernacular term was used in the History of William Marshal (c. 1230. On this basis, the paper concludes that in all probability, the nobles who held Rochester against the king would not have been condemned as traitors, at least by their aristocratic peers.Cuando en 1215 ciertos nobles y otros combatientes se rindieron y entregaron el castillo de Rochester al rey Juan éste quiso colgarles, pero el consejo de uno de sus nobles le hizo absternerse. ¿Habría sido legítimo condenar a la horca a los que habían guerreado contra el rey? Cuestiones relativas al derecho de traición al intentar determinar si la guerra contra el rey de Inglaterra fue considerada en la época un crimen laesae majestatis, proditio, o infidelitas, según la definición que dan a estos términos las fuentes latinas, han suscitado debates interminables entre los historiadores. Este artículo, por el contrario, se pregunta si los nobles que el rey Juan deseaba colgar eran o no culpables de traición, en el sentido vernáculo del término que es usado en L’histoire de Guillaume le Maréchal (hacia 1230. Sobre esta base, la conclusión del artículo es que los nobles que ocuparon el castillo de Rochester, casi con total seguridad, no habrían sido condenados como traidores, al menos por sus pares.

  13. ¿Son los errores congénitos del metabolismo causa prevenible de muerte súbita?

    Directory of Open Access Journals (Sweden)

    Roberto Álvarez Fumero

    2004-03-01

    Full Text Available El síndrome de muerte súbita del lactante (SMSL no es un proceso aislado, sino un hecho multifactorial y multicausal, del cual cada día se restan alteraciones potencialmente diagnosticables, para pasar a ser un diagnóstico de exclusión. Algunos errores congénitos del metabolismo (ECM han sido asociados al SMSL y/o a episodios aparentemente letales EAL, aunque la mayoría de ellos suelen tener alguna expresión clínica que los hace potencialmente diagnosticables antes de la muerte, lo que permite ser descartados de entre las causas del SMSL. De ellos, los más estrechamente relacionados con el SMSL son los trastornos de la betaoxidación mitocondrial de ácidos grasos. Solo del 3 al 5 % de los SMSL pueden guardar relación con ECM. El mayor impacto que representa el conocimiento de la asociación de SMSL y estos trastornos, es precisamente la posibilidad de su prevención. El personal médico debe conocer que la más eficiente forma de prevenir el SMSL relacionado con los ECM, es la búsqueda activa de lactantes de riesgo al realizar una exhaustiva anamnesis. Estos casos deben ser objeto de estudios metabólicos especializados, para lo cual es imprescindible conocer los requisitos de obtención, conservación y traslado de muestras al Laboratorio de Referencia.The sudden infant death syndrome (SIDS is not an isolated process, but a multifactorial and multicausal event, of which there are less potentially diagnosable alterations every day, turning into an exclusion diagnosis. Some congenital errors of metabolism have been associated with SDSI and/or with apparently lethal episodes, although most of them may have some clinical expression that makes them potentially diagnosable before death, allowing to eliminate them from the causes of SIDS. Of them, the most closely related to SIDS are the disorders of mitochondrial betaoxidation of fatty acids. Only from 3 to 5 % of the SIDS may be related to CEM. The greatest impact of knowing about the

  14. Son Excellence Madame Elisabeth Laurin Ambassadeur Représentant permanent de la France auprès de l’Office des Nations Unies et des autres organisations internationales en Suisse République française Son Excellence Monsieur Roberto Balzaretti Ambassadeur Directeur

    CERN Multimedia

    AUTHOR|(CDS)2099575

    2016-01-01

    Son Excellence Madame Elisabeth Laurin Ambassadeur Représentant permanent de la France auprès de l’Office des Nations Unies et des autres organisations internationales en Suisse République française Son Excellence Monsieur Roberto Balzaretti Ambassadeur Directeur,

  15. Abrogation by human menopausal gonadotropin on testicular ...

    African Journals Online (AJOL)

    Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of cancer cells including testicular cancer. Human Menopausal Gonadotropin (HMG) is a natural hormone necessary for human reproduction. This hormone is a leading modality of treatment for infertility as it contains equal amount of ...

  16. Urea-induced binding between diclofenac sodium and bovine serum albumin: a spectroscopic insight.

    Science.gov (United States)

    Dohare, Neeraj; Khan, Abbul Bashar; Athar, Fareeda; Thakur, Sonu Chand; Patel, Rajan

    2016-06-01

    We investigated the interaction of diclofenac sodium (Dic.Na) with bovine serum albumin (BSA) in the absence and presence of urea using different spectroscopic techniques. A fluorescence quenching study revealed that the Stern-Volmer quenching constant decreases in the presence of urea, decreasing further at higher urea concentrations. The binding constant and number of binding sites were also evaluated for the BSA-Dic.Na interaction system in the absence and presence of urea using a modified Stern-Volmer equation. The binding constant is greater at high urea concentrations, as shown by the fluorescence results. In addition, for the BSA-Dic.Na interaction system, a static quenching mechanism was observed, which was further confirmed using time-resolved fluorescence spectroscopy. UV-vis spectroscopy provided information about the formation of a complex between BSA and Dic.Na. Circular dichroism was carried out to explain the conformational changes in BSA induced by Dic.Na in the absence and presence of urea. The presence of urea reduced the α-helical content of BSA as the Dic.Na concentration varied. The distance r between the donor (BSA) and acceptor (Dic.Na) was also obtained in the absence and presence of urea, using fluorescence resonance energy transfer. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Koerker, D.J.; Sweet, I.R.; Baskin, D.G.

    1990-01-01

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  18. A case study of conflict management in bonobos: how does a bonobo (Pan paniscus) mother manage conflicts between her sons and her female coalition partner?

    Science.gov (United States)

    Legrain, L; Stevens, J; Alegria Iscoa, J; Destrebecqz, A

    2011-01-01

    Female coalitions are an important part of the social organization of bonobos. The strength of the mother-son relationship is another essential part of this social structure. A bonobo mother is therefore facing a dilemma when a conflict arises between her sons and her female coalition partners. Will she take her coalition partner's side and favour the social organization of the group or support her son in order to defend her offspring? In order to address this issue, we performed an observational study of the captive group at Planckendael (Belgium) and used social grooming and proximity to assess the relationship between individuals. As a case study, we focused on the relationships between Hortense, one of the group's mothers, her 3 sons Redi, Vifijo and Zamba, and her coalition partner Hermien. Surprisingly, we observed that Hortense preferentially supported her female coalition partner. For Hortense's social status in the group, it may be more important to maintain the strong relationship with her higher-ranking female coalition partner than to support her sons. Copyright © 2012 S. Karger AG, Basel.

  19. Death of a son is associated with risk of suicide among parous women in Taiwan: a nested case-control study.

    Science.gov (United States)

    Chen, Chih-Cheng; Kuo, Chien-Chun; Wu, Trong-Neng; Yang, Chun-Yuh

    2012-01-01

    The impact of the sex of a deceased child on maternal suicide has not been studied. We examined whether the death of a child, especially a son, increased the risk of suicide among parous Taiwanese women. This matched case-control study was done within a cohort of 1 292 462 Taiwanese women who experienced a first and singleton childbirth between 1 January 1978 and 31 December 1987 and were followed up until 31 December 2008. From the cohort, 2701 suicide cases were identified and 2701 controls were randomly selected. Multiple logistic regression was used to estimate the risk of suicide associated with the death of a child. The adjusted odds ratios (ORs) for suicide among mothers whose son had died were 2.60 (95% CI = 1.18-5.73), 2.58 (1.28-5.20), and 4.20 (0.79-22.45) for death of a son aged younger than 1 year, 1 to 17 years, and 18 years or older. The ORs for suicide associated with the death of a daughter were not statistically significant: the respective adjusted ORs were 1.86 (0.82-4.62), 1.38 (0.54-3.49), and 2.48 (0.40-15.51). The death of a child, especially a son, increased the risk of maternal suicide, which supports the notion that preference for a son is firmly rooted in traditional Chinese culture.

  20. Plantilla de enfermería y demanda de cuidados de ancianos hospitalizados, ¿son suficientes los recursos?

    Directory of Open Access Journals (Sweden)

    Alfonso Jesús Cruz Lendínez

    Full Text Available Introducción: El aumento de la población de personas mayores de 65 años hace cada vez más frecuente su ingreso en los hospitales. El tiempo de estancia hospitalaria de los ancianos suele ser más prolongado que el del resto de pacientes. Objetivo: Analizar la capacidad de prestación de cuidados de 3 unidades de hospitalización de un hospital público y compararla con la demanda de cuidados de los ancianos. Métodos: Estudio prospectivo observacional en 3 unidades de hospitalización de medicina interna de un hospital universitario de la red pública de Andalucía (España. Se ha incluido una muestra de 190 pacientes ancianos hospitalizados. Las variables recogidas fueron: demográficas, relacionadas con la hospitalización, demanda de cuidados y capacidad de prestación de cuidados de la plantilla de enfermería. Los datos se han obtenido del sistema de información del hospital, del conjunto mínimo básico de datos de pacientes y por observación directa mediante el método de nivel de cuidados (MNC. Resultados: La edad media de los ancianos hospitalizados fue de 77,4 años, con 21,1% de mayores de 85 años. La estancia media fue de 15,68 días. La estimación de la capacidad de prestación de cuidados de la plantilla de enfermería fue de 2,8 horas/paciente/día (con un índice de enfermeras tituladas del 60%. A partir de la medición de niveles de dependencia, la demanda de cuidados media de los ancianos fue de 4,9 horas/paciente/día. Esta diferencia supone un déficit anual de 51 profesionales de enfermería en la plantilla de las 3 unidades de hospitalización. Los factores que influyen en la demanda de cuidados de los ancianos son la edad, días de estancia hospitalaria, el diagnóstico médico y el destino del paciente al alta. También se encuentra una relación con la presencia de un familiar acompañando al paciente (cuidador familiar. Los cuidados básicos representan un 65,7% del total de cuidados requeridos. Conclusiones: La

  1. Enhanced resistance in Theobroma cacao against oomycete and fungal pathogens by secretion of phosphatidylinositol-3-phosphate-binding proteins.

    Science.gov (United States)

    Helliwell, Emily E; Vega-Arreguín, Julio; Shi, Zi; Bailey, Bryan; Xiao, Shunyuan; Maximova, Siela N; Tyler, Brett M; Guiltinan, Mark J

    2016-03-01

    The internalization of some oomycete and fungal pathogen effectors into host plant cells has been reported to be blocked by proteins that bind to the effectors' cell entry receptor, phosphatidylinositol-3-phosphate (PI3P). This finding suggested a novel strategy for disease control by engineering plants to secrete PI3P-binding proteins. In this study, we tested this strategy using the chocolate tree Theobroma cacao. Transient expression and secretion of four different PI3P-binding proteins in detached leaves of T. cacao greatly reduced infection by two oomycete pathogens, Phytophthora tropicalis and Phytophthora palmivora, which cause black pod disease. Lesion size and pathogen growth were reduced by up to 85%. Resistance was not conferred by proteins lacking a secretory leader, by proteins with mutations in their PI3P-binding site, or by a secreted PI4P-binding protein. Stably transformed, transgenic T. cacao plants expressing two different PI3P-binding proteins showed substantially enhanced resistance to both P. tropicalis and P. palmivora, as well as to the fungal pathogen Colletotrichum theobromicola. These results demonstrate that secretion of PI3P-binding proteins is an effective way to increase disease resistance in T. cacao, and potentially in other plants, against a broad spectrum of pathogens. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  2. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  3. Atmospheric Extinction Coefficients in the Ic Band for Several Major International Observatories: Results from the BiSON Telescopes, 1984-2016

    Science.gov (United States)

    Hale, S. J.; Chaplin, W. J.; Davies, G. R.; Elsworth, Y. P.; Howe, R.; Lund, M. N.; Moxon, E. Z.; Thomas, A.; Pallé, P. L.; Rhodes, E. J., Jr.

    2017-09-01

    Over 30 years of solar data have been acquired by the Birmingham Solar Oscillations Network (BiSON), an international network of telescopes used to study oscillations of the Sun. Five of the six BiSON telescopes are located at major observatories. The observational sites are, in order of increasing longitude: Mount Wilson (Hale) Observatory (MWO), California, USA; Las Campanas Observatory, Chile; Observatorio del Teide, Izaña, Tenerife, Canary Islands; the South African Astronomical Observatory, Sutherland, South Africa; Carnarvon, Western Australia; and the Paul Wild Observatory, Narrabri, New South Wales, Australia. The BiSON data may be used to measure atmospheric extinction coefficients in the {{{I}}}{{c}} band (approximately 700-900 nm), and presented here are the derived atmospheric extinction coefficients from each site over the years 1984-2016.

  4. Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

    Science.gov (United States)

    Sheikh, Ishfaq A; Beg, Mohd A

    2017-12-01

    Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Protection against Mitochondrial and Metal Toxicity Depends on Functional Lipid Binding Sites in ATP13A2

    Directory of Open Access Journals (Sweden)

    Shaun Martin

    2016-01-01

    Full Text Available The late endo-/lysosomal P-type ATPase ATP13A2 (PARK9 is implicated in Parkinson’s disease (PD and Kufor-Rakeb syndrome, early-onset atypical Parkinsonism. ATP13A2 interacts at the N-terminus with the signaling lipids phosphatidic acid (PA and phosphatidylinositol (3,5 bisphosphate (PI(3,5P2, which modulate ATP13A2 activity under cellular stress conditions. Here, we analyzed stable human SHSY5Y cell lines overexpressing wild-type (WT or ATP13A2 mutants in which three N-terminal lipid binding sites (LBS1–3 were mutated. We explored the regulatory role of LBS1–3 in the cellular protection by ATP13A2 against mitochondrial stress induced by rotenone and found that the LBS2-3 mutants displayed an abrogated protective effect. Moreover, in contrast to WT, the LBS2 and LBS3 mutants responded poorly to pharmacological inhibition of, respectively, PI(3,5P2 and PA formation. We further demonstrate that PA and PI(3,5P2 are also required for the ATP13A2-mediated protection against the toxic metals Mn2+, Zn2+, and Fe3+, suggesting a general lipid-dependent activation mechanism of ATP13A2 in various PD-related stress conditions. Our results indicate that the ATP13A2-mediated protection requires binding of PI(3,5P2 to LBS2 and PA to LBS3. Thus, targeting the N-terminal lipid binding sites of ATP13A2 might offer a therapeutic approach to reduce cellular toxicity of various PD insults including mitochondrial stress.

  6. Synthetic LPS-Binding Polymer Nanoparticles

    Science.gov (United States)

    Jiang, Tian

    Lipopolysaccharide (LPS), one of the principal components of most gram-negative bacteria's outer membrane, is a type of contaminant that can be frequently found in recombinant DNA products. Because of its strong and even lethal biological effects, selective LPS removal from bioproducts solution is of particular importance in the pharmaceutical and health care industries. In this thesis, for the first time, a proof-of-concept study on preparing LPS-binding hydrogel-like NPs through facile one-step free-radical polymerization was presented. With the incorporation of various hydrophobic (TBAm), cationic (APM, GUA) monomers and cross-linkers (BIS, PEG), a small library of NPs was constructed. Their FITC-LPS binding behaviors were investigated and compared with those of commercially available LPS-binding products. Moreover, the LPS binding selectivity of the NPs was also explored by studying the NPs-BSA interactions. The results showed that all NPs obtained generally presented higher FITC-LPS binding capacity in lower ionic strength buffer than higher ionic strength. However, unlike commercial poly-lysine cellulose and polymyxin B agarose beads' nearly linear increase of FITC-LPS binding with particle concentration, NPs exhibited serious aggregation and the binding quickly saturated or even decreased at high particle concentration. Among various types of NPs, higher FITC-LPS binding capacity was observed for those containing more hydrophobic monomers (TBAm). However, surprisingly, more cationic NPs with higher content of APM exhibited decreased FITC-LPS binding in high ionic strength conditions. Additionally, when new cationic monomer and cross-linker, GUA and PEG, were applied to replace APM and BIS, the obtained NPs showed improved FITC-LPS binding capacity at low NP concentration. But compared with APM- and BIS-containing NPs, the FITC-LPS binding capacity of GUA- and PEG-containing NPs saturated earlier. To investigate the NPs' binding to proteins, we tested the NPs

  7. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  8. DNA Binding Hydroxyl Radical Probes.

    Science.gov (United States)

    Tang, Vicky J; Konigsfeld, Katie M; Aguilera, Joe A; Milligan, Jamie R

    2012-01-01

    The hydroxyl radical is the primary mediator of DNA damage by the indirect effect of ionizing radiation. It is a powerful oxidizing agent produced by the radiolysis of water and is responsible for a significant fraction of the DNA damage associated with ionizing radiation. There is therefore an interest in the development of sensitive assays for its detection. The hydroxylation of aromatic groups to produce fluorescent products has been used for this purpose. We have examined four different chromophores which produce fluorescent products when hydroxylated. Of these, the coumarin system suffers from the fewest disadvantages. We have therefore examined its behavior when linked to a cationic peptide ligand designed to bind strongly to DNA.

  9. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    The employment of metal salts is quite limited in asymmetric catalysis, although it would provide an additional arsenal of safe and inexpensive reagents to create molecular functions with high optical purity. Cation chelation by polyethers increases the salts' solubility in conventional organic...... solvents, thus increasing their applicability in synthesis. The expansion of this concept to chiral polyethers led to the emergence of asymmetric cation-binding catalysis, where chiral counter anions are generated from metal salts, particularly using BINOL-based polyethers. Alkali metal salts, namely KF...... highly enantioselective silylation reactions in polyether-generated chiral environments, and leading to a record-high turnover in asymmetric organocatalysis. This can lead to further applications by the asymmetric use of other inorganic salts in various organic transformations....

  10. The helical structure of DNA facilitates binding

    International Nuclear Information System (INIS)

    Berg, Otto G; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

    2016-01-01

    The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction–diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general. (paper)

  11. Is a {mu}mol a {mu}mol? Growth and development of chrysanthemum cultivated under SON-T lighting and under LED-lighting; Is a {mu}mol a {mu}mol? Groei en ontwikkeling van chrysant geteeld onder SON-T belichting en onder LED verlichting

    Energy Technology Data Exchange (ETDEWEB)

    Meinen, E.; Marcelis, L.F.M.; Steenhuizen, J.W.; Dueck, T.A.

    2009-12-15

    Description of an experiment that was conducted, comparing LED lamps and SON-T (high pressure sodium) lamps. In climate rooms with LED (96% red sodium lamps) or SON-T lamps (without daylight), chrysanthemums were cultivated at two light intensities. Although the air temperature was the same in both treatments, the leaf temperature was clearly higher in the case of SON-T as a result of heat radiation. In the case of LED a more round leaves were observed. Plants cultivated under SON-T light developed closed crops much quicker and required a shorter reaction time (10 to 14 days at high and low light intensity). Yet, the harvest weight of the branches was the same. The net leaf photosynthesis was lower in chrysanthemums cultivated under LED lighting compared to plants cultivated under SON-T lighting. This is probably due to long-term cultivation under a spectrum of almost exclusively red light. The differences between SON-T and LED with regard to light color and heat radiation have significant consequences for growth and development. [Dutch] Een experiment is uitgevoerd om LED lampen en SON-T (hogedruk natriumlampen) lampen te vergelijken. In klimaatkamers met LED (96% rood en 4% blauw) of SON-T lampen (zonder daglichttoetreding) werden chrysanten geteeld bij 2 lichtintensiteiten. Hoewel de luchttemperatuur identiek was bij beide behandelingen was de bladtemperatuur duidelijk hoger bij SON-T als gevolg van warmtestraling. Onder LED belichting werd meer 'bol blad' waargenomen. Planten geteeld onder SON-T belichting ontwikkelden sneller een gesloten gewas en hadden een kortere reactietijd (10 tot 14 dagen bij hoge en lage lichtintensiteit). Maar het oogstgewicht van de takken was gelijk. De netto actuele bladfotosynthese was lager bij chrysanten geteeld onder LED belichting vergeleken met planten geteeld onder SON-T belichting. Dit is waarschijnlijk toe te schrijven aan langdurige teelt onder een spectrum met vrijwel alleen rood licht. De verschillen tussen SON

  12. De Masaccio à Stalker: pour une esthétique du seuil et de son franchissement 

    Directory of Open Access Journals (Sweden)

    Sylvie Castets

    2010-04-01

    Full Text Available Le seuil,abordé en tant que sujet représenté, est ici le moyen d’envisager la question  de la limite et de son dépassement dans le territoire de l’œuvre peinte, de l’installation et de la performance. La fresque de Masaccio, intitulée « Adam et Ève chassés du Paradis », réalisée vers 1425, constitue une étape décisive dans le traitement de l’espace de représentation. La suggestion d’une  profondeur, mais également, d’une épaisseur, apparaît, faisant basculer la peinture vers le naturalisme. Ainsi, au réalisme intellectuel du Moyen Age, se substitue un nouveau mode de figuration. L’artiste de la Renaissance quitte donc un territoire artistique pour explorer et poser les bases d’un art inédit. Dès lors, la toile, telle une zone de friction, se place et agit dans l’interstice séparant l’espace réel et l’espace représenté. La vision du spectateur, face au tableau, franchit ainsi le barrage de l’œuvre pour coloniser une fable topique amenée par l’illusion de la profondeur. La peinture est également le lieu où l’artiste révèle au spectateur, par le biais de stratagèmes plastiques, ses conditions de réalisation. A partir de là, une rupture s’opère entre la représentation et le fait de présenter. Art et vie s’interpénètrent alors, dans des installations ou des performances, offrant au spectateur un lieu milieu, dans lequel il est amené à s’affranchir de ces modèles. L’oeuvre est donc un seuil qu’il faut «traverser pour apprendre la solitude. » (Serres. Elle vibre d’instabilité et cristallise l’état singulier du changement. Enfin, elle conduit inéluctablement vers un devenir autre.The threshold as theme of representation is in this article used as a way to question the limit and its crossing in the territory of the painted work, of the installation and the performance. Masaccio’s fresco “The Expulsion from the Garden of Eden” of 1425 constitutes a decisive

  13. Fundamental considerations in ski binding analysis.

    Science.gov (United States)

    Mote, C D; Hull, M L

    1976-01-01

    1. The static adjustment of a ski binding by hand or by available machines is only an adjustment and is neither a static nor a dynamic evaluation of the binding design. Bindings of different design with identical static adjustments will perform differently in environments in which the forces are static or dynamic. 2. The concept of binding release force is a useful measure of binding adjustment, but it is inappropriate as a criterion for binding evaluation. First, it does not direct attention toward the injury causing mechanism, strain, or displacement in the leg. Second, it is only part of the evaluation in dynamic problems. 3. The binding release decision in present bindings is displacement controlled. The relative displacement of the boot and ski is the system variable. For any specified relative displacement the binding force can be any of an infinite number of possibilities determined by the loading path. 4. The response of the leg-ski system to external impulses applied to the ski is independent of the boot-ski relative motion as long as the boot recenters quickly in the binding. Response is dependent upon the external impulse plus system inertia, damping and stiffness. 5. When tested under half sinusoidal forces applied to a test ski, all bindings will demonstrate static and impulse loading regions. In the static region the force drives the binding to a relative release displacement. In the impulse region the initial velocity of the ski drives the binding to a release displacement. 6. The transition between the static and impulse loading regions is determined by the binding's capacity to store and dissipate energy along the principal loading path. Increased energy capacity necessitates larger external impulses to produce release. 7. In all bindings examined to date, the transmitted leg displacement or strain at release under static loading exceeds leg strain under dynamic or impact loading. Because static loading is responsible for many injuries, a skier

  14. Lead-Binding Proteins: A Review

    Directory of Open Access Journals (Sweden)

    Harvey C. Gonick

    2011-01-01

    Full Text Available Lead-binding proteins are a series of low molecular weight proteins, analogous to metallothionein, which segregate lead in a nontoxic form in several organs (kidney, brain, lung, liver, erythrocyte. Whether the lead-binding proteins in every organ are identical or different remains to be determined. In the erythrocyte, delta-aminolevulinic acid dehydratase (ALAD isoforms have commanded the greatest attention as proteins and enzymes that are both inhibitable and inducible by lead. ALAD-2, although it binds lead to a greater degree than ALAD-1, appears to bind lead in a less toxic form. What may be of greater significance is that a low molecular weight lead-binding protein, approximately 10 kDa, appears in the erythrocyte once blood lead exceeds 39 μg/dL and eventually surpasses the lead-binding capacity of ALAD. In brain and kidney of environmentally exposed humans and animals, a cytoplasmic lead-binding protein has been identified as thymosin β4, a 5 kDa protein. In kidney, but not brain, another lead-binding protein has been identified as acyl-CoA binding protein, a 9 kDa protein. Each of these proteins, when coincubated with liver ALAD and titrated with lead, diminishes the inhibition of ALAD by lead, verifying their ability to segregate lead in a nontoxic form.

  15. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug is bound...

  16. Bitopic Ligands and Metastable Binding Sites

    DEFF Research Database (Denmark)

    Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

    2017-01-01

    of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

  17. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Zhang

    Full Text Available BACKGROUND: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP and epididymal retinoic acid binding protein (ERABP carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs and cellular retinoic acid-binding proteins (CRABPs carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. CONCLUSIONS/SIGNIFICANCE: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.

  18. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number

    DEFF Research Database (Denmark)

    Mau Kai, C; Juul, A; McElreavey, K

    2008-01-01

    number, supplemented with haplogroup typing in deleted patients, were performed, in combination with clinical assessments in 264 fathers and their sons conceived by assisted reproduction techniques (ART), and in 168 fertile men with normal sperm concentration. RESULTS: In the ART fathers group...

  19. Understanding Gender Differences in Children's Risk Taking and Injury: A Comparison of Mothers' and Fathers' Reactions to Sons and Daughters Misbehaving in Ways that Lead to Injury

    Science.gov (United States)

    Morrongiello, Barbara A.; Zdzieborski, Daniel; Normand, Jackie

    2010-01-01

    This study compared reactions of mothers and fathers to the risk taking behavior of sons and daughters. Mother-father pairs (N = 52) imagined their 2-year-old boy or girl behaving in risky ways in common home situations that could, and did, result in injury. Emotional and parenting reactions to the behaviors were assessed before and after injury.…

  20. Parents' experience of living with and caring for an adult son or daughter with schizophrenia at home in Ireland: a qualitative study.

    Science.gov (United States)

    McAuliffe, R; O'Connor, L; Meagher, D

    2014-03-01

    This study explored the experience of parents living with, and caring for, an adult son or daughter with schizophrenia. There is increasing emphasis on the involvement of carers and users in the care for people with schizophrenia. 'A Vision for Change' highlights the need for a partnership approach and emphasizes that carers are an integral part in the planning and delivery of mental health services. In order to meet such requests, it was necessary to explore the meaning of caregiving for Irish families. A descriptive qualitative design was used to enable parents to describe their experiences. Semi-structured, in-depth interviews with a convenience sample of six parents in Ireland were carried out in 2007. The study encompassed four major themes: psychological tsunami, caring activities, coping with enduring illness and an uncertain pathway. Parents reported severe psychological distress when their son or daughter was diagnosed with schizophrenia. Their deep sense of loss was followed by acceptance of the situation. Feelings of love and a sense of responsibility helped to give meaning to their caring role. This study gave a voice to some parents of a son or daughter with schizophrenia. A family-centred approach should be at the core of care planning for this vulnerable population. © 2013 John Wiley & Sons Ltd.

  1. «¿Quién soy yo? ¿Quiénes son ellos/as?». Personajes en busca de identidad

    Directory of Open Access Journals (Sweden)

    Caretti, Laura

    2006-12-01

    Full Text Available Who am I? Who are they? These are the questions haunting the characters, created by writers such as Ibsen, Pirandello, Beckett and others, whose emblematic search for identity is explored in the article. The complex interconnections between subjectivity and alterity are focused within the coordinates of space (society and time (memory in their outward and inward movement. The characters are seen on stage relating also to the otherness of actors and spectators. Particular relief is given to the difference between the female and male search for identity in the light of contemporary historical changes.¿Quién soy yo? ¿Quiénes son ellos/as? Estas son las cuestiones que obsesionan a los personajes creados por escritores como Ibsen, Pirandello, Beckett y otros, cuya emblemática búsqueda de identidad se explora a lo largo de este artículo. Las complejas interconexiones entre subjetividad y alteridad son analizadas con las coordenadas del espacio (sociedad y el tiempo (memoria en su movimiento interno y externo. Los personajes son vistos en el escenario desde la alteridad de actores y espectadores. Un particular relieve se otorga a la diferencia entre la búsqueda de la identidad femenina y masculina a la luz de los cambios históricos contemporáneos.

  2. Why is Son Preference Declining in South Korea? The Role of Development and Public Policy, and the Implications for China and India

    OpenAIRE

    Chung, Woojin; Das Gupta, Monica

    2007-01-01

    For years, South Korea presented the puzzling phenomenon of steeply rising sex ratios at birth despite rapid development, including in women's education and formal employment. This paper shows that son preference decreased in response to development, but its manifestation continued until the mid-1990s due to improved sex-selection technology. The paper analyzes unusually rich survey data, ...

  3. Polyandrous females provide sons with more competitive sperm: Support for the sexy-sperm hypothesis in the rattlebox moth (Utetheisa ornatrix).

    Science.gov (United States)

    Egan, Andrea L; Hook, Kristin A; Reeve, H Kern; Iyengar, Vikram K

    2016-01-01

    Given the costs of multiple mating, why has female polyandry evolved? Utetheisa ornatrix moths are well suited for studying multiple mating in females because females are highly polyandrous over their life span, with each male mate transferring a substantial spermatophore with both genetic and nongenetic material. The accumulation of resources might explain the prevalence of polyandry in this species, but another, not mutually exclusive, possibility is that females mate multiply to increase the probability that their sons will inherit more-competitive sperm. This latter "sexy-sperm" hypothesis posits that female multiple mating and male sperm competitiveness coevolve via a Fisherian runaway process. We tested the sexy-sperm hypothesis by using competitive double matings to compare the sperm competition success of sons of polyandrous versus monandrous females. In accordance with sexy-sperm theory, we found that in 511 offspring across 17 families, the male whose polyandrous mother mated once with each of three different males sired significantly more of all total offspring (81%) than did the male whose monandrous mother was mated thrice to a single male. Interestingly, sons of polyandrous mothers had a significantly biased sex ratio of their brood toward sons, also in support of the hypothesis. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  4. Characterization of the binding of 2-mercaptobenzimidazole to bovine serum albumin.

    Science.gov (United States)

    Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

    2015-04-01

    2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment is potentially harmful to human health. In this article, the interaction of MBI with bovine serum albumin (BSA) was explored using spectroscopic and molecular docking methods under physiological conditions. The positively charged MBI can spontaneously bind with the negatively charged BSA through electrostatic forces with one binding site. The site marker competition experiments and the molecular docking study revealed that MBI bound into site II (subdomain IIIA) of BSA, which further led to some secondary structure and microenvironmental changes of BSA. This work provides useful information on understanding the toxicological actions of MBI at the molecular level. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Bu-Shen-Ning-Xin decoction: inhibition of osteoclastogenesis by abrogation of the RANKL-induced NFATc1 and NF-κB signaling pathways via selective estrogen receptor α

    Directory of Open Access Journals (Sweden)

    Wang L

    2015-07-01

    in osteoclast precursor cells; the inhibitory effect was abolished by methyl-piperidino-pyrazole but not the estrogen receptor β antagonist or androgen receptor antagonist.Conclusion: These results collectively suggest that administration of BSNXD presents inhibitory effects on osteoclast differentiation by abrogating the RANKL-induced nuclear factor of activated T-cells, cytoplasmic 1 and NF-κB signaling pathways downstream of estrogen receptor α, thereby contributing to the inhibitory effect on bone resorption.Keywords: herbal formula, osteoclastogenesis, estrogen receptor α, NF-κB, NFATc1

  6. Latino Parents' Awareness and Receipt of the HPV Vaccine for Sons and Daughters in a State with Low Three-Dose Completion.

    Science.gov (United States)

    Kepka, Deanna; Ding, Qian; Bodson, Julia; Warner, Echo L; Mooney, Kathi

    2015-12-01

    Latinos suffer a disproportionate burden of human papillomavirus (HPV)-preventable cancers, yet uptake and completion of the HPV vaccine among Latinos is below recommendations. Reasons for low HPV vaccine uptake among Latinos in Utah are unknown. We surveyed Latino parents of HPV vaccine age-eligible adolescents (N=118). Univariable analyses identified sociodemographic characteristics associated with HPV vaccine awareness, interest, and uptake for daughter(s) and/or son(s) using chi-square tests or Fisher's exact tests. More parents who had lived in the USA for 15 years or more had vaccinated their daughter (43.6 vs. 32.5%, p=0.035) compared to those living in the USA for shorter time periods. Parents born in Mexico reported their son had not received the HPV vaccine (74.6 vs. 58.3%, p=0.049) more than those born elsewhere. Parents with Mexican birthplace and ancestry reported not knowing about the HPV vaccine as the main barrier to vaccinating daughters (47.1 vs. 5.9%, p=0.002 for both) and sons (birthplace 38.3 vs. 10.3%, p=0.007; ancestry 37.1 vs. 11.1%, p=0.013) compared to those born or descending elsewhere. Non-acculturated parents with a son were more likely to report not knowing about the HPV vaccine as the main barrier to vaccine receipt (47.6 vs. 12.5%, pLatinos in an understudied region and complement prior research in other regions. This study may have implications for designing culturally tailored interventions to improve uptake of the HPV vaccine among the growing population of Latinos in Utah, and other states in the Intermountain West.

  7. New DNA-binding radioprotectors

    Science.gov (United States)

    Martin, Roger

    The normal tissue damage associated with cancer radiotherapy has motivated the development at Peter Mac of a new class of DNA-binding radioprotecting drugs that could be applied top-ically to normal tissues at risk. Methylproamine (MP), the lead compound, reduces radiation induced cell kill at low concentrations. For example, experiments comparing the clonogenic survival of transformed human keratinocytes treated with 30 micromolar MP before and dur-ing various doses of ionising radiation, with the radiation dose response for untreated cells, indicate a dose reduction factor (DRF) of 2. Similar survival curve experiments using various concentrations of MP, with parallel measurements of uptake of MP into cell nuclei, have en-abled the relationship between drug uptake and extent of radioprotection to be established. Radioprotection has also been demonstrated after systemic administration to mice, for three different endpoints, namely lung, jejunum and bone marrow (survival at 30 days post-TBI). The results of pulse radiolysis studies indicated that the drugs act by reduction of transient radiation-induced oxidative species on DNA. This hypothesis was substantiated by the results of experiments in which MP radioprotection of radiation-induced DNA double-strand breaks, assessed as -H2AX foci, in the human keratinocyte cell line. For both endpoints, the extent of radioprotection increased with MP concentration up to a maximal value. These results are consistent with the hypothesis that radioprotection by MP is mediated by attenuation of the extent of initial DNA damage. However, although MP is a potent radioprotector, it becomes cytotoxic at higher concentrations. This limitation has been addressed in an extensive program of lead optimisation and some promising analogues have emerged from which the next lead will be selected. Given the clinical potential of topical radioprotection, the new analogues are being assessed in terms of delivery to mouse oral mucosa. This is

  8. Synthesis and DNA-binding study of imidazole linked thiazolidinone derivatives.

    Science.gov (United States)

    War, Javeed Ahmad; Srivastava, Santosh Kumar; Srivastava, Savitri Devi

    2017-02-01

    A novel series of imidazole-linked thiazolidinone hybrid molecules were designed and synthesized through a feasible synthetic protocol. The molecules were characterized with Fourier transform infrared (FT-IR), 1 H nuclear magnetic resonance (NMR), 13 C NMR and high-resolution mass spectrometry (HRMS) techniques. In vitro susceptibility tests against Gram-positive (S. aureus and B. subtilis) and Gram-negative bacteria (E. coli and P. aeruginosa) gave highly promising results. The most active molecule (3e) gave a minimal inhibitory concentration (MIC) value of 3.125 μg/mL which is on par with the reference drug streptomycin. Structure-activity relationships revealed activity enhancement by nitro and chloro groups when they occupied meta position of the arylidene ring in 2-((3-(imidazol-1-yl)propyl)amino)-5-benzylidenethiazolidin-4-ones. DNA-binding study of the most potent molecule 3e with salmon milt DNA (sm-DNA) under simulated physiological pH was probed with UV-visible absorption, fluorescence quenching, gel electrophoresis and molecular docking techniques. These studies established that compound 3e has a strong affinity towards DNA and binds at DNA minor groove with a binding constant (K b ) 0.18 × 10 2  L mol -1 . Molecular docking simulations predicted strong affinity of 3e towards DNA with a binding affinity (ΔG) -8.5 kcal/mol. Van der Waals forces, hydrogen bonding and hydrophobic interactions were predicted as the main forces of interaction. The molecule 3e exhibited specific affinity towards adenine-thiamine base pairs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Binding of (/sup 3/H)imipramine to human platelet membranes with compensation for saturable binding to filters and its implication for binding studies with brain membranes

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, O.M.; Wood, K.M.; Williams, D.C.

    1984-08-01

    Apparent specific binding of (/sup 3/H)imipramine to human platelet membranes at high concentrations of imipramine showed deviation from that expected of a single binding site, a result consistent with a low-affinity binding site. The deviation was due to displaceable, saturable binding to the glass fibre filters used in the assays. Imipramine, chloripramine, desipramine, and fluoxetine inhibited binding to filters whereas 5-hydroxytryptamine and ethanol were ineffective. Experimental conditions were developed that eliminated filter binding, allowing assay of high- and low-affinity binding to membranes. Failure to correct for filter binding may lead to overestimation of binding parameters, Bmax and KD for high-affinity binding to membranes, and may also be misinterpreted as indicating a low-affinity binding component in both platelet and brain membranes. Low-affinity binding (KD less than 2 microM) of imipramine to human platelet membranes was demonstrated and its significance discussed.

  10. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    KAUST Repository

    Evoli, Stefania

    2016-11-10

    Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow\\'s drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.

  11. Thermodynamics of ligand binding to acyl-coenzyme A binding protein studied by titration calorimetry

    DEFF Research Database (Denmark)

    Færgeman, Nils J.; Sigurskjold, B W; Kragelund, B B

    1996-01-01

    Ligand binding to recombinant bovine acyl-CoA binding protein (ACBP) was examined using isothermal microcalorimetry. Microcalorimetric measurements confirm that the binding affinity of acyl-CoA esters for ACBP is strongly dependent on the length of the acyl chain with a clear preference for acyl-...

  12. Identification of Glossina morsitans morsitans odorant binding ...

    African Journals Online (AJOL)

    Tsetse flies are vectors of trypanosome parasites, causative agents of Trypanosomiasis in humans and animals. Odorant Binding Proteins (OBPs) are critical in insect olfaction as they bind volatile odours from the environment and transport them to receptors within olfactory receptor neurons for processing providing critical ...

  13. Triazatriangulene as binding group for molecular electronics

    DEFF Research Database (Denmark)

    Wei, Zhongming; Wang, Xintai; Borges, Anders

    2014-01-01

    The triazatriangulene (TATA) ring system was investigated as a binding group for tunnel junctions of molecular wires on gold surfaces. Self-assembled monolayers (SAMs) of TATA platforms with three different lengths of phenylene wires were fabricated, and their electrical conductance was recorded ...... with its high stability and directionality make this binding group very attractive for molecular electronic measurements and devices. (Figure Presented)....

  14. Localization-enhanced biexciton binding in semiconductors

    DEFF Research Database (Denmark)

    Langbein, Wolfgang Werner; Hvam, Jørn Märcher

    1999-01-01

    The influence of excitonic localization on the binding energy of biexcitons is investigated for quasi-three-dimensional and quasi-two-dimensional AlxGa1-xAs structures. An increase of the biexciton binding energy is observed for localization energies comparable to or larger than the free biexcito...

  15. Binding of corroded ions to human saliva.

    Science.gov (United States)

    Mueller, H J

    1985-05-01

    Employing equilibrium dialysis, the binding abilities of Cu, Al, Co and Cr ions from corroded Cu-Al and Co-Cr dental casting alloys towards human saliva and two of its gel chromatographic fractions were determined. Results indicate that both Cu and Co bind to human saliva i.e. 0.045 and 0.027 mg/mg protein, respectively. Besides possessing the largest binding ability, Cu also possessed the largest binding capacity. The saturation of Cu binding was not reached up to the limit of 0.35 mg protein/ml employed in the tests, while Co reached full saturation at about 0.2 mg protein/ml. Chromium showed absolutely no binding to human saliva while Al ions did not pass through the dialysis membranes. Compared to the binding with solutions that were synthetically made up to contain added salivary-type proteins, it is shown that the binding to human saliva is about 1 order of magnitude larger, at least for Cu ions.

  16. Intentional binding of visual effects.

    Science.gov (United States)

    Ruess, Miriam; Thomaschke, Roland; Kiesel, Andrea

    2018-04-01

    When an action produces an effect, the effect is perceived earlier in time compared to a stimulus without preceding action. This temporal bias is called intentional binding (IB) and serves as an implicit measure of sense of agency. Typically, IB is investigated by presenting a rotating clock hand while participants execute an action and perceive a resulting tone. Participants are asked to estimate the time point of tone onset by referring to the clock hand position. This time point estimate is compared to a time point estimate of a tone in a condition in which the tone occurs without preceding action. Studies employing this classic clock paradigm employed auditory action effects. We modified this paradigm to investigate potential IB of visual action effects, and, additionally, to investigate how IB differs for visual action effects (Experiment 1) in comparison to auditory action effects (Experiment 2). Our results show that, like the IB of an auditory effect, the time point of a visual action effect is shifted toward the causing action, and that the size of the IB depends on the delay duration of the effect. Comparable to auditory action effects, earlier action effects showed stronger IB compared to later action effects. Yet overall IB of the visual effects was weaker than IB of the auditory effects. As IB is seen as an indicator of sense of agency, this may have important implications for the design of human-machine interfaces.

  17. Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to human serum albumin.

    Science.gov (United States)

    Zhang, Yao; Lee, Philbert; Liang, Shichu; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

    2015-11-01

    Human serum albumin (HSA) is the most abundant protein in plasma, which plays a central role in drug pharmacokinetics because most compounds bound to HSA in blood circulation. To understand binding characterization of non-steroidal anti-inflammatory drugs to HSA, we resolved the structure of diclofenac and HSA complex by X-ray crystallography. HSA-palmitic acid-diclofenac structure reveals two distinct binding sites for three diclofenac in HSA. One diclofenac is located at the IB subdomain, and its carboxylate group projects toward polar environment, forming hydrogen bond with one water molecule. The other two diclofenac molecules cobind in big hydrophobic cavity of the IIA subdomain without interactive association. Among them, one binds in main chamber of big hydrophobic cavity, and its carboxylate group forms hydrogen bonds with Lys199 and Arg218, as well as one water molecule, whereas another diclofenac binds in side chamber, its carboxylate group projects out cavity, forming hydrogen bond with Ser480. © 2015 John Wiley & Sons A/S.

  18. Thermodynamics of ligand binding to histone deacetylase like amidohydrolase from Bordetella/Alcaligenes.

    Science.gov (United States)

    Meyners, Christian; Baud, Matthias G J; Fuchter, Matthew J; Meyer-Almes, Franz-Josef

    2014-03-01

    Thermodynamic studies on ligand-protein binding have become increasingly important in the process of drug design. In combination with structural data and molecular dynamics simulations, thermodynamic studies provide relevant information about the mode of interaction between compounds and their target proteins and therefore build a sound basis for further drug optimization. Using the example of histone deacetylases (HDACs), particularly the histone deacetylase like amidohydrolase (HDAH) from Bordetella/Alcaligenes, a novel sensitive competitive fluorescence resonance energy transfer-based binding assay was developed and the thermodynamics of interaction of both fluorescent ligands and inhibitors to histone deacetylase like amidohydrolase were investigated. The assay consumes only small amounts of valuable target proteins and is suitable for fast kinetic and mechanistic studies as well as high throughput screening applications. Binding affinity increased with increasing length of aliphatic spacers (n = 4-7) between the hydroxamate moiety and the dansyl head group of ligand probes. Van't Hoff plots revealed an optimum in enthalpy contribution to the free energy of binding for the dansyl-ligand with hexyl spacer. The selectivity in the series of dansyl-ligands against human class I HDAC1 but not class II HDACs 4 and 6 increased with the ratio of ΔH(0)/ΔG(0). The data clearly emphasize the importance of thermodynamic signatures as useful general guidance for the optimization of ligands or rational drug design. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Characterization of chlorophyll binding to LIL3.

    Science.gov (United States)

    Mork-Jansson, Astrid Elisabeth; Eichacker, Lutz Andreas

    2018-01-01

    The light harvesting like protein 3 (LIL 3) from higher plants, has been linked to functions in chlorophyll and tocopherol biosynthesis, photo-protection and chlorophyll transfer. However, the binding of chlorophyll to LIL3 is unclear. We present a reconstitution protocol for chlorophyll binding to LIL3 in DDM micelles. It is shown in the absence of lipids and carotenoids that reconstitution of chlorophyll binding to in vitro expressed LIL3 requires pre-incubation of reaction partners at room temperature. We show chlorophyll a but not chlorophyll b binding to LIL3 at a molar ratio of 1:1. Neither dynamic light scattering nor native PAGE, enabled a discrimination between binding of chlorophyll a and/or b to LIL3.

  20. (TH) diazepam binding to human granulocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bond, P.A.; Cundall, R.L.; Rolfe, B.

    1985-07-08

    (TH)-diazepam binds to sites on human granulocyte membranes, with little or no binding to platelets or lymphocytes. These (TH)-diazepam binding sites are of the peripheral type, being strongly inhibited by R05-4864 (Ki=6.23nM) but only weakly by clonazepam (Ki=14 M). Binding of (TH) diazepam at 0 is saturable, specific and stereoselective. Scatchard analysis indicates a single class of sites with Bmax of 109 +/- 17f moles per mg of protein and K/sub D/ of 3.07 +/- 0.53nM. Hill plots of saturation experiments gave straight lines with a mean Hill coefficient of 1.03 +/- 0.014. Binding is time dependent and reversible and it varies linearly with granulocyte protein concentration over the range 0.025-0.300 mg of protein. 11 references, 3 figures, 1 table.

  1. Factor VIIa binding and internalization in hepatocytes

    DEFF Research Database (Denmark)

    Hjortoe, G; Sorensen, B B; Petersen, L C

    2005-01-01

    The liver is believed to be the primary clearance organ for coagulation proteases, including factor VIIa (FVIIa). However, at present, clearance mechanisms for FVIIa in liver are unknown. To obtain information on the FVIIa clearance mechanism, we investigated the binding and internalization...... no effect. HEPG2 cells internalized FVIIa with a rate of 10 fmol 10(-5) cells h(-1). In contrast to HEPG2 cells, FVIIa binding to primary rat hepatocytes was completely independent of TF, and excess unlabeled FVIIa partly reduced the binding of 125I-FVIIa to rat hepatocytes. Further, compared with HEPG2...... cells, three- to fourfold more FVIIa bound to rat primary hepatocytes, and the bound FVIIa was internalized at a faster rate. Similar FVIIa binding and internalization profiles were observed in primary human hepatocytes. Plasma inhibitors had no effect on FVIIa binding and internalization in hepatocytes...

  2. Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors

    DEFF Research Database (Denmark)

    Heegaard, Anne-Marie; Xie, Zhongjian; Young, Marian Frances

    2004-01-01

    . In this study, we have investigated the mechanism by which TGF-beta(1), TGF-beta(2) and TGF-beta(3) stimulate biglycan mRNA expression in the osteoblastic cell line MG-63. The cells were transfected with a series of deletional human biglycan promoter constructs and a region in the biglycan 5' DNA was found...... to respond to TGF-beta(1) with increased transcriptional activity in a dose-dependent manner. Also TGF-beta(2) and TGF-beta(3), two structurally highly related TGF-beta isoforms stimulated biglycan transcription. A TGF-beta responsive region was identified within the first 218 bp of the human biglycan...... was abrogated by mithramycin, an inhibitor of Sp1 binding to GC-rich DNA sequences. A mutation in the Sp1 site at -216 to -208 within the -218 biglycan promoter construct substantially diminished the transcriptional up-regulation by TGF-beta(1). Taken together this data shows for the first time that TGF-beta(1...

  3. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

    International Nuclear Information System (INIS)

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M.; Heery, David M.

    2010-01-01

    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBPΔ998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.

  4. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M. [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Heery, David M., E-mail: david.heery@nottingham.ac.uk [Gene Regulation Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)

    2010-01-01

    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBP{Delta}998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.

  5. Mid- to late Holocene climate-driven regime shifts inferred from diatom, ostracod and stable isotope records from Lake Son Kol (Central Tian Shan, Kyrgyzstan)

    Science.gov (United States)

    Schwarz, Anja; Turner, Falko; Lauterbach, Stefan; Plessen, Birgit; Krahn, Kim J.; Glodniok, Sven; Mischke, Steffen; Stebich, Martina; Witt, Roman; Mingram, Jens; Schwalb, Antje

    2017-12-01

    Arid Central Asia represents a key region for understanding climate variability and interactions in the Northern Hemisphere. Patterns and mechanisms of Holocene climate change in arid Central Asia are, however, only partially understood. Multi-proxy data combining diatom, ostracod, sedimentological, geochemical and stable isotope analyses from a ca. 6000-year-old lake sediment core from Son Kol (Central Kyrgyzstan) show distinct and repeated changes in species assemblages. Diatom- and ostracod-inferred conductivity shifts between meso-euhaline and freshwater conditions suggest water balance and regime shifts. Organism-derived data are corroborated by stable isotope, mineralogical and geochemical records, underlining that Son Kol was affected by strong lake level fluctuations of several meters. The δ13Ccarb/δ18Ocarb correlation shows repeated switchovers from a closed to an open lake system. From 6000 to 3800 and 3250 to 1950 cal. yr BP, Son Kol was a closed basin lake with higher conductivities, increased nutrient availability and a water level located below the modern outflow. Son Kol became again a hydrologically open lake at 3800 and 1950 cal. yr BP. Comparisons to other local and regional paleoclimate records indicate that these regime shifts were largely controlled by changing intensity and position of the Westerlies and the Siberian Anticyclone that triggered changes in the amount of winter precipitation. A strong influence of the Westerlies ca. 5000-4400, 3800-3250 and since 1950 cal. yr BP enhanced the amount of precipitation during spring, autumn and winter, whereas cold and dry winters prevailed during phases with a strong Siberian Anticyclone and southward shifted Westerlies at ca. 6000-5000, 4400-3800 and 3250-1950 cal. yr BP. Similarities between variations in winter precipitation at Son Kol and records of the predominant NAO-mode further suggest a teleconnection between wet (dry) winter climate in Central Asia and a positive (negative) NAO

  6. Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

    Directory of Open Access Journals (Sweden)

    Bo Young Nam

    2017-06-01

    Full Text Available Peritoneal fibrosis is a major complication in peritoneal dialysis (PD patients, which leads to dialysis discontinuation. Periostin, increased by transforming growth factor β1 (TGF-β1 stimulation, induces the expression of extracellular matrix (ECM genes. Aberrant periostin expression has been demonstrated to be associated with PD-related peritoneal fibrosis. Therefore, the effect of periostin inhibition by an aptamer-based inhibitor on peritoneal fibrosis was evaluated. In vitro, TGF-β1 treatment upregulated periostin, fibronectin, α-smooth muscle actin (α-SMA, and Snail expression and reduced E-cadherin expression in human peritoneal mesothelial cells (HPMCs. Periostin small interfering RNA (siRNA treatment ameliorated the TGF-β1-induced periostin, fibronectin, α-SMA, and Snail expression and restored E-cadherin expression in HPMCs. Similarly, the periostin-binding DNA aptamer (PA also attenuated fibronectin, α-SMA, and Snail upregulation and E-cadherin downregulation in TGF-β1-stimulated HPMCs. In mice treated with PD solution for 4 weeks, the expression of periostin, fibronectin, α-SMA, and Snail was significantly increased in the peritoneum, whereas E-cadherin expression was significantly decreased. The thickness of the submesothelial layer and the intensity of Masson’s trichrome staining in the PD group were significantly increased compared to the untreated group. These changes were significantly abrogated by the intraperitoneal administration of PA. These findings suggest that PA can be a potential therapeutic strategy for peritoneal fibrosis in PD patients.

  7. Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.

    Science.gov (United States)

    Osaki, Takashi; Ozaki, Mineo; Takamura, Norito; Ogata, Kenji; Tokunaga, Jin; Setoguchi, Nao; Arimori, Kazuhiko

    2014-05-01

    Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients. The binding of diclofenac to albumin was investigated in the aqueous humor. In a diclofenac binding assay with albumin in the aqueous humor of individual patients, diclofenac was extracted from aliquots of the aqueous humor, and its total levels were measured using ultra high performance liquid chromatography (UHPLC). Free diclofenac levels were measured using ultrafiltration and UHPLC. The albumin-binding fraction of diclofenac was 0.8 or higher in the aqueous humor of some patients. Ibuprofen significantly inhibited diclofenac binding to site II of albumin in mimic aqueous humor, but not in pooled aqueous humor. This difference may have been due to the weak binding of diclofenac to site II in the pooled aqueous humor. Flurbiprofen was used instead of diclofenac. Flurbiprofen has been shown to bind more strongly than diclofenac to the same site of albumin. Thus, the inhibitory effect of ibuprofen on the binding of flurbiprofen to albumin was investigated in pooled aqueous humor. The results indicated that ibuprofen significantly inhibited the flurbiprofen binding. An effective diclofenac administration method may be established for clinical application by the instillation of an appropriate inhibitor of binding to the albumin site II. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  9. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    International Nuclear Information System (INIS)

    Gangi Setty, Thanuja; Cho, Christine; Govindappa, Sowmya; Apicella, Michael A.; Ramaswamy, S.

    2014-01-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states

  10. Specific insulin binding in bovine chromaffin cells; demonstration of preferential binding to adrenalin-storing cells

    International Nuclear Information System (INIS)

    Serck-Hanssen, G.; Soevik, O.

    1987-01-01

    Insulin binding was studied in subpopulations of bovine chromaffin cells enriched in adrenalin-producing cells (A-cells) or noradrenalin-producing cells (NA-cells). Binding of 125 I-insulin was carried out at 15 0 C for 3 hrs in the absence or presence of excess unlabeled hormone. Four fractions of cells were obtained by centrifugation on a stepwise bovine serum albumin gradient. The four fractions were all shown to bind insulin in a specific manner and the highest binding was measured in the cell layers of higher densities, containing mainly A-cells. The difference in binding of insulin to the four subpopulations of chromaffin cells seemed to be related to differences in numbers of receptors as opposed to receptor affinities. The authors conclude that bovine chromaffin cells possess high affinity binding sites for insulin and that these binding sites are mainly confined to A-cells. 24 references, 2 figures, 1 table

  11. Sodium Phenylbutyrate Enhances Astrocytic Neurotrophin Synthesis via Protein Kinase C (PKC)-mediated Activation of cAMP-response Element-binding Protein (CREB)

    Science.gov (United States)

    Corbett, Grant T.; Roy, Avik; Pahan, Kalipada

    2013-01-01

    Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are believed to be genuine molecular mediators of neuronal growth and homeostatic synapse activity. However, levels of these neurotrophic factors decrease in different brain regions of patients with Alzheimer disease (AD). Induction of astrocytic neurotrophin synthesis is a poorly understood phenomenon but represents a plausible therapeutic target because neuronal neurotrophin production is aberrant in AD and other neurodegenerative diseases. Here, we delineate that sodium phenylbutyrate (NaPB), a Food and Drug Administration-approved oral medication for hyperammonemia, induces astrocytic BDNF and NT-3 expression via the protein kinase C (PKC)-cAMP-response element-binding protein (CREB) pathway. NaPB treatment increased the direct association between PKC and CREB followed by phosphorylation of CREB (Ser133) and induction of DNA binding and transcriptional activation of CREB. Up-regulation of markers for synaptic function and plasticity in cultured hippocampal neurons by NaPB-treated astroglial supernatants and its abrogation by anti-TrkB blocking antibody suggest that NaPB-induced astroglial neurotrophins are functionally active. Moreover, oral administration of NaPB increased the levels of BDNF and NT-3 in the CNS and improved spatial learning and memory in a mouse model of AD. Our results highlight a novel neurotrophic property of NaPB that may be used to augment neurotrophins in the CNS and improve synaptic function in disease states such as AD. PMID:23404502

  12. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras tan pobres?

    Directory of Open Access Journals (Sweden)

    Abel Ignacio López

    2001-01-01

    Full Text Available Landes, David. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras son tan pobres?, Barcelona, Editorial Crítica, 1999, 604 páginas. ¿Porqué hay naciones pobres y naciones ricas y cuál es la contribución de la historia en la comprensión de esta cuestión? El autor entiende por cultura el espíritu de empresa, el conjunto de valores que guían la conducta de una población, el dominio de la ciencia, la tecnología y el espíritu racional.

  13. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras tan pobres?

    OpenAIRE

    Abel Ignacio López

    2010-01-01

    Landes, David. La riqueza y la pobreza de las naciones. ¿Por qué algunas son tan ricas y otras son tan pobres?, Barcelona, Editorial Crítica, 1999, 604 páginas. ¿Porqué hay naciones pobres y naciones ricas y cuál es la contribución de la historia en la comprensión de esta cuestión? El autor entiende por cultura el espíritu de empresa, el conjunto de valores que guían la conducta de una población, el dominio de la ciencia, la tecnología y el espíritu racional.

  14. The association between an abusive father-son relationship, quantity of alcohol consumption, and male-to-male alcohol-related aggression.

    Science.gov (United States)

    Miller, Peter; Hargreaves, Jessica; Curtis, Ashlee; Zinkiewicz, Lucy

    2013-09-01

    While alcohol consumption and heavy episodic (binge) drinking are well-established predictors of male-to-male alcohol-related aggression (MMARA), the role of the father-son relationship in MMARA has yet to be explored. This study therefore examined whether fathering by the biological father rather than another father figure, negative fathering, and gender role modeled by the father figure were significant predictors of involvement in MMARA, once drinking frequency and quantity and heavy episodic drinking were controlled for. A total of 121 university students aged 18 to 25 years (M = 20.63, SD = 1.77 years) voluntarily completed the online questionnaire. The only significant predictors of perpetration of MMARA were a more abusive paternal relationship and drinking quantity (number of standard drinks usually consumed when drinking). Negative father-son relationships may play a role in fostering young men's perpetration of MMARA in the barroom context. Copyright © 2013 by the Research Society on Alcoholism.

  15. Evaluación de anemia ferropénica en la primera infancia del Municipio de Sonsón-Antioquia, 2007

    OpenAIRE

    Castillo Salgado, Tulia Isabel; Pérez Escobar, Rocío

    2014-01-01

    Objetivo: Determinar la prevalencia de anemia por deficiencia de hierro en niños de la primera infancia del municipio de Sonsón – Antioquia, en el año 2007. Metodología: Se realizó un estudio descriptivo transversal en 391 niños de 0 a 84 meses de edad del Municipio de Sonsón, Antioquia. Se estudiaron los parámetros de hemoglobina y ferritina sérica utilizando puntos de corte de la Organización Mundial de la Salud (OMS). Se calcularon las medidas de frecuencia y de resumen y los intervalos de...

  16. Parental choice: what parents want in a son-in-law and a daughter-in-law across 67 pre-industrial societies.

    Science.gov (United States)

    Apostolou, Menelaos

    2010-11-01

    Parents are influential over mate choice, and in most human societies they choose spouses for their offspring according to their own preferences. However, surprising little is known about the qualities which make a woman desirable as a daughter-in-law and a man desirable as a son-in-law. Using evidence from 67 societies such traits are identified and three hypotheses are tested: first, the hypothesis is tested that parents desire in an in-law qualities which are beneficial to them and their kin. Second, it is hypothesized that such preferences are contingent upon the sex of the in-law, as traits are weighted differently in a daughter-in-law and in a son-in-law. The third hypothesis tested is that parental preferences vary according to the subsistence type of a given society, as traits are valued differently in agropastoral societies and foraging societies. The evidence presented here provides support for all three hypotheses.

  17. Human liver aldehyde dehydrogenase: coenzyme binding

    International Nuclear Information System (INIS)

    Kosley, L.L.; Pietruszko, R.

    1987-01-01

    The binding of [U- 14 C] NAD to mitochondrial (E2) and cytoplasmin(E1) aldehyde dehydrogenase was measured by gel filtration and sedimentation techniques. The binding data for NAD and (E1) yielded linear Scatchard plots giving a dissociation constant of 25 (+/- 8) uM and the stoichiometry of 2 mol of NAD bound per mol of E1. The binding data for NAD and (E2) gave nonlinear Scatchard plots. The binding of NADH to E2 was measured via fluorescence enhancement; this could not be done with E1 because there was no signal. The dissociation constant for E2 by this technique was 0.7 (+/- 0.4) uM and stoichiometry of 1.0 was obtained. The binding of [U- 14 C] NADH to (E1) and (E2) was also measured by the sedimentation technique. The binding data for (E1) and NADH gave linear Scatchard plots giving a dissociation constant of 13 (+/- 6) uM and the stoichiometry of 2.0. The binding data for NADH to (E2) gave nonlinear Scatchard plots. With (E1), the dissociation constants for both NAD and NADH are similar to those determined kinetically, but the stoichiometry is only half of that found by stopped flow technique. With (E2) the dissociation constant by fluorometric procedure was 2 orders of magnitude less than that from catalytic reaction

  18. Increased thyrotropin binding in hyperfunctioning thyroid nodules.

    Science.gov (United States)

    Müller-Gärtner, H W; Schneider, C; Bay, V; Tadt, A; Rehpenning, W; de Heer, K; Jessel, M

    1987-08-01

    The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

  19. 现代文明中的爱情悲剧%The Traglc Love in Modern Civilization·On lawrence's Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    曾文雄

    2001-01-01

    Lawrence's Sons and Lover reflects the people in modern civilization are killed off their capacity and emotions to respond to the natural beauty and the loveliness in the human being. There are conflicts in pursuing :instinct, rationality and spirituality.Through the discussion on the hero's tragiclove stories, we can find only if hese conflicts can be solved,perfect humanity will be gained·

  20. Yo no soy marinero, soy capitán:Usos sociopolíticos contemporáneos del fandango y el son jarocho

    Directory of Open Access Journals (Sweden)

    Rafael Figueroa­ Hernández

    2015-01-01

    Siguiendo las reglas musicales y líricas tradicionales del son jarocho, un creciente grupo de personas han estado usando el fandango como una manera de participar en protestas sociales de varias maneras: a creando o manteniendo identidad entre grupos subalternos, b diseminando ideas políticas y sociales a través de letras basadas en formas tradicionales y c mediante la participación directa en manifestaciones y marchas entre otras.