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Sample records for abrogates son binding

  1. Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4

    Directory of Open Access Journals (Sweden)

    Bryant Nia J

    2011-05-01

    Full Text Available Abstract Background Insulin stimulates exocytosis of GLUT4 from an intracellular store to the cell surface of fat and muscle cells. Fusion of GLUT4-containing vesicles with the plasma membrane requires the SNARE proteins Syntaxin 4, VAMP2 and the regulatory Sec1/Munc18 protein, Munc18c. Syntaxin 4 and Munc18c form a complex that is disrupted upon insulin treatment of adipocytes. Munc18c is tyrosine phosphorylated in response to insulin in these cells. Here, we directly test the hypothesis that tyrosine phosphorylation of Munc18c is responsible for the observed insulin-dependent abrogation of binding between Munc18c and Syntaxin 4. Results We show that Munc18c is directly phosphorylated by recombinant insulin receptor tyrosine kinase in vitro. Using pull-down assays, we show that phosphorylation abrogates binding of Munc18c to both Syntaxin 4 and the v-SNARE VAMP2, as does the introduction of a phosphomimetic mutation into Munc18c (Y521E. Conclusion Our data indicate that insulin-stimulated tyrosine phosphorylation of Munc18c impairs the ability of Munc18c to bind its cognate SNARE proteins, and may therefore represent a regulatory step in GLUT4 traffic.

  2. HCV NS5A abrogates p53 protein function by interfering with p53-DNA binding

    Institute of Scientific and Technical Information of China (English)

    Guo-Zhong Gong; Yong-Fang Jiang; Yan He; Li-Ying Lai; Ying-Hua Zhu; Xian-Shi Su

    2004-01-01

    AIM: To evaluate the inhibition effect of HCV NS5A on p53 transactivation on p21 promoter and explore its possible mechanism for influencing p53 function.METHODS: p53 function of transactivation on p21 promoter was studied with a luciferase reporter system in which the luciferase gene is driven by p21 promoter, and the p53-DNA binding ability was observed with the use of electrophoretic mobility-shift assay (EMSA). Lipofectin mediated p53 or HCV NS5A expression vectors were used to transfect hepatoma cell lines to observe whether HCV NS5A could abrogate the binding ability of p53 to its specific DNA sequence and p53 transactivation on p21 promoter.Western blot experiment was used for detection of HCV NS5A and p53 proteins expression.RESULTS: Relative luciferase activity driven by p21 promoter increased significantly in the presence of endogenous p53 protein. Compared to the control group, exogenous p53 protein also stimulated p21 promoter driven luciferase gene expression in a dose-dependent way. HCV NS5A protein gradually inhibited both endogenous and exogenous p53 transactivation on p21 promoter with increase of the dose of HCV NS5A expression plasmid. By the experiment of EMSA, we could find p53 binding to its specific DNA sequence and, when co-transfected with increased dose of HCV NS5A expression vector, the p53 binding affinity to its DNA gradually decreased and finally disappeared. Between the Huh 7 cells transfected with p53 expression vector alone or co-transfected with HCV NS5A expression vector, there was no difference in the p53 protein expression.CONCLUSION: HCV NS5A inhibits p53 transactivation on p21 promoter through abrogating p53 binding affinity to its specific DNA sequence. It does not affect p53 protein expression.

  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.

    2015-01-01

    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 A2 receptor (TxA2R) 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 TxA2R. In Chinese hamster ovary-K1 cells expressing the variant D304N TxA2R, U46619 did not increase cytosolic free Ca2+ concentration, indicating loss of receptor function. The TxA2R antagonist [3H]-SQ29548 showed an approximate 50% decrease in binding to platelets from P1 but absent binding to Chinese hamster ovary-K1 cells expressing variant D304N TxA2R. This is the second naturally occurring TxA2R 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 TxA2R 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 TxA2R function in vivo. PMID:19828703

  5. A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction.

    Science.gov (United States)

    Haan, C; Hermanns, H M; Heinrich, P C; Behrmann, I

    2000-07-01

    gp130 is the common signal-transducing receptor chain of interleukin (IL)-6-type cytokines. Here we describe, for the first time, a single amino acid substitution (Trp(666)-->Ala) in the membrane-proximal interbox1/2 region that abrogates activation of STAT (signal transducer and activator of transcription) transcription factors and the proliferative response of pro-B-cell transfectants. Moreover, association of the Janus kinase JAK1 is prevented. No signalling of heterodimeric IL-5 receptor (IL-5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp130 dimer contains the Trp(666)Ala mutation, indicating that it acts dominantly.

  6. Son: Part One

    Directory of Open Access Journals (Sweden)

    Jennifer Higgie

    2004-08-01

    Full Text Available It is 1842. Two Englishman set out on a Grand Tour of Europe and the Middle East. One is a young, gifted artist; the other a Gentleman. By the time they return to England, the artist has become a devotee of the Egyptian god Osiris. One night, after dining together in a small inn in Cobham, he violently murders his beloved father, believing him to be an imposter. Why? Son is a novel inspired by the life of Richard Dadd, one of the greatest Victorian painters and inmate of Bethlem Hospital - more commonly known as Bedlam. Part Two of Son will be published in Portal vol. 2, no. 1, January 2005.

  7. Son: Part Two

    Directory of Open Access Journals (Sweden)

    Jennifer Higgie

    2005-03-01

    Full Text Available It is 1842. Two Englishman set out on a Grand Tour of Europe and the Middle East. One is a young, gifted artist; the other a Gentleman. By the time they return to England, the artist has become a devotee of the Egyptian god Osiris. One night, after dining together in a small inn in Cobham, he violently murders his beloved father, believing him to be an imposter. Why? Son is a novel inspired by the life of Richard Dadd, one of the greatest Victorian painters and inmate of Bethlem Hospital - more commonly known as Bedlam. Part one of Son was published in PORTAL vol. 1, no. 2, in July 2004. This is the second and concluding part of the novel.

  8. 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.

  9. À chacun son puzzle

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    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

  10. Nutritional abrogation of photoimmunosuppression: in vivo investigations.

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    Pilkington, Suzanne M; Gibbs, Neil K; Friedmann, Peter S; Rhodes, Lesley E

    2014-01-01

    Skin cancer is a major public health concern, and the primary aetiological factor in the majority of skin cancers is ultraviolet radiation (UVR) exposure. UVR not only induces potentially mutagenic DNA damage but also suppresses cell-mediated immunity (CMI), allowing cancerous cells to escape destruction and progress to tumours. A considerable proportion of an individual's annual sun exposure is obtained outside the vacation period when topical and physical measures for photoprotection are irregularly used. Certain nutrients could provide an adjunctive protective role, and evidence is accruing from experimental studies to support their use in abrogation of photoimmunosuppression. Moreover, developments in clinical research methods to evaluate impact of solar-simulated radiation on cutaneous CMI allow the immune protective potential of nutritional agents to be examined in humans in vivo. This article summarises the mediation of CMI and its suppression by UVR, evaluates the methodology for quantitative assessment in vivo, reviews the human studies reported on nutritional abrogation of photoimmunosuppression including recent randomized controlled trials and discusses the mechanisms of photoprotection by the nutrients. This includes, in addition to antioxidants, novel studies of omega-3 polyunsaturated fatty acids and nicotinamide.

  11. Determinants of mitotic catastrophe on abrogation of the G2 DNA damage checkpoint by UCN-01.

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    On, Kin Fan; Chen, Yue; Ma, Hoi Tang; Chow, Jeremy P H; Poon, Randy Y C

    2011-05-01

    Genotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G(2) DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined. In this study, we tracked the fates of individual cells after checkpoint abrogation, focusing in particular on whether they undergo mitotic catastrophe. Surprisingly, while a subset of UCN-01-treated cells were immediately eliminated during the first mitosis after checkpoint abrogation, about half remained viable and progressed into G(1). Both the delay of mitotic entry and the level of mitotic catastrophe were dependent on the dose of radiation. Although the level of mitotic catastrophe was specific for different cell lines, it could be promoted by extending the mitosis. In supporting this idea, weakening of the spindle-assembly checkpoint, by either depleting MAD2 or overexpressing the MAD2-binding protein p31(comet), suppressed mitotic catastrophe. Conversely, delaying of mitotic exit by depleting either p31(comet) or CDC20 tipped the balance toward mitotic catastrophe. These results underscore the interplay between the level of DNA damage and the effectiveness of the spindle-assembly checkpoint in determining whether checkpoint-abrogated cells are eliminated during mitosis.

  12. Sons and daughters in China.

    Science.gov (United States)

    Robey, B

    1985-11-01

    Demographers from the East-West Population Institute (EWPI) and the China State Family Planning Commission, jointly analyzing data from computer tapes of China's 1982 national fertility survey, have produced new evidence of the extent to which families in China prefer male children. Evidence exists in almost every part of China that couples prefer sons to daughters, according to researchers Fred Arnold and Liu Zhaoxiang. Only Beijing and Shanghai are exceptions to this pattern. The persistence of such attidues in China demonstrates the difficulty of overcoming deeply rooted Confucian traditions. Following the Chinese revolution, the government guaranteed sexual equality in political, economic, and cultural life, but patriarchal attitudes still prevail, particularly in the countryside. Historically, couples have favored sons for a variety of reasons, including to continue the family name, provide security for the parents' old age, add to the family labor force, and perform ancestral rites. Believing that such attitudes block successful implementation of China's 1-child family policy, the government has launched a campaign to try to change them. At the time of the time of the 1982 fertility survey, China's 1-child certificate program had been in effect for 3 years. The program provides incentives such as monetary bonuses, preferential housing allocation, and special consideration for the child in education and job assignments to couples who agree not to have a 2nd child. According to the survey, 37% of all 1-child couples had accepted the 1-child certificate. Significantly, 60% of all 1-child certificate holders have a son. Of couples whose 1st child was a boy, 40% obtained the 1-child certificate, versus only 34% of those whose 1st child was a girl. Despite penalties for renouncing the 1-child certificate, about 1 out of every 10 mothers in the program had given birth to a 2nd child by the time of the survey. The 1st child of these mothers was twice as likely to be

  13. Achalasia in father and son.

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    Mackler, D; Schneider, R

    1978-11-01

    Achalasia has not been previously reported in father and son. A man, age 38, and his father, age 66, presented two years apart with symptoms of dysphagia and aspiration. The diagnosis of achalasia was made on the basis of x-ray and endoscopic findings and on esophageal motility studies performed on the father. Both responded well to pneumatic dilatation and have been asymptomatic for 24 months and 6 months, respectively. These cases again suggest a genetic basis for achalasia.

  14. 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...... of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies...

  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. 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.

  17. Son huasteco e identidad regional

    Directory of Open Access Journals (Sweden)

    Rosa María Bonilla Burgos

    2013-01-01

    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.

  18. Are we ready to abrogate compulsory vaccinations for children?

    Science.gov (United States)

    Martinelli, Domenico; Tafuri, Silvio; Fortunato, Francesca; Cozza, Vanessa; Germinario, Cinzia A; Prato, Rosa

    2015-01-01

    In Italy, vaccination against diphtheria, tetanus, polio and hepatitis B is compulsory for infants countrywide, except in Veneto region where since 2007 Health Authorities have experimented the suspension of mandatory vaccination. In light of the recent discussion on the potential abrogation in other regions, we explored the opinion of family pediatricians who play a crucial role in promoting immunization programmes in Italy. In November 2009, we interviewed by phone the family pediatricians working in Puglia region using a standardised, ad hoc and piloted questionnaire. Of the 596 contacted, 502 (84.2%) completed the questionnaire (54% female, median age = 52 y). Among the respondents, 72 (14.3%) would agree on the hypothesis of abrogation. This judgment was associated with having a good opinion on the level of awareness of the importance of vaccinations in the general public (OR = 6.6; 95% CI: 3.6-12.1) and having the perception of adequate organization of Vaccination Services in supporting the abrogation (OR = 3.6; 95% CI: 1.7-5.9). Family pediatricians appeared really sceptical about the abrogation of compulsory vaccination that could be hypothesized only increasing public awareness, communication skills and capability of Vaccination Services personnel in offering vaccinations.

  19. Adult Son-Parent Relationships and Their Associations with Sons' Psychological Distress.

    Science.gov (United States)

    Barnett, Rosalind C.; And Others

    1992-01-01

    Examined relationship between quality of adult sons' experiences in current relationships with parents and sons' psychological distress among 285 sons. Sons who reported positive relationship with their mother or father also reported low psychological distress. Presence or absence of female siblings moderated association between both son-mother…

  20. Policy-based SON management demonstrator

    NARCIS (Netherlands)

    Lohmuller, S.; Eisenblatter, A.; Frenzel, C.; Gotz, D.; Hahn, S.; Kurner, T.; Litjens, R.; Lobinger, A.; Sas, B.; Schmelz, L.C.; Turke, U.

    2015-01-01

    A Self-Organising Network (SON) represents an approach where the optimisation of a mobile radio network is automated through a set of independently operating SON functions. These SON functions, however, require to be configured in order to allow for an optimised network performance with respect to t

  1. New discoveries of old SON: a link between RNA splicing and cancer.

    Science.gov (United States)

    Hickey, Christopher J; Kim, Jung-Hyun; Ahn, Eun-Young Erin

    2014-02-01

    The SON protein is a ubiquitously expressed DNA- and RNA-binding protein primarily localized to nuclear speckles. Although several early studies implicated SON in DNA-binding, tumorigenesis and apoptosis, functional significance of this protein had not been recognized until recent studies discovered SON as a novel RNA splicing co-factor. During constitutive RNA splicing, SON ensures efficient intron removal from the transcripts containing suboptimal splice sites. Importantly, SON-mediated splicing is required for proper processing of selective transcripts related to cell cycle, microtubules, centrosome maintenance, and genome stability. Moreover, SON regulates alternative splicing of RNAs from the genes involved in apoptosis and epigenetic modification. In addition to the role in RNA splicing, SON has an ability to suppress transcriptional activation at certain promoter/enhancer DNA sequences. Considering the multiple SON target genes which are directly involved in cell proliferation, genome stability and chromatin modifications, SON is an emerging player in gene regulation during cancer development and progression. Here, we summarize available information from several early studies on SON, and highlight recent discoveries describing molecular mechanisms of SON-mediated gene regulation. We propose that our future effort on better understanding of diverse SON functions would reveal novel targets for cancer therapy.

  2. Preference for sons: past and present.

    Science.gov (United States)

    Li, D

    1997-10-01

    This brief article discusses the present and past preference for sons in China. The preference for sons is rooted in feudal views that men are superior to women. Preference for sons dates back to the Warring States Period, in about 500 B.C. Clan brotherhoods of men have existed for centuries. Historical records mention the practice of female infanticide. Patriarchal families believed that women were economically dependent on men and thus became their subjects. Daughters married, lived in their husband's home, and did not carry the responsibility of caring for their own parents. Couples with only daughters would seek a son-in-law to support them in old age. Rural families with no sons were looked down upon. Sons were expected to carry on the family lineage, increase the reputation of the family, and protect the family's interests. The lack of sons was a sign of humiliation and a curse. The founding of the People's Republic of China brought changes to son preference. The government attempted to increase women's status. In rural areas, women were given equal access to the land. Job opportunities were created for women during the industrialization drive. The Chinese government encouraged the repudiation of the negative impacts of the doctrines of Confucius and Mencius. Efforts were made to give men and women equal pay for equal work. Legislation was passed prohibiting arranged marriage, polygyny, and early marriage. A side effect of fertility decline is the renewed preference for sons. In Huangyan and Haining in Zhejiang, a developed province, the sex ratio at birth is normal. Sexual division of labor reinforces son preference.

  3. Carbamoylation abrogates the antioxidant potential of hydrogen sulfide.

    Science.gov (United States)

    Praschberger, Monika; Hermann, Marcela; Laggner, Christian; Jirovetz, Leopold; Exner, Markus; Kapiotis, Stylianos; Gmeiner, Bernhard M K; Laggner, Hilde

    2013-11-01

    Hydrogen sulfide (H2S) has been identified as the third gasotransmitter. Beside its role as signaling molecule in the cardiovascular and nervous system the antioxidant and cyto-protective properties of H2S have gained much attention. In the present study we show that cyanate, an uremic toxin which is found in abundant concentration in sera of patients suffering from chronic kidney disease (CKD), can abrogate the antioxidant and cytoprotective activity of H2S via S-carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H2S. Carbamoylation strongly inhibited the free radical scavenging (ABTS(+·) and alkylperoxyl ROO(·)) properties of H2S. The extent of intracellular ROS formation induced by ROO(·) was diminished by H2S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H2S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H2S but carbamoylation significantly reduced the effect. Thus, S-carbamoylation of low molecular weight thiols by abrogating their antioxidant potential may contribute to the higher oxidative stress observed in CKD.

  4. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    Science.gov (United States)

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.

  5. "Mama's Boy; Preacher's Son": A Memoir

    Science.gov (United States)

    Whitlock, Reta Ugena

    2010-01-01

    "Mama's Boy; Preacher's Son" is Kevin Jennings's autobiographical account of growing up gay in the Southern United States. In his memoir, Jennings shares formative experiences relating to his impoverished childhood and his career as teacher and social activist. His rich description of the influence of family relationships on his personal and…

  6. "Mama's Boy; Preacher's Son": A Memoir

    Science.gov (United States)

    Whitlock, Reta Ugena

    2010-01-01

    "Mama's Boy; Preacher's Son" is Kevin Jennings's autobiographical account of growing up gay in the Southern United States. In his memoir, Jennings shares formative experiences relating to his impoverished childhood and his career as teacher and social activist. His rich description of the influence of family relationships on his personal…

  7. 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.

  8. Compression des fichiers son de type wave.

    OpenAIRE

    BAKLI, Meriem

    2014-01-01

    Ce travail de projet de fin d’étude s’intéresse à une étude comparative sur la compression d’un fichier son. La compression est l'action utilisée pour réduire la taille physique d'un bloc d'information.. Il existe plusieurs algorithmes pour la compression comme HUFFMAN, …etc. Nous avons fait la compression d’un fichier son de format WAVE non compressé à un fichier MP3 compressé avec différent format de codage, différent frame et quelque soit le fichier mono où stéréo. A partir ...

  9. Paradox of Denials in All My Sons

    Institute of Scientific and Technical Information of China (English)

    雷慧慧

    2014-01-01

    Arthur Miller, who was one of the greatest American playwrights of the 20th century. In All My Sons, different sorts of denials lead to the family’s collapse and Keller’s death. Paradoxically, the very denial that is designed to protect him from prose-cution and incarceration is followed by a chain of events that lead to Keller’s own self-imprisonment and self-imposed execu-tion. Denial also exists in the history of some countries, such as Germany, Japan and America and so on. My paper aims to ex-plore the paradox of denial both in our history and in literature works. My paper will demonstrate that denial has some negative effects both on the outer-world and the inner-world through thorough analysis on the characters in All My Sons.

  10. 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.

  11. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    Science.gov (United States)

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.

  12. 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.

  13. ?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.

  14. 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.

  15. Abrogation of contaminating RNA activity in HIV-1 Gag VLPs

    Directory of Open Access Journals (Sweden)

    Shephard Enid G

    2011-10-01

    Full Text Available Abstract Background HIV-1 Gag virus like particles (VLPs used as candidate vaccines are regarded as inert particles as they contain no replicative nucleic acid, although they do encapsidate cellular RNAs. During HIV-1 Gag VLP production in baculovirus-based expression systems, VLPs incorporate the baculovirus Gp64 envelope glycoprotein, which facilitates their entry into mammalian cells. This suggests that HIV-1 Gag VLPs produced using this system facilitate uptake and subsequent expression of encapsidated RNA in mammalian cells - an unfavourable characteristic for a vaccine. Methods HIV-1 Gag VLPs encapsidating reporter chloramphenicol acetyl transferase (CAT RNA, were made in insect cells using the baculovirus expression system. The presence of Gp64 on the VLPs was verified by western blotting and RT-PCR used to detect and quantitate encapsidated CAT RNA. VLP samples were heated to inactivate CAT RNA. Unheated and heated VLPs incubated with selected mammalian cell lines and cell lysates tested for the presence of CAT protein by ELISA. Mice were inoculated with heated and unheated VLPs using a DNA prime VLP boost regimen. Results HIV-1 Gag VLPs produced had significantly high levels of Gp64 (~1650 Gp64 molecules/VLP on their surfaces. The amount of encapsidated CAT RNA/μg Gag VLPs ranged between 0.1 to 7 ng. CAT protein was detected in 3 of the 4 mammalian cell lines incubated with VLPs. Incubation with heated VLPs resulted in BHK-21 and HeLa cell lysates showing reduced CAT protein levels compared with unheated VLPs and HEK-293 cells. Mice inoculated with a DNA prime VLP boost regimen developed Gag CD8 and CD4 T cell responses to GagCAT VLPs which also boosted a primary DNA response. Heating VLPs did not abrogate these immune responses but enhanced the Gag CD4 T cell responses by two-fold. Conclusions Baculovirus-produced HIV-1 Gag VLPs encapsidating CAT RNA were taken up by selected mammalian cell lines. The presence of CAT protein indicates

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. Adolescents with Nonresident Fathers: Are Daughters more Disadvantaged than Sons?

    OpenAIRE

    Mitchell, Katherine Stamps; Booth, Alan; KING, VALARIE

    2009-01-01

    This study examined sons' and daughters' involvement with nonresident fathers and associated outcomes (N=4,663). Results indicate that sons and daughters report equal involvement with nonresident fathers on most measures of father investment, although sons report more overnight visits, sports, and movies, and feeling closer to their fathers compared to daughters. Sons and daughters generally benefit from nonresident father involvement in the same way in internalizing and externalizing problem...

  3. Adolescents with Nonresident Fathers: Are Daughters More Disadvantaged than Sons?

    Science.gov (United States)

    Mitchell, Katherine Stamps; Booth, Alan; King, Valarie

    2009-01-01

    This study examined sons' and daughters' involvement with nonresident fathers and associated outcomes (N = 4,663). Results indicated that sons and daughters reported equal involvement with nonresident fathers on most measures of father investment, although sons reported more overnight visits, sports, and movies and feeling closer to their fathers…

  4. Peroxisome proliferator-activated receptor-gamma abrogates Smad-dependent collagen stimulation by targeting the p300 transcriptional coactivator.

    Science.gov (United States)

    Ghosh, Asish K; Bhattacharyya, Swati; Wei, Jun; Kim, Suyeon; Barak, Yaacov; Mori, Yasuji; Varga, John

    2009-09-01

    Ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) abrogate the stimulation of collagen gene transcription induced by transforming growth factor-beta (TGF-beta). Here, we delineate the mechanisms underlying this important novel physiological function for PPAR-gamma in connective tissue homeostasis. First, we demonstrated that antagonistic regulation of TGF-beta activity by PPAR-gamma ligands involves cellular PPAR-gamma, since 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) failed to block TGF-beta-induced responses in either primary cultures of PPAR-gamma-null murine embryonic fibroblasts, or in normal human skin fibroblasts with RNAi-mediated knockdown of PPAR-gamma. Next, we examined the molecular basis underlying the abrogation of TGF-beta signaling by PPAR-gamma in normal human fibroblasts in culture. The results demonstrated that Smad-dependent transcriptional responses were blocked by PPAR-gamma without preventing Smad2/3 activation. In contrast, the interaction between activated Smad2/3 and the transcriptional coactivator and histone acetyltransferase p300 induced by TGF-beta, and the accumulation of p300 on consensus Smad-binding DNA sequences and histone H4 hyperacetylation at the COL1A2 locus, were all prevented by PPAR-gamma. Wild-type p300, but not a mutant form of p300 lacking functional histone acetyltransferase, was able to restore TGF-beta-induced stimulation of COL1A2 in the presence of PPAR-gamma ligands. Collectively, these results indicate that PPAR-gamma blocked Smad-mediated transcriptional responses by preventing p300 recruitment and histone H4 hyperacetylation, resulting in the inhibition of TGF-beta-induced collagen gene expression. Pharmacological activation of PPAR-gamma thus may represent a novel therapeutic approach to target p300-dependent TGF-beta profibrotic responses such as stimulation of collagen gene expression.

  5. Sulforaphane Potentiates the Efficacy of 17-Allylamino 17-Demethoxygeldanamycin Against Pancreatic Cancer Through Enhanced Abrogation of Hsp90 Chaperone Function

    Science.gov (United States)

    Li, Yanyan; Zhang, Tao; Schwartz, Steven J.; Sun, Duxin

    2013-01-01

    Heat shock protein 90 (Hsp90), an essential molecular chaperone that regulates the stability of a wide range of oncogenic proteins, is a promising target for cancer therapeutics. We investigated the combination efficacy and potential mechanisms of sulforaphane, a dietary component from broccoli and broccoli sprouts, and 17-allylamino 17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, in pancreatic cancer. MTS assay demonstrated that sulforaphane sensitized pancreatic cancer cells to 17-AAG in vitro. Caspase-3 was activated to 6.4-fold in response to simultaneous treatment with sulforaphane and 17-AAG, whereas 17-AAG alone induced caspase-3 activity to 2-fold compared to control. ATP binding assay and coimmunoprecipitation revealed that sulforaphane disrupted Hsp90-p50Cdc37 interaction, whereas 17-AAG inhibited ATP binding to Hsp90. Concomitant use of sulforaphane and 17-AAG synergistically downregulated Hsp90 client proteins in Mia Paca-2 cells. Co-administration of sulforaphane and 17-AAG in pancreatic cancer xenograft model led to more than 70% inhibition of the tumor growth, whereas 17-AAG alone only suppressed the tumor growth by 50%. Our data suggest that sulforaphane potentiates the efficacy of 17-AAG against pancreatic cancer through enhanced abrogation of Hsp90 function. These findings provide a rationale for further evaluation of broccoli/broccoli sprout preparations combined with 17-AAG for better efficacy and lower dose-limiting toxicity in pancreatic cancer. PMID:21875325

  6. 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.......2-3.0) examined by the same procedure. Boys of pesticide-exposed mothers showed decreased penile length, testicular volume, serum concentrations of testosterone, and inhibin B. Serum concentrations of sex hormone-binding globulin, follicle-stimulating hormone, and the luteinizing hormone:testosterone ratio were...

  7. Enhancement and abrogation : modifications of host immune status influence IL-2 and LAK cell immunotherapy

    NARCIS (Netherlands)

    E.P. Steller (Erick)

    1988-01-01

    textabstractThis thesis will discuss the role immune cells and the host immune system can play in enhancement and abrogation of this novel immunotherapy with interleukin 2 and lymphokine-activated killer cells. Chapter 3 and 4 will discuss the scoring methods in this intraperitoneal cancer and immun

  8. Is the distant relationship of fathers and homosexual sons related to the sons' erotic preference for male partners, or to the sons' atypical gender identity, or to both?

    Science.gov (United States)

    Freund, K; Blanchard, R

    1983-01-01

    Study 1 compared the retrospectively reported father-son relationships of four groups of adult males: (a) Gynephiles (males who erotically prefer physically mature females), (b) androphiles (who prefer physically mature males), (c) a combined group of heterosexual pedophiles and pedohebephiles (the latter being attracted to pubescent as well as prepubescent females), and (d) a combined group of homosexual pedophiles and pedohebephiles (the latter attracted to pubescent as well as prepubescent males). The gynephiles were paid volunteers; the latter three groups were patients. The androphiles, the only group among those compared known to exhibit a measurably greater degree of cross gender identity in childhood, were also the only group to report significantly poorer father-son relations. The homosexual pedo/pedohebephiles, who also prefer male partners but who exhibit typical male gender identity in childhood, did not differ in father-son relations from the gynephiles or the heterosexual pedo/pedohebephiles. Study 2 showed that, within a sample of nonpatient volunteer androphiles, those individuals who reported the greatest degree of cross gender behavior in childhood also tended to report the worst relationships with their fathers. This correlation was replicated within a sample of androphilic patients in Study 3. The consistent pattern of results obtained from these three studies suggests that the emotionally distant relationships of fathers and androphilic sons relate to the sons' atypical childhood gender identity (or observable gender role behavior) rather than to the sons' erotic preference for male partners per se.

  9. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Oshiumi

    Full Text Available The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3.

  10. Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-beta induction.

    Science.gov (United States)

    Oshiumi, Hiroyuki; Ikeda, Masanori; Matsumoto, Misako; Watanabe, Ayako; Takeuchi, Osamu; Akira, Shizuo; Kato, Nobuyuki; Shimotohno, Kunitada; Seya, Tsukasa

    2010-12-08

    The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR) protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs) where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells) with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3.

  11. 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 (p<0.001), husband's education (p<0.001) and socioeconomic class (p<0.001). There was no significant impact of religion (p-0.142) on desire for sons. Impact of independent variables on daughters desired was similar but less pronounced. There was candid son preference among the respondents. Gender discrimination can be attenuated by adequately addressing son preference at all tiers.

  12. Patrilineal Ability: Nurturing Giftedness in Grandfathers, Fathers, and Sons

    Science.gov (United States)

    Smith, Fiona

    2015-01-01

    The identification of his son's high ability can cause a father to confront his own experiences as a gifted child and adult and change his emotional life, family dynamics, and career. Over the past decade, Fiona Smith has worked closely with numerous multi-generations of grandfathers, fathers, and sons in Australia to analyze their backgrounds,…

  13. Like Godfather, Like Son: Exploring the Intergenerational Nature of Crime

    Science.gov (United States)

    Hjalmarsson, Randi; Lindquist, Matthew J.

    2012-01-01

    Sons (daughters) with criminal fathers have 2.06 (2.66) times higher odds of having a criminal conviction than those with noncriminal fathers. One additional paternal sentence increases sons' (daughters') convictions by 32 (53) percent. Compared to traditional labor market measures, the intergenerational transmission of crime is lower than that…

  14. 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…

  15. 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.

  16. 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.

  17. Resolution of pathological identification between mother and son following rhinoplasty.

    Science.gov (United States)

    Hussain, M F; Gomersall, J D

    1976-10-01

    The case here described shows that severe psychological disturbance can be caused by identification between mother and son, resulting in preoccupation with a part of the body, which in the opinion of those outside the relationship, shows no gross abnormality. Similar delusional beliefs to those held by the mother were induced in the son, when he reached the age at which these beliefs occurred in the mother, in whom they were incompletely resolved. Plastic surgery, in the absence of gross deformity, brought relief of the distress caused by this type of psychopathology. Relief occurred in the conflicts of both mother and son, even though operation was on the latter, only.

  18. Causal Attributions and Parents' Acceptance of Their Homosexual Sons.

    Science.gov (United States)

    Belsky, Yael; Diamond, Gary M

    2015-01-01

    This Internet-based study examined the association between Israeli parents' attributions regarding the cause of their son's homosexuality and their level of acceptance of their homosexual son. The sample (N = 57) was recruited via Internet Web sites (gay forums and support groups). Findings suggest that more essentialist (versus constructivist) causal attributions were associated with higher levels of parental acceptance. Length of time parents knew of their son's homosexual orientation predicted the degree to which their attributions were essentialist. Implications are discussed.

  19. 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)

  20. 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....... A significantly increased risk of cryptorchidism but not hypospadias was found in sons of women working in gardening (adjusted odds ratio = 1.67; 95% confidence interval, 1.14-2.47). The risks were not increased in sons of men working in farming or gardening. The increased risk of cryptorchidism among sons...

  1. Mother-son incest as a defence against psychosis.

    Science.gov (United States)

    Bachmann, K M; Bossi, J

    1993-09-01

    In the following, a case of mother-adult son incest is described and explained from a psychoanalytical viewpoint. Two theories are put forward: (a) Mother-son incest may occur as a defence against psychosis, and (b) the incest represents an unconscious search for triangulation, a process in which external authorities (such as, for example, a court of law) may function as surrogates for persons who have been missed in the pre-oedipal past. It is therefore possible to understand mother-son incest symbolically as an indicator of pre-oedipal needs of the son and of the mother's longing for the absent partner. The incest is, however, not only a cry for help; it is also to be regarded as an attempt to solve the problem for both people involved. Looked at in this way, new ways of understanding and new possibilities for therapy emerge.

  2. Remarks on Psychological Analyses of Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    杨艳微

    2007-01-01

    Sons and Lovers is considered to be D.H.Lawrene's first masterpiece. Social critique and psychological exploration are two props of creative works of D.H.Lawrence. There are two points of view in literature world about the novel Sons and Lovers: One is its critical function which criticizes the destroy of capitalistic industrial civilization to human body and mind. The other is psychological analyses. The tragedy of the characters attributes to the Oedipus complex.

  3. 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)

  4. Expressions of peroxisome proliferator-activated receptors (PPARs) are directly influenced by permeability barrier abrogation and inflammatory cytokines and depressed PPARα modulates expressions of chemokines and epidermal differentiation-related molecules in keratinocytes.

    Science.gov (United States)

    Adachi, Yasuko; Hatano, Yutaka; Sakai, Takashi; Fujiwara, Sakuhei

    2013-09-01

    Previous studies have demonstrated that the activation of peroxisome proliferator-activated receptors (PPARs) not only has positive effects on permeability barrier homoeostasis but also has anti-inflammatory effects by an as yet unknown mechanism. Reduced expression of PPARα in lesion of human atopic dermatitis (AD) and in epidermis of murine AD-like dermatitis has been demonstrated. This study revealed that expression of PPARα alone among PPARs (α, β/δ and γ) was suppressed by both permeability barrier abrogation and additional existence of Th2 cytokine in cultured normal human keratinocytes. In addition, expressions of transglutaminase 1 and loricrin and those of thymus and activation-related chemokine and regulated on activation normal T-cell expressed in cultured human keratinocytes were reduced and enhanced, respectively, by transfection with siRNA for PPARα. In conclusion, depressed PPARα in keratinocytes might be involved in a relationship between permeability barrier abrogation and allergic inflammation and could be a therapeutic target which accounts for both the aspects in AD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. 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.

  6. 50 Things My Son Doesn’t Need Me For

    Directory of Open Access Journals (Sweden)

    Tracey Kershaw

    2016-12-01

    Full Text Available ‘50 things my son doesn’t need me for’ (2011 explores the changing relationship between the artist and her son, and speaks about issues of loss. The artist’s interest is with the details and familiarity of everyday events. She focuses on unremarkable maternal experiences of daily life that relate to a particular time but which articulate both the extraordinary and the momentous, and represent the more fundamental changes that will inevitably occur as her son grows older. In the video, the artist is seen writing on a blackboard, and then erasing, 50 things that her son no longer needs her for. The video draws on the temporary nature of the items on the list; how quickly those things disappear. The artist focuses on the notion of loss as experienced from the mother’s perspective. The work explores feelings of maternal ambivalence, trapped in monotony, and the inherent contradictions with positive memories of closeness with her son.

  7. Violating Bell's inequality beyond Cirel'son's bound

    CERN Document Server

    Cabello, A

    2002-01-01

    Cirel'son inequality states that the absolute value of the combination of quantum correlations appearing in the Clauser-Horne-Shimony-Holt (CHSH) inequality is bound by $2 \\sqrt 2$. It is shown that the correlations of two qubits belonging to a three-qubit system can violate the CHSH inequality beyond $2 \\sqrt 2$. Such a violation is not in conflict with Cirel'son's inequality because it requires a choice of pairs of qubits which is only meaningful in a local-realistic theory. The maximum allowed violation of the CHSH inequality, 4, can be achieved using the Greenberger-Horne-Zeilinger state.

  8. 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.

  9. ¿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.

  10. Observations of a Father: My Son Has Spina Bifida.

    Science.gov (United States)

    Remmel, Carl L.

    1982-01-01

    The author reviews his experiences as the father of a child with spina bifida, a congenital problem in which the spine is not completely enclosed. He recounts his feelings upon first finding out about the condition and his son's subsequent surgeries and crises. (CL)

  11. Origins, Form, and Development of the Son Jarocho: Veracruz, Mexico.

    Science.gov (United States)

    Loza, Steven J.

    1982-01-01

    Son Jarocho (specifically from Veracruz) is a song-and-dance form originating in Spain and implanted in Mexico during 17th- and 18th-century colonization. The jarocho style of music today is one of Latin America's most unique forms, using one to four instruments and characterized by its distinctive rhythm. (LC)

  12. African American Single Mothers Raising Sons: Implications for Family Therapy

    Science.gov (United States)

    Gantt, Ann L.; Greif, Geoffrey L.

    2009-01-01

    Being raised by a single mother is one factor that has been suggested as contributing to the plight of African American males. Yet few studies have focused specifically on African American single mothers' experiences with raising sons. This qualitative study explored the following questions: (1) What are the experiences of African American single…

  13. Who Will Help My Son?: A Family's Journey with Dyslexia.

    Science.gov (United States)

    DeBrew, Jacqueline

    2017-08-01

    It may seem unusual for a nurse to intervene and assist a child with a learning disability, but a mental health nurse who knows the warning signs of dyslexia is able to help families who are going through a difficult time. The current article details the author's experience regarding her son's dyslexia diagnosis. For her family, a nurse was a valuable resource. The impact the struggle had not only on her son, but also her family, and the changes brought about by getting a diagnosis and treatment, demonstrate the impact that nurses can have when family-focused care is provided. [Journal of Psychosocial Nursing and Mental Health Services, 55(8), 27-30.]. Copyright 2017, SLACK Incorporated.

  14. An ecological reading of the sons and lovers

    Institute of Scientific and Technical Information of China (English)

    徐萌萌

    2012-01-01

    1 .Introduction D.H. Lawrence is one of the greatest writers in the English lit- erature history. The author makes a textual analysis of the novel-- Sons and Lovers, David Herbert Lawrence's third novel Which is also his first masterpiece. The novel is recognized as the pioneer work among English novels and now has become one of the most widespread readings. As his representative, sons and lovers is a work filled with ecological elements, which discovered lots of social and psychological problems through the description of the character Paul's growing. Under the backgrounds of the author's own growing experiences and Industry Revolution, the natural circumstances has been ruined, the sick relationship in the worker's family,

  15. Conflicts between Spirit and Body in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    赵佳

    2009-01-01

    The purpose of this paper is to analyze the conflicts between spirit and body that exist among characters in Sons and Lovers. By stating the complicated relationships of Mr. and Mrs. Morel, two sons and their mother, and the protagonist Paul and two women, Miriam and Clara, spirit and body collides and conflicts emerge from time to time. Conflicts between blood ties and lovers' affairs, moral principles and incest, and chastity and lust are reflected on char-acters, especially Paul in the novel. It concludes that Mrs. Morel's influence on Paul's spirit and thought is great. Her spiritual domination on Paul is the main factor for these conflicts. Her death at the end of the story will be a brand-new start of Paul's life.

  16. Maternal smoking in pregnancy and reproductive hormones in adult sons.

    Science.gov (United States)

    Ramlau-Hansen, C H; Thulstrup, A M; Olsen, J; Ernst, E; Andersen, C Y; Bonde, J P

    2008-12-01

    Smoking during pregnancy has been reported to alter levels of reproductive hormones in adult sons. From a Danish pregnancy cohort established in 1984-1987, 347 out of 5109 sons were selected according to their exposure to tobacco smoke in foetal life. From February 2005 to January 2006, a blood sample from each young man (18-21 years) was collected and analysed for reproductive hormones. There were no apparent trends of increasing or decreasing hormonal levels with increased exposure to maternal tobacco smoking during pregnancy. Only the free testosterone/free estradiol ratios increased with increased maternal smoking during pregnancy (p for trend = 0.05). No trends for increasing odds ratios for high follicle-stimulating hormone (> or =25 percentile) or low inhibin B (hormones later in life, but the data may suggest a shift in the hypothalamo-pituitary-gonadal axis towards higher androgenicity. This result was, however, of only borderline significance and could be because of chance.

  17. Fathers and sons: Freud's discovery of the Oedipus complex.

    Science.gov (United States)

    Fuchsman, Kenneth A

    2004-01-01

    Freud's path to the Oedipus complex reveals conceptual inconsistencies. These uncertainties concern fathers, brothers and sons, and the place of the oedipal triad within the family romance. Freud's uncovering of the Oedipus complex emerged, in large part, from his self-analysis of his childhood years in Freiberg. Freud's father was 20 years older than his third wife, and had two adult sons, all of whom lived in Freiberg. In 1897, when Freud announces the Oedipus complex, he stresses his love of his mother and jealousy of his father. Yet in 1924 Freud wrote that his adult brother, Philipp, had taken his father's place as the child's rival. The oedipal complex alters if there are four players rather than three. Freud's concept of an oedipal triangle does not adequately explain the psychological dynamics of his childhood. Fuller conceptual clarity would occur if the dynamics of the Oedipus complex were placed within the family context in which it unfolds.

  18. Private Transfers within the Family: Mothers, Fathers, Sons and Daughters

    OpenAIRE

    Donald Cox

    2003-01-01

    Despite recent advances in data collection and the growing number of empirical studies that examine private intergenerational transfers, there still exist significant gaps in our knowledge. Who transfers what to whom, and why do they it? I argue that some of these gaps could be filled by departing from the standard parent-child framework and concentrating instead on fathers, mothers, sons and daughters in a way that accounts for fundamental--and sometimes obvious--male-female differences in c...

  19. Son preference in Indian families: absolute versus relative wealth effects.

    Science.gov (United States)

    Gaudin, Sylvestre

    2011-02-01

    The desire for male children is prevalent in India, where son preference has been shown to affect fertility behavior and intrahousehold allocation of resources. Economic theory predicts less gender discrimination in wealthier households, but demographers and sociologists have argued that wealth can exacerbate bias in the Indian context. I argue that these apparently conflicting theories can be reconciled and simultaneously tested if one considers that they are based on two different notions of wealth: one related to resource constraints (absolute wealth), and the other to notions of local status (relative wealth). Using cross-sectional data from the 1998-1999 and 2005-2006 National Family and Health Surveys, I construct measures of absolute and relative wealth by using principal components analysis. A series of statistical models of son preference is estimated by using multilevel methods. Results consistently show that higher absolute wealth is strongly associated with lower son preference, and the effect is 20%-40% stronger when the household's community-specific wealth score is included in the regression. Coefficients on relative wealth are positive and significant although lower in magnitude. Results are robust to using different samples, alternative groupings of households in local areas, different estimation methods, and alternative dependent variables.

  20. Like Father, Like Son? Intergenerational Educational Mobility in India.

    Science.gov (United States)

    Azam, Mehtabul; Bhatt, Vipul

    2015-12-01

    Using the nationally representative India Human Development Survey (IHDS), we create a unique son-father matched data set that is representative of the entire adult male population (aged 20-65) in India. We use these data to document the evolution of intergenerational transmission of educational attainment in India over time, among different castes and states for the birth cohorts of 1940-1985. We find that educational persistence, as measured by the regression coefficient of father's education as a predictor of son's education, has declined over time. This implies that increases in average educational attainment are driven primarily by increases among children of less-educated fathers. However, we do not find such a declining trend in the correlation between educational attainment of sons and fathers, which is another commonly used measure of persistence. To understand the source of such a discrepancy between the two measures of educational persistence, we decompose the intergenerational correlation and find that although persistence has declined at the lower end of the fathers' educational distribution, it has increased at the top end of that distribution.

  1. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD).

    Science.gov (United States)

    Marques, Raquel M; Teixeira, Luzia; Aguas, Artur P; Ribeiro, Joana C; Costa-e-Silva, António; Ferreira, Paula G

    2014-02-04

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection.

  2. Silence of MCL-1 upstream signaling by shRNA abrogates multiple myeloma growth.

    Science.gov (United States)

    Wang, Mengchang; Wu, Di; Liu, Pengbo; Deng, Jiusheng

    2014-01-01

    Multiple myeloma (MM) is an incurable B-cell cancer with accumulated clonal abnormal plasma cells in bone marrow of patients. MCL-1 (myeloid cell leukemia sequence 1) protein is an anti-apoptotic molecule in MM cells and regulated by pro-inflammatory cytokine IL-6 and downstream signaling molecules STAT3, PI3K and MAPK. The purpose of this study is to investigate the effect of STAT3, PI3K and MAPK gene silence on MCL-1 expression in human MM cells and the consequence of cell survival. Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down STAT3, PI3K or MAPK genes. Gene and protein expression was quantified by quantitative real-time PCR and Western Blot. MM cell apoptosis was examined by annexin-V FITC/propidium iodide staining. Efficient silence of STAT3, PI3K, MAPK1 or MAPK2 gene robustly abrogated IL-6 enhanced MCL-1 expression and suppressed MM cell growth. Silencing STAT3 gene inhibited PI3K expression, silencing PI3K markedly abrogated STAT3 and MAPK production. Inhibition of MAPK2 gene by shMAPK2 suppressed STAT3, PI3K and MAPK1 expression in the cells. Silencing of STAT3, PI3K and MAPK2 together completely blocked MCL-1 expression in MM cells. There is a syngeneic effect among the three independent STAT3, PI3K and MAPK2 survival-signaling pathways related to MCL-1 expression in MM cells. shRNAs silencing of STAT3, PI3K and MAPK2 together could provide an effective strategy to treat MM.

  3. [Bladder cancer at an early age in father and son].

    Science.gov (United States)

    Ovsiannikov, D; Stöhr, R; Hartmann, A; Böttrich, R; Hengstler, J G; Golka, K

    2011-12-01

    Bladder cancer may be caused by external factors like tobacco smoking, but may also be familial. We report on a father and son who developed this tumour at the ages of 45 and 35. Testing various genetic markers including the mismatch repair proteins MLH1, MSH2 and MSH6, whose loss is associated with a higher risk for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome), did not point to a familial disease. Thus the heavy smoking habits of the two patients must be considered as causal.

  4. Adolescent sexual matricide following repetitive mother-son incest.

    Science.gov (United States)

    Schlesinger, L B

    1999-07-01

    A case of a 16-year-old male who committed a sexual matricide following years of mother-son incest is reported. After murdering his mother by strangulation, which itself was sexually arousing, the youngster engaged in both vaginal and anal necrophilia. The homicide occurred while the perpetrator was in a dissociative state and experiencing what has been referred to as a catathymic crisis: the sudden release of emotionally charged psychic conflict and tension, resulting in extreme violence within an interpersonal bond. Discussion of maternal image and maternal sexual conduct in relationship to the psychosexual development of adolescent males offers insight into the motivation in this extremely rare case.

  5. Experimental Violation of Bell Inequality beyond Cirel'son's Bound

    CERN Document Server

    Chen, Y A; Pan, J W; Yang, T; Zhang, A N; Zhao, Z; Cabello, Adan; Chen, Yu-Ao; Pan, Jian-Wei; Yang, Tao; Zhang, An-Ning; Zhao, Zhi

    2006-01-01

    The correlations between two qubits belonging to a three-qubit system can violate the Clauser-Horne-Shimony-Holt-Bell inequality beyond Cirel'son's bound [A. Cabello, Phys. Rev. Lett. 88, 060403 (2002)]. We experimentally demonstrate such a violation by 7 standard deviations by using a three-photon polarization-entangled Greenberger-Horne-Zeilinger state produced by Type-II spontaneous parametric down-conversion. In addition, using part of our results, we obtain a violation of the Mermin inequality by 39 standard deviations.

  6. ¿Son las mujeres una minoría?

    OpenAIRE

    Osborne, Raquel

    1996-01-01

    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. sociolog...

  7. Son preference, sex selection, and kinship in Vietnam.

    Science.gov (United States)

    Guilmoto, Christophe Z

    2012-01-01

    This article examines the recent rise in the sex ratio at birth in Vietnam and relates its emergence to kinship systems and ethnic composition using 2009 census micro-data. Presentation of the main socioeconomic and ethnic differentials in birth masculinity is followed by a review of the three intermediate factors leading to increases in the sex ratio at birth: prenatal technology, declining fertility, and gender bias. An indirect measurement of fertility behavior is used to demonstrate the close association between levels of the sex ratio at birth and the intensity of son preference. Data on household composition indicate that Vietnam is characterized by the co-existence of kinship patterns typical of East and Southeast Asia. Son preference in Vietnam is found to be related to the prevalence of more traditional patrilineal systems. The article concludes by considering the implications of the cultural dimensions of prenatal sex selection for policy responses and for the likely future change in the sex ratio at birth.

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

    Science.gov (United States)

    Kaufer, Benedikt B; Arndt, Sina; Trapp, Sascha; Osterrieder, Nikolaus; Jarosinski, Keith W

    2011-10-01

    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 against virus

  9. Tetrandrine: A Potent Abrogator of G2 Checkpoint Function in Tumor Cells and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To assess the ability of tetrandrine (Tet) to enhance the sensitivity to irradiation and its mechanism in cell lines of human breast cancer p53-mutant MCF-7/ADR, p53-wild-type MCF-7 and human colon carcinoma p53-mutant HT-29 as well as in C26 colorectal carcinoma-bearing BALB/c mice. Methods MCF-7/ADR, HT-29 and MCF-7 cells were exposed to irradiation in the absence or presence of tetrandrine. The effect of Tet on the cytotoxicity of X-irradiation in these three cells was determined and the effect of tetrandrine on cell cycle arrest induced by irradiation in its absence or presence was studied by flow cytometry, Moreover, mitotic index measurement determined mitosis of cells to enter mitosis. Western blotting was employed to detect cyclin B1 and Cdc2 proteins in extracts from irradiated or non-irradiated cells of MCF-7/ADR, HT-29 and MCF-7 treated with tetrandrine at various concentrations. Tumor growth delay assay was conducted to determine the radio-sensitization of tetrandrine in vivo. Results Clonogenic assay showed that tetrandrine markedly enhanced the lethal effect of X-rays on p53-mutant MCF-7/ADR and HT-29 cells and the sensitization enhancement ratio (SER) of tetrandrine was 1.51 and 1.63, but its SER was only 1.1 in p53-wt MCF-7 cells. Irradiated p53-mutant MCF-7/ADR and HT-29 cells were only arrested in G2/M phase while MCF-7 cells were arrested in G1 and G2/M phases. Radiation-induced G2 phase arrests were abrogated by tetrandrine in a concentration-dependent manner in MCF-7/ADR and HT-29 cells,whereas redistribution within MCF-7 cell cycle changed slightly. The proportion of cells in M phase increased from 1.3% to 14.7% in MCF-7/ADR cells, and from 1.5% to 13.2% in HT-29 cells, but 2.4% to 7.1% in MCF-7 cells. Furthermore, the levels of cyclin B 1 and Cdc2 expression decreased after X-irradiation in MCF-7/ADR and HT-29 cells, and the mitotic index was also lower. Tet could reverse the decrease and induce the irradiated cells to enter mitosis

  10. Diabetes abrogates sex differences and aggravates cardiometabolic risk in postmenopausal women

    Science.gov (United States)

    2013-01-01

    Background The aim of this study is to evaluate the effect of gender and menopause in cardiometabolic risk in a type 2 diabetes mellitus (T2DM) population, based on classical and non-traditional markers. Methods Seventy four volunteers and 110 T2DM patients were enrolled in the study. Anthropometric data, blood pressure, body mass index (BMI), waist circumference (WC) and the following serum markers were analyzed: glucose, Total-c, TGs, LDL-c, Oxidized-LDL, total HDL-c and large and small HDL-c subpopulations, paraoxonase 1 activity, hsCRP, uric acid, TNF-α, adiponectin and VEGF. Results Non-diabetic women, compared to men, presented lower glycemia, WC, small HDL-c, uric acid, TNF-α and increased large HDL-c. Diabetes abrogates the protective effect of female gender, since diabetic women showed increased BMI, WC, small HDL-c, VEGF, uric acid, TNF-α and hsCRP, as well as reduced adiponectin, when compared with non-diabetic. In diabetic females, but not in males, WC is directly and significantly associated with TNF-α, VEGF, hsCRP and uric acid; TNF-α is directly associated with VEGF and hsCRP, and inversely with adiponectin. Postmenopausal females presented a worsen cardiometabolic profile, viewed by the increased WC, small HDL-c, VEGF, uric acid, TNF-α and hsCRP. In this population, WC is directly and significantly associated with TNF-α, VEGF, hsCRP; TNF-α is directly associated with VEGF; and uric acid is inversely associated with large HDL-c and hsCRP with adiponectin, also inversely. Conclusions Diabetes abrogates the protective effect of gender on non-diabetic women, and postmenopausal diabetic females presented worsen cardiometabolic risk, including a more atherogenic lipid sketch and a pro-inflammatory and pro-angiogenic profile. The classical cardiovascular risk factors (CVRFs) fail to completely explain these differences, which are better clarified using “non-traditional” factors, such as HDL-c subpopulations, rather than total HDL-c content, and

  11. 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

  12. Co-Identity with Son Is Core Component in Father's Development: Same-Gendered Father/Son Relationships Foster Relational Development in Fathers

    Science.gov (United States)

    Watson-Phillips, Carol

    2017-01-01

    What is the crucible of a father's relationally transformative growth in connection with his sons? In this article, the author first contextualizes relational theory, and then explores the idea that co-identity with a son provides the mortar and pestle for a father's development in same-gendered relationships. In connection with his son, a father…

  13. Terapia vocal e sons nasais: efeitos sobre disfonias hiperfuncionais

    Directory of Open Access Journals (Sweden)

    Simone Rattay Andrade

    2016-02-01

    Full Text Available RESUMO Buscou-se verificar os efeitos de um programa fonoterapêutico que incluiu orientação vocal e postural, adequação da função respiratória e a técnica de sons nasais em disfonias hiperfuncionais. Foi realizado um estudo de casos clínicos, observacional, longitudinal, não controlado, de caráter quantitativo que analisou três sujeitos do sexo feminino com idade média de 31,33 anos que apresentavam disfonias hiperfuncionais. Os sujeitos foram submetidos a: videolaringoscopia, avaliação vocal perceptivoauditiva e acústica, coleta de tempos máximos de fonação, triagem postural e determinação do tipo respiratório durante a fala, antes e após um programa terapêutico composto por orientação, conscientização e treinamento vocal com sons nasais durante 16 sessões de fonoterapia, uma vez na semana com treinamento em domicílio. Os dados foram analisados por meio dos testes não-paramétricos Mann-Whitney e Qui-quadrado, com nível de significância de 5%. Pós-terapia, observou-se que a postura corporal passou de desalinhada para alinhada e o tipo respiratório de superior para costodiafragmático abdominal; houve diminuição das medidas acústicas em relação ao grau e número de subharmônicos na maioria significante dos sujeitos, além de melhoras teciduais e diminuição do edema na mucosa das pregas vocais e na região aritenoide, e melhora da coaptação glótica. Após a execução de um programa fonoterapêutico com orientação vocal e postural, adequação da função respiratória e uso da técnica de sons nasais em disfonias hiperfuncionais, observou-se melhora significante da postura corporal, do tipo respiratório, das medidas acústicas sugestivas de ruído à emissão vocal, e efeitos positivos sobre o tecido e o fechamento das pregas vocais.

  14. [Meaning of becoming mother and son/daughter through massage].

    Science.gov (United States)

    Márquez Doren, Francisca; Lucchini Raies, Camila; Rivera Martínez, Soledad

    2014-06-01

    Revealing the experience of mothers when massaging their children to know the phenomenon in the context of a mother-child healthy development. 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? 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. This practice should be considered as an option in the programs that promote the comprehensive health of the mother and child.

  15. 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.

  16. Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke.

    Science.gov (United States)

    Acosta, Sandra A; Tajiri, Naoki; Hoover, Jaclyn; Kaneko, Yuji; Borlongan, Cesar V

    2015-09-01

    Adult stem cell therapy is an experimental stroke treatment. Here, we assessed homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) in chronic stroke. At 60 days post stroke, adult Sprague-Dawley rats received intravenous hBMSCs (4×10(6) labeled or nonlabeled cells) or vehicle (saline). A sham surgery group served as additional control. In vivo imaging was conducted between 1 hour and 11 days post transplantation, followed by histological examination. Labeled hBMSCs migrated to spleen which emitted significantly higher fluorescent signal across all time points, especially during the first hour, and were modestly detected in the head region at the 12 hours and 11 days, compared with nonlabeled hBMSCs and vehicle-infused stroke animals, or sham (Pcells in gray and white matter, and a 43% diminution in tumor necrosis factor-α cell density in the spleen of transplanted stroke animals compared with vehicle-infused stroke animals (Pstroke possibly by abrogating the inflammation-plagued secondary cell death. © 2015 The Authors.

  17. Upregulation of neurovascular communication through filamin abrogation promotes ectopic periventricular neurogenesis

    Science.gov (United States)

    Houlihan, Shauna L; Lanctot, Alison A; Guo, Yan; Feng, Yuanyi

    2016-01-01

    Neuronal fate-restricted intermediate progenitors (IPs) are derived from the multipotent radial glia (RGs) and serve as the direct precursors for cerebral cortical neurons, but factors that control their neurogenic plasticity remain elusive. Here we report that IPs’ neuron production is enhanced by abrogating filamin function, leading to the generation of periventricular neurons independent of normal neocortical neurogenesis and neuronal migration. Loss of Flna in neural progenitor cells (NPCs) led RGs to undergo changes resembling epithelial-mesenchymal transition (EMT) along with exuberant angiogenesis that together changed the microenvironment and increased neurogenesis of IPs. We show that by collaborating with β-arrestin, Flna maintains the homeostatic signaling between the vasculature and NPCs, and loss of this function results in escalated Vegfa and Igf2 signaling, which exacerbates both EMT and angiogenesis to further potentiate IPs’ neurogenesis. These results suggest that the neurogenic potential of IPs may be boosted in vivo by manipulating Flna-mediated neurovascular communication. DOI: http://dx.doi.org/10.7554/eLife.17823.001 PMID:27664421

  18. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  19. Coenzyme q10 abrogated the 28 days aluminium chloride induced oxidative changes in rat cerebral cortex.

    Science.gov (United States)

    Majumdar, Anuradha S; Nirwane, Abhijit; Kamble, Rahul

    2014-05-01

    The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Subacute exposure to AlCl3(5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L-deprenyl (1 mg/kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3.

  20. Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.

    Science.gov (United States)

    Suo, Guangli; Sadarangani, Anil; Tang, Wingchung; Cowan, Bryan D; Wang, Jean Y J

    2014-09-01

    Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.

  1. Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB

    Directory of Open Access Journals (Sweden)

    Wang-Jian Zha

    2013-01-01

    Full Text Available Persistent activation of nuclear factor κB (NF-κB has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA- induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL- 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1 levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

  2. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.

    Science.gov (United States)

    Huang, Yan; Wang, Dandan; Wang, Xin; Zhang, Yijie; Liu, Tao; Chen, Yuting; Tang, Yanhong; Wang, Teng; Hu, Dan; Huang, Congxin

    2016-01-01

    CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling.

  3. Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.

    Science.gov (United States)

    Wang, Weimin; Kryczek, Ilona; Dostál, Lubomír; Lin, Heng; Tan, Lijun; Zhao, Lili; Lu, Fujia; Wei, Shuang; Maj, Tomasz; Peng, Dongjun; He, Gong; Vatan, Linda; Szeliga, Wojciech; Kuick, Rork; Kotarski, Jan; Tarkowski, Rafał; Dou, Yali; Rattan, Ramandeep; Munkarah, Adnan; Liu, J Rebecca; Zou, Weiping

    2016-05-19

    Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate stromal-mediated chemoresistance. Capitalizing upon the interplay between chemotherapy and immunotherapy holds high potential for cancer treatment.

  4. Lipoteichoic acid synthesis inhibition in combination with antibiotics abrogates growth of multidrug-resistant Enterococcus faecium.

    Science.gov (United States)

    Paganelli, Fernanda L; van de Kamer, Tim; Brouwer, Ellen C; Leavis, Helen L; Woodford, Neil; Bonten, Marc J M; Willems, Rob J L; Hendrickx, Antoni P A

    2017-03-01

    Enterococcus faecium is a multidrug-resistant (MDR) nosocomial pathogen causing significant morbidity in debilitated patients. New antimicrobials are needed to treat antibiotic-resistant E. faecium infections in hospitalised patients. E. faecium incorporates lipoteichoic acid (LTA) (1,3-polyglycerol-phosphate linked to glycolipid) in its cell wall. The small-molecule inhibitor 1771 [2-oxo-2-(5-phenyl-1,3,4-oxadiazol-2-ylamino)ethyl 2-naphtho[2,1-b]furan-1-ylacetate] specifically blocks the activity of Staphylococcus aureus LtaS synthase, which polymerises 1,3-glycerolphosphate into LTA polymers. Here we characterised the effects of the small-molecule inhibitor 1771 on the growth of E. faecium isolates, alone (28 strains) or in combination with the antibiotics vancomycin, daptomycin, ampicillin, gentamicin or linezolid (15 strains), and on biofilm formation (16 strains). Inhibition of LTA synthesis at the surface of the cell by compound 1771 in combination with current antibiotic therapy abrogates enterococcal growth in vitro but does not affect mature E. faecium biofilms. Targeting LTA synthesis may provide new possibilities to treat MDR E. faecium infections.

  5. 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.

  6. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

    Directory of Open Access Journals (Sweden)

    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  7. Ethics of intergenerational (father-to-son) sperm donation.

    Science.gov (United States)

    Bredenoord, Annelien L; Lock, Matthias T W T; Broekmans, Frank J M

    2012-05-01

    In the ever changing field of reproductive medicine, clinics are regularly confronted with requests for novel variants of medically assisted reproduction. Particularly third-party (assisted) reproduction, which requires the involvement of an oocyte or sperm donor, is ethically and psychologically complex due to the parties involved, but nevertheless widely accepted. A particular type of third party reproduction concerns intrafamilial medically assisted reproduction (IMAR), where the donor is a family member of the recipients. In IMAR, some of the ethical and psychological issues associated with third party reproduction are intensified. The precise impact and consequences, however, remain speculative due to the lack of information regarding IMAR. Both the ESHRE Task Force on Ethics and Law and the Human Fertilization and Embryology Authority have recently highlighted the lack of information and the need for debate. In order to contribute to the discussion and knowledge on IMAR, we present a couple that recently visited our academic clinic with a request for a very particular variant of IMAR: first degree, intergenerational father-to-son sperm donation. As our academic hospital did not have experience with this variant of IMAR, our interdisciplinary Ethics Committee for Reproductive Medicine extensively discussed the request, resulting in an advisory report on the ethics of IMAR in general and father-to-son sperm donation in particular. Here, we will first present the andrological and social background of the couple and subsequently discuss the ethical considerations that led to the approval of their request. We will conclude the paper with recommendations for a morally sound practice of IMAR.

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

    DEFF Research Database (Denmark)

    Ramlau-Hansen, Cecilia; Stoltenberg, Christian Ditlev 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....

  9. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress

    Indian Academy of Sciences (India)

    INDRAJEET GHODKE; K MUNIYAPPA

    2016-12-01

    In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX) protein complex plays pivotal roles in double-strandbreak (DSB) repair, replication stress and telomere length maintenance. Another protein linked to DSB repair is Sae2,which regulates MRX persistence at DSBs. However, very little is known about its role in DNA replication stress andrepair. Here, we reveal a crucial role for Sae2 in DNA replication stress. We show that different mutant alleles of SAE2cause hypersensitivity to genotoxic agents, and when combined with Δmre11 or nuclease-defective mre11 mutantalleles, the double mutants are considerably more sensitive suggesting that the sae2 mutations synergize with mre11mutations. Biochemical studies demonstrate that Sae2 exists as a dimer in solution, associates preferentially withsingle-stranded and branched DNA structures, exhibits structure-specific endonuclease activity and cleaves thesesubstrates from the 5′ end. Furthermore, we show that the nuclease activity is indeed intrinsic to Sae2. Interestingly,sae2G270D protein possesses DNA-binding activity, but lacks detectable nuclease activity. Altogether, our data suggesta direct role for Sae2 nuclease activity in processing of the DNA structures that arise during replication and DNAdamage and provide insights into the mechanism underlying Mre11-Sae2-mediated abrogation of replication stress-relateddefects in S. cerevisiae.

  10. CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation

    Science.gov (United States)

    Siddiqui, Y H; Kershaw, R M; Humphreys, E H; Assis Junior, E M; Chaudhri, S; Jayaraman, P-S; Gaston, K

    2017-01-01

    PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion. PMID:28134934

  11. Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms.

    Science.gov (United States)

    Stonesifer, Connor; Corey, Sydney; Ghanekar, Shaila; Diamandis, Zachary; Acosta, Sandra A; Borlongan, Cesar V

    2017-07-23

    Ischemic stroke is a leading cause of death worldwide. A key secondary cell death mechanism mediating neurological damage following the initial episode of ischemic stroke is the upregulation of endogenous neuroinflammatory processes to levels that destroy hypoxic tissue local to the area of insult, induce apoptosis, and initiate a feedback loop of inflammatory cascades that can expand the region of damage. Stem cell therapy has emerged as an experimental treatment for stroke, and accumulating evidence supports the therapeutic efficacy of stem cells to abrogate stroke-induced inflammation. In this review, we investigate clinically relevant stem cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), very small embryonic-like stem cells (VSELs), neural stem cells (NSCs), extraembryonic stem cells, adipose tissue-derived stem cells, breast milk-derived stem cells, menstrual blood-derived stem cells, dental tissue-derived stem cells, induced pluripotent stem cells (iPSCs), teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N), c-mycER(TAM) modified NSCs (CTX0E03), and notch-transfected mesenchymal stromal cells (SB623), comparing their potential efficacy to sequester stroke-induced neuroinflammation and their feasibility as translational clinical cell sources. To this end, we highlight that MSCs, with a proven track record of safety and efficacy as a transplantable cell for hematologic diseases, stand as an attractive cell type that confers superior anti-inflammatory effects in stroke both in vitro and in vivo. That stem cells can mount a robust anti-inflammatory action against stroke complements the regenerative processes of cell replacement and neurotrophic factor secretion conventionally ascribed to cell-based therapy in neurological disorders. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. 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.

  13. Mammalian target of rapamycin inhibitor abrogates abnormal osteoclastogenesis in neurofibromatosis type 1

    Institute of Scientific and Technical Information of China (English)

    LIU Ning; XU Ning; WEI Li-hui; CHAI Guo-lin

    2013-01-01

    Background Neurofibromatosis type 1 (NF1) is the most common genetic syndrome predisposing patients to various tumors due to dysregulation of the Ras signaling pathway.Recent research has shown NF1 patients also suffer a spectrum of bone pathologies.The pathogenesis of NF1 bone diseases is largely unknown.There is no current treatment.By Nf1 heterozygote (Nf1+/-) mice and Nf1 conditional knockout mice,we and other groups demonstrated abnormal osteoblast and osteoclast function due to dysregulation of Ras signaling.However,the specific downstream effector pathways linked to NF1 abnormal osteoblastogenesis and osteoclastogenesis have not been defined.In this study,we investigated the Ras downstream effector related with NF1 bone disease.Methods We used Nf1+/+ and Nf1+/-mice as normal and NF1 models.Bone stromal cells extracted from Nf1+/+ and Nf1+/-mice were induced osteoclasts.The osteoclast cell was stained by tartrate resistant acid phosphatase staining.The osteoclast cell number was counted and the surface area of osteoclast cells was calculated under the microscope.The mRNA of mammalian target of rapamycin (mTOR) was determined by quantitative reverse-transcription-polymerase chain reaction.The presence of ribosomal protein S6 kinase was determined by Western blotting.Results Compared with Nf1+/+ mice,Nf1+/-mice had about 20% more of osteoclast cells.These osteoclast cells werelarger in size with more nuclei.Hyperactive mTOR was detected in Nf1+/-osteoclast cells.Inhibition of mTOR signalingby rapamycin in Nf1+/-osteoclasts abrogated abnormalities in cellular size and number.Conclusion mTOR pathway inhibition may represent a viable therapy for NF1 bone diseases.

  14. Effects of immunosuppression on avian coccidiosis: cyclosporin A but not hormonal bursectomy abrogates host protective immunity.

    Science.gov (United States)

    Lillehoj, H S

    1987-01-01

    The effects of cyclosporin A (CsA) treatment and hormonal bursectomy on Eimeria tenella infection of chickens were investigated to evaluate the role of humoral antibody and cell-mediated immunity (CMI) in the host protective immunity to an intestinal protozoan disease, coccidiosis. Hormonal bursectomy had no significant effect on the host response to E. tenella. CsA treatment had a differential effect on the course of disease depending on how CsA was given relative to infection. Daily administration of CsA for 7 days beginning 1 day before primary infection with E. tenella enhanced disease resistance, whereas a single dose of CsA given before primary infection enhanced disease susceptibility compared with that of untreated controls. Chickens treated with CsA during the primary infection were resistant to reinfection at 5 weeks post-primary infection. Treatment of chickens immune to E. tenella with CsA at the time of secondary infection abrogated their resistance to reinfection despite the presence of high levels of coccidia-specific secretory immunoglobulin A and serum immunoglobulin G. Splenic lymphocytes obtained after CsA treatment demonstrated a substantially depressed concanavalin A response, but not a depressed lipopolysaccharide response. Because CsA was not directly toxic to parasites in vivo when administered during the secondary infection, these results suggest that CsA interacts with the immune system to allow priming during the primary infection, while interfering with the effector function of CMI during the secondary infection. Taken together, present findings indicate that CMI plays a major role in host protective immunity to E. tenella. PMID:3496277

  15. 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.

  16. Abrogation of red blood cell G6PD enzyme activity through Heat treatment: development of survey material for the UK NEQAS G6PD scheme.

    Science.gov (United States)

    Roper, D R; De la Salle, B; Soni, V; Fletcher, K; Green, J A

    2017-06-01

    Participation in external quality assessment (EQA) is central to the maintenance of high-quality laboratory results in patient diagnosis and clinical trials. Laboratories in the TAF112582 DETECTIVE study (ClinicalTrials.gov identifier: NCT01376167) are enrolled in the United Kingdom National Quality Assessment Scheme (UK NEQAS) for glucose-6-phosphate dehydrogenase (G6PD) quantitative assay, which utilizes ovine (sheep) blood as a readily available source of apparently G6PD-deficient survey material. A substitute for sheep blood was sought because some non-UK sites in the study encountered participation difficulties due to the strict regulations on the import of sheep blood into their countries. G6PD activity in normal human donor blood was abrogated by the action of heat under controlled conditions. Residual G6PD activity in the heated samples was measured by UK NEQAS using the Trinity Biotech 345 kit (Trinity Biotech) and a Jenway 6715 UV/Vis spectrophotometer with external temperature control to monitor enzyme kinetics and linearity over a set time. Heat-treated material was also assayed for G6PD activity and assessed for its acceptability as EQA survey material by selected UK laboratories. Blood heated at 45 °C for 15 h showed a reduction in G6PD activity of 76.3 ± 4.6% (n = 6) and was considered acceptable as EQA material in terms of appearance and behaviour by the majority of UK sites in the trial. We have developed a simple heat-treatment procedure to produce EQA survey material with low/intermediate G6PD activity, similar to that found in females heterozygous for G6PD deficiency. © 2017 The Authors. International Journal of Laboratory Hematology Published by John Wiley & Sons Ltd.

  17. 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...

  18. ¿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.

  19. ¿Las agencias son unidades administrativas especiales?

    Directory of Open Access Journals (Sweden)

    Consuelo Sarria

    2015-06-01

    Full Text Available Al plantearse como tema del artículo el de si las agencias son unidades administrativas especiales, el trabajo debe abordar dos conceptos aparentemente diferentes en cuanto al contenido y la génesis, pues de un lado se tiene conocimiento de las unidades administrativas especiales creadas con la finalidad de realizar actividades propias de un ministerio o departamento administrativo, y que, en consecuencia, siguiendo lineamientos jurisprudenciales, debían formar parte de la estructura de aquellos o estos. No obstante el reproche doctrinal referido a que a ciertas unidades administrativas se les otorgaba personería jurídica, llama la atención el cambio de criterio jurisprudencial que las avaló, y la manera en que a partir de la Constitución de 1991 se regularon unidades con o sin personería jurídica. Al abordar el tema de las agencias del Estado resulta relevante el origen anglosajón del término y la ausencia de características que las identifiquen, y la ausencia de un régimen común. Se hace especial mención a la reforma de 2011 y a cómo se crearon varias Agencias del Estado, algunas definidas como Unidades Administrativas Especiales, ante lo que cabe interrogarse sobre la correspondencia entre ambas nociones.

  20. Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to reduced T cell priming and inhibition of disease effector mechanisms.

    Science.gov (United States)

    Agarwal, Rajeev K; Horai, Reiko; Viley, Angelia M; Silver, Phyllis B; Grajewski, Rafael S; Su, Shao Bo; Yazdani, Arrash T; Zhu, Wei; Kronenberg, Mitchell; Murray, Peter J; Rutschman, Robert L; Chan, Chi-Chao; Caspi, Rachel R

    2008-04-15

    Experimental autoimmune uveitis (EAU) induced by immunization of animals with retinal Ags is a model for human uveitis. The immunosuppressive cytokine IL-10 regulates EAU susceptibility and may be a factor in genetic resistance to EAU. To further elucidate the regulatory role of endogenous IL-10 in the mouse model of EAU, we examined transgenic (Tg) mice expressing IL-10 either in activated T cells (inducible) or in macrophages (constitutive). These IL-10-Tg mice and non-Tg wild-type controls were immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein. Constitutive expression of IL-10 in macrophages abrogated disease and reduced Ag-specific immunological responses. These mice had detectable levels of IL-10 in sera and in ocular extracts. In contrast, expression of IL-10 in activated T cells only partially protected from EAU and marginally reduced Ag-specific responses. All IL-10-Tg lines showed suppression of Ag-specific effector cytokines. APC from Tg mice constitutively expressing IL-10 in macrophages exhibited decreased ability to prime naive T cells, however, Ag presentation to already primed T cells was not compromised. Importantly, IL-10-Tg mice that received interphotoreceptor retinoid-binding protein-specific uveitogenic T cells from wild-type donors were protected from EAU. We suggest that constitutively produced endogenous IL-10 ameliorates the development of EAU by suppressing de novo priming of Ag-specific T cells and inhibiting the recruitment and/or function of inflammatory leukocytes, rather than by inhibiting local Ag presentation within the eye.

  1. ¿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.

  2. SysSon: A Sonification Platform for Climate Data

    Science.gov (United States)

    Visda, Goudarzi; Hanns Holger, Rutz; Katharina, Vogt

    2014-05-01

    Climate data provide a challenging working basis for sonification. Both model data and measured data are assessed in collaboration with the Wegener Center for Climate and Global Change. The multi dimensionality and multi variety of climate data has a great potential for auditory displays. Furthermore, there is consensus on global climate change and the necessity of intensified climate research today in the scientific community and general public. Sonification provides a new means to communicate scientific results and inform a wider audience. SysSon is a user centered auditory platform for climate scientists to analyze data. It gives scientists broader insights by extracting hidden patterns and features from data that is not possible using a single modal visual interface. A variety of soundscapes to chose from lessens the fatigue that comes with repeated and sustained listening to long streams of data. Initial needs assessments and user tests made the work procedures and the terminology of climate scientists clear and informed the architecture of our system. Furthermore, experiments evaluated the sound design which led to a more advanced soundscape and improvement of the auditory display. We present a novel interactive sonification tool which combines a workspace for the scientists with a development environment for sonification models. The tool runs on different operating systems and is released as open source. In the standalone desktop application, multiple data sources can be imported, navigated and manipulated either via text or a graphical interface, including traditional plotting facilities. Sound models are built from unit generator graphs which are enhanced with matrix manipulation functions. They allow us to systematically experiment with elements known from the visual domain, such as range selections, scaling, thresholding, markers and labels. The models are organized in an extensible library, from which the user can choose and parametrize. Importance is

  3. Hope for the future: 3. Planning for sons.

    Science.gov (United States)

    Qutub, S A

    1995-01-01

    The Pakistan Institute for Environment-Developed Action Research (PIEDAR) has been active during 1992-95 in 25 rural villages of Kabirwala tahsil, Khanewal District, Punjab region, Pakistan. Participatory rural appraisal strategies are used to help communities understand the relationship between family size and sustainable land use patterns. The fertility rate in villages is over 6 children per woman. Over 9/10 women are familiar with the concept of family planning, 7/10 know of a specific method, but only 1/10 uses contraception. Religious taboos are but one reason for the gap between knowledge and use. 15% of couples report opposition by the husband or mother-in-law. A major determinant of large family size is attributed to problem of land security, which is prevalent throughout the province. About 50% of arable land is tied up in legal battles. The farms use a wheat-cotton cropping pattern, which relies on intensive labor inputs for peak periods. Many sons help families retain the land. The Village Organization was directed to focus on the land use problems of villages and to make recommendations. Action plans are developed with step by step implementation for every land parcel in order to increase productivity. Villagers working within this community organization experience how exchanges can be made to benefit each other. The structural organization of this emerging network is useful for cutting across social, traditional, and hierarchical structures to become a new foundation for economic relations. Traditional centers of power become useless to the economic functioning of the community, and more democratic forms of governance emerge. It has been argued that rural fertility is not influenced by tradition and irrationality but by socioeconomic necessity. If so, time will change reproductive trends; unfortunately, the process of social change is slow. Independent catalytic agents are needed for speeding up the process, while civil society needs the State to

  4. On the“Oedipus Complex”in Sons and Lovers-Mother is a lover of her son

    Institute of Scientific and Technical Information of China (English)

    王瑞瑒

    2014-01-01

    Sons and Lovers is one of Lawrence’s most famous novels. It mainly concerns about the love affairs among the main character-Paul, his mother and his two girlfriends. The mother’s strange love has affected the boys for a long time, which even has made him lose the ability to love other girls. As a result, Paul gradually has the“Oedipus Complex”towards his mother, and it has influenced the whole lifetime of himself. During the competition of grasp the heart of Paul, Miriam and Clara are all the los-ers, while they both can’t drag Paul out of the influence from his mother. It is not until the death of his mother does Paul finally escape from the control of his mother. All the origins can be concluded into one thing-that is the Paul’s“Oedipus Complex”towards his mother. What is the“Oedipus Complex”, and how does it reflect in the main content? How does it influence the emotions of Paul step by step? This essay will elaborate it in detail.

  5. Abrogation of p53-induced apoptosis by the hepatitis B virus X gene.

    NARCIS (Netherlands)

    X.W. Wang (Xin Wei); M.K. Gibson (Michael); W. Vermeulen (Wim); H. Yeh; K. Forrester; H.-W. Stürzbecher; J.H.J. Hoeijmakers (Jan); C.C. Harris

    1996-01-01

    textabstractThe p53 tumor suppressor gene product is a transcriptional transactivator and a potent apoptotic inducer. The fact that many of the DNA tumor virus oncoproteins bind to p53 and affect these p53 functions indicates that this interaction is an important step in oncogenic transformation. We

  6. Dessiner son parcours professionnel, pour en tirer des enseignements

    Directory of Open Access Journals (Sweden)

    Pascale Corten-Gualtieri

    2011-02-01

    Full Text Available Dans le cadre de la formation continue pour des enseignants du supérieur, une activité d’expression visuelle a soutenu une posture réflexive à propos du développement professionnel de chacun. Il a été demandé aux enseignants de dessiner leur parcours professionnel en le comparant à un parcours routier. Ce dessin a ensuite servi de support aux enseignants pour dégager les leviers et les freins de leur développement professionnel, puis pour clarifier leur(s perspective(s d’évolution professionnelle. Cadrage théorique et échanges en binômes ont enrichi ce regard distancié. L’ensemble de ces activités constitue une préparation efficace et motivante à la rédaction d’un portfolio dans lequel l’enseignant analyse ses pratiques et son développement professionnels. Cet article décrit le cadre théorique et les modalités de cet ensemble d’activités ; il analyse ensuite les résultats obtenus, essentiellement à partir de l’étude du corpus de dessins réalisés par les enseignants, et d’une enquête d’évaluation réalisée auprès de ceux-ci.A recent visual creative activity carried out during a continuous education programme for teachers in higher education enhances reflective practice regarding professional development. Teachers were asked to draw their professional path as they would draw a route map. On the basis of this drawing, they were able to highlight the levers and obstacles in their professional development and then clarify their perspectives in terms of professional growth. This analysis was emphasized using a theoretical framework and exchanges in teams of two. All activities comprised an effective and stimulating preparation for writing a portfolio in which the teachers analyzed their professional practices and development. This article describes the theoretical framework and methods used during these activities; it then analyzes the results obtained based on the study of the various drawings made

  7. 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.…

  8. 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.…

  9. 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.

  10. 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.

  11. SON68 glass dissolution driven by magnesium silicate precipitation

    Science.gov (United States)

    Fleury, Benjamin; Godon, Nicole; Ayral, André; Gin, Stéphane

    2013-11-01

    Experimental results are reported on the effect of magnesium silicate precipitation on the mechanisms and rate of borosilicate glass dissolution. Leaching experiments with SON68 glass, a borosilicate containing no Mg, were carried out in initially deionized water at 50 °C with a glass-surface-area-to-solution-volume ratio of 20,000 m-1. After 29 days of alteration the experimental conditions were modified by the addition of Mg to trigger the precipitation of Mg-silicate. Additional experiments were conducted to investigate the importance of other parameters such as pH or dissolved silica on the mechanisms of precipitation of Mg-silicates and their consequences on the glass dissolution rate. Mg-silicates precipitate immediately after Mg is added. The amount of altered glass increases with the quantity of added Mg, and is smaller when silicon is added in solution. A time lag is observed between the addition of magnesium and the resumption of glass alteration because silicon is first provided by partial dissolution of the previously formed alteration gel. It is shown that nucleation does not limit Mg-silicate precipitation. A pH above 8 is necessary for the phase to precipitate under the investigated experimental conditions. On the other hand the glass alteration kinetics limits the precipitation if the magnesium is supplied in solution at a non-limiting rate. The concentration of i in solution was analyzed as well as that of boron. The quantity of i released from the glass is estimated with the assumption that i and B are released congruently at the glass dissolution front. The remained quantity of the element i is then supposed to be in the gel or in the secondary phase. In this paper, we do not make a difference between gel and hydrated glass using the same word 'gel' whereas Gin et al. [40] makes this difference. Recent papers [40,41] discussed about different key issues related to the passivation properties of the alteration layer including the hydrated glass

  12. 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.

  13. The Plasminogen-Binding Group A Streptococcal M Protein-Related Protein Prp Binds Plasminogen via Arginine and Histidine Residues▿

    Science.gov (United States)

    Sanderson-Smith, Martina L.; Dowton, Mark; Ranson, Marie; Walker, Mark J.

    2007-01-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G streptococci. While competition experiments indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective concentration = 0.34 μM), Prp nonetheless binds plasminogen with high affinity and at physiologically relevant concentrations of plasminogen (Kd = 7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site indicates that unlike the majority of plasminogen receptors, Prp does not interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine of lysine residues Lys96 and Lys101 reduced but did not abrogate plasminogen binding by Prp. Plasminogen binding was abolished only with the additional mutagenesis of Arg107 and His108 to alanine. Furthermore, mutagenesis of Arg107 and His108 abolished plasminogen binding by Prp despite the presence of Lys96 and Lys101 in the binding site. Thus, binding to plasminogen via arginine and histidine residues appears to be a conserved mechanism among plasminogen-binding M proteins. PMID:17012384

  14. The plasminogen-binding group A streptococcal M protein-related protein Prp binds plasminogen via arginine and histidine residues.

    Science.gov (United States)

    Sanderson-Smith, Martina L; Dowton, Mark; Ranson, Marie; Walker, Mark J

    2007-02-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G streptococci. While competition experiments indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective concentration = 0.34 microM), Prp nonetheless binds plasminogen with high affinity and at physiologically relevant concentrations of plasminogen (K(d) = 7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site indicates that unlike the majority of plasminogen receptors, Prp does not interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine of lysine residues Lys(96) and Lys(101) reduced but did not abrogate plasminogen binding by Prp. Plasminogen binding was abolished only with the additional mutagenesis of Arg(107) and His(108) to alanine. Furthermore, mutagenesis of Arg(107) and His(108) abolished plasminogen binding by Prp despite the presence of Lys(96) and Lys(101) in the binding site. Thus, binding to plasminogen via arginine and histidine residues appears to be a conserved mechanism among plasminogen-binding M proteins.

  15. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  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. IL-4 abrogates TH17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells

    Science.gov (United States)

    Guenova, Emmanuella; Skabytska, Yuliya; Hoetzenecker, Wolfram; Weindl, Günther; Sauer, Karin; Tham, Manuela; Kim, Kyu-Won; Park, Ji-Hyeon; Seo, Ji Hae; Ignatova, Desislava; Cozzio, Antonio; Levesque, Mitchell P.; Volz, Thomas; Köberle, Martin; Kaesler, Susanne; Thomas, Peter; Mailhammer, Reinhard; Ghoreschi, Kamran; Schäkel, Knut; Amarov, Boyko; Eichner, Martin; Schaller, Martin; Clark, Rachael A.; Röcken, Martin; Biedermann, Tilo

    2015-01-01

    Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ–producing TH1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12–producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4–mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/TH17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/TH17 responses without blocking IL-12/TH1, selective IL-4–mediated IL-23/TH17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12–dependent TH1 responses. PMID:25646481

  18. Radiosensitization of metformin in pancreatic cancer cells via abrogating the G2 checkpoint and inhibiting DNA damage repair.

    Science.gov (United States)

    Wang, Zheng; Lai, Song-Tao; Ma, Ning-Yi; Deng, Yun; Liu, Yong; Wei, Dong-Ping; Zhao, Jian-Dong; Jiang, Guo-Liang

    2015-12-01

    Recent evidences have demonstrated the potential of metformin as a novel agent for cancer prevention and treatment. Here, we investigated its ability of radiosensitization and the underlying mechanisms in human pancreatic cancer cells. In this study, we found that metformin at 5 mM concentration enhanced the radiosensitivity of MIA PaCa-2 and PANC-1 cells, with sensitization enhancement ratios of 1.39 and 1.27, respectively. Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation. Furthermore, metformin inhibited both expression and irradiation-induced foci formation of Rad51, a key player in homologous recombination repair, ultimately leading to persistent DNA damage, as reflected by γ-H2AX and 53BP1 signaling. Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51. Our data suggest that metformin radiosensitizes pancreatic cancer cells in vitro via abrogation of the G2 checkpoint and inhibition of DNA damage repair. However, the in vivo study is needed to further confirm the findings from the in vitro study.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... that during pregnancy in 1984-1987 were enrolled in a mother-child cohort and gave information on their pre-pregnancy height and weight from which we calculated their BMI. Information on sons' pubertal development, assessed by age when starting regular shaving, voice break, acne and first nocturnal emission...... 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...

  20. Comparison of father-son relationship in Chinese and American films

    Institute of Scientific and Technical Information of China (English)

    倪秀飞

    2015-01-01

    The depiction of human emotions is never lacking in filmography, and affection between family members accounts for the top spot to become the most deeply touching one, especially the father-son relationship. Compared with mother-daughter and mother-son relationship, father-son relationship is often full of tension, turning out to be more introverted. So, in which way do films and television shows at home and broad represent vividly and truly about the father-child relationship?

  1. Mothers' causal explanations for their son's schizophrenia: relationship to depression and guilt.

    Science.gov (United States)

    Natale, A; Barron, C

    1994-08-01

    This study investigated the relationship between mothers' causal explanations for their son's schizophrenia and the depression and guilt mothers experience. Thirty-three mothers who were primary caregivers to a schizophrenic son were interviewed using the Causal Dimension Scale and the Multiscore Depression Inventory. Twenty-nine mothers generated 50 causal explanations for their son's schizophrenia. The most frequently cited causal category was physiological/biological factors. Guilt was associated with causal explanations characterized as internal, whereas depression was unrelated to causal dimensions. The findings support the need to assess mothers' causal explanations for their son's schizophrenia and to research the health consequences of causal explanations.

  2. 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

    2017-02-21

    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.

  3. 78 FR 6128 - Accreditation of R. Markey & Sons, Inc., Markan Laboratories, as a Commercial Laboratory

    Science.gov (United States)

    2013-01-29

    ... SECURITY U.S. Customs and Border Protection Accreditation of R. Markey & Sons, Inc., Markan Laboratories, as a Commercial Laboratory AGENCY: U.S. Customs and Border Protection, Department of Homeland Security. ACTION: Notice of accreditation of R. Markey & Sons, Inc., Markan Laboratories, as a...

  4. 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

  5. Synaptotagmin-1 binds to PIP(2)-containing membrane but not to SNAREs at physiological ionic strength.

    Science.gov (United States)

    Park, Yongsoo; Seo, Jong Bae; Fraind, Alicia; Pérez-Lara, Angel; Yavuz, Halenur; Han, Kyungreem; Jung, Seung-Ryoung; Kattan, Iman; Walla, Peter Jomo; Choi, MooYoung; Cafiso, David S; Koh, Duk-Su; Jahn, Reinhard

    2015-10-01

    The Ca(2+) sensor synaptotagmin-1 is thought to trigger membrane fusion by binding to acidic membrane lipids and SNARE proteins. Previous work has shown that binding is mediated by electrostatic interactions that are sensitive to the ionic environment. However, the influence of divalent or polyvalent ions, at physiological concentrations, on synaptotagmin's binding to membranes or SNAREs has not been explored. Here we show that binding of rat synaptotagmin-1 to membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2) is regulated by charge shielding caused by the presence of divalent cations. Surprisingly, polyvalent ions such as ATP and Mg(2+) completely abrogate synaptotagmin-1 binding to SNAREs regardless of the presence of Ca(2+). Altogether, our data indicate that at physiological ion concentrations Ca(2+)-dependent synaptotagmin-1 binding is confined to PIP2-containing membrane patches in the plasma membrane, suggesting that membrane interaction of synaptotagmin-1 rather than SNARE binding triggers exocytosis of vesicles.

  6. Fertility Intention, Son Preference, and Second Childbirth: Survey Findings from Shaanxi Province of China.

    Science.gov (United States)

    Jiang, Quanbao; Li, Ying; Sanchez-Barricarte, Jesús J

    2016-02-01

    China is characterized by a low fertility intention, a strong preference for sons, as well as a stringent birth control policy. In this study, we used data from a Fertility Intention and Behavior Survey of 2101 questionnaires conducted in 2013 in Shaanxi Province of northwestern China, and event history analysis methods to examine the effect of fertility intention and preference for sons on the probability of having a second child. The results not only validate the correlation of fertility intention with having a second child empirically, even in the low fertility intention and stringent birth control context of China, but also show that women with a preference for sons were less likely to have a second child. Women with son preference turn to sex-selective abortion to ensure that their first child is a son, thus reducing the likelihood of a second child and decreasing the fertility rate. Our findings also shed light on China's potential fertility policy adjustment.

  7. 'Too many girls, too much dowry': son preference and daughter aversion in rural Tamil Nadu, India.

    Science.gov (United States)

    Diamond-Smith, Nadia; Luke, Nancy; McGarvey, Stephen

    2008-10-01

    The southern Indian state of Tamil Nadu has experienced a dramatic decline in fertility, accompanied by a trend of increased son preference. This paper reports on findings from qualitative interviews with women in rural villages about their fertility decision-making. Specifically addressed are the reasons behind increasing son preference and the consequences of this change. Findings suggest that daughter aversion, fuelled primarily by the perceived economic burden of daughters due to the proliferation of dowry, is playing a larger role in fertility decision-making than son preference. The desire for a son is often trumped by the worry over having many daughters. Women use various means of controlling the sex of their children, which in this study appear to be primarily female infanticide. It is important to distinguish between son preference and daughter aversion and to examine repercussions of low fertility within this setting.

  8. Pathways to prevention: improving nonresident African American fathers' parenting skills and behaviors to reduce sons' aggression.

    Science.gov (United States)

    Howard Caldwell, Cleopatra; Antonakos, Cathy L; Assari, Shervin; Kruger, Daniel; De Loney, E Hill; Njai, Rashid

    2014-01-01

    This study describes a test of the Fathers and Sons Program for increasing intentions to avoid violence and reducing aggressive behaviors in 8- to 12-year-old African American boys by enhancing the parenting skills satisfaction and parenting behaviors of their nonresident fathers. The study included 158 intervention and 129 comparison group families. Structural equation model results indicated that the intervention was effective for improving fathers' parenting skills satisfaction, which was positively associated with sons' satisfaction with paternal engagement. Sons' paternal engagement satisfaction was positively associated with their intentions to avoid violence. Although aggressive behaviors were lower for comparison group sons, the intervention effectively reduced sons' aggressive behaviors indirectly by enhancing fathers' parenting behaviors. Support for family-centered youth violence prevention efforts is discussed.

  9. Polyandrous females produce sons that are successful at post-copulatory competition.

    Science.gov (United States)

    Klemme, I; Bäumer, J; Eccard, J A; Ylönen, H

    2014-03-01

    Some of the genetic benefit hypotheses put forward to explain multiple male mating (polyandry) predict that sons of polyandrous females will have an increased competitive ability under precopulatory or post-copulatory competition via paternally inherited traits, such as attractiveness or fertilization efficiency. Here, we tested these predictions by comparing the competitive ability of sons of experimentally monandrous and polyandrous female bank voles (Myodes glareolus), while controlling for potential material and maternal effects. In female choice experiments, we found no clear preference for sons of either monandrous or polyandrous mothers. Moreover, neither male type was dominant over the other, indicating no advantage in precopulatory male contest competition. However, in competitive matings, sons of polyandrous mothers significantly increased their mating efforts (mating duration, intromission number). In line with this, paternity success was biased towards sons of polyandrous mothers. Because there was no evidence for maternal effects, our results suggest that female bank voles gain genetic benefits from polyandry.

  10. 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.

  11. 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

  12. Snakes and snails and mermaid tails: raising a gender-variant son.

    Science.gov (United States)

    Kelso, Tony

    2011-10-01

    This article is a first-person account of a father's journey to lovingly accept his young gender-variant son, who began to show traits and preferences more common to girls almost from birth. The dad's efforts to discover constructive parenting strategies for raising his boy are also detailed. Experiences described begin with guilt and awareness of his own difficulty in coming to terms with his son's behavior, progress toward seeking and finding support and guidance, and eventually learning to embrace his son as he is, perhaps with questions about his own liberality and apprehensions about his boy's future.

  13. Mother-Son Interactions in Families of Boys with Attention-Deficit/hyperactivity Disorder with and without Oppositional Behavior.

    Science.gov (United States)

    Seipp, Carla M.; Johnston, Charlotte

    2005-01-01

    Parenting responsiveness and over-reactivity were assessed among 25 mothers of 7-9-year-old sons with Attention-Deficit/Hyperactivity Disorder (ADHD) and oppositional behavior (Oppositional Defiant, OD), 24 mothers of sons with ADHD only, and 38 mothers of nonproblem sons. Responsiveness was observed during mother-son play and clean-up…

  14. Abrogation of Chk1-mediated S/G2 checkpoint by UCN-01 enhances ara-C-induced cytotoxicity in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Rong-guang SHAO; Chun-Xia CAO; Yves POMMIER

    2004-01-01

    AIM: To investigate whether 7-hydroxystaurosporine (UCN-01) affects cell cycle progression in arabinosylcytosine (ara-C) treated human colon carcinoma HT-29 cells. METHODS: Cytotoxicity, DNA synthesis, cell cycle distribution,protein level, and kinase activity were determined by clonogenic assay, flow cytometry, DNA synthesis assay,immunoblotting, and kinase assays, respectively. RESULTS: UCN-01 abrogated an S/G2-phase checkpoint in HT29 cells treated with ara-C. When UCN-01 was added after treatment with ara-C, the rate of recovery of DNA synthesis was enhanced and colony-forming ability diminished. Thus, premature recovery of DNA synthesis was associated with increased cytotoxicity. Measurements of cyclin A and B protein levels, Cdk2 and Cdc2 kinase activities, Cdc25C phosphorylation, and Chkl kinase activity were consistent with UCN-01-induced abrogation of the S/G2-phase checkpoint in ara-C treated cells. CONCLUSION: The abrogation of the S/G2 checkpoint may be due to inhibition of Chkl kinase by UCN-01. The enhanced cytotoxicity produced when UCN-01 was combined with ara-C suggested a rationale for the use of this drug combination for tumors that might be susceptible to cell cycle checkpoint abrogation.

  15. 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...... 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. DISCUSSION: We describe how educational campaigns aimed at informing the public about the benefits of daughter(s) for older parents...

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

    National Research Council Canada - National Science Library

    Dana Percec

    2014-01-01

    ...-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...

  17. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?".

    Science.gov (United States)

    Teive, Hélio A G; Munhoz, Renato P; Simões, Jefferson C

    2012-04-01

    Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  18. 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

    OBJECTIVES: Previous studies indicate an increased risk of cryptorchidism, incomplete testicular descent, among sons of women working with pesticides. This study assessed the risk of cryptorchidism among boys of parents employed as horticultural workers and farmers using nationwide registers...... 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...... 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...

  19. SON controls cell-cycle progression by coordinated regulation of RNA splicing.

    Science.gov (United States)

    Ahn, Eun-Young; DeKelver, Russell C; Lo, Miao-Chia; Nguyen, Tuyet Ann; Matsuura, Shinobu; Boyapati, Anita; Pandit, Shatakshi; Fu, Xiang-Dong; Zhang, Dong-Er

    2011-04-22

    It has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splicing of cell-cycle regulators. Downregulation of SON leads to severe impairment of spindle pole separation, microtubule dynamics, and genome integrity. These molecular defects result from inadequate RNA splicing of a specific set of cell-cycle-related genes that possess weak splice sites. Furthermore, we show that SON facilitates the interaction of SR proteins with RNA polymerase II and other key spliceosome components, suggesting its function in efficient cotranscriptional RNA processing. These results reveal a mechanism for controlling cell-cycle progression through SON-dependent constitutive splicing at suboptimal splice sites, with strong implications for its role in cancer and other human diseases.

  20. 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.

  1. Sons or Daughters? Endogenous Sex Preferences and the Reversal of the Gender Educational Gap

    OpenAIRE

    Hazan, Moshe; ZOABI, Hosny

    2012-01-01

    This paper provides a new explanation for the narrowing and reversal of the gender education gap. It highlights the indirect effect of returns to human capital on parents' preferences for sons and the resulting demand for children and education. We assume that parents maximize the full income of their children and that males have an additional income, independently of their level of education. This additional income has two effects. First, it biases parental preferences towards sons. Second, ...

  2. 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.

  3. 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.

  4. Some reflections on a case of mother/adolescent son incest.

    Science.gov (United States)

    Shengold, L

    1980-01-01

    A rare case of mother/adolescent son incest is presented. The son, treated in analysis, was not psychotic. Questions are raised about why father/daughter incest appears to be much more common than mother/son incest. Part of the answer, I speculate, has to do with the special psychic dangers for both mother and son, perhaps phylogenetically-based, which attach to the fantasy and the possibility of impregnating the mother. Where the incest taboo is violated, the primary responsibility would appear to be the parent's; the parent is frequently motivated by a compulsion to repeat his or her own incestuous past. In the case presented the probably psychotic mother had raised her son to look like a girl for several years, and he had been the victim of a homosexual assault at the age of 6. The incest at puberty seems to have helped him reverse a psychic position of subjection to the pre-oedipal mother, to have modified his rage and reinforced his masculinity. It also produced some of the arrogance, alongside a need for failure and punishment that evoke the legend of Oedipus. The mother, fearful of the possibility of getting pregnant, had abruptly stopped the incest. It had been repressed, and became conscious again when the son entered analysis. He then left his treatment without being able to work through much of the terror consequent to the consummation of incest, and with some of the feeling of oedipal triumph retained.

  5. Daughters increase longevity of fathers, but daughters and sons equally reduce longevity of mothers.

    Science.gov (United States)

    Jasienska, Grazyna; Nenko, Ilona; Jasienski, Michal

    2006-01-01

    Reproduction is energetically and physiologically expensive, and an individual investing resources into producing offspring should suffer costs such as deterioration in health condition and possibly shorter life span. Since the energetic and nutritional demands of pregnancy and breastfeeding render reproductive costs much higher in women than in men, women with a large number of children should show signs of deterioration in condition, while men with large families should not. However, whether reproductive costs reduce longevity in women is still questionable, and in men this issue has not been adequately addressed. In addition, since sons are energetically more expensive to produce than daughters, having sons should have a more pronounced negative impact on maternal longevity than having daughters. Here we document a striking disparity in the impact of children on the life span of mothers and fathers in a Polish rural population. We show for the first time that number of daughters was positively related to a longer life span of their fathers, increasing their longevity on average by 74 weeks per daughter born, while number of sons did not have a significant effect on paternal longevity. In contrast, in women, the number of daughters and number of sons reduced maternal longevity and did so to the same extent, on average by 95 weeks per son or daughter, indicating that for women, the costs of having sons and daughters are similar.

  6. Matricide by Mentally Disordered Sons: Gaining a Criminological Understanding Beyond Mental Illness--A Descriptive Study.

    Science.gov (United States)

    Catanesi, Roberto; Rocca, Gabriele; Candelli, Chiara; Carabellese, Felice

    2015-12-01

    Matricide is one of the rarest of reported murders and has always been considered one of the most abhorrent crimes. Psychiatric investigations as to why a son might murder his mother yield indications of a high rate of mental illness, primarily psychotic disorders, in perpetrators. In an attempt to gain an in-depth understanding of the role of the mother-son bond in the etiology of matricide by mentally disordered sons, this article presents a qualitative study of nine cases of matricide examined at two Italian Forensic Psychiatry Departments between 2005 and 2010 and retrospective analysis of forensic psychiatry reports on the offenders. Most matricides suffered from psychotic disorders, especially schizophrenia. Nevertheless, not all the perpetrators had psychotic symptoms at the time of the crime. A "pathologic" mother-son bond was found in all cases. However, mental illness is not the only variable related to matricide and, taken alone, is not enough to explain the crime. Several factors in the history of the mother and son need to be probed, especially how their relationship developed over the years. The peculiar dynamics of the mother-son relationship and the unique personalities and life experiences of both subjects are the real key to cases of matricide. © The Author(s) 2014.

  7. 蓝鲸SonD动态服务部署系统%Blue Whale SonD: A Service-on-sDemand Management System

    Institute of Scientific and Technical Information of China (English)

    刘振军; 许鲁; 尹洋

    2005-01-01

    蓝鲸SonD(Service on Demand)服务按需部署系统是一个满足开放、动态环境的服务器部署管理系统.其服务器部署机制能根据应用环境对不同类型和数量服务器的动态需求,将物理服务器资源与存储资源快速、灵活地结合为可运行的服务器供应用系统使用.SonD的服务器部署架构以底层存储为核心,将服务器映像以网络磁盘的形式和物理服务器进行动态绑定来完成部署工作.在存储层次上SonD系统采用一种新型的复合式快照架构,并在此基础上应用块设备级别的缓存共享技术,使得服务器部署系统在服务器创建、再分配以及存储空间占用等方面有显著改进.

  8. Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA.

    Science.gov (United States)

    Subramanian, Aishwarya; Andronache, Adrian; Li, Yao-Cheng; Wade, Mark

    2016-03-29

    BH3 mimetic compounds induce tumor cell death through targeted inhibition of anti-apoptotic BCL2 proteins. Resistance to one such compound, ABT-737, is due to increased levels of anti-apoptotic MCL1. Using chemical and genetic approaches, we show that resistance to ABT-737 is abrogated by inhibition of the mitochondrial RING E3 ligase, MARCH5. Mechanistically, this is due to increased expression of pro-apoptotic BCL2 family member, NOXA, and is associated with MARCH5 regulation of MCL1 ubiquitylation and stability in a NOXA-dependent manner. MARCH5 expression contributed to an 8-gene signature that correlates with sensitivity to the preclinical BH3 mimetic, navitoclax. Furthermore, we observed a synthetic lethal interaction between MCL1 and MARCH5 in MCL1-dependent breast cancer cells. Our data uncover a novel level at which the BCL2 family is regulated; furthermore, they suggest targeting MARCH5-dependent signaling will be an effective strategy for treatment of BH3 mimetic-resistant tumors, even in the presence of high MCL1.

  9. 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.

  10. CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis

    Science.gov (United States)

    Barthels, Christian; Ogrinc, Ana; Steyer, Verena; Meier, Stefanie; Simon, Ferdinand; Wimmer, Maria; Blutke, Andreas; Straub, Tobias; Zimber-Strobl, Ursula; Lutgens, Esther; Marconi, Peggy; Ohnmacht, Caspar; Garzetti, Debora; Stecher, Bärbel; Brocker, Thomas

    2017-01-01

    Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+ dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+ (RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103+ DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103+ DCs in LP and a low frequency of RORγt+Helios− iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity. PMID:28276457

  11. L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation.

    Science.gov (United States)

    Fortin, G; Yurchenko, K; Collette, C; Rubio, M; Villani, A-C; Bitton, A; Sarfati, M; Franchimont, D

    2009-04-01

    Allele variants in the L-carnitine (LCAR) transporters OCTN1 (SLC22A4, 1672 C --> T) and OCTN2 (SLC22A5, -207 G --> C) have been implicated in susceptibility to Crohn's disease (CD). LCAR is consumed in the diet and transported actively from the intestinal lumen via the organic cation transporter OCTN2. While recognized mainly for its role in fatty acid metabolism, several lines of evidence suggest that LCAR may also display immunosuppressive properties. This study sought to investigate the immunomodulatory capacity of LCAR on antigen-presenting cell (APC) and CD4+ T cell function by examining cytokine production and the expression of activation markers in LCAR-supplemented and deficient cell culture systems. The therapeutic efficacy of its systemic administration was then evaluated during the establishment of colonic inflammation in vivo. LCAR treatment significantly inhibited both APC and CD4+ T cell function, as assessed by the expression of classical activation markers, proliferation and cytokine production. Carnitine deficiency resulted in the hyperactivation of CD4+ T cells and enhanced cytokine production. In vivo, protection from trinitrobenzene sulphonic acid colitis was observed in LCAR-treated mice and was attributed to the abrogation of both innate [interleukin (IL)-1beta and IL-6 production] and adaptive (T cell proliferation in draining lymph nodes) immune responses. LCAR therapy may therefore represent a novel alternative therapeutic strategy and highlights the role of diet in CD.

  12. TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation.

    Science.gov (United States)

    Sun, C; Dobi, A; Mohamed, A; Li, H; Thangapazham, R L; Furusato, B; Shaheduzzaman, S; Tan, S-H; Vaidyanathan, G; Whitman, E; Hawksworth, D J; Chen, Y; Nau, M; Patel, V; Vahey, M; Gutkind, J S; Sreenath, T; Petrovics, G; Sesterhenn, I A; McLeod, D G; Srivastava, S

    2008-09-11

    The high prevalence of TMPRSS2-ERG rearrangements ( approximately 60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

  13. History of son preference and sex selection in India and in the west.

    Science.gov (United States)

    Bandyopadhyay, Sutapa; Singh, Amarjeet

    2003-01-01

    In the history of mankind, there was a time when women dominated the world. In due course of time, as the patriarchal societies evolved, the status of women gradually declined. Sons were preferred to daughters. In India, the Brahmin community promoted such customs and rituals, which gave more and more importance to sons eg. Lighting the funeral pyre of the father was told to be a pre-condition for salvation of his spirit. Similarly, in western civilization also women were considered to be weak. In consonance with such a mind-set man has been trying various techniques for sex-selection since antiquity eg. for acquiring a son choosing a special day, time and posture for sexual intercourse, special diet, charms and amulet and prayers etc. In Vedas also punsavana karma has been described as a technique for acquiring a son. Apart from these techniques, female infanticide has also been used as a way to create a male dominated, son-worshipping society. On development of the technique of ultrasonography as an example of progress of science and technology, man has devised a new way of killing females in womb itself, which has resulted in continuous decline in female: male sex ratio in India. To stop this, Indian Govt. promulgated PNDT Act 1994. But considering the widely prevalent practice of use of various regimen of sex-pre-selection by people as well as unscrupulous medical practitioners, Govt. of India has amended this Act (2002). Still, as authors have found in one of their studies, sex-selection drugs are being used widely by north Indians for getting a son. Here, it should be noted that sex-selection methods are being used in west also. But the perspective is different. There, it is not used for female feticide or for acquiring a son. Rather, it is more an effort towards demonstrating the control of man over the NATURE.

  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.

  15. Son Preference in India: Shedding Light on the North-South Gradient

    Directory of Open Access Journals (Sweden)

    Daniela Klaus

    2014-12-01

    Full Text Available Dieser Beitrag liegt nur in englischer Sprache vor. Son preference is widespread in India and deep-rooted in its history. It is a matter of concern because it produces an imbalanced juvenile sex ratio. There are far fewer girls than boys. The figures vary greatly among the Indian states suggesting a major north-south gradient in son preference accompanied by a minor west-east gradient. The aim of this paper is to explain the regional pattern. We provide an application of the value of children-approach according to which the decision to have children is made on the calculus of benefits and costs related to children. In the light of the socioeconomic and sociocultural background in India, we propose that (potential parents’ expectations of benefits and costs are biased in favour of sons. This is suggested, therefore, as the key motivation for the preference for male offspring. However, region-specifics in the level of affluence, the educational level, the mode of production, the meaning and importance of religion, and the kinship regime are assumed to produce stronger son preference in north India compared to south India. This mediation-model is tested using the Indian sub-sample of the international Value of Children-study. Data were collected in Uttar Pradesh (north-central India and Puducherry (south-east India. Mothers aged 16 to 65 were interviewed in 2002 and 2010. Based on 1,173 respondents, a structural equation model was carried out to test the hypothesised composition effects related to the region and the mediating position of sex-specific benefits and costs. Initial findings confirm that the national son preference pattern is more likely to be found among north Indian mothers than south Indian mothers. As assumed, the sex-specific balance of benefits and costs contributes to the explanation of son preference. However, there is little evidence that the benefits and costs mediate between the region-specific socioeconomic and

  16. Two Dimensional Analytical Modeling for SOI and SON MOSFET and Their Performance Comparison

    Directory of Open Access Journals (Sweden)

    Saptarsi Ghosh

    2011-01-01

    Full Text Available During last few decade continuous device performance improvements have been achieved through a combination of device scaling, new device structures and material property improvement to its fundamental limits. Conventional silicon (bulk CMOS technology can’t overcome the fundamental physical limitations belong to sub-micro or nanometer region which leads to alternative device technology like Silicon-on-Insulator (SOI technology and its recent innovative modification Silicon-On-Nothing (SON MOSFET. Analytical simulation is very important to understand the relative performance of those devices under different structural and operational parameter variations. For present analytical simulation asymmetric structure of Silicon-On-Insulator (SOI MOSFET and Silicon-On-Nothing (SON MOSFET are considered. The proposed structure of SON MOSFET is similar to that of the SOI MOSFET with the only exception being the oxide layer here is substituted with air which has much lower permittivity than Silicon-dioxide. Variation of threshold voltage against effective channel lengths is compared for both the structures. From our simulation it is observed that the proposed SON model has lower drain to source current (IDS than SOI model. In our modeling based on solution of two dimensional Poisson’s equation short channel effects such as DIBL and fringing field effects are also taken into account. SON is found to provide better suppression of SCE s than SOI. The results predicted by our analytical simulation hold good agreement with experimental results.

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

    OpenAIRE

    Blanco de Alvarado-Ortiz, Teresa; Facultad de Medicina Humana. Universidad de San Martín de Porres, Lima, Perú.

    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...

  18. Maternal distancing strategies toward twin sons, one with mild hearing loss: a case study.

    Science.gov (United States)

    Muñoz-Silva, Alicia; Sánchez-García, Manuel

    2004-01-01

    The authors apply descriptive and sequential analyses to a mother's distancing strategies toward her 3-year-old twin sons in puzzle assembly and book reading tasks. One boy had normal hearing and the other a mild hearing loss (threshold: 30 dB). The results show that the mother used more distancing behaviors with the son with a hearing loss, and thus gave greater encouragement to this son's cognitive development. These results differ from those of previous studies of deaf or hard of hearing children, whose participants generally had severe or profound hearing loss. In those studies, parents of deaf children used more low-level distancing than parents of normally hearing children. The results of the present study are discussed in terms of their implications for the parenting of twins and of children with mild hearing loss.

  19. Court says mother has right to stop HIV drugs for son.

    Science.gov (United States)

    1998-10-02

    A mother in Maine was charged with child neglect for refusing to administer triple combination therapy to her 4-year-old son, who is HIV positive. The mother based her decision on her own experience with monotherapy and on her older daughter's experiences of the harmful side effects of AZT. Upon her daughter's death, the mother discontinued AZT treatment for herself and her son. After the mother refused a pediatrician's suggestion to start triple combination therapy for her son, the doctor reported the mother to the Department of Human Services, who then charged her with neglect. According to Newport District Judge Douglas Clapp, the mother has shown great concern for her child, and since the relative advantages of the proposed treatment are unclear, the ultimate decision of treatment should be the mother's decision. Many AIDS advocates have stated that antiretroviral therapy has shown significant benefits and recommend that treatment decisions be reached through a trusting partnership between patients and their doctors.

  20. Marital conflict and boys' peer relationships: the mediating role of mother-son emotional reciprocity.

    Science.gov (United States)

    Lindsey, Eric W; MacKinnon-Lewis, Carol; Campbell, Jessica; Frabutt, James M; Lamb, Michael E

    2002-12-01

    This study examined the role of mother-son emotional reciprocity in connections between marital conflict and the quality of boys' peer relationships. Parents from 84 intact families with preadolescent boys reported on the level of conflict in their marital relationship. Observations of mother-son interaction were coded for emotional reciprocity, and assessments of boys' peer relationships were obtained from both teachers and classmates. No direct connection between marital conflict and boys' peer relationships was observed. Rather, marital conflict affected boys' social competence indirectly, through its effect on the emotions expressed between mother and son. The findings support the proposal that emotional processes play an important role in connections between marital conflict and children's peer relationships and suggest that family emotional expressiveness deserves greater attention in both research and intervention.

  1. The Relationship between Paul and His Mother in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    ZhangYanxia

    2010-01-01

    Sons and lovers is the greatest work written by D.H.Lawrence.In the novel,the mother,Mrs Morel devotes all her love on her sons,first on William,who dies after leaving home,then on her second son,Paul,and he also has the affection upon his mother.Thus it makes him incapable of dealing the relationship with other women.This Oedipus complex influences his life and emotion.How does this kind of emotion come into being? Why does Paul have this kind of abnormal love? Maybe there are a lot of reasons,and they will be discussed in detail in the following paragraphs.

  2. Antioxidants Abrogate Alpha-Tocopherylquinone-Mediated Down-Regulation of the Androgen Receptor in Androgen-Responsive Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Alexandra M Fajardo

    Full Text Available Tocopherylquinone (TQ, the oxidation product of alpha-tocopherol (AT, is a bioactive molecule with distinct properties from AT. In this study, AT and TQ are investigated for their comparative effects on growth and androgenic activity in prostate cancer cells. TQ potently inhibited the growth of androgen-responsive prostate cancer cell lines (e.g., LAPC4 and LNCaP cells, whereas the growth of androgen-independent prostate cancer cells (e.g., DU145 cells was not affected by TQ. Due to the growth inhibitory effects induced by TQ on androgen-responsive cells, the anti-androgenic properties of TQ were examined. TQ inhibited the androgen-induced activation of an androgen-responsive reporter and inhibited the release of prostate specific antigen from LNCaP cells. TQ pretreatment was also found to inhibit AR activation as measured using the Multifunctional Androgen Receptor Screening assay. Furthermore, TQ decreased androgen-responsive gene expression, including TM4SF1, KLK2, and PSA over 5-fold, whereas AT did not affect the expression of androgen-responsive genes. Of importance, the antiandrogenic effects of TQ on prostate cancer cells were found to result from androgen receptor protein down-regulation produced by TQ that was not observed with AT treatment. Moreover, none of the androgenic endpoints assessed were affected by AT. The down-regulation of androgen receptor protein by TQ was abrogated by co-treatment with antioxidants. Overall, the biological actions of TQ were found to be distinct from AT, where TQ was found to be a potent inhibitor of cell growth and androgenic activity in androgen-responsive prostate cancer cells.

  3. Oral delivery of Brucella spp. recombinant protein U-Omp16 abrogates the IgE-mediated milk allergy

    Science.gov (United States)

    Smaldini, Paola Lorena; Ibañez, Andrés Esteban; Fossati, Carlos Alberto; Cassataro, Juliana; Docena, Guillermo Horacio

    2014-01-01

    Food allergies are increasingly common disorders and no therapeutic strategies are yet approved. The unlipidated Omp16 (U-Omp16) is the outer membrane protein of 16 kDa from B. abortus and possesses a mucosal adjuvant property. In this study, we aimed to examine the U-Omp16 capacity to abrogate an allergen-specific Th2 immune response when it is administered as an oral adjuvant in a mouse model of food allergy.   Balb/c mice were sensitized with cholera toxin and cow’s milk proteins (CMP) by gavage and simultaneously treated with U-Omp16 and CMP. Oral challenge with CMP was performed to evaluate the allergic status of mice. Symptoms, local (small bowel cytokine and transcription factor gene expression) and systemic (specific isotypes and spleen cell-secreted cytokines) parameters, and skin tests were done to evaluate the immune response. We found that the oral administration of U-Omp16 with CMP during sensitization dampened the allergic symptoms, with negativization of immediate skin test and increased skin DTH response. Serum specific IgE and IL-5 were inhibited and a Th1 response was promoted (specific IgG2a antibodies and CMP-induced IFN-γ secretion). We found at the mucosal site an inhibition of the gene expression corresponding to IL-13 and Gata-3, with an induction of IFN-γ and T-bet. These results indicated that the oral administration of U-Omp16 significantly controlled the allergic response in sensitized mice with a shift of the balance of Th1- and Th2-T cells toward Th1 predominance. These findings suggest that U-Omp16 may be useful as a Th1-directing adjuvant in an oral vaccine. PMID:25424811

  4. 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.

  5. Transformation abrogates an early G1-phase arrest point required for specification of the Chinese hamster DHFR replication origin.

    Science.gov (United States)

    Wu, J R; Keezer, S M; Gilbert, D M

    1998-03-16

    The origin decision point (ODP) was originally identified as a distinct point during G1-phase when Chinese hamster ovary (CHO) cell nuclei experience a transition that is required for specific recognition of the dihydrofolate reductase (DHFR) origin locus by Xenopus egg extracts. Passage of cells through the ODP requires a mitogen-independent protein kinase that is activated prior to restriction point control. Here we show that inhibition of an early G1-phase protein kinase pathway by the addition of 2-aminopurine (2-AP) prior to the ODP arrests CHO cells in G1-phase. Transformation with simian virus 40 (SV40) abrogated this arrest point, resulting in the entry of cultured cells into S-phase in the presence of 2-AP and a disruption of the normal pattern of initiation sites at the DHFR locus. Cells treated with 2-AP after the ODP initiated replication specifically within the DHFR origin locus. Transient exposure of transformed cells to 2-AP during the ODP transition also disrupted origin choice, whereas non-transformed cells arrested in G1-phase and then passed through a delayed ODP after removal of 2-AP from the medium. We conclude that mammalian cells have many potential sites at which they can initiate replication. Normally, events occurring during the early G1-phase ODP transition determine which of these sites will be the preferred initiation site. However, if chromatin is exposed to S-phase-promoting factors prior to this transition, mammalian cells, like Xenopus and Drosophila embryos, can initiate replication without origin specification.

  6. Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-β.

    Science.gov (United States)

    Boye, Louise; Welsby, Iain; Lund, Lisbeth Drozd; Goriely, Stanislas; Frøkiaer, Hanne

    2016-11-01

    Lactobacillus acidophilus induces a potent interferon-β (IFN-β) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -dependent mechanism, in turn leading to strong interleukin-12 (IL-12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus-induced IFN-β and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-β and IL-12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) -dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-β and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN-β and IL-12 production is inhibited by TLR stimulation from the plasma membrane.

  7. A combination of an anti-SLAMF6 antibody and ibrutinib efficiently abrogates expansion of chronic lymphocytic leukemia cells

    Science.gov (United States)

    Yigit, Burcu; Halibozek, Peter J.; Chen, Shih-Shih; O'Keeffe, Michael S.; Arnason, Jon; Avigan, David; Gattei, Valter; Bhan, Atul; Cen, Osman; Longnecker, Richard; Chiorazzi, Nicholas; Wang, Ninghai; Engel, Pablo; Terhorst, Cox

    2016-01-01

    The signaling lymphocyte activation molecule family [SLAMF] of cell surface receptors partakes in both the development of several immunocyte lineages and innate and adaptive immune responses in humans and mice. For instance, the homophilic molecule SLAMF6 (CD352) is in part involved in natural killer T cell development, but also modulates T follicular helper cell and germinal B cell interactions. Here we report that upon transplantation of a well-defined aggressive murine B220+CD5+ Chronic Lymphocytic Leukemia (CLL) cell clone, TCL1-192, into SCID mice one injection of a monoclonal antibody directed against SLAMF6 (αSlamf6) abrogates tumor progression in the spleen, bone marrow and blood. Similarly, progression of a murine B cell lymphoma, LMP2A/λMyc, was also eliminated by αSlamf6. But, surprisingly, αSLAMF6 neither eliminated TCL1-192 nor LMP2A/λMyc cells, which resided in the peritoneal cavity or omentum. This appeared to be dependent upon the tumor environment, which affected the frequency of sub-populations of the TCL1-192 clone or the inability of peritoneal macrophages to induce Antibody Dependent Cellular Cytotoxicity (ADCC). However, co-administering αSlamf6 with the Bruton tyrosine kinase (Btk) inhibitor, ibrutinib, synergized to efficiently eliminate the tumor cells in the spleen, bone marrow, liver and the peritoneal cavity. Because an anti-human SLAMF6 mAb efficiently killed human CLL cells in vitro and in vivo, we propose that a combination of αSlamf6 with ibrutinib should be considered as a novel therapeutic approach for CLL and other B cell tumors. PMID:27029059

  8. Vaccinating sons against HPV: results from a U.S. national survey of parents.

    Directory of Open Access Journals (Sweden)

    Jaime L Taylor

    Full Text Available PURPOSE: The quadrivalent HPV vaccination was approved for use in males ages 9 to 26 in 2009 and recommended for routine administration in 2011. The purpose of this study was to uncover predictable commonalities amongst parents who chose to vaccinate their 11-17 year old sons against HPV. METHODS: We compiled data from a U.S. national sample of 779 parents with sons 11-17 years old using a web-based survey to gather information about behavioral and sociodemographic factors which predicted receipt of 1 or more HPV vaccine doses based on parental report. Predictors were first modeled individually for univariable associations. Significant predictors (p<0.10 were combined in a multivariable model. RESULTS: In the adjusted model, independent predictors included receipt of flu vaccination, health insurance coverage and sexual health topic discussions with sons. Sons who had received a flu shot in the last two years more frequently received at least one dose of the vaccine (OR 1.82; 95% CI 1.45-2.26. Sons covered by private health insurance had decreased odds of HPV vaccination (OR 0.56 95% CI 0.37-0.83. Lastly, parents who had discussed sexual health topics with their sons were more likely to vaccinate (OR 1.61; 95% CI 1.37-1.89. CONCLUSIONS: Male vaccination rates in the U.S. have increased, but males continue to be under-immunized. Utilization of health care is an important factor in HPV vaccine uptake; therefore, health care providers should use every contact as an opportunity to vaccinate. Communication about sexual health topics may provide a forum for parents and health care providers to have conversations about HPV vaccination as those more comfortable discussing these topics may also be more comfortable discussing HPV vaccination.

  9. Proyecto de consolidación de Son Espases Vell, Palma de Mallorca

    OpenAIRE

    ANTÓN ESTEVE, NURIA

    2011-01-01

    Trabajo científico técnico. El presente proyecto se centra en la consolidación de una casa pallesa, antigua casa de aperos, situada en el solar de Son Espases, de proporciones humildes y con diversas intervenciones a lo largo de distintas épocas, y que guarda muchos de los elementos tradicionales de la arquitectura popular mallorquina, así como sus sistemas constructivos. Antón Esteve, N. (2011). Proyecto de consolidación de Son Espases Vell, Palma de Mallorca. http://hdl.handle.net/10251/...

  10. Jarana y Fandango son símbolos de la nueva identidad de México

    OpenAIRE

    Bruno Bartra

    2015-01-01

    En la última década el son jarocho, música originaria del Estado mexicano de Veracruz, se ha abierto paso en la escena musical neoyorquina. Vinculada a una diáspora de clase media conformada por músicos profesionales, intérpretes y profesores, así como por empresarios cuyos lujosos restaurantes en Manhattan o Brooklyn sirven como foros para estos artistas, lideran esta escena Bandas como Radio Jarocho o Jarana Beat, que comparten dos objetivos musicales: por un lado, fusionar el son jarocho c...

  11. Proyecto de consolidación de Son Espases Vell, Palma de Mallorca

    OpenAIRE

    ANTÓN ESTEVE, NURIA

    2011-01-01

    Trabajo científico técnico. El presente proyecto se centra en la consolidación de una casa pallesa, antigua casa de aperos, situada en el solar de Son Espases, de proporciones humildes y con diversas intervenciones a lo largo de distintas épocas, y que guarda muchos de los elementos tradicionales de la arquitectura popular mallorquina, así como sus sistemas constructivos. Antón Esteve, N. (2011). Proyecto de consolidación de Son Espases Vell, Palma de Mallorca. http://hdl.handle.net/10251/...

  12. Les descripteurs d'un son Librairie Matlab SPL et fichiers de descriptions ".sig""

    OpenAIRE

    Lemaitre, Guillaume; Gallo, Emmanuel

    2006-01-01

    Le traitement du signal audio rapide travaille avec des descriptions compactes des sons plutôt qu'avec les sons eux-mêmes. Dans une première partie nous introduisons cette notion de description et nous proposons un état de l'art des différents types de description utilisés. Ces descriptions incorporent le plus souvent des quantités telles que l'énergie ou le spectre de puissance à court-terme. Cependant, énergie et puissance sont des concepts qui sont souvent confondus ou mal interprétés, et ...

  13. An Analysis on Paul's Emotional Experience with Freud's Psychoanalytical Theory in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    胡嘉薏; 范丽娟

    2016-01-01

    David Herbert Lawrence is one of the most important and controversial writers. Sons and Lovers, one of .his most influential novels, is his first full-length and semi-autobiographical novel. This novel describes the growing process and the emotional experiences of a coal mine worker's son Paul. This paper takes Freud's psychoanalytic theory as the theoretical basis. By analyzing three different patterns of relationships among Paul and three women, including mother Morel, lover Miriam and mistress Clara, this paper finally comes to a conclusion that the real love should be based on the harmony of the personality structure and the unity of the body and the soul.

  14. The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

    OpenAIRE

    Nozoe, Karen T.; Helena Hachul, MD, PhD; Camila Hirotsu, PhD; Daniel N. Polesel, MSc; Gustavo A. Moreira, MD, PhD; Sergio Tufik, MD, PhD; Monica L. Andersen, PhD

    2014-01-01

    Introduction: The task of the caregiver, especially a caregiving mother of a son with a chronic and fatal disease, may interfere with their quality of sleep, sexuality, and some hormone levels. Aim: The aim of this study was to evaluate the sexual function and the quality of sleep of caregiving mothers of sons with Duchenne muscular dystrophy (DMD). Methods: We evaluated 20 caregiving mothers of sons with DMD and 20 caregiving mothers of sons without any neuromuscular or chronic disease...

  15. Attention deficit hyperactivity disorder associated with orbitofrontal epilepsy in a father and a son.

    Science.gov (United States)

    Powell, A L; Yudd, A; Zee, P; Mandelbaum, D E

    1997-04-01

    The authors report on a father and son with frontal lobe epilepsy and symptoms of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity is a syndrome defined by criteria that include inattention, impulsive behavior, impaired concentration and motor restlessness. It does not require medical or neurobehavioral evaluation to determine an underlying etiology. The father is a 45-year-old man evaluated for possible ADHD. His referral came after the diagnosis of ADHD in his 6-year-old son who responded well to treatment with methylphenidate HCL. Neurobehavioral evaluation of the father suggested frontal lobe dysfunction. Magnetic resonance imaging and electroencephalography (EEG) were normal. Brain 99mTc HMPAO single-photon emission computed tomography (SPECT) revealed left orbitofrontal hypoperfusion. Additional history from his wife revealed episodic symptoms suggestive of nonconvulsive epilepsy that included nonresponsive staring, complex automatic behavior, and amnesic lacunas. Treatment of the father with carbmazepine produced dramatic improvement. Subsequent evaluation of his son, currently on maintenance treatment with methylphenidate HCL for ADHD, elicited a history consistent with atonic and simple motor partial epilepsy. The son's brain SPECT revealed bilateral orbitofrontal hypoperfusion defects. Attention deficit hyperactivity disorder is a syndrome that may be caused by frontal lobe lesions or epilepsy. In the setting of possible ADHD, neurological evaluation is warranted. Although overreliance on structural imaging or EEG in such an evaluation must be discouraged, brain SPECT may be useful to evaluate patients with symptoms of attention disorders for frontal epilepsy.

  16. Non-commutative Poisson Algebra Structures on the Lie Algebra son(CQ)

    Institute of Scientific and Technical Information of China (English)

    Jie Tong; Quanqin Jin

    2007-01-01

    Non-commutative Poisson algebras are the algebras having both an associativealgebra structure and a Lie algebra structure together with the Leibniz law.In this paper,the non-commutative poisson algebra structures on son(CQ) are determined.

  17. 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…

  18. 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.

  19. 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.

  20. Familial achalasia of the esophagus in mother and son: a possible pathogenetic relationship.

    Science.gov (United States)

    Chawla, K; Chawla, S K; Alexander, L L

    1979-11-01

    Familial achalasia most often has been recorded in siblings, and only rarely (twice previously) in a parent and offspring. This report concerns a third case of achalasia in a parent and offspring (mother and son). Clinical and radiographic features of the esophageal achalasia are presented. The possibility that genetic factors may play a role in the etiology of this disorder is discussed.

  1. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?"

    Directory of Open Access Journals (Sweden)

    Hélio A. G. Teive

    2012-04-01

    Full Text Available Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  2. Men as caregivers of the elderly: support for the contributions of sons

    Directory of Open Access Journals (Sweden)

    Collins CR

    2014-11-01

    Full Text Available Cynthia R Collins Loyola University New Orleans, College of Social Sciences/School of Nursing, New Orleans, LA, USA Abstract: Emerging practice research on filial sources of health care support has indicated that there is a growing trend for sons to assume some responsibility for the health care needs of their aging parents. The purpose of this work is to propose that outcomes observed through a secondary analysis of data from a previous mixed methods research project, conducted with a sample of 60 elderly women residing in independent living centers, supports this concept in elder care. The present study is a retrospective interpretation utilizing the original database to examine the new question, “What specific roles do sons play in caregiving of their elderly mothers?” While daughters presently continue to emerge in existing health care studies as the primary care provider, there is a significant pattern in these data for older patients to depend upon sons for a variety of instrumental activities of daily living. As the baby-boomers age, there is more of cohort trend for their families to be smaller, adult daughters to be employed, and for adult children to be more geographically mobile. These factors may combine to make health care support networks more limited for the current aging population, challenging the elderly and their health care providers to revisit the cultural gender norms that are used to identify caregivers. Keywords: sons as caregivers, male caregivers, aging parents, filial support, informal caregivers 

  3. Analysis of the Female Images in Sons and Lovers from the Feminist Perspective

    Institute of Scientific and Technical Information of China (English)

    付晓芳

    2015-01-01

    This thesis is an attempt to analyze the novel Sons and Lovers from the feminist perspective to expose women's suppressed and subordinate situation as “the other” in the patriarchal society, and to unmask the repression and predicament of immanent women.

  4. Better-surviving barn swallow mothers produce more and better-surviving sons.

    Science.gov (United States)

    Romano, Andrea; Costanzo, Alessandra; Caprioli, Manuela; Parolini, Marco; Ambrosini, Roberto; Rubolini, Diego; Saino, Nicola

    2016-05-01

    Sex allocation theory predicts that parents are selected to bias their progeny sex ratio (SR) toward the sex that will benefit the most from parental quality. Because parental quality may differentially affect survival of sons and daughters, a pivotal test of the adaptive value of SR adjustment is whether parents overproduce offspring of the sex that accrues larger fitness advantages from high parental quality. However, this crucial test of the long-term fitness consequences of sex allocation decisions has seldom been performed. In this study of the barn swallow (Hirundo rustica), we showed a positive correlation between the proportion of sons and maternal annual survival. We then experimentally demonstrated that this association did not depend on the differential costs of rearing offspring of either sex. Finally, we showed that maternal lifespan positively predicted lifespan of sons but not of daughters. Because in barn swallows lifespan is a strong determinant of lifetime reproductive success, the results suggest that mothers overproduce offspring of the sex that benefits the most from maternal quality. Hence, irrespective of mechanisms causing the SR bias and mother-son covariation in lifespan, we provide strong evidence that sex allocation decisions of mothers can highly impact on their lifetime fitness.

  5. Terascale Physics Opportunities at a High Statistics, High Energy Neutrino Scattering Experiment: NuSOnG

    CERN Document Server

    Adams, T; Bugel, L; Camilleri, L; Conrad, J M; De Gouvêa, A; Fisher, P H; Formaggio, J A; Jenkins, J; Karagiorgi, G; Kobilarcik, T R; Kopp, S; Kyle, G; Loinaz, W A; Mason, D A; Milner, R; Moore, R; Morfín, J G; Nakamura, M; Naples, D; Nienaber, P; Olness, F I; Owens, J F; Pate, S F; Pronin, A; Seligman, W G; Shaevitz, M H; Schellman, H; Schienbein, I; Syphers, M J; Tait, T M P; Takeuchi, T; Tan, C Y; Van de Water, R G; Yamamoto, R K; Yu, J Y

    2008-01-01

    This article presents the physics case for a new high-energy, ultra-high statistics neutrino scattering experiment, NuSOnG (Neutrino Scattering on Glass). This experiment uses a Tevatron-based neutrino beam to obtain over an order of magnitude higher statistics than presently available for the purely weak processes $\

  6. the glory of the son of man in revelation 13. reflections on mysticism ...

    African Journals Online (AJOL)

    The second part then explains the vision in terms of the mystical revelation .... insights about the angelic, glorious status of the Son of Man affect the way in ...... hair, white like wool and eyes that made the whole house bright like the sun so that ...

  7. Revisiting the streptavidin-biotin binding by using an aptamer and displacement isothermal calorimetry titration.

    Science.gov (United States)

    Kuo, Tai-Chih; Tsai, Ching-Wei; Lee, Peng-Chen; Chen, Wen-Yih

    2015-03-01

    The association constant of a well-known streptavidin-biotin binding has only been inferred from separately measured kinetic parameters. In a single experiment, we obtained Ka 1 × 10(12)  M(-1) by using a streptavidin-binding aptamer and ligand-displacement isothermal titration calorimetry. This study explores the challenges of determining thermodynamic parameters and the derived equilibrium binding affinity of tight ligand-receptor binding. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Hepatitis C Virus Core Protein Abrogates the DDX3 Function That Enhances IPS-1-Mediated IFN–Beta Induction

    OpenAIRE

    2010-01-01

    The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR) protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta promoter activation,...

  9. Major ion chemistry of the Son River, India: Weathering processes, dissolved fluxes and water quality assessment

    Indian Academy of Sciences (India)

    Chinmaya Maharana; Sandeep Kumar Gautam; Abhay Kumar Singh; Jayanth K Tripathi

    2015-08-01

    River Son, draining diverse lithologies in the subtropical climate of the peninsular sub-basin of the Ganga basin, is one of the major tributaries of the Ganga River. 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 major ionic species in the river water. Most of the measured parameters exhibit a relatively lower concentration in the post-monsoon as compared to pre-monsoon season. The water chemistry highlights the influence of continental weathering aided by secondary contributions from ground water, saline/alkaline soils and anthropogenic activities in the catchment. Results also reflect the dominance of carbonate weathering over silicate weathering in controlling water composition. The Son River delivers about 4.2 million tons of dissolved loads annually to the Ganga River, which accounts for ∼6% of the total annual load carried by the Ganga River to the Bay of Bengal. The average CDR of the Son River is 59.5 tons km−2 yr−1, which is less than the reported 72 tons km−2 yr−1 of the Ganga River and higher than the global average of 36 tons km−2 yr−1. The water chemistry for the pre-monsoon and post-monsoon periods shows a strong seasonal control on solute flux and CDR values. The water chemistry indicates that the Son River water is good to excellent in quality for irrigation and also suitable for drinking purposes.

  10. Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.

    Directory of Open Access Journals (Sweden)

    Rebecca K Chance

    2015-09-01

    Full Text Available Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and vertebrates. Here we show that endocytic trafficking of the Robo receptor in response to Slit-binding is necessary for its repulsive signaling output. Dose-dependent genetic interactions and in vitro Robo activation assays support a role for Clathrin-dependent endocytosis, and entry into both the early and late endosomes as positive regulators of Slit-Robo signaling. We identify two conserved motifs in Robo's cytoplasmic domain that are required for its Clathrin-dependent endocytosis and activation in vitro; gain of function and genetic rescue experiments provide strong evidence that these trafficking events are required for Robo repulsive guidance activity in vivo. Our data support a model in which Robo's ligand-dependent internalization from the cell surface to the late endosome is essential for receptor activation and proper repulsive guidance at the midline by allowing recruitment of the downstream effector Son of Sevenless in a spatially constrained endocytic trafficking compartment.

  11. Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.

    Science.gov (United States)

    Chance, Rebecca K; Bashaw, Greg J

    2015-09-01

    Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and vertebrates. Here we show that endocytic trafficking of the Robo receptor in response to Slit-binding is necessary for its repulsive signaling output. Dose-dependent genetic interactions and in vitro Robo activation assays support a role for Clathrin-dependent endocytosis, and entry into both the early and late endosomes as positive regulators of Slit-Robo signaling. We identify two conserved motifs in Robo's cytoplasmic domain that are required for its Clathrin-dependent endocytosis and activation in vitro; gain of function and genetic rescue experiments provide strong evidence that these trafficking events are required for Robo repulsive guidance activity in vivo. Our data support a model in which Robo's ligand-dependent internalization from the cell surface to the late endosome is essential for receptor activation and proper repulsive guidance at the midline by allowing recruitment of the downstream effector Son of Sevenless in a spatially constrained endocytic trafficking compartment.

  12. Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, L-NAME and L-arginine worsen.

    Science.gov (United States)

    Medvidovic-Grubisic, Maria; Stambolija, Vasilije; Kolenc, Danijela; Katancic, Jadranka; Murselovic, Tamara; Plestina-Borjan, Ivna; Strbe, Sanja; Drmic, Domagoj; Barisic, Ivan; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag

    2017-08-01

    Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects. Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV. L-NAME + magnesium-rats and L-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, L-NAME + L-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by L-NAME or L-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro. BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both L-NAME and L-arginine to affect the same events adversely. These events were also opposed by BPC 157.

  13. Abrogation of E-cadherin-mediated cellular aggregation allows proliferation of pluripotent mouse embryonic stem cells in shake flask bioreactors.

    Directory of Open Access Journals (Sweden)

    Lisa Mohamet

    Full Text Available BACKGROUND: A fundamental requirement for the exploitation of embryonic stem (ES cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of a consistent quality in a cost-effective manner. However, undifferentiated ES cells are not ideally suited to suspension culture due to the formation of cellular aggregates, ultimately limiting scalability. Significant advances have been made in recent years in the culture of ES cells, including automated adherent culture and suspension microcarrier or embryoid body bioreactor culture. However, each of these methods exhibits specific disadvantages, such as high cost, additional downstream processes or reduced cell doubling times. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that abrogation of the cell surface protein E-cadherin, using either gene knockout (Ecad-/- or the neutralising antibody DECMA-1 (EcadAb, allows culture of mouse ES cells as a near-single cell suspension in scalable shake flask culture over prolonged periods without additional media supplements. Both Ecad-/- and EcadAb ES cells exhibited adaptation phases in suspension culture, with optimal doubling times of 7.3 h±0.9 and 15.6 h±4.7 respectively and mean-fold increase in viable cell number of 95.1±2.0 and 16±0.9-fold over 48 h. EcadAb ES cells propagated as a dispersed cell suspension for 15 d maintained expression of pluripotent markers, exhibited a normal karyotype and high viability. Subsequent differentiation of EcadAb ES cells resulted in expression of transcripts and proteins associated with the three primary germ layers. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of the culture of pluripotent ES cells as a near-single cell suspension in a manual fed-batch shake flask bioreactor and represents a significant improvement on current ES cell culture techniques. Whilst this proof-of-principle method would be useful for the culture of human ES and iPS cells, further steps are

  14. Abrogation of Nrf2 impairs antioxidant signaling and promotes atrial hypertrophy in response to high-intensity exercise stress.

    Science.gov (United States)

    Kumar, Radhakrishnan Rajesh; Narasimhan, Madhusudhanan; Shanmugam, Gobinath; Hong, Jennifer; Devarajan, Asokan; Palaniappan, Sethu; Zhang, Jianhua; Halade, Ganesh V; Darley-Usmar, Victor M; Hoidal, John R; Rajasekaran, Namakkal S

    2016-04-05

    Anomalies in myocardial structure involving myocyte growth, hypertrophy, differentiation, apoptosis, necrosis etc. affects its function and render cardiac tissue more vulnerable to the development of heart failure. Although oxidative stress has a well-established role in cardiac remodeling and dysfunction, the mechanisms linking redox state to atrial cardiomyocyte hypertrophic changes are poorly understood. Here, we investigated the role of nuclear erythroid-2 like factor-2 (Nrf2), a central transcriptional mediator, in redox signaling under high intensity exercise stress (HIES) in atria. Age and sex-matched wild-type (WT) and Nrf2(-/-) mice at >20 months of age were subjected to HIES for 6 weeks. Gene markers of hypertrophy and antioxidant enzymes were determined in the atria of WT and Nrf2(-/-) mice by real-time qPCR analyses. Detection and quantification of antioxidants, 4-hydroxy-nonenal (4-HNE), poly-ubiquitination and autophagy proteins in WT and Nrf2(-/-) mice were performed by immunofluorescence analysis. The level of oxidative stress was measured by microscopical examination of di-hydro-ethidium (DHE) fluorescence. Under the sedentary state, Nrf2 abrogation resulted in a moderate down regulation of some of the atrial antioxidant gene expression (Gsr, Gclc, Gstα and Gstµ) despite having a normal redox state. In response to HIES, enlarged atrial myocytes along with significantly increased gene expression of cardiomyocyte hypertrophy markers (Anf, Bnf and β-Mhc) were observed in Nrf2(-/-) when compared to WT mice. Further, the transcript levels of Gclc, Gsr and Gstµ and protein levels of NQO1, catalase, GPX1 were profoundly downregulated along with GSH depletion and increased oxidative stress in Nrf2(-/-) mice when compared to its WT counterparts after HIES. Impaired antioxidant state and profound oxidative stress were associated with enhanced atrial expression of LC3 and ATG7 along with increased ubiquitination of ATG7 in Nrf2(-/-) mice subjected to HIES

  15. Instabilities of Spherical Solutions with Multiple Galileons and SO(N) Symmetry

    CERN Document Server

    Andrews, Melinda; Khoury, Justin; Trodden, Mark

    2010-01-01

    The 4-dimensional effective theory arising from an induced gravity action for a co-dimension greater than one brane consists of multiple galileon fields pi^I, I=1...N, invariant under separate Galilean transformations for each scalar, and under an internal SO(N) symmetry. We study the viability of such models by examining spherically symmetric solutions. We find that for general, non-derivative couplings to matter invariant under the internal symmetry, such solutions exist and exhibit a Vainshtein screening effect. By studying perturbations about such solutions, we find both an inevitable gradient instability and fluctuations propagating at superluminal speeds. These findings suggest that more general, derivative couplings to matter are required for the viability of SO(N) galileon theories.

  16. Mesure ambulatoire de la pression artérielle, son utilité en pratique quotidienne

    OpenAIRE

    Krzesinski, Jean-Marie

    1994-01-01

    Si la nécessité du traitement de l'hypertension artérielle est un fait accepté de façon universelle, la question à propos des niveaux de pression artérielle qui méritent une intervention reste débattue. Cette difficulté trouve son origine dans une telle variabilité de la pression artérielle que les mesures au cabinet de consultation représentent seulement une vue limitée de son réel profil sur 24 heures. Le développement d'enregistreurs portatifs de la pression artérielle par méthode non i...

  17. Planning a Career in Engineering: Parental Effects on Sons and Daughters

    Directory of Open Access Journals (Sweden)

    Jerry A. Jacobs

    2017-01-01

    Full Text Available This paper examines the extent to which prospective engineers follow in their parents’ footsteps. Specifically, we investigate the connection between fathers’ and mothers’ employment in the engineering profession and the career plans of sons and daughters. We develop a number of reasons to expect an occupation-specific intergenerational association in this field, as well as hypotheses regarding gender-specific role-modeling. Data are drawn from the UCLA HERI Freshman Survey data spanning 1971 to 2011. The results point to clear and substantial effects on sons and daughters’ plans to pursue engineering, connections that cannot be explained by typical pathways such as social background, education and values. The evidence points to a pattern of increasing salience of mothers with respect to the career plans of their children, especially their daughters. The implications of these findings for the under-representation of women in engineering and for gender-specific family dynamics are discussed in the conclusion.

  18. 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 includes Jon Engle sitting on side door frame working on portion of wing. Joe Engle is behind him working on a wing strut (34329); Joe Engle works on tightening bolt (34330); Jon Engle works on portion of wing which connects to the cockpit. Joe Engle works on connecting strut to wing (34331).

  19. Pragmatic Analysis of a Dialogue in Laurence’s Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    李桂芝; 马宏

    2008-01-01

    This article provides a pragmatic analysis of a dialogue in Laurence’s Sons and Lovers from the perspectives of turn-taking,cooperative principle,politeness principle and speech act theory. A detailed analysis shows that pragmatic theories provide a good approach to the appreciation of fiction and that such kind of analysis based on a relatively precise methodology proves to be an effective approach to capture the richness of characters.

  20. 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 includes Jon Engle sitting on side door frame working on portion of wing. Joe Engle is behind him working on a wing strut (34329); Joe Engle works on tightening bolt (34330); Jon Engle works on portion of wing which connects to the cockpit. Joe Engle works on connecting strut to wing (34331).

  1. The mystery of the perpetual motion clock of Geiser and Son

    Science.gov (United States)

    Piguet, Jean-Michel

    A description of the operation and mechanisms of a so called perpetual motion clock is given. At the end of the 18th and beginning of the 19th century, the achievement of perpetual motion was one of the Neuchatel clockmakers' great interests. Some watchmakers presented scientists and the public with constructions which, at first sight, seemed to have solved the problem. In 1815 a really interesting clock mechanism invented by Jean Geiser and his son was presented in Neuchatel.

  2. ‘Lest we forget’*: a veteran and son share a ‘warfare tourism’ experience

    OpenAIRE

    Fallon, Paul; Robinson, Peter

    2016-01-01

    Warfare tourism’ represents an increasingly significant dimension of contemporary tourism. This paper provides a fresh perspective on participation in ‘warfare tourism’ by investigating the behaviour and experiences of a living veteran and his son returning to two theatres of war in which the veteran had served in the Royal Navy during the Second World War. Active interviews with the two family members were used to gather rich data regarding the two extended trips, which had been funded by ‘H...

  3. 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.

  4. Evaluasi Algoritma Wouthuyzen dan Son untuk Pendugaan Sea Surface Salinity (SSS (Studi Kasus: Perairan Utara Pamekasan

    Directory of Open Access Journals (Sweden)

    Nafizah - Nafizah

    2017-01-01

    Full Text Available Pulau Madura merupakan pulau penghasil garam terbesar di Indonesia. Salah satu parameter yang digunakan dalam penentuan daerah potensi tambak garam adalah salinitas perairan (Sea Surface Salinity. Untuk memetakan persebaran salinitas perairan sebagai salah satu data pendukung dalam menganalisis potensi tambak garam dapat memanfaatkan citra satelit. Berbagai metode ekstraksi informasi salinitas perairan telah dikembangkan dan dimanfaatkan. Pengkajian pengukuran salinitas telah dilakukan dan menghasilkan algoritma salinitas perairan. Dalam penelitian ini, dilakukan evaluasi pada dua algoritma yang berbeda yaitu algoritma Wouthuyzen (2008 dan algoritma Son (2009 untuk melakukan estimasi nilai salinitas perairan di perairan utara Pamekasan, Madura. Sebelum dilakukan pemrosesan dengan algoritma, Citra Landsat-8 1T dikoreksi atmosfer dengan Second Simulation of a Satellite Signal in the Solar Spectrum-Vector (6SV. Hasil kajian ini menunjukkan bahwa perbedaan nilai salinitas perairan dari algoritma Wouthuyzen  dengan data in-situ berkisar antara 2,66 hingga 3,91 psu. Sedangkan selisih salinitas algoritma Son dengan data in-situ 2,14 hingga 3,00 psu. Adapun nilai NMAE algoritma Wouthuyzen dengan data in-situ sebesar 7,2 %, sedangkan pada algoritma Son sebesar 10,6 %.

  5. 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.

  6. Son Preference and Family Planning Practices among Married Men in Mumbai, India

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To study son preferences and the contraceptive knowledge, attitude and practices of Indian Male Subjects & Methods The data was obtained through a semi-structured interview schedule caried out in 2 687 married men at Mumbai City, India in 1999.Results About 80% of men felt two children as their ideal family size, while 82%desired two children i.e. one son and one daughter. 8. 2% of men had strong prefer ence for two or more sons because of family lineage, old age support and to support each other.23. 1% of the couples had used contraceptives in the past, 48% of couples were not using any contraceptive method at the time of survey. Male participation in spacing contraceptive methods was 23% i.e. condom 21.9% and withdrawal 1.1%. Though awareness (99. 9% ) and knowledge (95. 2% ) of condom was high, only 42. 8% of subjects knew use the correct of the method. Only 2. 4% of them thought about accept ing vasectomy, while others reported various misconception.Conclusion This study suggests a pressing need for effective intervention strategies,both at the community level and the clinic level, backed with efficient motivation, coun seling and provision of quality services in urban areas.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Nozar Niazi

    2013-07-01

    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. Key words: stylistics, D.H. Lawrence, Sons and Lovers

  9. Cultural bias in the SON-R test: comparative study of Brazilian and dutch children

    Directory of Open Access Journals (Sweden)

    Peter J. Tellegen

    Full Text Available The present study, including 83 Brazilian and 51 Dutch children, evaluated the presence of cultural bias in items of the SON-R 5½-17 that make use of concrete objects and situations. Two procedures were followed to detect item bias. The first consisted of asking the children, immediately after an incorrect answer, whether they recognized the pictures. The second procedure compared item difficulties of the Brazilian children with those of the Dutch children belonging to the standardization sample of the SON-R 5½-17. Fourteen items were detected with bias: ten of these favored the Dutch group and four the Brazilian group. The cultural disadvantage for Brazilian children is rather small, taking the large amount of investigated items into account. This study indicated which items of the SON-R 5½-17 should be improved, not only for reasons of cultural bias, but also because children, irrespective of their cultural background, encountered problems with the recognition of several pictures.

  10. The Experiences and Meanings That Shape Heterosexual Fathers' Relationships With Their Gay Sons in South Africa.

    Science.gov (United States)

    Livingston, Jacques; Fourie, Eduard

    2016-12-01

    Gay men's relationships with their mothers are likely to be more positive than their relationships with their fathers, and fathers are less likely to be told, less likely to be told first, and more likely to react negatively to disclosure than mothers. Drawing on an interpretivist approach, an individual in-depth interview strategy was adopted in the study as a means of gathering data from six Afrikaans-speaking White fathers, between the ages of 53 and 61 years (median: 55.5 years), residing in Gauteng, South Africa. Interviews were audio-recorded and transcribed for later coding and analysis. Through thematic network analysis, eight organizing themes emerged and were explored. For the purpose of this article only three organizing themes are discussed, namely "subliminal awareness prior to coming out," "epistemic rupture of internal systems of ideas/beliefs," and "acceptance as a complex and ongoing dialectical and reconciliatory process." The themes support the view that most parents are neither totally rejecting nor fully accepting of their gay sons. Although the fathers may have attained a level of "loving denial" in the relationships with their gay sons, most continue to struggle with the meaning and expression of same-sex sexuality. Despite these challenges, it is recognized that the fathers are adapting to changing circumstances and are trying to find ways to tolerate, accommodate, and in some ways accept their gay sons.

  11. 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.

  12. 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.

  13. Analyzing binding data.

    Science.gov (United States)

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  14. Paternal correlates of adolescent marijuana use in the context of the mother-son and parental dyads.

    Science.gov (United States)

    Brook, J S; Whiteman, M; Gordon, A S; Brook, D W

    1983-11-01

    This study was designed to examine the paternal determinants of male adolescent marijuana use in the context of the mother-son and parental relationships. In addition, parental factors affecting experimental vs regular use of marijuana were examined. Two hundred forty-six male college students and their fathers were administered written questionnaires. Results indicated that the father's personality attributes and socialization techniques are associated with the son's use of marijuana despite control on the mother-son relationship. Fathers of marijuana users score higher on measures of psychopathology and unconventionality, and are less likely to have established close relationships with their sons. In addition, marijuana users more than nonusers have unaffectionate mothers and parents with less harmonious marital relations. Also of importance were interactions within the family system. The significance of these second-order effects highlights the importance of examining the father-son relation in the context of mother-son and parental interactions.

  15. 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.

  16. 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.

  17. Data and Analysis Methods of the Son-O-Mermaid and MERMAID Experiments

    Science.gov (United States)

    Simon, J. D.; Simons, F. J.; Nolet, G.

    2014-12-01

    Here we present, for the first time, the results from pilot deployments of the Son-O-Mermaid project, an autonomously drifting, oceangoing data-collection platform that can be cheaply deployed without the need for a costly research vessel, and that records and transmits hydroacoustic signals (with a target of those generated by teleseismic earthquakes) in near real-time. Both deployments employ three identical hydrophones spaced about 70 cm apart at the end of a 700 m long cable attached to a surface buoy that houses electronics, communications, and a GPS location package. The maiden voyage occurred October 8, 2012, in Exuma Bay, Bahamas and returned 25 hours of acoustic data. A second deployment is to take place in September 2014, with near-immediate data relay via Iridium modem. The experimental setup is different from the MERMAID instrument, which sinks to a midcolumn depth and surfaces to transmit waveforms when an event detection algorithm is triggered. MERMAIDs have recorded hundreds of seismic traces from 18 active floats in the Indian and Mediterranean Oceans with a signal-to-noise ratio suitable for global tomography. As with earthquake early-warning studies, both Son-O-Mermaid and MERMAID benefit from rapid and accurate event detection, discrimination, and measurement technology. With this triple purpose in mind we continue to improve methods (in the time-domain, via spectrogram analysis and using wavelets) that we illustrate on the latest and some of the older data, as well. While hydroacoustic data have numerous other applications beyond seismology (whale calls, ice calving, weather patterns, and so on) the Son-O-Mermaid and MERMAID instruments may potentially revolutionize seismic data collection in the oceans. Moreover, in the near future they will be fitted with more or different instruments, becoming multipurpose and multidisciplinary platforms for all types of scientific research in and of the oceans. In seismology we envision a future when the

  18. 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.

  19. Guillaume Rondelet (1507-1566): Cardinal physician and anatomist who dissected his own son.

    Science.gov (United States)

    Mian, Asma; Watanabe, Koichi; Shoja, Mohammadali M; Loukas, Marios; Tubbs, R Shane

    2014-04-01

    The 16th century French anatomist Guillaume Rondelet will be remembered as a great naturalist and a founder of ichthyology. Little known to most is that Rondelet was a proficient anatomist and contemporary to Vesalius and in fact, both studied anatomy under Johannes Guinter. Even less known is that he established the first dissecting theatre at Montpellier and it was here that he would dissect his infant son in an attempt to identify the cause of death. In this article, we review the life and contributions to anatomy of Rondelet.

  20. CHIRAL RING OF Sp(N) AND SO(N) SUPERSYMMETRIC GAUGE THEORY IN FOUR DIMENSIONS

    Institute of Scientific and Technical Information of China (English)

    E. WITTEN

    2003-01-01

    The chiral ring of classical supersymmetric Yang-Mills theory with gauge group Sp(N) or SO(N) is computed, extending previous work (of Cachazo, Douglas, Seiberg, and the author)for SU(N). The result is that, as has been conjectured, the ring is generated by the usualglueball superfield S ~ Tr WαWα, with the relation Sh = 0, h being the dual Coxeter number.Though this proposition has important implications for the behavior of the quantum theory,the statement and (for the most part) the proofs amount to assertions about Lie groups withno direct reference to gauge theory.

  1. The steam-powered brewery Ignjat Bajloni & Sons 1888-1946

    Directory of Open Access Journals (Sweden)

    Lukić Nenad M.

    2015-01-01

    Full Text Available The steam-powered brewery Ignjat Bajloni & Sons was the second Belgrade brewery which modernised the production process by shifting from manual to steam power. The paper outlines, chronologically and thematically, the development and operations of the brewery, key events in its history, and a brief history of the Bajloni family who owned it for the whole sixty years. The paper is based on the largely unpublished archival material, relevant literature and newspaper articles. The chronological limit set to the paper is the year 1946, but it gives a brief description of the operation of the brewery until its final shutdown in 2006.

  2. Non-Abelian Vortices in SO(N) and USp(N) Gauge Theories

    CERN Document Server

    Eto, Minoru; Gudnason, Sven Bjarke; Konishi, Kenichi; Nagashima, Takayuki; Nitta, Muneto; Ohashi, Keisuke; Vinci, Walter

    2009-01-01

    Non-Abelian BPS vortices in SO(N) x U(1) and USp(2N) x U(1) gauge theories are constructed in maximally color-flavor locked vacua. We study in detail their moduli and transformation properties under the exact symmetry of the system. Our results generalize non-trivially those found earlier in supersymmetric U(N) gauge theories. The structure of the moduli spaces turns out in fact to be considerably richer here than what was found in the U(N) theories. We find that vortices are generally of the semi-local type, with power-like tails of profile functions.

  3. ¿Son las creencias religiosas razonables? : verificación o falsación

    OpenAIRE

    2008-01-01

    Este trabajo está orientado a responder la pregunta ¿son la creencias religiosas razonables? Para ello, se hace un esbozo, primero de qué significan las creencias en general, para luego abarcar las creencias religiosas en particular. En este punto se realiza una descripción de las teorías de la verificación y la falsación. Posteriormente, se detallan las distintas posiciones relacionadas con las expresiones religiosas. Finalmente, se presenta un enfrentamiento entre aquellos que consideran la...

  4. Performance of the Birmingham Solar-Oscillations Network (BiSON)

    CERN Document Server

    Hale, S J; Chaplin, W J; Davies, G R; Elsworth, Y P

    2015-01-01

    The Birmingham Solar-Oscillations Network (BiSON) has been operating with a full complement of six stations since 1992. Over 20 years later, we look back on the network history. The meta-data from the sites have been analysed to assess performance in terms of site insolation, with a brief look at the challenges that have been encountered over the years. We explain how the international community can gain easy access to the ever-growing dataset produced by the network, and finally look to the future of the network and the potential impact of nearly 25 years of technology miniaturisation.

  5. 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.

  6. Autismo y Programa Son-Rise: Intervención sobre un caso

    OpenAIRE

    López Camarero, Irene

    2013-01-01

    En este documento se estudian los distintos tipos de trastorno del espectro autista, distinguiendo las características de cada uno de ellos y las posibles causas que pueden originarlos. Partiendo de esta base, se plantean distintos métodos o programas existentes en nuestra sociedad para trabajar con este colectivo y lograr que desarrollen sus capacidades en el máximo nivel posible. Tras una breve explicación de algunos de ellos, nos centramos en el Programa Son-Rise, método poco conocid...

  7. Acercamiento al son guatemalteco tradicional desde una perspectiva histórica

    OpenAIRE

    de Gandarias, Igor

    2015-01-01

    Este artículo recorre sintéticamente la ruta histórica seguida por el son guatemalteco tradicional, a partir de la ubicación temporal de sus com- portamientos musicales dentro de los procesos históricos de occidenta- lización y mestizaje que los originaron. Inicia con el sustrato tímbrico de instrumentos sonoros mayas prehispánicos que perviven en un sector de la producción conocida. Le siguen, además de otros instrumentos musicales, los aportes tonales, rítmicos y texturales de origen europe...

  8. 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.

  9. 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.

  10. 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.

  11. ¿Son fiables los productos que encontramos en los supermercados?

    OpenAIRE

    Olivares Zabalandicoechea, Maitane; Zuloaga Zubieta, Olatz

    2012-01-01

    Duración (en horas): De 21 a 30 horas. Destinatario: Estudiante En este recurso didáctico se presenta la metodología en base a proyectos utilizada en el proceso de enseñanza-aprendizaje de la asignatura optativa "Cromatografía y Técnicas Afines" que se imparte en el segundo ciclo de la Licenciatura de Química. El proyecto, que lleva como título "¿Son fiables los productos que encontramos en los supermercados?", permite al alumno aprender los distintos métodos analíticos para el a...

  12. Two qubits of a W state violate Bell's inequality beyond Cirel'son's bound

    CERN Document Server

    Cabello, A

    2002-01-01

    It is shown that the correlations between two qubits selected from a trio prepared in a W state violate the Clauser-Horne-Shimony-Holt inequality more than the correlations between two qubits in any quantum state. Such a violation beyond Cirel'son's bound is smaller than the one achieved by two qubits selected from a trio in a Greenberger-Horne-Zeilinger state [A. Cabello, Phys. Rev. Lett. 88, 060403 (2002)]. However, it has the advantage that all local observers can know from their own measurements whether their qubits belongs or not to the selected pair.

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

    Directory of Open Access Journals (Sweden)

    Gabel Pernille

    2011-11-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions The data are compatible with a slightly increased risk of cryptorchidism in sons of women

  14. The Tragic Marriage of the Morel Couple in Sons and Lovers

    Institute of Scientific and Technical Information of China (English)

    YUAN Shuai

    2016-01-01

    In Sons and Lovers, one of William Faulkner’s most famous novels, the marriage between Walter Morel and Gertrude Coppard was inarguably a tragic one. However, as for the reason, it was not explicitly represented in the novel. This paper at-tempts to delve into the reason of this failed marriage and put forward an argument that this failure could be attributed to the con-flict between sex and social class with the help of the theory of dominance and subordinance put forward by Kate Millett.

  15. Psychosocial adjustment process of mothers caring for young men with traumatic brain injury: focusing on the mother-son relationship.

    Science.gov (United States)

    Fumiyo, Ishikawa; Sumie, Suzuki; Akiko, Okumiya; Yasuko, Shimizu

    2009-10-01

    This study focuses on the mother-son relationship of 13 mothers caring for single sons between the ages of 15 and 30 years who have higher brain dysfunction due to a traumatic brain injury. We aimed to elucidate the psychosocial adjustment process of mothers for 5 years following the injury to facilitate the social rehabilitation of both mother and son. Data obtained through a semistructured interview method were analyzed using a modified grounded theory approach. After 56 concepts were identified, 18 categories and then 8 core categories were semantically created. The 8 core categories were (a) avoid contact with son, (b) support son based on mother's own desire, (c) support son alone without external support, (d) realize mother's care limits and seek external support sources, (e) request and utilize external support, (f) support and work toward son's independence while monitoring his interactions with others, (g) mother considers own feelings and reenters society, and (h) strive for continued care of son with mother's acquired energy and efficient management skills. These were grouped into the following five stages: (a) avoidance, (b-c) closed, (d) support seeking, (e-f) withdrawal, and (g-h) reconstruction.

  16. 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.

  17. Trust and disclosure of sexual orientation in gay males' mother-son relationships.

    Science.gov (United States)

    Miller, R J; Boon, S D

    2000-01-01

    This study explored the possibility that changes in feelings of trust for mother are associated with gay males' decisions to disclose (or withhold) their sexual orientation in their mother-son relationships. Fifty gay and bisexual males completed a questionnaire about their coming out experiences in the context of their relationships with their mothers. As part of this questionnaire, they completed a retrospective graphical trust history task that involved plotting the degree of trust they felt for their mothers over time and across important events (such as disclosure). Results are discussed in terms of gay men's expectations about their mothers' responses to disclosure, the evidence for stability versus change in their memories regarding the nature of their feelings of maternal trust over time, the complexity of the trust histories participants drew, similarity between disclosers and non-disclosers in the shape of their trust curves, and the types of events and experiences that constituted the timeline or "plot" in the stories participants told about their mother-son relationships. This study offers the first empirical evidence to support speculations linking disclosure of sexual orientation to the climate of trust that exists in the relationship between discloser and target (e.g., Holtzen, Kenny & Mahalik, 1995).

  18. Symbolism of the Shadows in Son of Man by Roa Bastos

    Institute of Scientific and Technical Information of China (English)

    Patricia G. Montenegro

    2015-01-01

    In his novel Son of Man, Augusto Roa Bastos uses images and symbols of shadows to represent the ramifications ofthe Paraguayan Dr. Jose Rodriguez de Francia's dictatorship. Rodriguez de Francia's legacy, which begins duringthe postcolonial years and extends well into the 20th century, resonates in the novel in soeio-political structures andcharacters' ideologies and behaviors. It allows for plantation owners to enslave workers and their families; itconfines and oppresses people through unfounded legends and myths; and among other things, it creates a falseidea of purpose and patriotism in the Chaco War (1932-1935), which in the end lets down the soldiers. Tocounteract these deleterious social conditions, Roa Bastos creates surreal characters, such as a fantastic helper whoaids plantation workers to escape dehumanizing situations. Roa Bastos also narrates how the people in Itapr, asmall town, make an idol of a Christ statue carved by one of their own. However, when the two Goiburfl brothersreplace the statue by crucifying their sister's rapist, the people's myth is destroyed. Likewise, Roa Bastos availshimself of Christian and Catholic concepts and symbols to transpose them into a humanistic ideology so as toconvey hope to his people through a new perspective. In this way, a new Annunciation takes place when the son ofa raped woman is born. In the end, Roa Bastos lets the course of these warped transpositions take their logicaldenouement: In the absence of a purpose beyond an earthly existence, death becomes the narrator's option.

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

    Directory of Open Access Journals (Sweden)

    Nguyen Quang Tuan

    2016-08-01

    Full Text Available The 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.

  20. 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.

  1. Malaria and enterobiasis among Karen Long-neck tribe in Mae Hong Son Province.

    Science.gov (United States)

    Nithikathkul, Choosak; Polseela, Panida; Poodendan, Wilawan; Brodsky, Marc; Rakprapapant, Derek; Chadchatreechan, Suparp; Phethleart, Aree; Sukthana, Yaowalark; Leemingsawat, Somjai

    2003-01-01

    In Thailand, Mae Hong Son Province is highly endemic for malaria. Knowing this, the local Health Department has introduced a program to educate local residents about the risk factors, in particular the dangers and symptoms of malaria. This study was conducted to evaluate these efforts, by determining the number of malaria infections in a segment of the population, and also by testing for enterobiasis among a group of its children. Two villages in Mae Hong Son Province were chosen for this purpose with a combined population of about 300. Of these, 195 were screened for malaria. Two subjects were diagnosed positive for malaria by microscopy. One of these two villages was chosen to screen for Enterobius vermicularis infection in children as well. Out of 69 stool samples, five (7%) showed infection with E. vermicularis: three with a low number of eggs (1-50), and two with a high number of eggs (>100). Compared with infection rates in similar studies, the results of this study indicate that the Health Department's efforts are meeting with relative success. The low prevalence of infection indicates that the villagers are using the information they have received to help combat infection.

  2. ‘Too many girls, too much dowry’: son preference and daughter aversion in rural Tamil Nadu, India

    Science.gov (United States)

    DIAMOND-SMITH, NADIA; LUKE, NANCY; MCGARVEY, STEPHEN

    2013-01-01

    The southern Indian state of Tamil Nadu has experienced a dramatic decline in fertility, accompanied by a trend of increased son preference. This paper reports on findings from qualitative interviews with women in rural villages about their fertility decision-making. Specifically addressed are the reasons behind increasing son preference and the consequences of this change. Findings suggest that daughter aversion, fuelled primarily by the perceived economic burden of daughters due to the proliferation of dowry, is playing a larger role in fertility decision-making than son preference. The desire for a son is often trumped by the worry over having many daughters. Women use various means of controlling the sex of their children, which in this study appear to be primarily female infanticide. It is important to distinguish between son preference and daughter aversion and to examine repercussions of low fertility within this setting. PMID:18821352

  3. [Separation in the mother-son relationship: an adolescent problem in Rainer Maria Rilke's story "Silent accompaniment"].

    Science.gov (United States)

    Wittstruck, W

    1995-01-01

    The story 'Quiet Accompanying' by Ranier Maria Rilke's early work is of special interest for research on adolescence. The story is a literary contribution to the separation conflict of parents and their maturing children, especially the separation crisis in the mother-son relationship. The story's suspense is derived from the son's desire to begin a new phase in life and his experience of being powerless regarding his ties to his family. Thereby the adolescent crisis of the male main character is indirectly picked out as the main theme in the description of the mother's separation crisis. In the mother's 'dream' where the departure for a sunday excursion is described, an image of the son's adolescence with the components search for identity, separation and closeness develops. The son's efforts finally fail because mother and son are captured in their relationship characterized by conflicts and fears.

  4. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression.

    Science.gov (United States)

    Srivastava, Mrinal; Nambiar, Mridula; Sharma, Sheetal; Karki, Subhas S; Goldsmith, G; Hegde, Mahesh; Kumar, Sujeet; Pandey, Monica; Singh, Ram K; Ray, Pritha; Natarajan, Renuka; Kelkar, Madhura; De, Abhijit; Choudhary, Bibha; Raghavan, Sathees C

    2012-12-21

    DNA Ligase IV is responsible for sealing of double-strand breaks (DSBs) during nonhomologous end-joining (NHEJ). Inhibiting Ligase IV could result in amassing of DSBs, thereby serving as a strategy toward treatment of cancer. Here, we identify a molecule, SCR7 that inhibits joining of DSBs in cell-free repair system. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I. SCR7 inhibits NHEJ in a Ligase IV-dependent manner within cells, and activates the intrinsic apoptotic pathway. More importantly, SCR7 impedes tumor progression in mouse models and when coadministered with DSB-inducing therapeutic modalities enhances their sensitivity significantly. This inhibitor to target NHEJ offers a strategy toward the treatment of cancer and improvement of existing regimens. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Leukotriene A4 hydrolase: Selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375

    Science.gov (United States)

    Rudberg, Peter C.; Tholander, Fredrik; Thunnissen, Marjolein M. G. M.; Samuelsson, Bengt; Haeggström, Jesper Z.

    2002-01-01

    Leukotriene A4 (LTA4, 5S-trans-5,6-oxido-7,9-trans-11,14-cis-eicosatetraenoic acid) hydrolase (LTA4H)/aminopeptidase is a bifunctional zinc metalloenzyme that catalyzes the final and rate-limiting step in the biosynthesis of leukotriene B4 (LTB4, 5S,12R-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid), a classical chemoattractant and immune modulating lipid mediator. Two chemical features are key to the bioactivity of LTB4, namely, the chirality of the 12R-hydroxyl group and the cis-trans-trans geometry of the conjugated triene structure. From the crystal structure of LTA4H, a hydrophilic patch composed of Gln-134, Tyr-267, and Asp-375 was identified in a narrow and otherwise hydrophobic pocket, believed to bind LTA4. In addition, Asp-375 belongs to peptide K21, a previously characterized 21-residue active site-peptide to which LTA4 binds during suicide inactivation. In the present report we used site-directed mutagenesis and x-ray crystallography to show that Asp-375, but none of the other candidate residues, is specifically required for the epoxide hydrolase activity of LTA4H. Thus, mutation of Asp-375 leads to a selective loss of the enzyme's ability to generate LTB4 whereas the aminopeptidase activity is preserved. We propose that Asp-375, possibly assisted by Gln-134, acts as a critical determinant for the stereoselective introduction of the 12R-hydroxyl group and thus the biological activity of LTB4. PMID:11917124

  6. Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens

    Energy Technology Data Exchange (ETDEWEB)

    Chruszcz, Maksymilian; Pomés, Anna; Glesner, Jill; Vailes, Lisa D.; Osinski, Tomasz; Porebski, Przemyslaw J.; Majorek, Karolina A.; Heymann, Peter W.; Platts-Mills, Thomas A.E.; Minor, Wladek; Chapman, Martin D. (INDOOR Bio.); (UV); (UVHS)

    2012-07-11

    House dust mites produce potent allergens, Der p 1 and Der f 1, that cause allergic sensitization and asthma. Der p 1 and Der f 1 are cysteine proteases that elicit IgE responses in 80% of mite-allergic subjects and have proinflammatory properties. Their antigenic structure is unknown. Here, we present crystal structures of natural Der p 1 and Der f 1 in complex with a monoclonal antibody, 4C1, which binds to a unique cross-reactive epitope on both allergens associated with IgE recognition. The 4C1 epitope is formed by almost identical amino acid sequences and contact residues. Mutations of the contact residues abrogate mAb 4C1 binding and reduce IgE antibody binding. These surface-exposed residues are molecular targets that can be exploited for development of recombinant allergen vaccines.

  7. 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.

  8. 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...... in the conversational interactions. The findings were interpreted and discussed within an interactionist framework. FINDINGS: The participants in the study described their experiences as a double trauma, which included the trauma of the suicide attempt(s) and the subsequent psychosocial impact on the family's well......-being. The pressure on the parents was intense and the fundamentally unpredictable character of suicide attempts was frequently emphasized. CONCLUSION: Being the parent of a child who attempts suicide meant managing a life-threatening situation and the additional moral stigma. In part, the participants did...

  9. Pincio y los Estados Unidos que no son los Estados Unidos

    Directory of Open Access Journals (Sweden)

    Franco Zangrilli

    2015-07-01

    Full Text Available Lo neofantástico en Tommaso Pincio se distingue de lo fantástico posmoderno de nuestros escritores. Se basa en la realidad estadounidense contemporánea; la introduce en un proceso de elaboraciones enfáticas, mezclas, transfiguraciones, y la convierte en el símbolo de otro mundo, de un planeta extraño. Pincio llega a esta operación creativa gracias a su conocimiento de las tradiciones y de las costumbres, de la historia, de la cultura y de la literatura de los Estados Unidos. De todo eso quiere darse una idea en este ensayo, analizando la segunda novela de Pincio, Spazio sfinito, en la que se representa a unos Estados Unidos que no son Estados Unidos.

  10. Mother-son relationship as a risk factor for depressive symptoms among methamphetamine users.

    Science.gov (United States)

    Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; Patterson, Thomas L

    2012-02-01

    Retrospective reports of children's relationships with their parents have been associated with increased risk for depressive symptoms in adulthood. This study examined four dimensions of the current mother-child relationship (affection, criticism, over-involvement, conflict) in relation to depressive symptoms in a sample of 270 HIV-positive men who have sex with men (MSM). Depressive symptoms were positively associated with overt conflict or disagreement with mothers and perceived over-involvement by mothers, and inversely related to frequency of contact with mothers. These findings suggest that clinicians who treat HIV-positive methamphetamine-using MSM with depressive symptoms should evaluate issues in the mother-son relationship and consider family-based therapies as an adjunct to treatment.

  11. Supersymmetric SO(N) from a Planck-scale statistical theory

    CERN Document Server

    Allen, Roland E

    2010-01-01

    Several refinements are made in a theory which starts with a Planck-scale statistical picture and ends with supersymmetry and a coupling of fundamental fermions and bosons to SO(N) gauge fields. In particular, more satisfactory treatments are given for (1) the transformation from the initial Euclidean form of the path integral for fermionic fields to the usual Lorentzian form, (2) the corresponding transformation for bosonic fields (which is much less straightforward), (3) the transformation from an initial primitive supersymmetry to the final standard form (containing, e.g., scalar sfermions and their auxiliary fields), (4) the initial statistical picture, and (5) the transformation to an action which is invariant under general coordinate transformations.

  12. Mystery solved: Our son's autism and extreme self-injury is genetic and treatable.

    Science.gov (United States)

    Bartel, Tanja

    2017-05-01

    Our 17-year-old autistic son Jake is declining at the same rate his peers are developing. He has the pimples, the sudden height, and the hormones. But the right side of his body slumps like someone who has had a stroke. Once right handed, he now uses only his left hand. At 15, he knocked his eyes off their parallel tracks by slamming his temple into the corner of a wooden post. One eye looks straight ahead while the other looks up and to the side. Both optic nerves are damaged. All the damage is self-inflicted. He has been banging and punching his head since babyhood. © 2017 Wiley Periodicals, Inc.

  13. L’emploi industriel en France et son évolution 1994-2004

    Directory of Open Access Journals (Sweden)

    Régis Guillaume

    2008-07-01

    Full Text Available Le déclin de l’emploi industriel est souvent appréhendé comme le symbole des difficultés de la France à maintenir son rang dans une économie toujours plus mondialisée et plus concurrentielle. L’article vise, à partir des statistiques de l’emploi, à montrer que la diminution des effectifs est loin d’être homogène et que, depuis une dizaine d’années, elle s’accompagne d’un redéploiement géographique de forte intensité. On a construit à cet effet des agrégats spécifiques permettant de prendre en compte le devenir des filières productives majeures.

  14. 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.

  15. Padoue et son contado (Xe-XIIIe siècle)

    OpenAIRE

    Rippe, Gérard

    2013-01-01

    L'ouvrage traite d’un objet classique – une cité et son contado – à l’aide des concepts mis au point par l’historiographie récente. Après avoir décrit le cadre territorial hérité de l’Antiquité et du haut Moyen Âge, elle analyse l’évolution de ce territoire et de ses institutions du Xe au XIIe siècle, notamment la naissance et la constitution d’une société féodale à laquelle s’intègrent même les « arimanni » , puis l’« incastellamento » et sa signification démographique et politique, enfin l’...

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

    OpenAIRE

    Tania Ximena Salcedo Goméz

    2013-01-01

    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....

  17. El vídeoclip, l'art d'unir imatges i sons

    OpenAIRE

    2011-01-01

    Aquest projecte es basa en la cerca, estudi i realització d’un vídeo musical com a obra artística que uneix imatges i sons. Primerament s’analitza el videoclip, l’origen, la finalitat, les classes de videoclips i el mercat actual. Posteriorment es selecciona una versió de la cançó Boadicea d’Enya per realitzar-ne el vídeo musical i es fa una pre-producció on s’idea l’esquema del videoclip i les imatges que es gravaran. Després de la producció es realitza la post-producció amb la unió de le...

  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. JOURNEY OF A WORKING MOTHER AND HER SON WITH DOWN SYNDROME.

    Science.gov (United States)

    Shahzad, Saadia

    2015-01-01

    Trisomy 21, chromosomal disorder related with Down syndrome (DS), is the most common cause leading to learning disability among all races and all human population. Having a child with Down syndrome in developed world has now become less of an unfortunate incidence in the lives of the parents; not because they do not realize the tough road ahead for their child as compared to other siblings but due to the fact that they have got a comprehensive and cohesive support system running for these children at every stage of life that builds up the child to his/her full potential. The present special communication is about personal experience of a working mother with her son with Down syndrome.

  20. Dioxin and Polychlorinated Biphenyl Concentrations in Mother's Serum and the Timing of Pubertal Onset in Sons

    Science.gov (United States)

    Humblet, Olivier; Williams, Paige L.; Korrick, Susan A.; Sergeyev, Oleg; Emond, Claude; Birnbaum, Linda S.; Burns, Jane S.; Altshul, Larisa; Patterson, Donald G.; Turner, Wayman E.; Lee, Mary M.; Revich, Boris; Hauser, Russ

    2013-01-01

    Background Animal studies have demonstrated that timing of pubertal onset can be altered by prenatal exposure to dioxins or polychlorinated biphenyls (PCBs), but studies of human populations have been quite limited. Methods We assessed the association between maternal serum concentrations of dioxins and PCBs and the sons’ age of pubertal onset in a prospective cohort of 489 mother–son pairs from Chapaevsk, Russia, a town contaminated with these chemicals during past industrial activity. The boys were recruited at ages 8 to 9 years, and 4 years of annual follow-up data were included in the analysis. Serum samples were collected at enrollment from both mothers and sons for measurement of dioxin and PCB concentrations using high-resolution mass spectrometry. The sons’ pubertal onset—defined as pubertal stage 2 or higher for genitalia (G) or pubic hair (P), or testicular volume >3 mL—was assessed annually by the same physician. Results In multivariate Cox models, elevated maternal serum PCBs were associated with earlier pubertal onset defined by stage G2 or higher (4th quartile hazard ratio = 1.7 [95% confidence interval = 1.1– 2.5]), but not for stage P2 or higher or for testicular volume >3 mL. Maternal serum concentrations of dioxin toxic equivalents were not consistently associated with the sons’ pubertal onset, although a dose-related delay in pubertal onset (only for G2 or higher) was seen among boys who breast-fed for 6 months or more. Conclusions Maternal PCB serum concentrations measured 8 or 9 years after sons’ births—which may reflect sons’ prenatal and early-life exposures—were associated with acceleration in some, but not all, measures of pubertal onset. PMID:21968773

  1. "Fathers" and "sons" of theories in cell physiology: the membrane theory.

    Science.gov (United States)

    Matveev, V V; Wheatley, D N

    2005-12-16

    The last 50 years in the history of life sciences are remarkable for a new important feature that looks as a great threat for their future. A profound specialization dominating in quickly developing fields of science causes a crisis of the scientific method. The essence of the method is a unity of two elements, the experimental data and the theory that explains them. To us, "fathers" of science, classically, were the creators of new ideas and theories. They were the true experts of their own theories. It is only they who have the right to say: "I am the theory". In other words, they were carriers of theories, of the theoretical knowledge. The fathers provided the necessary logical integrity to their theories, since theories in biology have still to be based on strict mathematical proofs. It is not true for sons. As a result of massive specialization, modern experts operate in very confined close spaces. They formulate particular rules far from the level of theory. The main theories of science are known to them only at the textbook level. Nowadays, nobody can say: "I am the theory". With whom, then is it possible to discuss today on a broader theoretical level? How can a classical theory--for example, the membrane one--be changed or even disproved under these conditions? How can the "sons" with their narrow education catch sight of membrane theory defects? As a result, "global" theories have few critics and control. Due to specialization, we have lost the ability to work at the experimental level of biology within the correct or appropriate theoretical context. The scientific method in its classic form is now being rapidly eroded. A good case can be made for "Membrane Theory", to which we will largely refer throughout this article.

  2. L'art de faire parler les pierres : Bande-son de Bertrand de la Peine

    Directory of Open Access Journals (Sweden)

    Isabelle Dangy

    2012-12-01

    Full Text Available Bande-Son, de Bertrand de la Peine, fait défiler trois figures de l’artiste qui suggèrent pour l’activité artistique un domaine de définition. À la pointe de la contemporanéité, Sven Langhens est un acousticien qui s’attache à rendre audible le chant de l’infime, celui des bêtes minuscules et même celui des pierres. Avant lui, au XVIIIe siècle, Rudolf Erich Raspe, auteur des Aventures du baron de Munchhausen, s’était déjà lancé sur les traces de pierres chantantes. Enfin, légèrement en retrait par rapport à ces deux figures originales dont il orchestre les rapports, le narrateur propose une poétique reflétant et court-circuitant à la fois les recherches de ses deux personnages. Leur interaction culminera dans une installation en Provence, qui, transcendant la distinction entre les différents sujets de l’art et leur objet, parviendra à piéger dans un miroir la force du vent.Bertrand de la Peine Bande-Son scrolls three artist figures who suggest a domain of definition for artistic activity. At the forefront of the contemporary, Sven Langhens is an acoustician who strives to make audible the voice of the tiny, tiny animals and even the stones. Before him, in the eighteenth century, Rudolf Erich Raspe, author of The Surprising Adventures of Baron Munchausen, had already run on the footsteps of singing stones. Finally, slightly down compared to the two original figures, the narrator reports their relationships and offers a poetic reflecting and bypassing his characters research. Their interaction will culminate in an installation in Provence, which transcends the distinction between the different subjects of art and object, succeeding in trapping the wind by a mirror’s force.

  3. [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.

  4. 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.

  5. 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.

  6. Membrane translocation of t-SNARE protein syntaxin-4 abrogates ground-state pluripotency in mouse embryonic stem cells

    Science.gov (United States)

    Hagiwara-Chatani, Natsumi; Shirai, Kota; Kido, Takumi; Horigome, Tomoatsu; Yasue, Akihiro; Adachi, Naoki; Hirai, Yohei

    2017-01-01

    Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive tools for regenerative medicine therapies. However, aberrant cell populations that display flattened morphology and lose ground-state pluripotency often appear spontaneously, unless glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase kinase (MEK1/2) are inactivated. Here, we show that membrane translocation of the t-SNARE protein syntaxin-4 possibly is involved in this phenomenon. We found that mouse ES cells cultured without GSK3β/MEK1/2 inhibitors (2i) spontaneously extrude syntaxin-4 at the cell surface and that artificial expression of cell surface syntaxin-4 induces appreciable morphological changes and mesodermal differentiation through dephosphorylation of Akt. Transcriptome analyses revealed several candidate elements responsible for this, specifically, an E-to P-cadherin switch and a marked downregulation of Zscan4 proteins, which are DNA-binding proteins essential for ES cell pluripotency. Embryonic carcinoma cell lines F9 and P19CL6, which maintain undifferentiated states independently of Zscan4 proteins, exhibited similar cellular behaviors upon stimulation with cell surface syntaxin-4. The functional ablation of E-cadherin and overexpression of P-cadherin reproduced syntaxin-4-induced cell morphology, demonstrating that the E- to P-cadherin switch executes morphological signals from cell surface syntaxin-4. Thus, spontaneous membrane translocation of syntaxin-4 emerged as a critical element for maintenance of the stem-cell niche. PMID:28057922

  7. 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

  8. Isolation of a cdc28 mutation that abrogates the dependence of S phase on completion of M phase of the budding yeast cell cycle

    Indian Academy of Sciences (India)

    Santanu Kumar Ghosh; Pratima Sinha

    2000-01-01

    We have isolated a mutation in the budding yeast Saccharomyces cerevisisae CDC28 gene that allows cdc13 cells, carrying damaged DNA, to continue with the cell division cycle. While cdc13 mutant cells are arrested as large-budded cells at the nonpermissive temperature 37°C, the cdc13 cdc28 double mutant culture showed cells with one or more buds, most of which showed apical growth. The additional buds emerged without the intervening steps of nuclear division and cell separation. We suggest that the cdc28 mutation abrogates a checkpoint function and allows cells with damaged or incompletely replicated DNA an entry to another round of cell cycle and bypasses the mitotic phase of the cell cycle.

  9. Combinatorial treatment using targeted MEK and SRC inhibitors synergistically abrogates tumor cell growth and induces mesenchymal-epithelial transition in non-small-cell lung carcinoma.

    Science.gov (United States)

    Chua, Kian Ngiap; Kong, Li Ren; Sim, Wen Jing; Ng, Hsien Chun; Ong, Weijie Richard; Thiery, Jean Paul; Huynh, Hung; Goh, Boon Cher

    2015-10-01

    Oncogenesis in non-small cell lung cancer (NSCLC) is regulated by a complex signal transduction network. Single-agent targeted therapy fails frequently due to treatment insensitivity and acquired resistance. In this study, we demonstrate that co-inhibition of the MAPK and SRC pathways using a PD0325901 and Saracatinib kinase inhibitor combination can abrogate tumor growth in NSCLC. PD0325901/Saracatinib at 0.25:1 combination was screened against a panel of 28 NSCLC cell lines and 68% of cell lines were found to be sensitive (IC50 cell migration and matrigel invasion. The co-inhibition of MAPK and SRC induced strong G1/G0 cell cycle arrest in the NSCLC lines, inhibited anchorage independent growth and delayed tumor growth in H460 and H358 mouse xenografts. These data provide rationale for further investigating the combination of MAPK and SRC pathway inhibitors in advanced stage NSCLC.

  10. T cells bearing anti-CD19 and/or anti-CD38 chimeric antigen receptors effectively abrogate primary double-hit lymphoma cells.

    Science.gov (United States)

    Mihara, Keichiro; Yoshida, Tetsumi; Takei, Yoshifumi; Sasaki, Naomi; Takihara, Yoshihiro; Kuroda, Junya; Ichinohe, Tatsuo

    2017-06-08

    Patients with B cell lymphomas bearing MYC translocation combined with translocation involving other genes, such as BCL2, BCL3, or BCL6, defined as double-hit lymphoma (DHL), have a poor prognosis. Recent studies expanded the concept to include double-expressing lymphoma (DEL) that co-overexpresses MYC protein with either of those proteins. Accordingly, we defined cytogenetic DHL and DEL as primary DHL. An adoptive T cell immunotherapy with a chimeric antigen receptor (CAR) has been clinically shown to exhibit cytotoxicity in refractory neoplasias. We revealed the marked cytotoxicity of anti-CD19- and/or anti-CD38-CAR T cells against primary DHL cells from patients. CD19- and/or CD38-specific T cells were co-cultured with cytogenetic DHL (n = 3) or DEL (n = 2) cells from five patients for 3 days. We examined whether T cells retrovirally transduced with each vector showed cytotoxicity against DHL cells. Anti-CD19- and/or anti-CD38-CAR T cells were co-cultured with primary DHL cells at an E:T ratio of 1:2 for 3 days. Anti-CD19- and anti-CD38-CAR T cells completely abrogated these DHL cells, respectively. Anti-CD19-CAR T cells synergistically exerted collaborative cytotoxicity against these primary DHL cells with anti-CD38-CAR T cells. Therefore, refractory DHL cells can be efficiently abrogated by the clinical use of T cells with anti-CD19- and/or anti-CD38-CAR.

  11. Membrane binding domains

    OpenAIRE

    Hurley, James H.

    2006-01-01

    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  12. Fathers' Trait Verbal Aggressiveness and Argumentativeness as Predictors of Adult Sons' Perceptions of Fathers' Sarcasm, Criticism, and Verbal Aggressiveness.

    Science.gov (United States)

    Beatty, Michael J.; And Others

    1994-01-01

    Finds that approximately 40% of the variance in adult sons' reports of fathers' messages (sarcasm, criticism, and verbal aggressiveness) was attributable to fathers' self-reported argumentativeness and verbal aggression. (SR)

  13. Ethnic differences in the mother-son relationship of incarcerated and non-incarcerated male adolescents in the Netherlands

    National Research Council Canada - National Science Library

    Veen, Violaine C; Stevens, Gonneke Wjm; Doreleijers, Theo Ah; Deković, Maja; Pels, Trees; Vollebergh, Wilma Am

    2011-01-01

    .... To date, little is known about the parent-child relationship of these adolescents. This study examines the mother-son relationships of Moroccan and native Dutch delinquent adolescents and their association with adolescent delinquency...

  14. Inhibitory effect of morphine on excitatory synaptic transmission via presynaptic mechanism in rat SON neurons in brain slices

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-bin; HU San-jue; JU Gong

    2001-01-01

    To observe the effects of morphine on the excitatory postsynaptic currents (EPSCs) and miniature EPSCs (mEPSCs) in rat supraoptic nucleus (SON) neurons and to explore its synaptic mechanism. Methods: Using whole-cell voltage-clamp recording technique in the brain slices, the EPSCS and mEPSCs of rat SON neurons were recorded, respectively. Results: Morphine (20 μmol/L) decreased the frequency of EPSCs and mEPSCs (by 65% for EPSCS and by 45% for mEPSCs), and reduced the amplitude of EPSCs by 44% in all SON neurons, but the amplitude distribution ofmEPSCs was not affected. Conclusion: Morphine inhibits the excitatory transmissions via presynaptic mechanisms in SON neurons from rat brain slices.

  15. LAS DOS SE HACEN CON SANGRE: LA VIOLENCIA REPETIDA EN TODOS LOS GATOS SON PARDOS, DE CARLOS FUENTES

    National Research Council Canada - National Science Library

    Víctor Manuel Sanchis Amat

    2016-01-01

    ... by Octavio Paz in Postdata, essay annotated to El Laberinto de la Soledad. From the notion of "referential transference" laid out by Daniel Meyran, we can analyze the play Todos los Gatos son Pardos...

  16. 2-D Crustal thermal structure along Thuadara-Sindad DSS profile across Narmada-Son lineament, central India

    National Research Council Canada - National Science Library

    Rai, S N; Thiagarajan, S

    2007-01-01

    Central India is traversed by a WSW-ENE trending Narmada-Son lineament (NSL) which is characterized by the presence of numerous hot springs, feeder dykes for Deccan Traps and seismicity all along its length...

  17. Ethnic differences in the mother-son relationship of incarcerated and non-incarcerated male adolescents in the Netherlands

    Directory of Open Access Journals (Sweden)

    Pels Trees

    2011-06-01

    Full Text Available Abstract Background In the Netherlands, youths of Moroccan origin account for a disproportionately large percentage of the population in juvenile justice institutions. Previous research showed that Moroccan adolescents in pre-trial arrest are characterized by less serious offending behavior (i.e., primarily property-based and lower levels of mental health problems than native Dutch adolescents in pre-trial arrest. To date, little is known about the parent-child relationship of these adolescents. This study examines the mother-son relationships of Moroccan and native Dutch delinquent adolescents and their association with adolescent delinquency. Methods In the present study, differences in the mother-son relationship characteristics between families of incarcerated (N = 129 and non-incarcerated (N = 324 adolescents were examined, and it was analyzed if these differences between incarcerated and non-incarcerated adolescents were the same for Moroccans and native Dutch. Data collection for the incarcerated sample took place from 2006 to 2008. Comparison data were used of interviews conducted with mothers originating from former larger studies in the general Dutch population. Latent Class Analysis was performed in order to identify types of mother-son relationship. Logistic regression analyses were used to identify the relationships between mother-son relationship types, incarceration and ethnicity. Results A three class model of mother-son relationship types was found: a low-conflict mother-son relationship type, a high-conflict mother-son relationship type, and a neglectful mother-son relationship type. Compared to the native Dutch adolescents, Moroccans (both in the incarcerated and non-incarcerated population more often showed a neglectful mother-son relationship type. For Moroccans, no differences in mother-son relationship types were found between the incarcerated and non-incarcerated adolescents, whereas considerable differences occurred

  18. Ethnic differences in the mother-son relationship of incarcerated and non-incarcerated male adolescents in the Netherlands.

    Science.gov (United States)

    Veen, Violaine C; Stevens, Gonneke Wjm; Doreleijers, Theo Ah; Deković, Maja; Pels, Trees; Vollebergh, Wilma Am

    2011-06-29

    In the Netherlands, youths of Moroccan origin account for a disproportionately large percentage of the population in juvenile justice institutions. Previous research showed that Moroccan adolescents in pre-trial arrest are characterized by less serious offending behavior (i.e., primarily property-based) and lower levels of mental health problems than native Dutch adolescents in pre-trial arrest. To date, little is known about the parent-child relationship of these adolescents. This study examines the mother-son relationships of Moroccan and native Dutch delinquent adolescents and their association with adolescent delinquency. In the present study, differences in the mother-son relationship characteristics between families of incarcerated (N = 129) and non-incarcerated (N = 324) adolescents were examined, and it was analyzed if these differences between incarcerated and non-incarcerated adolescents were the same for Moroccans and native Dutch. Data collection for the incarcerated sample took place from 2006 to 2008. Comparison data were used of interviews conducted with mothers originating from former larger studies in the general Dutch population. Latent Class Analysis was performed in order to identify types of mother-son relationship. Logistic regression analyses were used to identify the relationships between mother-son relationship types, incarceration and ethnicity. A three class model of mother-son relationship types was found: a low-conflict mother-son relationship type, a high-conflict mother-son relationship type, and a neglectful mother-son relationship type. Compared to the native Dutch adolescents, Moroccans (both in the incarcerated and non-incarcerated population) more often showed a neglectful mother-son relationship type. For Moroccans, no differences in mother-son relationship types were found between the incarcerated and non-incarcerated adolescents, whereas considerable differences occurred between the native Dutch incarcerated and non

  19. The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Karen T. Nozoe

    2014-08-01

    Conclusions: This study indicates that caregiving mothers of sons with DMD show major risk for sexual dysfunction and a reduction in their quality of sleep mediated in part by the hormonal changes related to stress. Nozoe KT, Hachul H, Hirotsu C, Polesel DN, Moreira GA, Tufik S, and Andersen ML. The relationship between sexual function and quality of sleep in caregiving mothers of sons with Duchenne muscular dystrophy. Sex Med 2014;2:133–140.

  20. Estructuras de pobreza en el agro ¿por qué son pobres los campesinos?

    Directory of Open Access Journals (Sweden)

    Eugenio Pedro Giovenardi

    1992-01-01

    Full Text Available La pobreza campesina persiste a pesar de los programas de carácter especial que se adelantan desde hace muchos años, tanto por iniciativa de los gobiernos latinoamericanos, como de organismos internacionales. Las fórmulas, las medidas, las estrategias adoptadas hasta ahora para aminorar la pobreza, se enmarcan en un cuadro de soluciones coyunturales o segmentarias, sin un conducto lógico que permita influir positivamente los elementos de un plan global e integral de acción. Son programas de crédito individual para la producción, pero sin estrategias de comercialización. Otros son de capacitación y educación, pero desconectados de la realidad económica que envuelve los campesinos. En el presente ensayo, se busca formular una estrategia de carácter estructural, analizando el conjunto de las relaciones económicas del complejo rural, escenario donde actúan todos los agentes responsables de la producción agrícola desde la siembra hasta el consumo. Se analizan las causas estructurales de la riqueza, los puntos de acumulación o agregados y su capacidad de generar y retener los valores que se van creando alrededor del producto, y su expresión corno centros de decisión de precios, de políticas económicas y de reinversión de los excedentes producidos. Se examinan la mecánica de la transferencia de valores de un agregado a otro y los elementos de decisión de cada punto de acumulación. Se recogen algunas inquietudes del poco éxito de los programas de desarrollo rural y se reafirma la convicción de que los campesinos pueden llegar a ser ricos, sin miedo de emplear este término, siempre y cuando el gobierno y la sociedad civil se decidan a tornar medidas integrales capaces de erradicar las causas de la pobreza. En otras palabras, introducir la actividad campesina en las estructuras de riqueza, a través de empresas asociativas planificadas para administrar el complejo económico rural.

  1. 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.

  2. Decorin is a novel VEGFR-2-binding antagonist for the human extravillous trophoblast.

    Science.gov (United States)

    Khan, Gausal A; Girish, Gannareddy V; Lala, Neena; Di Guglielmo, Gianni M; Lala, Peeyush K

    2011-08-01

    Extravillous trophoblasts (EVT) of the human placenta invade the uterine decidua and its arteries to ensure successful placentation. We previously identified two decidua-derived molecules, TGF-β and a TGF-β-binding proteoglycan decorin (DCN), as negative regulators of EVT proliferation, migration, and invasiveness and reported that DCN acts via multiple tyrosine kinase receptors [epidermal growth factor-receptor (EGF-R), IGF receptor-1 (IGFR1), and vascular endothelial growth factor 2 receptor (VEGFR-2)]. Because binding of DCN to VEGFR-2 has never been reported earlier, present study explored this binding, the approximate location of VEGFR-2-binding site in DCN, and its functional role in our human first trimester EVT cell line HTR-8/SVneo. Based on far-Western blotting and coimmunoprecipitation studies, we report that DCN binds both native (EVT expressed) and recombinant VEGFR-2 and that this binding is abrogated with a VEGFR-2 blocking antibody, indicating an overlap between the ligand-binding and the DCN-binding domains of VEGFR-2. We determined that (125)I-labeled VEGF-E (a VEGFR-2 specific ligand) binds EVT with a dissociation constant (K(d)) of 566 pM, and DCN displaced this binding with an inhibition constant (K(i)) of 3.93-5.78 nM, indicating a 7- to 10-fold lower affinity of DCN for VEGFR-2. DCN peptide fragments derived from the leucine rich repeat 5 domain that blocked DCN-VEGFR-2 interactions or VEGF-E binding in EVT cells also blocked VEGF-A- and VEGF-E-induced EVT cell proliferation and migration, indicative of functional VEGFR-2-binding sites of DCN. Finally, DCN inhibited VEGF-E-induced EVT migration by interfering with ERK1/2 activation. Our findings reveal a novel role of DCN as an antagonistic ligand for VEGFR-2, having implications for pathophysiology of preeclampsia, a trophoblast hypoinvasive disorder in pregnancy, and explain its antiangiogenic function.

  3. Analyzing radioligand binding data.

    Science.gov (United States)

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  4. 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.

  5. Los saberes indígenas son patrimonio de la humanidad

    Directory of Open Access Journals (Sweden)

    José Narciso Jamioy Muchavisoy

    1997-10-01

    Full Text Available Bajo la premisa de que narrar en pocas palabras los saberes milenarios de los distintos pueblos es irrespetuoso e irresponsable, ya que se puede caer en interpretaciones superficiales y erradas sobre aquellos conocimientos que para ellos son sagrados, el autor se limita a presentar un panorama muy general de cómo dichos conocimientos generan vida e identidad en las nuevas generaciones mediante procesos de tradición oral por los padres, abuelos, tíos y, en especial, por los ancianos sabedores de los pueblos y comunidades indígenas. La explicación es fruto de sus experiencias como hijo de una familia que conservó la tradición Kamëntsá, como acompañante en algunas actividades de reflexión realizadas con voceros del ordennacional y con las comunidades de los pueblos Arhuaco, Paéz, Guambiano,Pastos, Ticuna, Cofán e Inga. Así mismo, de sus vivencias como estudian- te, docente de colegio, catedrático universitario e investigador.

  6. Two sons and a daughter: sex composition and women's reproductive behaviour in Madhya Pradesh, India.

    Science.gov (United States)

    Edmeades, Jeffrey; Pande, Rohini; Macquarrie, Kerry; Falle, Tina; Malhotra, Anju

    2012-11-01

    This article examines how the sex composition of women's current children at the start of a pregnancy interval influences both fertility desires and the full range of reproductive actions women may take to realize them, including temporary contraception, abortion and sterilization, in Madhya Pradesh, India, where popular notions of ideal family size and sex composition are dominated by son preference. The analysis is conducted using a dataset of 9127 individual pregnancy intervals from a 2002 statewide representative survey of 2444 women aged 15-39 with at least one child. The results indicate that women's preferences go beyond a singular preference for male children, with the preferred composition of children being two boys and one girl. Women with this composition are 90% less likely to report having wanted another pregnancy (OR 0.097, p < 0.01) relative to those with two girls. These preferences have significant implications for reproductive actions. While sex composition has no statistically significant effect on the use of temporary contraception, those with the preferred sex composition are twice as likely to attempt abortion (OR 2.436, p < 0.01) and twelve times more likely to be sterilized (OR 12.297, p < 0.01) relative to those with two girls only.

  7. Maternal Child Sexual Abuse Is Associated With Lower Maternal Warmth Toward Daughters but Not Sons.

    Science.gov (United States)

    Cross, Dorthie; Kim, Ye Ji; Vance, L Alexander; Robinson, Gabriella; Jovanovic, Tanja; Bradley, Bekh

    2016-01-01

    Mothers with a history of child sexual abuse report less warmth toward their children, but whether this association differs by child gender is unknown. We examined the association of maternal child sexual abuse and warmth across child gender, accounting for depression, post-traumatic stress disorder, and child physical abuse. We verbally administered self-report measures to a cross-sectional sample of 154 mothers with a child between 8 and 12 years old. Eighty-five mothers based warmth responses on a son, and 69 on a daughter. We conducted a hierarchical multiple regression, including child gender, maternal child sexual abuse, child physical abuse, depression, post-traumatic stress disorder, and 4 two-way interaction terms with child gender. Maternal depression predicted decreased warmth, regardless of child gender, and maternal child sexual abuse predicted decreased warmth, but only toward daughters. Given previous research suggesting that maternal warmth predicts child well-being, the current finding may represent an important avenue of intergenerational transmission of risk in girls.

  8. 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.

  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. Mothers, fathers, sons and daughters: parental sensitivity in families with two children.

    Science.gov (United States)

    Hallers-Haalboom, Elizabeth T; Mesman, Judi; Groeneveld, Marleen G; Endendijk, Joyce J; van Berkel, Sheila R; van der Pol, Lotte D; Bakermans-Kranenburg, Marian J

    2014-04-01

    Most studies on early childhood parenting include only mothers. Fathers are rarely observed in interaction with their young children, although they play an important role in the socialization of their children. In this study, we observed parenting of mothers and fathers toward their sons and daughters in families with two children, using a within-family approach in a sample with systematically varying family constellations. Participants included 389 families with two children (1 and 3 years of age). Parenting practices were coded during free play using the Emotional Availability Scales (Biringen, 2008). Findings revealed that mothers showed higher levels of sensitivity and lower levels of intrusiveness toward their children than fathers. Furthermore, mothers and fathers were more sensitive and less intrusive toward their oldest child than toward their youngest child. Fathers' higher intrusiveness toward the youngest child was only found in the case of a youngest boy. Child gender was not related to parenting in any of the other analyses. Our results suggest that parent gender is more salient than child gender in the prediction of parenting practices in early childhood.

  11. A Novel Dynamic Adjusting Algorithm for Load Balancing and Handover Co-Optimization in LTE SON

    Institute of Scientific and Technical Information of China (English)

    Wen-Yu Li; Xiang Zhang; Shu-Cong Jia; Xin-Yu Gu; Lin Zhang; Xiao-Yu Duan; Jia-Ru Lin

    2013-01-01

    With the development of mobile internet and multi-media service,advanced techniques need to be applied in wireless network to improve user experience.Long term evolution (LTE) systems,which can offer up to 100Mbps downlink date rates,have been deployed in USA and Korea.However,because plenty of complex physical layer algorithms are utilized,network planning and optimization become heavy burdens for LTE network operators.Self-organizing network (SON) is a promising method to overcome this problem by automatically selecting and adjusting key parameters in LTE systems.In this paper,we present a dynamic adjusting algorithm to improve both handover and load balancing performance by introducing a weighted co-satisfaction factor (CSF).Analysis and system level simulation are conducted to exhibit the performance improvement of the proposed scheme.Results show that the proposed method outperforms the conventional solutions in terms of the network handover success ratio and load balancing gains significantly.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Une pensée en action du son au théâtre

    Directory of Open Access Journals (Sweden)

    Jean-Paul Quéinnec

    2011-09-01

    Full Text Available En cherchant à ne plus soumettre le son à l’action dramatique, le statut de la dramaturgie théâtrale (textuelle et scénique se met à dériver. Un glissement de la pensée comme de la pratique qui appelle une écoute à d’autres références théoriques et méthodologiques. Cet article s’appuie sur une recherche création en dramaturgie sonore qui explore la notion d’intermédialité et la création performative au théâtre. Un vécu expérientiel de la matérialité sonore (texte, objet, espace qui développe un concept que nous nommons « dramaturgie informe » car le théâtre contemporain devenu matière vive et complexe s’avère difficile à isoler pour être défini.

  15. A Novel Stochastic Learning Automata Based SON Interference Mitigation Framework for 5G HetNets

    Directory of Open Access Journals (Sweden)

    M. N. Qureshi

    2016-12-01

    Full Text Available Long Term Evolution Advanced (LTE-A Heterogeneous Networks (HetNet are an important aspect of 5th generation mobile communication systems. They consists of high power macrocells along with low power cells i.e. picocells and femtocells to fill up macrocell coverage gaps. HetNet permit deployment of femtocells by users for added flexibility, but then interference issues between neighbouring cells have to be addressed as all femtocells use the same frequency channels for transmission. To mitigate this problem, LTE-A standard offers two new features, one is carrier aggregation in which Component Carriers (CC form the basic aggregate units shared among cells and the other is enhanced Inter-Cell Interference Co-ordination (eICIC through X2 interface. The physical implementation of these features is left open to research. This paper investigates two distinct techniques for orthogonal CC selection through Stochastic Cellular Learning Automata (SCLA to improve the QoS performance of a femtocell. The first, technique uses SCLA with user feedback, and the second technique uses SCLA with a central publishing server where all cells upload their past used CC vectors. SCLA methods are better suited for Self Organizing Network (SON as they do not require synchronized cell coordination, have low complexity and have good optimization characteristics. The simulation results show that the techniques enhance the cell edge performance considerably.

  16. Helium mobility in SON68 borosilicate nuclear glass: A nuclear reaction analysis approach

    Energy Technology Data Exchange (ETDEWEB)

    Bès, R., E-mail: rene.bes@cnrs-orleans.fr [CNRS, UPR3079 CEMHTI, 1D Avenue de la Recherche Scientifique, 45071 Orléans cedex 2 (France); Sauvage, T. [CNRS, UPR3079 CEMHTI, 1D Avenue de la Recherche Scientifique, 45071 Orléans cedex 2 (France); Université d’Orléans, Faculté des Sciences, Avenue du Parc Floral, BP 6749, 45067 Orléans cedex 2 (France); Peuget, S. [CEA/DEN/VRH/DTCD/SECM/LMPA Marcoule (France); Haussy, J. [CEA, DAM, DIF, F-91297 Arpajon (France); Chamssedine, F. [Université Libanaise, Faculté des Sciences V, Nabatiyeh (Lebanon); Oliviero, E. [CSNSM, CNRS/IN2P3 and Université Paris-Sud, Bât. 104-108, F-91405 Orsay (France); Fares, T. [CEA/DEN/VRH/DTCD/SECM/LMPA Marcoule (France); Vincent, L. [Institut d’Electronique Fondamentale, CNRS and Université Paris-Sud, UMR 8622, F-91405 Orsay (France)

    2013-11-15

    The {sup 3}He behavior in the non active R7T7 type borosilicate glass called SON68 has been investigated using the implantation method to introduce helium in the material. Nuclear Reaction Analysis (NRA) was performed to follow the helium concentration depth profile evolution as a function of annealing time and temperature. In addition, in situ Transmission Electron Microscopy (TEM) has been implemented to study the formation of helium bubbles during both implantation and annealing processes. Numerical modeling with two different approaches is proposed and discussed to investigate the helium mobility mechanisms. Our study reveals for helium incorporation by implantation at low temperature the presence of several helium populations with disparate diffusivities. The most mobile helium fraction would be attributed to atomic diffusion. The corresponding activation energy value (0.61 eV) extracted from Arrhenius graphs is in good agreement with literature data. The results also highlight that the damages associated to helium sursaturation are the source of small helium clusters formation, with a reduced mobility instead of the atomic mobility measured by the infusion technique. Small cavities that support this assumption have been observed by TEM at low temperature.

  17. Mediaeval manuscript bindings

    Directory of Open Access Journals (Sweden)

    Jedert Vodopivec

    1999-01-01

    Full Text Available The present article represents an excerpt from the final chapters of the research study titled "The development of structures in mediaeval manuscript bindings - interdependence with conservatory methods". In it, aims, methods of work, archive and library materials used and directions for conservatory methods are presented. Besides, the research study includes also a historcial overview of book bindings, detailed analysis of separate structural elements in Slovenian mediaeval bindings, comprehensive presentation of separate structures, the techniques of binding and materials of the preserved mediaeval bindings in Slovenian public archives and libraries, terminological dictionary of specific professional terms related to binding as a segment of a book, and a catalogue of all analysed bindings, containing a survey of ajI detectable data, sketches,graphite prints and photographs.

  18. Ureaplasma urealyticum binds mannose-binding lectin.

    Science.gov (United States)

    Benstein, Barbara D; Ourth, Donald D; Crouse, Dennis T; Shanklin, D Radford

    2004-10-01

    Mannose-binding C-type lectin (MBL) is an important component of innate immunity in mammals. Mannose-binding lectin (MBL), an acute phase protein, acts as an opsonin for phagocytosis and also activates the mannan-binding lectin complement pathway. It may play a particularly significant role during infancy before adequate specific protection can be provided by the adaptive immune system. Ureaplasma urealyticum has been linked to several diseases including pneumonia and chronic lung disease (CLD) in premature infants. We therefore investigated the ability of U. urealyticum to bind MBL. A guinea pig IgG anti-rabbit-MBL antiserum was produced. An immunoblot (dot-blot) assay done on nitrocellulose membrane determined that the anti-MBL antibody had specificity against both rabbit and human MBL. Pure cultures of U. urealyticum, serotype 3, were used to make slide preparations. The slides containing the organisms were then incubated with nonimmune rabbit serum containing MBL. Ureaplasma was shown to bind rabbit MBL with an immunocytochemical assay using the guinea pig IgG anti-rabbit MBL antiserum. Horseradish peroxidase (HRP)-labeled anti-guinea pig IgG was used to localize the reaction. The anti-MBL antiserum was also used in an immunocytochemical assay to localize U. urealyticum in histological sections of lungs from mice specifically infected with this organism. The same method also indicated binding of MBL by ureaplasma in human lung tissue obtained at autopsy from culture positive infants. Our results demonstrate that ureaplasma has the capacity to bind MBL. The absence of MBL may play a role in the predisposition of diseases related to this organism.

  19. Ligand binding mechanics of maltose binding protein.

    Science.gov (United States)

    Bertz, Morten; Rief, Matthias

    2009-11-13

    In the past decade, single-molecule force spectroscopy has provided new insights into the key interactions stabilizing folded proteins. A few recent studies probing the effects of ligand binding on mechanical protein stability have come to quite different conclusions. While some proteins seem to be stabilized considerably by a bound ligand, others appear to be unaffected. Since force acts as a vector in space, it is conceivable that mechanical stabilization by ligand binding is dependent on the direction of force application. In this study, we vary the direction of the force to investigate the effect of ligand binding on the stability of maltose binding protein (MBP). MBP consists of two lobes connected by a hinge region that move from an open to a closed conformation when the ligand maltose binds. Previous mechanical experiments, where load was applied to the N and C termini, have demonstrated that MBP is built up of four building blocks (unfoldons) that sequentially detach from the folded structure. In this study, we design the pulling direction so that force application moves the two MBP lobes apart along the hinge axis. Mechanical unfolding in this geometry proceeds via an intermediate state whose boundaries coincide with previously reported MBP unfoldons. We find that in contrast to N-C-terminal pulling experiments, the mechanical stability of MBP is increased by ligand binding when load is applied to the two lobes and force breaks the protein-ligand interactions directly. Contour length measurements indicate that MBP is forced into an open conformation before unfolding even if ligand is bound. Using mutagenesis experiments, we demonstrate that the mechanical stabilization effect is due to only a few key interactions of the protein with its ligand. This work illustrates how varying the direction of the applied force allows revealing important details about the ligand binding mechanics of a large protein.

  20. 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

  1. The relationship between sexual function and quality of sleep in caregiving mothers of sons with duchenne muscular dystrophy.

    Science.gov (United States)

    Nozoe, Karen T; Hachul, Helena; Hirotsu, Camila; Polesel, Daniel N; Moreira, Gustavo A; Tufik, Sergio; Andersen, Monica L

    2014-08-01

    The task of the caregiver, especially a caregiving mother of a son with a chronic and fatal disease, may interfere with their quality of sleep, sexuality, and some hormone levels. The aim of this study was to evaluate the sexual function and the quality of sleep of caregiving mothers of sons with Duchenne muscular dystrophy (DMD). We evaluated 20 caregiving mothers of sons with DMD and 20 caregiving mothers of sons without any neuromuscular or chronic disease. All of them voluntarily responded to the evaluating questionnaires about their sexuality and their quality of sleep, and gave blood samples to evaluate their hormonal levels. All mothers were evaluated using the questionnaire of Female Sexual Function Index (FSFI) and the Pittsburgh questionnaire (PSQI). The blood samples were tested to determine serum levels of testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, progesterone, adrenocorticotropic hormone, and cortisol. Caregiving mothers of sons with DMD had significantly lower scores in the FSFI questionnaire, suggesting a higher risk for sexual dysfunction. The PSQI demonstrated that these caregiving mothers present increased sleep latency, reduced sleep efficiency, daytime dysfunction, and poor sleep quality. Blood tests showed a rise in cortisol levels, which correlated with the compromised sexuality and quality of sleep. This study indicates that caregiving mothers of sons with DMD show major risk for sexual dysfunction and a reduction in their quality of sleep mediated in part by the hormonal changes related to stress. Nozoe KT, Hachul H, Hirotsu C, Polesel DN, Moreira GA, Tufik S, and Andersen ML. The relationship between sexual function and quality of sleep in caregiving mothers of sons with Duchenne muscular dystrophy. Sex Med 2014;2:133-140.

  2. 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...

  3. A Possible Link Between the Pubertal Growth of Girls and Prostate Cancer in Their Sons

    Science.gov (United States)

    BARKER, DAVID J.P.; OSMOND, CLIVE; THORNBURG, KENT L.; KAJANTIE, EERO; ERIKSSON, JOHAN G.

    2012-01-01

    Objectives Among women attending antenatal clinics during 1934–1944 a large intercristal diameter, the maximum distance between the pelvic iliac crests, was associated with a raised incidence of breast and ovarian cancer in the daughters in later life. At puberty, the intercristal diameter of girls enlarges rapidly under the influence of estrogen. We speculated that high maternal estrogen concentrations during pregnancy initiate hormonal cancers in their daughters. Here, we examine the association between the mothers’ intercristal diameters and prostate cancer in their sons. Methods Using the national cancer registry we identified 221 cases of prostate cancer among 6,975 men born during 1934–1944 in Helsinki, Finland. Four thousand four hundred and one of these men had their mother’s bony pelvic measurements recorded: there were 149 cases among them. Results Hazard ratios for prostate cancer rose as the mother’s intercristal diameter increased; but this association was restricted to men who were born before 40 weeks of gestation. Among these men the hazard ratio was 1.27 (95% CI 1.09–1.48; P = 0.002). The hazard ratio was 2.2 (1.3–3.7; P < 0.001) in men whose mothers weighed more than 80 kg in late pregnancy compared with those whose mothers weighed 60 kg or less. Conclusions These findings are consistent with a conceptual framework for the origins of hormonally dependent cancers that invokes exposure of embryonic tissue to maternal sex hormones followed by resetting of the fetal hypothalamic-gonadotropin axis in late gestation. We hypothesize that compensatory prepubertal growth among girls is associated with hormonal cancers in the next generation. PMID:22287160

  4. Protein Binding Pocket Dynamics.

    Science.gov (United States)

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  5. Analytical Modeling of SON MOSFET and Realization Inverter Circuit for High Speed and Ultra Dense Low Power Circuits

    Directory of Open Access Journals (Sweden)

    Kousik Naskar

    2012-06-01

    Full Text Available In the recent years, there has been considerable interest in the realization of high speed, small-size and low-power consuming devices and systems. As a consequence, the search for new principle of operation of the small-size, high speed and low-power device is becoming more and more important. In our earlier paper, it has been established that SON technology, not only improve the dc performance with reduce a short-channel effect and threshold voltage, it also improves the frequency response due to improvement in conductance and reduced parasitic effect. Further, it is already in our knowledge that SCEs are suppressed in dual material gate MOSFETs because of the perceivable step in the surface-potential profile, which screens the drain potential. The concept of dual material gate has been applied to SON MOSFETs structure and the features exhibited by resulting new SON structure has been examined for the first time by developing an analytical model and the result agree well with the MEDICI simulation values. In order to substantiate the merits of the proposed SON MOSFETs, a MOS Inverter is realized using the SON MOSFETs and its performance is investigated as an aid to the high-speed, ultra-dense and low-power circuit related work.

  6. 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.

  7. Does antibody binding to diverse antigens predict future infection?

    Science.gov (United States)

    Owen, J P; Waite, J L; Holden, K Z; Clayton, D H

    2014-11-01

    We studied diverse antigen binding in hosts and the outcome of parasitism. We used captive-bred F1 descendants of feral rock pigeons (Columba livia) challenged with blood-feeding flies (Hippoboscidae) and a protozoan parasite (Haemoproteus). Enzyme-linked immunosorbent assays (ELISAs) and immunoblots were used to test (i) whether pre-infection IgY antigen binding predicts parasite fitness and (ii) whether antigen binding changes after infection. Assays used extracts from three pigeon parasites (northern fowl mite, Salmonella bacteria and avian pox virus), as well as nonparasitic molecules from cattle, chicken and keyhole limpet. Binding to hippoboscid and S. enterica extracts were predictive of hippoboscid fly fitness. Binding to extracts from hippoboscids, pox virus and nonparasitic organisms was predictive of Haemoproteus infection levels. Antigen binding to all extracts increased after parasite challenge, despite the fact that birds were only exposed to flies and Haemoproteus. Immunoblots suggested innate Ig binding to parasite-associated molecular markers and revealed that new antigens were bound in extracts after infection. These data suggest that host antibody binding to diverse antigens predicts parasite fitness even when the antigens are not related to the infecting parasite. We discuss the implications of these data for the study of host-parasite immunological interaction. © 2014 John Wiley & Sons Ltd.

  8. Inhibition of lanthanide nanocrystal-induced inflammasome activation in macrophages by a surface coating peptide through abrogation of ROS production and TRPM2-mediated Ca(2+) influx.

    Science.gov (United States)

    Yao, Han; Zhang, Yunjiao; Liu, Liu; Xu, Youcui; Liu, Xi; Lin, Jun; Zhou, Wei; Wei, Pengfei; Jin, Peipei; Wen, Long-Ping

    2016-11-01

    Lanthanide-based nanoparticles (LNs) hold great promise in medicine. A variety of nanocrystals, including LNs, elicits potent inflammatory response through activation of NLRP3 inflammasome. We have previously identified an LNs-specific surface coating peptide RE-1, with the sequence of 'ACTARSPWICG', which reduced nanocrystal-cell interaction and abrogated LNs-induced autophagy and toxicity in both HeLa cells and liver hepatocytes. Here we show that RE-1 coating effectively inhibited LNs-induced inflammasome activation, mostly mediated by NLRP3, in mouse bone marrow derived macrophage (BMDM) cells, human THP-1 cells and mouse peritoneal macrophages and also reduced LNs-elicited inflammatory response in vivo. RE-1 coating had no effect on cellular internalization of LNs in BMDM cells, in contrast to the situation in HeLa cells where cell uptake of LNs was significantly inhibited by RE-1. To elucidate the molecular mechanism underlying the inflammasome-inhibiting effect of RE-1, we assessed several parameters known to influence nanocrystal-induced NLRP3 inflammasome activation. RE-1 coating did not reduce potassium efflux, which occurred after LNs treatment in BMDM cells and was necessary but insufficient for LNs-induced inflammasome activation. RE-1 did decrease lysosomal damage induced by LNs, but the inhibitor of cathepsin B did not affect LNs-elicited caspase 1 activation and IL-1β release, suggesting that lysosomal damage was not critically important for LNs-induced inflammasome activation. On the other hand, LNs-induced elevation of intracellular reactive oxygen species (ROS), critically important for inflammasome activation, was largely abolished by RE-1 coating, with the reduction on NADPH oxidase-generated ROS playing a more prominent role for RE-1's inflammasome-inhibiting effect than the reduction on mitochondria-generated ROS. ROS generation further triggered Ca(2+) influx, an event that was mediated by Transient Receptor Potential M2 (TRPM2) and was

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

    Science.gov (United States)

    Kuroda, Shinji; Tam, Justina; Roth, Jack A; Sokolov, Konstantin; Ramesh, Rajagopal

    2014-01-01

    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 G2/M checkpoint by inhibiting BRCA1, Chk1, and phospho-Cdc2/CDK1 protein expression. In vivo therapy studies showed 225-NP treatment reduced EGFR phosphorylation, increased γH2AX foci, and induced tumor cell apoptosis, resulting in suppression of tumor growth. Conclusion The 225-NP treatment induces DNA damage and abrogates G2/M phase of the cell cycle, leading to cellular apoptosis and suppression of lung tumor growth

  10. 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

  11. Python bindings for libcloudph++

    OpenAIRE

    Jarecka, Dorota; Arabas, Sylwester; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python ...

  12. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  13. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python bindings to access libcloudph++ from Fortran is presented.

  14. Design and Analysis of a High Speed, Power Efficient 8 Bit ALU Based on SOI / SON MOSFET Technology

    Directory of Open Access Journals (Sweden)

    Subhramita Basak

    2014-01-01

    Full Text Available This paper shows an overall performance comparative analysis in terms of Average Power Consumption, Average Delay and Power-Delay Product for an 8 bit Arithmetic Logic Unit (ALU using bulk MOS, Silicon-on-Insulator (SOI and Silicon-on-Nothing (SON technology. The entire design is done in 32nm technology for all the three cases (Bulk, SOI & SON and then compared. The comparisons have been carried out with the help of the simulation runs on Synopsys HSpice tool, and that clearly indicates, for lower Supply Voltages (Vdd, SOI / SON technology provides a significant reduction in Average Power Consumption, Average Delay and Power-Delay Product compared to that of Bulk MOS technology.

  15. I-SonReb: an improved NDT method to evaluate the in situ strength of carbonated concrete

    Science.gov (United States)

    Breccolotti, Marco; Bonfigli, Massimo F.

    2015-10-01

    Concrete strength evaluated in situ by means of the conventional SonReb method can be highly overestimated in presence of carbonation. This latter, in fact, is responsible for the physical and chemical alteration of the outer layer of concrete. As most of the existing concrete structures are subjected to carbonation, it is of high importance to overcome this problem. In this paper, an Improved SonReb method (I-SonReb) for carbonated concretes is proposed. It relies on the definition of a correction coefficient of the measured Rebound index as a function of the carbonated concrete cover thickness, an additional parameter to be measured during in situ testing campaigns. The usefulness of the method has been validated showing the improvement in the accuracy of concrete strength estimation from two sets of NDT experimental data collected from investigations on real structures.

  16. OSMANLI’NIN SON DÖNEMİNİN SOSYO EKONOMİK BUHRANLARI VE MALİ EMPERYALİZM

    OpenAIRE

    KALABAK, Ali Yasin

    2014-01-01

    Bu çalışmada yayılan Kapitalizmin Osmanlı Devletine etkileri ve yaşadığı savaşlardan dolayı Osmanlı Devleti’nin son dönemlerinde içerisinde bulunduğu sosyo-ekonomik buhranlar incelenecektir. İncelememiz sırasında kullanacağımız veriler İktisat Tarihi ile alakalı yazılı kaynaklardan elde edilecektir. Osmanlı Devletinin son dönemlerinde sahip olduğu eğitim ve sağlık sisteminin analiziyle başlayacak olan çalışmamız Osmanlı Devleti’nin son dönem nüfus yapısıyla devam edecektir. Çalışmanın ilerley...

  17. The Gelfand-Zeitlin integrable system and its action on generic elements of gl(n) and so(n)

    CERN Document Server

    Colarusso, Mark

    2008-01-01

    In recent work Bertram Kostant and Nolan Wallach ([KW1], [KW2]) have defined an interesting action of a simply connected Lie group $A$ isomorphic to \\mathbb{C}^{{n\\choose 2}} on gl(n) using a completely integrable system derived from Gelfand-Zeitlin theory. In this paper we show that an analogous action of \\mathbb{C}^{d} exists on the complex orthogonal Lie algebra so(n), where d is half the dimension of a regular adjoint orbit in so(n). In [KW1], Kostant and Wallach describe the orbits of $A$ on a certain Zariski open subset of regular semisimple elements in gl(n). We extend these results to the case of so(n). We also make brief mention of the author's results in [Col1], which describe all $A$-orbits of dimension {n\\choose 2} in gl(n).

  18. Le developpement de flexorage et son devenir industriel The Development of Flexodrilling

    Directory of Open Access Journals (Sweden)

    Thiery J. R.

    2006-11-01

    Full Text Available Après un rappel des avantages et inconvénients comparés du forage rotary et du flexoforage, cet article retrace l'historique du développement, par l'Institut Français du Pétrole (IFP du flexoforage. La première période a vu la mise au point du flexoforage léger, et son application à la reconnaissance des fonds marins. Dans la deuxième phase, les composants principaux du flexoforage profond ont été créés par l'IFP et expérimentés en URSS dans le cadre d'un accord de coopération franco-soviétique. La troisième phase du développement correspond en fait, à l'industrialisation du procédé. Elle a été marquée, en 1974, par la création de la société Foraflex et la réalisation de deux campagnes de forage pour la compagnie Nam à Groningue. L'article décrit les étapes actuellement en cours de cette industrialisation et les perspectives relatives au devenir industriel du procédé. After reviewing the comparative advantages of rotary drilling and flexodrilling, this article tracesthe historical developmentof flexodrilling by Institut Français du Pétrole(IFP. During the first phase, light flexodrilling was developed and applied ta seabed reconnaissance. In the second phase, IFP created the main components of deep flexodrilling which were experimented in lheSoviet Union under the terms of the French-Soviet Cooperation Agreement. The third phase of development actually corresponds to the industrialization of the process. In 1974 is was mdrked by the creation of Société Floraflex and two drilling campaigns for Nom at Groningen,the Netherlands. The article describes the current stages of this industrialization and the industrial outlook for the process.

  19. Por qué ser justos. ¿Son las normas de justicia sociales o morales?

    Directory of Open Access Journals (Sweden)

    Rodríguez López, Blanca

    2013-08-01

    Full Text Available In the last few years, there has been a good amount of theoretical work around the concept of social norm. The work of Cristina Bicchieri and Jon Elster has been specially interesting and intense in this field. Although their respective approaches present substantive differences, they both agree in defining social norms in contrast with other related concepts, such as moral norms. Notwithstanding this basic agreement, they disagree when classifying norms of justice. For Bicchieri these are social norms, while Elster’s view is more complex and he classifies different norms of justice in different categories: some are social while others are semi moral o moral. In this paper I focus on the treatment of one specific norm of justice, the norm of egalitarian distribution, which is a social norm for Bichieri but a moral norm from Elster’s view. With the aid of some recent experiments, I conclude that Elster’s view is more promising, at least when analyzing this particular norm.Durante los últimos años, el concepto de norma social ha sido objeto de un intenso trabajo teórico, en el que cabe destacar las aportaciones de Cristina Bicchieri y Jon Elster. Pese a las diferencias de sus respectivos planteamientos, ambos coinciden en definir el concepto por oposición a otro tipo de normas, en especial las morales. Este acuerdo no impide, sin embargo, que clasifiquen las normas de justicia de manera diferente: mientras que para Bicchieri se trata de normas sociales, Elster clasifica distintas normas de justicia en distintas categorías (sociales, cuasi morales y morales.En este trabajo, y con ayuda de algunos experimentos recientes, se analiza el caso de una norma de justicia, la norma de reparto igualitario, y se defiende que, pese a que los experimentos no son concluyentes, hay algunos factores que apuntan a la mayor validez de la teoría de Elster para el tratamiento y la conceptualización de esta norma.

  20. Mutational analysis of hemoglobin binding and heme utilization by a bacterial hemoglobin receptor.

    Science.gov (United States)

    Fusco, W G; Choudhary, N R; Council, S E; Collins, E J; Leduc, I

    2013-07-01

    Iron is an essential nutrient for most living organisms. To acquire iron from their environment, Gram-negative bacteria use TonB-dependent transporters that bind host proteins at the bacterial surface and transport iron or heme to the periplasm via the Ton machinery. TonB-dependent transporters are barrel-shaped outer membrane proteins with 22 transmembrane domains, 11 surface-exposed loops, and a plug domain that occludes the pore. To identify key residues of TonB-dependent transporters involved in hemoglobin binding and heme transport and thereby locate putative protective epitopes, the hemoglobin receptor of Haemophilus ducreyi HgbA was used as a model of iron/heme acquisition from hemoglobin. Although all extracellular loops of HgbA are required by H. ducreyi to use hemoglobin as a source of iron/heme, we previously demonstrated that hemoglobin binding by HgbA only involves loops 5 and 7. Using deletion, substitution, and site-directed mutagenesis, we were able to differentiate hemoglobin binding and heme acquisition by HgbA. Deletion or substitution of the GYEAYNRQWWA region of loop 5 and alanine replacement of selected histidines affected hemoglobin binding by HgbA. Conversely, mutation of the phenylalanine in the loop 7 FRAP domain or substitution of the NRQWWA motif of loop 5 significantly abrogated utilization of heme from hemoglobin. Our findings show that hemoglobin binding and heme utilization by a bacterial hemoglobin receptor involve specific motifs of HgbA.

  1. TonB interacts with BtuF, the Escherichia coli periplasmic binding protein for cyanocobalamin.

    Science.gov (United States)

    James, Karron J; Hancock, Mark A; Gagnon, Jean-Nicolas; Coulton, James W

    2009-10-06

    By its direct contact with outer membrane receptor BtuB, the cytoplasmic membrane transducer TonB delivers energy that mediates cyanocobalamin uptake in Escherichia coli. This activity has been generally proposed to be the role of TonB in cyanocobalamin uptake. We now report the discovery and characterization of interactions between TonB and periplasmic binding protein BtuF. Phage display experiments predicted interaction between TonB and BtuF, identifying potential binding residues on each protein. Dynamic light scattering experiments measured a complex of 55 kDa, consistent with a TonB-BtuF heterodimer. The hydrodynamic radius of the complex was unchanged in the presence of cyanocobalamin. Surface plasmon resonance measured TonB-BtuF interaction kinetics that were independent of cyanocobalamin and that deviated from a simple binding model. Binding isotherms from intrinsic fluorescence suggested a multifaceted interaction that was independent of cyanocobalamin. In addition, the presence of TonB did not abrogate subsequent binding of cyanocobalamin by BtuF. Taken together, these data support a previously proposed model wherein TonB serves as a scaffold to optimally position BtuF for initial binding of cyanocobalamin and for its subsequent release. These results substantiate a diverse role for TonB with its multiple protein-protein interactions in bacterial nutrient uptake systems.

  2. ¿Son los Planes de Desarrollo un mecanismo eficaz para el fortalecimiento de las democracias participativas?

    OpenAIRE

    2011-01-01

    El autor se interroga acerca de si el Consejo Nacional de Planeación, al igual que los consejos territoriales, son escenarios para el ejercicio de la democracia y si su participación, en la construcción de los planes de desarrollo, constituye un instrumento eficaz para su fortalecimiento o son, por el contrario, un espejismo en la praxis de la democracia en Colombia. En la primera parte se mencionan algunas versiones de democracia desde Lincoln, pasando por las versiones de Tocqueville, Shump...

  3. Son de mar : Aproximación al universo narrativo de Manuel Vicent

    OpenAIRE

    Ferrer, Margarita Maria

    2014-01-01

    Son de mar –premio Alfaguara 1999– es una novela que se ubica aproximadamente “nel mezzo del camin” de la producción narrativa de Manuel Vicent, a 33 años de la publicación de su primer obra, El resuello (1966). Son de mar es una novela de la madurez, y en ella podemos analizar algunas cuestiones que caracterizan el universo narrativo de Vicent, universo que incluye novelas, relatos, artículos y columnas periodísticas recopiladas y publicadas en libros. El término universo apunta a una noción...

  4. 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

  5. Indirubin Inhibits LPS-Induced Inflammation via TLR4 Abrogation Mediated by the NF-kB and MAPK Signaling Pathways.

    Science.gov (United States)

    Lai, Jin-Lun; Liu, Yu-Hui; Liu, Chang; Qi, Ming-Pu; Liu, Rui-Ning; Zhu, Xi-Fang; Zhou, Qiu-Ge; Chen, Ying-Yu; Guo, Ai-Zhen; Hu, Chang-Min

    2017-02-01

    Indirubin plays an important role in the treatment of many chronic diseases and exhibits strong anti-inflammatory activity. However, the molecular mode of action during mastitis prophylaxis remains poorly understood. In this study, a lipopolysaccharide (LPS)-induced mastitis mouse model showed that indirubin attenuated histopathological changes in the mammary gland, local tissue necrosis, and neutrophil infiltration. Moreover, indirubin significantly downregulated the production of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). We explored the mechanism whereby indirubin exerts protective effects against LPS-induced inflammation of mouse mammary epithelial cells (MMECs). The addition of different concentrations of indirubin before exposure of cells to LPS for 1 h significantly attenuated inflammation and reduced the concentrations of the three inflammatory cytokines in a dose-dependent manner. Indirubin downregulated LPS-induced cyclooxygenase-2 (COX-2) and Toll-like receptor 4 (TLR4) expression, inhibited phosphorylation of the LPS-induced nuclear transcription factor-kappa B (NF-kB) P65 protein and its inhibitor IkBα of the NF-kB signaling pathway. Furthermore, indirubin suppressed phosphorylation of P38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signal pathways. Thus, indirubin effectively suppressed LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways and may be useful for mastitis prophylaxis.

  6. 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.

  7. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells.

    Science.gov (United States)

    Dominitzki, Sabine; Fantini, Massimo C; Neufert, Clemens; Nikolaev, Alexei; Galle, Peter R; Scheller, Jürgen; Monteleone, Giovanni; Rose-John, Stefan; Neurath, Markus F; Becker, Christoph

    2007-08-15

    Chronic inflammatory diseases may develop when regulatory T cells (Tregs) fail to control the balance between tolerance and immunity. Alternatively, activated immune cells might prevent the induction or activation of Tregs in such diseases. In this study, we demonstrate that trans-signaling into T cells via the soluble IL-6 receptor completely abrogates the de novo induction of adaptive Tregs. Mechanistically, IL-6 trans-signaling augmented the expression of the TGF-beta signaling inhibitor SMAD7. Consequently, SMAD7 overexpression in T cells using newly created transgenic mice rendered CD4(+)CD25(-) T cells resistant to the induction of FoxP3. Finally, IL-6 trans-signaling inhibited Treg-mediated suppression in a murine model of colitis. In summary, IL-6 trans-signaling into T cells emerges as a key pathway for blockade of the development of adaptive Tregs and thus may play a pivotal role in shifting the balance between effector and regulatory T cell numbers in chronic inflammatory and autoimmune diseases.

  8. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.

    2005-01-01

    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  9. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    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. (PSB)

  10. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  11. ¿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.

  12. Thermodynamics of fragment binding.

    Science.gov (United States)

    Ferenczy, György G; Keserű, György M

    2012-04-23

    The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, polar, water-soluble fragments. In order to understand this phenomenon, we analyzed high resolution X-ray data of protein-ligand complexes from the Protein Data Bank and found that fragments bind to proteins with two near optimal geometry H-bonds on average. The linear extent of the fragment binding site was found not to be larger than 10 Å, and the H-bonding region was found to be restricted to about 5 Å on average. The number of conserved H-bonds in proteins cocrystallized with multiple different fragments is also near to 2. These fragment binding sites that are able to form limited number of strong H-bonds in a hydrophobic environment are identified as hot spots. An estimate of the free-energy gain of H-bond formation versus apolar desolvation supports that fragment sized compounds need H-bonds to achieve detectable binding. This suggests that fragment binding is mostly enthalpic that is in line with their observed binding thermodynamics documented in Isothermal Titration Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment based approaches. The binding of larger compounds tends to more rely on apolar desolvation with a corresponding increase of the entropy content of their binding free-energy. These findings explain the reported size-dependence of maximal available affinity and ligand efficiency both behaving differently in the small molecule region featured by strong H-bond formation and in the larger molecule region featured by apolar desolvation.

  13. PilN Binding Modulates the Structure and Binding Partners of the Pseudomonas aeruginosa Type IVa Pilus Protein PilM.

    Science.gov (United States)

    McCallum, Matthew; Tammam, Stephanie; Little, Dustin J; Robinson, Howard; Koo, Jason; Shah, Megha; Calmettes, Charles; Moraes, Trevor F; Burrows, Lori L; Howell, P Lynne

    2016-05-20

    Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1-12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybrid data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1-12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. We propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.

  14. 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.

  15. 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…

  16. Return Migration, Investment in Children, and Intergenerational Mobility: Comparing Sons of Foreign- and Native-Born Fathers

    Science.gov (United States)

    Dustmann, Christian

    2008-01-01

    This paper studies parental investment in education and intergenerational earnings mobility for father-son pairs with native- and foreign-born fathers. We illustrate within a simple model that for immigrants, investment in their children is related to their return migration probability. In our empirical analysis, we include a measure for return…

  17. A two-dimensional analytical-model-based comparative threshold performance analysis of SOI-SON MOSFETs

    Institute of Scientific and Technical Information of China (English)

    Sanjoy Deb; Saptarsi Ghosh; N Basanta Singh; A K De; Subir Kumar Sarkar

    2011-01-01

    A generalized threshold voltage model based on two-dimensional Poisson analysis has been developed for SOI/SON MOSFETs.Different short channel field effects,such as fringing fields,junction-induced lateral fields and substrate fields,are carefully investigated,and the related drain-induced barrier-lowering effects are incorporated in the analytical threshold voltage model.Through analytical model-based simulation,the threshold voltage roll-off and subthreshold slope for both structures are compared for different operational and structural parameter variations.Results of analytical simulation are compared with the results of the ATLAS 2D physicsbased simulator for verification of the analytical model.The performance of an SON MOSFET is found to be significantly different from a conventional SOI MOSFET.The short channel effects are found to be reduced in an SON,thereby resulting in a lower threshold voltage roll-offand a smaller subthreshold slope.This type of analysis is quite useful to figure out the performance improvement of SON over SOI structures for next generation short channel MOS devices.

  18. Gender and Patterns of Concerned Responsiveness in Representations of the Mother-Daughter and Mother-Son Relationship

    Science.gov (United States)

    Butler, Ruth; Shalit-Naggar, Rachel

    2008-01-01

    Given that girls show more interpersonal concern than boys, it was predicted that more mother-daughter than mother-son dyads would develop a relationship of mutual concerned responsiveness (CR). Two hundred and twenty-six Israeli children (7-8 years old) and 91 mother-child pairs provided narratives of mother-child interactions. At high levels of…

  19. Antecedents and Outcomes of Joint Trajectories of Mother-Son Conflict and Warmth during Middle Childhood and Adolescence

    Science.gov (United States)

    Trentacosta, Christopher J.; Criss, Michael M.; Shaw, Daniel S.; Lacourse, Eric; Hyde, Luke W.; Dishion, Thomas J.

    2011-01-01

    This study investigated the development of mother-son relationship quality from ages 5 to 15 in a sample of 265 low-income families. Nonparametric random effects modeling was utilized to uncover distinct and homogeneous developmental trajectories of conflict and warmth; antecedents and outcomes of the trajectory groups also were examined. Four…

  20. Mothers' and Fathers' Perceptions of Change and Continuity in their Relationships with Young Adult Sons and Daughters

    Science.gov (United States)

    Proulx, Christine M.; Helms, Heather M.

    2008-01-01

    Guided by contemporary feminist revisions of individual theories on adolescent development, interviews with 142 parent dyads were conducted to better understand the variation in mothers' and fathers' perceptions of changes and continuities in their relationships with their firstborn young adult sons and daughters. A between-families content…

  1. Self-Regulation in Early Adolescence: Relations with Mother-Son Relationship Quality and Maternal Regulatory Support and Antagonism

    Science.gov (United States)

    Moilanen, Kristin L.; Shaw, Daniel S.; Fitzpatrick, Amber

    2010-01-01

    The purpose of the current investigation was to examine relations among maternal regulatory support, maternal antagonism, and mother-son relationship quality in relation to boys' self-regulation during early adolescence. As part of a larger longitudinal study on 263 low-income, ethnically diverse boys, multiple informants and methods were used to…

  2. 77 FR 72906 - Chessie Logistics Co., LLC-Acquisition and Operation Exemption-J. Emil Anderson & Son, Inc.

    Science.gov (United States)

    2012-12-06

    ... Surface Transportation Board Chessie Logistics Co., LLC--Acquisition and Operation Exemption-- J. Emil Anderson & Son, Inc. Chessie Logistics Co., LLC (Chessie), a noncarrier, has filed a verified notice of... copy of each pleading must be served on Ariel A. Erbacher, Legal Counsel, Chessie Logistics Co., LLC...

  3. 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.

  4. Mothers' and Fathers' Perceptions of Change and Continuity in their Relationships with Young Adult Sons and Daughters

    Science.gov (United States)

    Proulx, Christine M.; Helms, Heather M.

    2008-01-01

    Guided by contemporary feminist revisions of individual theories on adolescent development, interviews with 142 parent dyads were conducted to better understand the variation in mothers' and fathers' perceptions of changes and continuities in their relationships with their firstborn young adult sons and daughters. A between-families content…

  5. Superb fairy-wren (Malurus cyaneus sons and daughters acquire song elements of mothers and social fathers

    Directory of Open Access Journals (Sweden)

    Christine eEvans

    2016-02-01

    Full Text Available Birdsong is regarded as a classic example of a sexually-selected trait and has been primarily studied in systems with male song. Complex solo female song is emerging from the shadows of overlooked phenomena. In males, rearing conditions affect male song complexity, and males with complex songs are often more successful at mate attraction and territorial defense. Little is known about the ontogeny or function of complex female song. Here we examine song elements in fledgling superb fairy-wrens (Malurus cyaneus in relation to the song elements of adult tutors. Male and female superb fairy-wrens produce solo song year-round to defend a territory. We ask if sons and daughters acquire song elements from sex-specific vocal tutors. We found that sons and daughters produced the song elements of their mothers and social fathers, and that sons and daughters had comparable song element repertoires at age 7-10 weeks. We conclude that sons and daughters increase their song element repertoire when vocally imitating elements from several vocal tutors, and that both sexes acquire elements from male and female vocal tutors in this system.

  6. The Dynamics of Son Preference, Technology Diffusion, and Fertility Decline Underlying Distorted Sex Ratios at Birth: A Simulation Approach.

    Science.gov (United States)

    Kashyap, Ridhi; Villavicencio, Francisco

    2016-10-01

    We present a micro-founded simulation model that formalizes the "ready, willing, and able" framework, originally used to explain historical fertility decline, to the practice of prenatal sex selection. The model generates sex ratio at birth (SRB) distortions from the bottom up and attempts to quantify plausible levels, trends, and interactions of son preference, technology diffusion, and fertility decline that underpin SRB trajectories at the macro level. Calibrating our model for South Korea, we show how even as the proportion with a preference for sons was declining, SRB distortions emerged due to rapid diffusion of prenatal sex determination technology combined with small but growing propensities to abort at low birth parities. Simulations reveal that relatively low levels of son preference (about 20 % to 30 % wanting one son) can result in skewed SRB levels if technology diffuses early and steadily, and if fertility falls rapidly to encourage sex-selective abortion at low parities. Model sensitivity analysis highlights how the shape of sex ratio trajectories is particularly sensitive to the timing and speed of prenatal sex-determination technology diffusion. The maximum SRB levels reached in a population are influenced by how the readiness to abort rises as a function of the fertility decline.

  7. Pathways to Prevention: Improving Nonresident African American Fathers' Parenting Skills and Behaviors to Reduce Sons' Aggression

    Science.gov (United States)

    Caldwell, Cleopatra Howard; Antonakos, Cathy L.; Assari, Shervin; Kruger, Daniel; De Loney, E. Hill; Njai, Rashid

    2014-01-01

    This study describes a test of the Fathers and Sons Program for increasing intentions to avoid violence and reducing aggressive behaviors in 8-to 12-year-old African American boys by enhancing the parenting skills satisfaction and parenting behaviors of their nonresident fathers. The study included 158 intervention and 129 comparison group…

  8. Beating the Odds: How Single Black Mothers Influence the Educational Success of Their Sons Enrolled in Failing Schools

    Science.gov (United States)

    Robinson, Quintin L.; Werblow, Jacob

    2012-01-01

    The academy has given little attention to academically successful Black males and the factors that may lead to their successes. This multiple case study design, however, examined the ways in which single-Black mothers influence the educational success of their sons by focusing on the mothers of academically successful 11th grade Black males. Data…

  9. Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor synergy in triple-negative breast cancer.

    Science.gov (United States)

    Madden, Julie M; Mueller, Kelly L; Bollig-Fischer, Aliccia; Stemmer, Paul; Mattingly, Raymond R; Boerner, Julie L

    2014-09-01

    Triple-negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive disease. They have a high rate of relapse and often develop resistance to standard chemotherapy. Many TNBCs have elevated epidermal growth factor receptor (EGFR) but are resistant to EGFR inhibitors as monotherapy. In this study, we sought to find a combination therapy that could sensitize TNBC to EGFR inhibitors. Phospho-mass spectrometry was performed on the TNBC cell line, BT20, treated with 0.5 μM gefitinib. Immunoblotting measured protein levels and phosphorylation. Colony formation and growth assays analyzed the treatment on cell proliferation, while MTT assays determined the synergistic effect of inhibitor combination. A Dual-Luciferase reporter gene plasmid measured translation. All statistical analysis was done on CalucuSyn and GraphPad Prism using ANOVAs. Phospho-proteomics identified the mTOR pathway to be of interest in EGFR inhibitor resistance. In our studies, combining gefitinib and temsirolimus decreased cell growth and survival in a synergistic manner. Our data identified eIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy. Decreased eIF4B phosphorylation correlated with drops in growth, viability, clonogenic survival, and cap-dependent translation. Taken together, these data suggest EGFR and mTOR inhibitors abrogate growth, viability, and survival via disruption of eIF4B phosphorylation leading to decreased translation in TNBC cell lines. Further, including an mTOR inhibitor along with an EGFR inhibitor in TNBC with increased EGFR expression should be further explored. Additionally, translational regulation may play an important role in regulating EGFR and mTOR inhibitor synergy and warrant further investigation.

  10. Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats.

    Science.gov (United States)

    Hagar, Hanan; Medany, Azza El; Salam, Reem; Medany, Gamila El; Nayal, Omina A

    2015-02-01

    Cisplatin is one of the most potent chemotherapeutic antitumor drugs used in the treatment of a wide range of solid tumors. Its primary dose-limiting side effect is nephrotoxicity. This study aims to investigate the effect of betaine supplementation on cisplatin-induced nephrotoxicity. A single intraperitoneal injection of cisplatin (5mg/kg) deteriorated the kidney functions as reflected by elevated blood urea nitrogen and serum creatinine levels. Oxidative/nitrosative stress was evident in cisplatin group by increased renal thiobarbituric acid-reactive substances (TBARS), an indicator of lipid peroxidation, reduced renal total antioxidant status and increased renal nitrite concentration. Cisplatin resulted in a decline in the concentrations of reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase in renal tissues. Renal tumor necrosis factor-α (TNF-α) was also elevated. Expressions of nuclear factor-kappa B (NF-κB) and caspase-3 were up-regulated in renal tissues as indicated by immunohistochemical analysis. Histopathological changes were observed in cisplatin group. Betaine supplementation (250 mg/kg/day) orally via gavage for 21 days prior to cisplatin injection was able to protect against deterioration in kidney function, abrogate the decline in antioxidants enzymes and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, betaine inhibited NF-κB and caspase-3 activation and improved the histological changes induced by cisplatin. Thus, the present study demonstrated the renoprotective nature of betaine by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in kidney tissues of cisplatin treated rats. Betaine could be a beneficial dietary supplement to attenuate cisplatin nephrotoxicity.

  11. 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.

  12. 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.

  13. Salvia miltiorrhiza water-soluble extract, but not its constituent salvianolic acid B, abrogates LPS-induced NF-κB signalling in intestinal epithelial cells

    Science.gov (United States)

    Kim, J S; Narula, A S; Jobin, C

    2005-01-01

    Herbal medicine has become an increasing popular therapeutic alternative among patients suffering from various inflammatory disorders. The Salvia miltiorrhizae water-soluble extract (SME) have been shown to possess antioxidant and anti-inflammatory properties in vitro. However, the mechanism of action and impact of SME on LPS-induced gene expression is still unknown. We report that SME significantly abrogated LPS-induced IκB phosphorylation/degradation, NF-κB transcriptional activity and ICAM-1 gene expression in rat IEC-18 cells. Chromatin immunoprecipitation assay demonstrated that LPS-induced RelA recruitment to the ICAM-1 gene promoter was inhibited by SME. Moreover, in vitro kinase assay showed that SME directly inhibits LPS induced IκB kinase (IKK) activity in IEC-18 cells. To investigate the physiological relevance of SME inhibitory activity on NF-κB signalling, we used small intestinal explants and primary intestinal epithelial cells derived from a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis-elements (cis-NF-κBEGFP). SME significantly blocked LPS-induced EGFP expression and IκBα phosphorylation in intestinal explants and primary IECs, respectively. However, salvianolic acid B, an activate component of SME did not inhibit NF-κB transcriptional activity and IκB phosphorylation/degradation in IEC-18 cells. These results indicate that SME blocks LPS-induced NF-κB signalling pathway by targeting the IKK complex in intestinal epithelial cells. Modulation of bacterial product-mediated NF-κB signalling by natural plant extracts may represent an attractive strategy towards the prevention and treatment of intestinal inflammation. PMID:15996193

  14. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA).

    Science.gov (United States)

    van de Donk, Niels W C J; Otten, Henny G; El Haddad, Omar; Axel, Amy; Sasser, A Kate; Croockewit, Sandra; Jacobs, Joannes F M

    2016-06-01

    Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). In this clinical case study we demonstrate that daratumumab can be detected as an individual monoclonal band in serum immunofixation electrophoresis (IFE). M-protein follow-up by IFE is part of the International Myeloma Working Group (IMWG) criteria to assess treatment response. Therefore, it is crucial that the daratumumab band is not confused with the endogenous M-protein of the patient during IFE interpretation. Moreover, a significant number of IgG-κ M-proteins co-migrate with daratumumab. Co-migration introduces a bias in the M-protein quantification since pharmacokinetic studies show that daratumumab peak plasma concentrations reach up to 1 g/L. More importantly, co-migration can mask clearance of the M-protein by IFE which is necessary for classification of complete response by IMWG criteria (negative serum IFE). For optimal M-protein monitoring the laboratory specialist needs to be informed when patients receive daratumumab, and it is essential that the laboratory specialist is aware that a slow migrating band in the γ-region in those patients may be derived from the daratumumab. A daratumumab specific IFE reflex assay (DIRA) has been developed and can be utilized to abrogate interference. The here described mAb interference is not limited to daratumumab, and as therapeutic antibodies gain approval and enter into common clinical practice, laboratory specialists will need additional processes to characterize IFE interference and distinguish endogenous M-protein from therapeutic antibodies.

  15. Insulin and GSK3β-inhibition abrogates the infarct sparing-effect of ischemic postconditioning in ex vivo rat hearts.

    Science.gov (United States)

    Helgeland, Erik; Wergeland, Anita; Sandøy, Rune M; Askeland, Maren; Aspevik, Anne; Breivik, Lars; Jonassen, Anne K

    2017-06-01

    Pharmacological treatment of reperfusion injury using insulin and GSK3β inhibition has been shown to be cardioprotective, however, their interaction with the endogenous cardioprotective strategy, ischemic postconditioning, is not known. Langendorff perfused ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. For the first 15 min of reperfusion hearts received either vehicle (Ctr), insulin (Ins) or a GSK3β inhibitor (SB415286; SB41), with or without interruption of ischemic postconditioning (IPost; 3 × 30 s of global ischemia). In addition, the combination of insulin and SB41 for 15 min was assessed. Insulin, SB41 or IPost significantly reduced infarct size versus vehicle treated controls (IPost 33.5 ± 3.3%, Ins 33.5 ± 3.4%, SB41 30.5 ± 3.0% vs. Ctr 54.7 ± 6.8%, p < 0.01). Combining insulin and SB415286 did not confer additional cardioprotection compared to the treatments given alone (SB41 + Ins 26.7 ± 3.5%, ns). Conversely, combining either of the pharmacological reperfusion treatments with IPost completely abrogated the cardioprotection afforded by the treatments separately (Ins + IPost 59.5 ± 3.4% vs. Ins 33.5 ± 3.4% and SB41 + IPost 50.2 ± 6.6% vs. SB41 30.5 ± 3.0%, both p < 0.01), and was associated with blunted Akt, GSK3β and STAT3 phosphorylation. Pharmacological reperfusion treatment with insulin and SB41 interferes with the cardioprotection afforded by ischemic postconditioning.

  16. Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio.

    Directory of Open Access Journals (Sweden)

    Suresh C Bairwa

    Full Text Available White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1 administration. Myocytes were treated with ET-1 (10 nM for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK, an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin-dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.

  17. Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio.

    Science.gov (United States)

    Bairwa, Suresh C; Rajapurohitam, Venkatesh; Gan, Xiaohong Tracey; Mangat, Rabban; Proctor, Spencer D; Karmazyn, Morris

    2016-01-01

    White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin-dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.

  18. 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

  19. 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)

  20. Applicability of the SON-R 6-40 Non-verbal Intelligence Test in China%SON-R6-40非言语智力测验在中国的适用性

    Institute of Scientific and Technical Information of China (English)

    徐建平; 郭枝; 王茜; Peter Tellegen

    2014-01-01

    SON-R 6-40非言语智力测验是以非文字形式测量个体推理与空间能力的智力评估工具.研究旨在考查SON-R6-40在中国的适用性.根据全国人口分布,在中国六大行政区6至40岁年龄人群中施测了1721人,通过与荷兰/德国混合样本比较,分析该测验的跨文化等值水平.结果表明:(1)测验信度与结构跨样本一致,说明该测验在两种文化下结构等值;(2)多样本验证性因素分析证明了该测验的测量单位等值性.因此,SON-R 6-40适合在中国推广使用以及用于智力的跨文化比较研究.

  1. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  2. SCH529074, a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth-suppressive function to mutant p53 and interrupts HDM2-mediated ubiquitination of wild type p53.

    Science.gov (United States)

    Demma, Mark; Maxwell, Eugene; Ramos, Robert; Liang, Lianzhu; Li, Cheng; Hesk, David; Rossman, Randall; Mallams, Alan; Doll, Ronald; Liu, Ming; Seidel-Dugan, Cynthia; Bishop, W Robert; Dasmahapatra, Bimalendu

    2010-04-02

    Abrogation of p53 function occurs in almost all human cancers, with more than 50% of cancers harboring inactivating mutations in p53 itself. Mutation of p53 is indicative of highly aggressive cancers and poor prognosis. The vast majority of mutations in p53 occur in its core DNA binding domain (DBD) and result in inactivation of p53 by reducing its thermodynamic stability at physiological temperature. Here, we report a small molecule, SCH529074, that binds specifically to the p53 DBD in a saturable manner with an affinity of 1-2 microm. Binding restores wild type function to many oncogenic mutant forms of p53. This small molecule reactivates mutant p53 by acting as a chaperone, in a manner similar to that previously reported for the peptide CDB3. Binding of SCH529074 to the p53 DBD is specifically displaced by an oligonucleotide with a sequence derived from the p53-response element. In addition to reactivating mutant p53, SCH529074 binding inhibits ubiquitination of p53 by HDM2. We have also developed a novel variant of p53 by changing a single amino acid in the core domain of p53 (N268R), which abolishes binding of SCH529074. This amino acid change also inhibits HDM2-mediated ubiquitination of p53. Our novel findings indicate that through its interaction with p53 DBD, SCH529074 restores DNA binding activity to mutant p53 and inhibits HDM2-mediated ubiquitination.

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

    Energy Technology Data Exchange (ETDEWEB)

    Adams, T.; /Florida State U.; Batra, P.; /Columbia U.; Bugel, Leonard G.; /Columbia U.; Camilleri, Leslie Loris; /Columbia U.; Conrad, Janet Marie; /MIT; de Gouvea, A.; /Northwestern U.; Fisher, Peter H.; /MIT; Formaggio, Joseph Angelo; /MIT; Jenkins, J.; /Northwestern U.; Karagiorgi, Georgia S.; /MIT; Kobilarcik, T.R.; /Fermilab /Texas U.

    2009-06-01

    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.

  4. ¿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.

  5. 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.

  6. Exploring Mothers’ and Fathers’ Relationships with Sons Versus Daughters: Links to Adolescent Adjustment in Mexican Immigrant Families

    Science.gov (United States)

    Updegraff, Kimberly A.; Delgado, Melissa Y.; Wheeler, Lorey A.

    2009-01-01

    Drawing on ecological and gender socialization perspectives, this study examined mothers’ and fathers’ relationships with young adolescents, exploring differences between mothers and fathers, for sons versus daughters, and as a function of parents’ division of paid labor. Mexican immigrant families (N = 162) participated in home interviews and seven nightly phone calls. Findings revealed that mothers reported higher levels of acceptance toward adolescents and greater knowledge of adolescents’ daily activities than did fathers, and mothers spent more time with daughters than with sons. Linkages between parent-adolescent relationship qualities and youth adjustment were moderated by adolescent gender and parents’ division of paid labor. Findings revealed, for example, stronger associations between parent–adolescent relationship qualities and youth adjustment for girls than for boys. PMID:19779582

  7. Exploring Mothers' and Fathers' Relationships with Sons Versus Daughters: Links to Adolescent Adjustment in Mexican Immigrant Families.

    Science.gov (United States)

    Updegraff, Kimberly A; Delgado, Melissa Y; Wheeler, Lorey A

    2009-04-01

    Drawing on ecological and gender socialization perspectives, this study examined mothers' and fathers' relationships with young adolescents, exploring differences between mothers and fathers, for sons versus daughters, and as a function of parents' division of paid labor. Mexican immigrant families (N = 162) participated in home interviews and seven nightly phone calls. Findings revealed that mothers reported higher levels of acceptance toward adolescents and greater knowledge of adolescents' daily activities than did fathers, and mothers spent more time with daughters than with sons. Linkages between parent-adolescent relationship qualities and youth adjustment were moderated by adolescent gender and parents' division of paid labor. Findings revealed, for example, stronger associations between parent-adolescent relationship qualities and youth adjustment for girls than for boys.

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

    CERN Document Server

    Adams, T; Bugel, L; Camilleri, L; Conrad, J M; De Gouvêa, A; Fisher, P H; Formaggio, J A; Jenkins, J; Karagiorgi, G; Kobilarcik, T R; Kopp, S; Kyle, G; Loinaz, W A; Mason, D A; Milner, R; Moore, R; Morfín, J G; Nakamura, M; Naples, D; Nienaber, P; Olness, F I; Owens, J F; Pate, S F; Pronin, A; Seligman, W G; Shaevitz, M H; Schellman, H; Schienbein, I; Syphers, M J; Tait, T M P; Takeuchi, T; Tan, C Y; Van de Water, R G; Yamamoto, R K; Yu, J Y

    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.

  9. Kauffman Knot Invariant from SO(N) or Sp(N) Chern-Simons theory and the Potts Model

    CERN Document Server

    Astorino, Marco

    2010-01-01

    The expectation value of Wilson loop operators in three-dimensional SO(N) Chern-Simons gauge theory gives a known knot invariant: the Kauffman polynomial. Here this result is derived, at the first order, via a simple variational method. With the same procedure the skein relation for Sp(N) are also obtained. Jones polynomial arises as special cases: Sp(2), SO(-2) and SL(2,R). These results are confirmed and extended up to the second order, by means of perturbation theory, which moreover let us establish a duality relation between SO(+/-N) and Sp(-/+N) invariants. A correspondence between the firsts orders in perturbation theory of SO(-2), Sp(2) or SU(2) Chern-Simons quantum holonomies and the partition function of the Q=4 Potts Model is built.

  10. 养儿防老和母以子贵:是儿子还是儿女双全?%Old- age Support and Mother's Family Status. Sons Only or Both Sons and Daughters?

    Institute of Scientific and Technical Information of China (English)

    尹银

    2012-01-01

    了解养儿防老、母以子贵等传统生育文化的影响对中国稳定低生育水平至关重要。使用2008年中国老年人健康因素跟踪调查数据,通过logistic回归分析子女性别对老年父亲、母亲生活质量(包括生活满意度和婚姻满意度)、家庭地位(包括经济决策权和自我决策权)的影响发现,儿子的作用大大下降,儿女双全除了增加老年父亲的婚姻满意度以外,并没有提高老年人的生活质量,养儿未必能防老;生育儿子或儿女双全并没有提高老年母亲的家庭地位,甚至有儿子的老年母亲的经济决策权还更低;老年人自身的社会经济因素显著提高了老年人的生活质量和家庭地位。养儿防老、母以子贵等传统生育文化影响逐渐减弱,这对中国稳定低生育水平是一个利好的消息。%It is important to study the influences of traditional fertility culture (such as old - age sup- port and mother' s status depending on sons) on China's fertility. Using 2008 Chinese Longitudinal Healthy Longevity Survey, the paper analyzes the impact of sex of children on life quality of elderly par- ents (including life satisfaction and marital satisfaction) and family status (including economic decision - making power and self decision - making authority). Regression results show that son' s influence has decreased. Having both sons and daughters does not improve life quality of the elderly parents, but increases marital satisfaction of the elderly fathers. Bringing up sons not necessarily provides sup- port for ageing parents. Having sons or both sons and daughters may not help to improve family status of the elderly mothers, and the elderly mothers having sons only have even lower economic decision - making power. Social and economic situation of the elderly significantly improves their life quality and family status. Thus, influences of traditional fertility culture have been gradually weakening

  11. A Brief Introduction to Paul in Sons and Lovers——From Self-absence to Self-realization

    Institute of Scientific and Technical Information of China (English)

    张灵机

    2008-01-01

    Paul,the main character in the novel Sons and Lovers,experiences a tough psychological development.At the beginning,he relies heavily on his mother and serves as the medium of her dream and ambitions,leading him to a lost self.Whereas,in his attempt,though it is painful,he finally finds a true self of his own maintaining a harmonious unity with various social relations.

  12. Using the Nonverbal Test SON-R2 ½ - 7 [a] to Assess Children with Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Elizeu Coutinho de Macedo

    2013-11-01

    Full Text Available The relevance of cognitive assessment in Autism Spectrum Disorders is due to the association between cognitive deficits and severity of symptoms, adaptive functioning, prognosis and planning of more effective interventions.Thus, the aim of this study was to verify the non-verbal test of intelligence SON-R 2 ½ - 7 [a] adequacy in ASD group of children. The participants were 18 boys aged 4 and 7 years old, diagnosed based on the DSM-IV-TR and scored on screening instruments. The nonverbal intelligence test SON-R 2 ½ - 7 [a], the Autism Behavior Checklist (ABC, the Autism Screening Questionnaire (ASQ and the Vineland Adaptive Behavior Scales (VABS were used. The results showed that 55.6% of the group had IQs below average, and there was significant difference between the performance of TEA group and normative sample in the four subtests that compose the instrument. Intra-group analysis showed statistically significant differences between subtests, although these showed significant positive correlations with each other. Negative and significant correlations were observed between IQ Total in SON-R 2 ½ - 7 [a] the ABC and ASQ, as well as positive and significant correlations were observed between Total IQ and VABS. The results corroborate previous findings that indicate moderate relationships between intelligence, severityof symptoms and functionality, as well as the presence of specific profile of nonverbal performance in ASD group.

  13. "Wenn ich leben soll, so sei es mit dir!" The relationship of father and son in Goethe's "Wilhelm Meisters Wanderjahre".

    Science.gov (United States)

    Lee, Charlotte

    2011-01-01

    The relationship between father and son is a highly nuanced and persistent theme in Goethe's late novel Wilhelm Meisters Wanderjahre, but has received relatively little critical attention. Drawing on various aspects of the text, from the relationship between Wilhelm and his own son Felix, to the theme of migration from the ‘fatherland’, this essay contends that the relationship of the younger generation to the older traces a pattern of departure and return. The development in the son of an identity distinct and independent from that of the father is a preoccupation of the earlier chapters of the Wanderjahre in particular; but this process of individuation tends to be accompanied in the novel by continued, even increased, identification with the father, which may be conscious or unconscious. All the various stages of this fluctuating relationship are telescoped into a few rich, enigmatic images in the novel's closing scene, in which the threat of separation and the desire for proximity are held in suspension.

  14. 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.

  15. The in vitro biological activity of the HLA-DR-binding clinical IgG4 antibody 1D09C3 is a consequence of the disruption of cell aggregates and can be abrogated by Fab arm exchange.

    NARCIS (Netherlands)

    Hansen, K.; Ruttekolk, I.R.R.; Glauner, H.B.; Becker, F.; Brock, R.E.; Hannus, S.

    2009-01-01

    Antibodies of the IgG4 subclass, directed against cell surface antigens have received attention as therapeutic molecules due to their poor induction of the complement system. The MHC class II-directed IgG4 antibody 1D09C3 has been explored for the treatment of lymphomas. The mechanism-of-action is s

  16. 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....

  17. 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

  18. 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.

  19. 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

  20. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

    Directory of Open Access Journals (Sweden)

    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  1. Abrogation of IL-4 receptor-α-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response.

    Science.gov (United States)

    Müller, Uwe; Stenzel, Werner; Piehler, Daniel; Grahnert, Andreas; Protschka, Martina; Köhler, Gabriele; Frey, Oliver; Held, Josephin; Richter, Tina; Eschke, Maria; Kamradt, Thomas; Brombacher, Frank; Alber, Gottfried

    2013-08-01

    In the murine model of pulmonary infection with Cryptococcus neoformans, IL-4 receptor α (IL-4Rα)-dependent polyfunctional T(h)2 cells induce disease progression associated with alternative activation of lung macrophages. To characterize the effector role of IL-4Rα-dependent alternatively activated macrophages (aaMph), we intra-nasally infected mice with genetically ablated IL-4Rα expression on macrophages (LysM(Cre)IL-4Rα(-/lox) mice) and IL-4Rα(-/lox) littermates. LysM(Cre)IL-4Rα(-/lox) mice were significantly more resistant to pulmonary cryptococcosis with higher survival rates and lower lung burden than non-deficient heterozygous littermates. Infected LysM(Cre)IL-4Rα(-/lox) mice had reduced but detectable numbers of aaMph expressing arginase-1, chitinase-like enzyme (YM1) and CD206. Similar pulmonary expression of inducible nitric oxide synthase was found in LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) control mice, but macrophages from LysM(Cre)IL-4Rα(-/lox) mice showed a higher potential to produce nitric oxide. In contrast to the differences in the macrophage phenotype, pulmonary T(h)2 responses were similar in infected LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) mice with each mouse strain harboring polyfunctional T(h)2 cells. Consistently, type 2 pulmonary allergic inflammation associated with eosinophil recruitment and epithelial mucus production was present in lungs of both LysM(Cre)IL-4Rα(-/lox) and IL-4Rα(-/lox) mice. Our results demonstrate that, despite residual IL-4Rα-independent alternative macrophage activation and ongoing T(h)2-dependent allergic inflammation, abrogation of IL-4Rα-dependent aaMph is sufficient to confer resistance in pulmonary cryptococcosis. This is even evident on a relatively resistant heterozygous IL-4Rα(+/-) background indicating a key contribution of macrophage IL-4Rα expression to susceptibility in allergic bronchopulmonary mycosis.

  2. Activation of p38 and JNK MAPK pathways abrogates requirement for new protein synthesis for phorbol ester mediated induction of select MMP and TIMP genes.

    Science.gov (United States)

    Sampieri, Clara L; Nuttall, Robert K; Young, David A; Goldspink, Deborah; Clark, Ian M; Edwards, Dylan R

    2008-03-01

    The human matrix metalloproteinase (MMP) gene family includes 24 genes whose regulated expression, together with that of four tissue inhibitors of metalloproteinases (TIMPs), is essential in tissue remodelling and cell signalling. Quantitative real-time-PCR (qPCR) analysis was used to evaluate the shared and unique patterns of control of these two gene families in human MRC-5 and WI-38 fibroblasts in response to the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA). The requirement for ongoing translation was analysed using three protein synthesis inhibitors, anisomycin, cycloheximide and emetine. PMA induced MMP1, 3, 8, 9, 10, 12, 13, 14 and TIMP1 and TIMP3 RNAs after 4-8 h, and induction of all except MMP9 and TIMP3 was blocked by all protein synthesis inhibitors. However, even though all inhibitors effectively blocked translation, PMA-induction of MMP9 and TIMP3 was blocked by emetine but was insensitive to cycloheximide and anisomycin. Anisomycin alone induced MMP9 and TIMP3, along with MMP25 and MMP19. The extracellular signal-regulated kinases (ERKs)-1/2 were strongly activated by PMA, while anisomycin activated the c-Jun N-terminal kinase (JNK) and p38 pathways, and cycloheximide activated p38, but emetine had no effect on the stress-activated mitogen-activated protein kinase (MAPK) pathways. The involvement of the p38 and JNK pathways in the selective effects of anisomycin and cycloheximide on MMP/TIMP expression was supported by use of pharmacological inhibitors. These data confirm that most inducible MMPs and TIMP1 behave as "late" activated, protein synthesis-dependent genes in fibroblasts. However, the requirement of protein synthesis for PMA-induction of MMPs and TIMPs is not universal, since it is abrogated for MMP9 and TIMP3 by stimulation of the stress-activated MAPK pathways. The definition of clusters of co-regulated genes among the two gene families will aid in bioinformatic dissection of control mechanisms.

  3. The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer cells via abrogating the function of the AHA1/Hsp90 complex.

    Science.gov (United States)

    Liu, Hui-Juan; Jiang, Xiao-Xiao; Guo, Yi-Zhen; Sun, Fang-Hui; Kou, Xin-Hui; Bao, Yong; Zhang, Zhu-Qing; Lin, Zhao-Hu; Ding, Ting-Bo; Jiang, Lan; Lei, Xin-Sheng; Yang, Yong-Hua

    2017-10-01

    cancer cells in vitro and in vivo via AHA1 abrogation.

  4. 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.

  5. Insights into dynamic mitotic chromatin organization through the NIMA kinase suppressor SonC, a chromatin-associated protein involved in the DNA damage response.

    Science.gov (United States)

    Larson, Jennifer R; Facemyer, Eric M; Shen, Kuo-Fang; Ukil, Leena; Osmani, Stephen A

    2014-01-01

    The nuclear pore complex proteins SonA and SonB, the orthologs of mammalian RAE1 and NUP98, respectively, were identified in Aspergillus nidulans as cold-sensitive suppressors of a temperature-sensitive allele of the essential mitotic NIMA kinase (nimA1). Subsequent analyses found that sonB1 mutants exhibit temperature-dependent DNA damage sensitivity. To understand this pathway further, we performed a genetic screen to isolate additional conditional DNA damage-sensitive suppressors of nimA1. We identified two new alleles of SonA and four intragenic nimA mutations that suppress the temperature sensitivity of the nimA1 mutant. In addition, we identified SonC, a previously unstudied binuclear zinc cluster protein involved with NIMA and the DNA damage response. Like sonA and sonB, sonC is an essential gene. SonC localizes to nuclei and partially disperses during mitosis. When the nucleolar organizer region (NOR) undergoes mitotic condensation and removal from the nucleolus, nuclear SonC and histone H1 localize in a mutually exclusive manner with H1 being removed from the NOR region and SonC being absent from the end of the chromosome beyond the NOR. This region of chromatin is adjacent to a cluster of nuclear pore complexes to which NIMA localizes last during its progression around the nuclear envelope during initiation of mitosis. The results genetically extend the NIMA regulatory system to include a protein with selective large-scale chromatin location observed during mitosis. The data suggest a model in which NIMA and SonC, its new chromatin-associated suppressor, might help to orchestrate global chromatin states during mitosis and the DNA damage response.

  6. Universal stress protein Rv2624c alters abundance of arginine and enhances intracellular survival by ATP binding in mycobacteria

    Science.gov (United States)

    Jia, Qiong; Hu, Xinling; Shi, Dawei; Zhang, Yan; Sun, Meihao; Wang, Jianwei; Mi, Kaixia; Zhu, Guofeng

    2016-01-01

    The universal stress protein family is a family of stress-induced proteins. Universal stress proteins affect latency and antibiotic resistance in mycobacteria. Here, we showed that Mycobacterium smegmatis overexpressing M. tuberculosis universal stress protein Rv2624c exhibits increased survival in human monocyte THP-1 cells. Transcriptome analysis suggested that Rv2624c affects histidine metabolism, and arginine and proline metabolism. LC-MS/MS analysis showed that Rv2624c affects the abundance of arginine, a modulator of both mycobacteria and infected THP-1 cells. Biochemical analysis showed that Rv2624c is a nucleotide-binding universal stress protein, and an Rv2624c mutant incapable of binding ATP abrogated the growth advantage in THP-1 cells. Rv2624c may therefore modulate metabolic pathways in an ATP-dependent manner, changing the abundance of arginine and thus increasing survival in THP-1 cells. PMID:27762279

  7. TIRAP, an Adaptor Protein for TLR2/4, Transduces a Signal from RAGE Phosphorylated upon Ligand Binding

    Science.gov (United States)

    Sakaguchi, Masakiyo; Murata, Hitoshi; Yamamoto, Ken-ichi; Ono, Tomoyuki; Sakaguchi, Yoshihiko; Motoyama, Akira; Hibino, Toshihiko; Kataoka, Ken; Huh, Nam-ho

    2011-01-01

    The receptor for advanced glycation end products (RAGE) is thought to be involved in the pathogenesis of a broad range of inflammatory, degenerative and hyperproliferative diseases. It binds to diverse ligands and activates multiple intracellular signaling pathways. Despite these pivotal functions, molecular events just downstream of ligand-activated RAGE have been surprisingly unknown. Here we show that the cytoplasmic domain of RAGE is phosphorylated at Ser391 by PKCζ upon binding of ligands. TIRAP and MyD88, which are known to be adaptor proteins for Toll-like receptor-2 and -4 (TLR2/4), bound to the phosphorylated RAGE and transduced a signal to downstream molecules. Blocking of the function of TIRAP and MyD88 largely abrogated intracellular signaling from ligand-activated RAGE. Our findings indicate that functional interaction between RAGE and TLRs coordinately regulates inflammation, immune response and other cellular functions. PMID:21829704

  8. Cell surface syndecan-1 contributes to binding and function of macrophage migration inhibitory factor (MIF) on epithelial tumor cells.

    Science.gov (United States)

    Pasqualon, Tobias; Lue, Hongqi; Groening, Sabine; Pruessmeyer, Jessica; Jahr, Holger; Denecke, Bernd; Bernhagen, Jürgen; Ludwig, Andreas

    2016-04-01

    Surface expressed proteoglycans mediate the binding of cytokines and chemokines to the cell surface and promote migration of various tumor cell types including epithelial tumor cells. We here demonstrate that binding of the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) to epithelial lung and breast tumor cell lines A549 and MDA-MB231 is sensitive to enzymatic digestion of heparan sulphate chains and competitive inhibition with heparin. Moreover, MIF interaction with heparin was confirmed by chromatography and a structural comparison indicated a possible heparin binding site. These results suggested that proteoglycans carrying heparan sulphate chains are involved in MIF binding. Using shRNA-mediated gene silencing, we identified syndecan-1 as the predominant proteoglycan required for the interaction with MIF. MIF binding was decreased by induction of proteolytic shedding of syndecan-1, which could be prevented by inhibition of the metalloproteinases involved in this process. Finally, MIF induced the chemotactic migration of A549 cells, wound closure and invasion into matrigel without affecting cell proliferation. These MIF-induced responses were abrogated by heparin or by silencing of syndecan-1. Thus, our study indicates that syndecan-1 on epithelial tumor cells promotes MIF binding and MIF-mediated cell migration. This may represent a relevant mechanism through which MIF enhances tumor cell motility and metastasis.

  9. Terms of Binding

    NARCIS (Netherlands)

    Sevcenco, A.

    2006-01-01

    The present dissertation aimed at achieving two goals. First, it constitutes an attempt to widen the search for phenomena that bear relevance to the idea that binding has a syntactic residue and is not, therefore, an exclusively semantic matter. Second, it tried to provide the technical means to acc

  10. 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.

  11. MD-2 binds cholesterol.

    Science.gov (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  12. 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

  13. 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.

  14. "Los homosexuales no son como los champiñones. El problema del anacronismo en Historia de las Ciencias"

    OpenAIRE

    Vázquez García, Francisco

    2013-01-01

    Consideramos en principio que, del mismo modo que una persona puede caracterizarse por el color de su pelo o de sus ojos, puede ser también clasificada a partir de su “orientación sexual”, siendo así heterosexual, homosexual o bisexual. Es decir, estimamos que la orientación sexual es un rasgo “natural”, de modo que homosexuales, heterosexuales y bisexuales son otros tantos objetos naturales, del mismo modo que las manzanas, las piñas o los champiñones. Por eso, los biólogos que estudian el c...

  15. In the Name of the Son (and the Daughter): Intergenerational Mobility in the United States, 1850-1930

    OpenAIRE

    2013-01-01

    This paper provides a new perspective on intergenerational mobility in the United States in the late 19th and early 20th centuries. We devise an empirical strategy that allows to calculate intergenerational elasticities between fathers and children of both sexes. The key insight of our approach is that the information about socio-economic status conveyed by first names can be used to create a pseudo-link not only between fathers and sons, but also between fathers and daughters. The latter is ...

  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. 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)

  18. La importancia del deporte y los eventos deportivos. ¿Son realmente dinamizadores socioeconómicos?

    OpenAIRE

    2015-01-01

    El deporte es una industria muy potente y transversal que genera muchos beneficios económicos y sociales. Uno de los grandes responsables de que el deporte produzca beneficios en la economía así como en la sociedad son los eventos deportivos. En el presente documento se introducirá el deporte como sector económico para tener una idea de lo amplio que es, quien interviene y hacia dónde se dirige; se analizará el impacto socioeconómico de los grandes eventos deportivos, aquellos eventos globale...

  19. Sons of the Buddha. Continuities and Ruptures in a Burmese Monastic Tradition, Jason A. Carbine

    Directory of Open Access Journals (Sweden)

    Guillaume Rozenberg

    2012-11-01

    Full Text Available Version sensiblement remaniée d’une thèse de doctorat, l’ouvrage de Jason Carbine envisage la « culture religieuse bouddhique birmane » sous l’angle de l’institution monastique, de ses représentations et de ses rouages. Il se concentre sur une branche particulière de la communauté monastique birmane, la branche Shwegyin, du nom du village natal de son fondateur, le moine Ashin Jāgara (1822-1894. Cette branche, établie vers 1860, comptait 40 000 membres (novices et moines en 1999, soit 10 % ...

  20. "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

  1. 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 bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  2. Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function.

    Science.gov (United States)

    Wadhwa, R; Sugihara, T; Yoshida, A; Nomura, H; Reddel, R R; Simpson, R; Maruta, H; Kaul, S C

    2000-12-15

    MKT-077, a cationic rhodacyanine dye analogue has been under preclinical cancer therapeutical trials because of its selective toxicity to cancer cells. Its cellular targets and mechanism of action remain poorly understood. Here we report that MKT-077 binds to an hsp70 family member, mortalin (mot-2), and abrogates its interactions with the tumor suppressor protein, p53. In cancer cells, but not in normal cells, MKT-077 induced release of wild-type p53 from cytoplasmically sequestered p53-mot-2 complexes and rescued its transcriptional activation function. Thus, MKT-077 may be particularly useful for therapy of cancers with wild-type p53.

  3. 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.

  4. 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

    2003-01-01

    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

  5. 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

    2003-01-01

    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

  6. 75 FR 5359 - In the Matter of L. Luria & Son, Inc., Lew Corp. (n/k/a Questus Global Limited), Library Bureau...

    Science.gov (United States)

    2010-02-02

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION In the Matter of L. Luria & Son, Inc., Lew Corp. (n/k/a Questus Global Limited), Library Bureau... current and accurate information concerning the securities of L. Luria & Son, Inc. because it has not...

  7. 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.

  8. 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. PMID:25679206

  9. Expression of multiple sexual signals by fathers and sons in the East-Mediterranean barn swallow: are advertising strategies heritable?

    Directory of Open Access Journals (Sweden)

    Yoni Vortman

    Full Text Available 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.

  10. Self-Regulation in Early Adolescence: Relations with Mother–Son Relationship Quality and Maternal Regulatory Support and Antagonism

    Science.gov (United States)

    Shaw, Daniel S.; Fitzpatrick, Amber

    2011-01-01

    The purpose of the current investigation was to examine relations among maternal regulatory support, maternal antagonism, and mother–son relationship quality in relation to boys’ self-regulation during early adolescence. As part of a larger longitudinal study on 263 low-income, ethnically diverse boys, multiple informants and methods were used to examine associations among parenting practices and mother–son relationship quality in relation to boys’ self-regulation at ages 10 and 11. Multivariate analyses indicated that high levels of regulatory supportive parenting and relationship quality and low levels of antagonistic parenting independently predicted high levels of boys’ self-regulation at age 10. Only antagonistic parenting and relationship quality explained variance in levels of boys’ self-regulation at age 11 after accounting for prior self-regulation. The findings suggest that parenting and the context of the parent–child relationship are linked to self-regulation during early adolescence; however, it appears that parental antagonism and relationship quality, not maternal regulatory supportive parenting, contribute to rank-order change in self-regulation abilities. Implications of these results for research and practice are discussed. PMID:19960238

  11. ¿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.

  12. Aging parents' caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey.

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography.

  13. Aging parents’ caregiving and rehabilitating a brain-injured son: an autoethnography of a 10-year journey

    Science.gov (United States)

    Hassan, Syed Tajuddin Syed; Jamaludin, Husna

    2014-01-01

    This autoethnography withdraws from information accumulated through a 10-year period of daily-weekly-monthly descriptive observation-recording (triangulated- parents & house-helper) of caregiving and rehabilitating of our brain injured son (survivor/care-receiver). We present it as an interactive voice of verbal conversation, thoughts, insights, and interpretations. It is delivered as a series of articulation intra-pulsated with our interrogation of societal-cultural-religious perspectives, norms and biases, and aligns with the CAP (Creative Analytical Practices) method of Ellis. This autoethnography glows from the richness of information which encapsulates the challenges confronting us the aging parent caregivers, the gradual incremental mind mending achievement of our son, and the interactive verbalizations and thoughts, of the caregivers, care-receiver, and other persons. The overwhelming mental and physical pain and struggle of the survivor and the aging caregivers and their sense of celebratory-satisfaction with rehabilitation progress are highlighted. Interpretation and valuation of positive and negative responses of other persons provide a critical matrix to this autoethnography. We intend to inform other caregivers and relevant healthcare professionals through this autoethnography. PMID:25763170

  14. Application of the GRAAL model to leaching experiments with SON68 nuclear glass in initially pure water

    Energy Technology Data Exchange (ETDEWEB)

    Frugier, P., E-mail: pierre.frugier@cea.f [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Chave, T. [ICSM Site de Marcoule, DEN/MAR/ICSM/LSFC, UMR 5257, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Gin, S. [CEA Marcoule, DTCD/SECM/LCLT, BP 17171, 30207 Bagnols-sur-Ceze Cedex (France); Lartigue, J.-E. [CEA Cadarache, DEN/CAD/DTN/SMTM/LMTE, 13108 Saint-Paul-Lez-Durance Cedex (France)

    2009-08-01

    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.

  15. SON 68 nuclear glass alteration kinetics between pH 7 and pH 11.5

    Science.gov (United States)

    Gin, S.; Mestre, J. P.

    2001-05-01

    The effect of the pH was investigated on the mechanisms of SON 68 (R7T7-type) glass alteration under `saturation' conditions in order to delimit the pH range within which a stable, protective gel is formed. Static experiments were conducted at 90°C with an S/ V ratio of 50 cm-1 at various imposed pH values: 7, 8, 9.5, 10, 10.5, 11 and 11.5. An additional experiment was conducted with no restriction on the pH. The kinetic study showed that a protective gel formed in all the test media, although its stability was pH-dependent: at pH 11 or higher, the precipitation of a potassium and sodium aluminosilicate led to the degradation of the gel and the lose of its protective properties. This phenomenon resulted in renewed glass alteration, leading to complete and rapid degradation of the glass into alteration products. The aluminosilicate precipitation was found to be limited by the solubility of aluminum. Below pH 10, this type of secondary phase is unlikely to precipitate and the gel should remain stable. This study, based on thermodynamic and kinetic considerations, suggests that aqueous alteration of the French SON 68 nuclear glass results in the formation of a protective gel with long-term stability between pH 7 and pH 10.

  16. Pre-binding prior to full engagement improves loading conditions for front-row players in contested Rugby Union scrums.

    Science.gov (United States)

    Preatoni, E; Cazzola, D; Stokes, K A; England, M; Trewartha, G

    2016-12-01

    We investigated the effect of a "PreBind" engagement protocol on the biomechanics of contested Rugby Union scrummaging at different playing levels. "PreBind" requires front-row props to take a bind on opposing players prior to the engagement, and to maintain the bind throughout the scrum duration. Twenty-seven teams from five different playing levels performed live scrums under realistic conditions. Video analysis, pressures sensors, and inertial measurement units measured biomechanical outcomes as teams scrummaged following different engagement protocols: the CTPE (referee calls "crouch-touch-pause-engage"), the CTS ("crouch-touch-set"), and the PreBind ("crouch-bind-set") variants. PreBind reduced the set-up distance between the packs (-27%) and the speed at which they came into contact by more than 20%. The peak biomechanical stresses acting on front rows during the engagement phase were decreased in PreBind by 14-25% with respect to CTPE and CTS, without reducing the capability to generate force in the subsequent sustained push. No relevant main effects were recorded for playing level due to within-group variability and there were no interaction effects between playing level and engagement protocol. Pre-binding reduced many mechanical quantities that have been indicated as possible factors for chronic and acute injury, and may lead to safer engagement conditions without affecting subsequent performance. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. 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

  18. Red Son Rising.

    Science.gov (United States)

    Arnold, Adele R.

    Among the Native Americans, few tribes were as warlike as the Apaches of the Southwest. The courage and ferocity of Apache warriors like Geronimo, Cochise, Victorio, and Mangas Coloradas is legendary. Based on a true story, this book is about an Apache boy who was captured by an enemy tribe and sold to a white man. Carlos Gentile, a photographer…

  19. Sweet Sorrow's Son.

    Science.gov (United States)

    Brothers, Deborah

    1997-01-01

    Presents an award-winning essay about a teacher's relationship with a troubled student placed in his alternative classroom. Shows how the two worked together on science, math, and "Romeo and Juliet." (TB)

  20. Vider son Verdun trait

    Directory of Open Access Journals (Sweden)

    Olivier Parenteau

    2009-09-01

    Full Text Available « Le bataillon, fleuri comme un grand cimetière,avait traversé la ville à la débandade. »Roland Dorgelès, Les Croix de boisLa trahison des poètesEn France, comme ce fut le cas dans toutes les sociétés belligérantes, la Première Guerre mondiale a engendré la production d’un important arsenal de textes poétiques. Cet engouement lyrique, qui s’est manifesté dès les premiers jours d’août 1914, s’est maintenu tout au long du conflitet n’a pas perdu de sa vigueur aussitôt les armes déposées. Ces po...

  1. Red Son Rising.

    Science.gov (United States)

    Arnold, Adele R.

    Among the Native Americans, few tribes were as warlike as the Apaches of the Southwest. The courage and ferocity of Apache warriors like Geronimo, Cochise, Victorio, and Mangas Coloradas is legendary. Based on a true story, this book is about an Apache boy who was captured by an enemy tribe and sold to a white man. Carlos Gentile, a photographer…

  2. 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

  3. The patient with schizophrenia and his father. The father's role and personality traits in the dynamics of the family with a son suffering from schizophrenia.

    Science.gov (United States)

    Urlić, Ivan; Agius, Mark

    2007-09-01

    The role of the father in the onset and development of schizophrenic disorder/disturbance is very often secondary as compared to that of the mother. This study deals with the father's sphere in the family with a patient/son suffering from schizophrenia, the traits of his personality and his relationship with his son/patient, and with his wife/the mother of the patient. The methods applied were clinical interview, structured interview and semantic differential. The following statistical procedures were used: correlation, componential, discriminative, factor and quasicanonical analyses. The results include some characteristic excerpts from clinical interviews with patients/sons and their fathers, projective perception of current family relationships, quasicanonical analysis of the father's, mother's and son's experiences of the patient's/son's early childhood, and the projective view of the father. Among the conclusions reached, the phenomenon of "dead father" is emphasized as one of the main factors in the onset and development of schizophrenic disorder/disturbance.

  4. Binding Principles A and B

    Institute of Scientific and Technical Information of China (English)

    陈源

    2014-01-01

    This paper focuses on the discussion of how Binding Principle A and Binding Principe B help with the interpretation of reference in English and Chinese. They are supposedly universal across languages.

  5. Disruption of NAD~+ binding site in glyceraldehyde 3-phosphate dehydrogenase affects its intranuclear interactions

    Institute of Scientific and Technical Information of China (English)

    Manali; Phadke; Natalia; Krynetskaia; Anurag; Mishra; Carlos; Barrero; Salim; Merali; Scott; A; Gothe; Evgeny; Krynetskiy

    2015-01-01

    AIM:To characterize phosphorylation of human glyceraldehyde 3-phosphate dehydrogenase(GAPDH),and mobility of GAPDH in cancer cells treated with chemotherapeutic agents. METHODS:We used proteomics analysis to detect and characterize phosphorylation sites within human GAPDH. Site-specific mutagenesis and alanine scanning was then performed to evaluate functional significance of phosphorylation sites in the GAPDH polypeptide chain. Enzymatic properties of mutated GAPDH variants were assessed using kinetic studies. Intranuclear dynamics parameters(diffusion coefficient and the immobile fraction) were estimated using fluorescence recovery after photobleaching(FRAP) experiments and confocal microscopy. Molecular modeling experiments were performed to estimate the effects of mutations on NAD+ cofactor binding.RESULTS:Using MALDI-TOF analysis,we identified novel phosphorylation sites within the NAD+ binding center of GAPDH at Y94,S98,and T99. Using polyclonal antibody specific to phospho-T99-containing peptide within GAPDH,we demonstrated accumulation of phospho-T99-GAPDH inthe nuclear fractions of A549,HCT116,and SW48 cancer cel s after cytotoxic stress. We performed site-mutagenesis,and estimated enzymatic properties,intranuclear distribution,and intranuclear mobility of GAPDH mutated variants. Site-mutagenesis at positions S98 and T99 in the NAD+ binding center reduced enzymatic activity of GAPDH due to decreased affinity to NAD+(Km = 741 ± 257 μmol/L in T99 I vs 57 ± 11.1 μmol/L in wild type GAPDH. Molecular modeling experiments revealed the effect of mutations on NAD+ binding with GAPDH. FRAP(fluorescence recovery after photo bleaching) analysis showed that mutations in NAD+ binding center of GAPDH abrogated its intranuclear interactions. CONCLUSION:Our results suggest an important functional role of phosphorylated amino acids in the NAD+ binding center in GAPDH interactions with its intranuclear partners.

  6. Surface localization of high-mobility group nucleosome-binding protein 2 on leukemic B cells from patients with chronic lymphocytic leukemia is related to secondary autoimmune hemolytic anemia.

    Science.gov (United States)

    Morande, Pablo E; Borge, Mercedes; Abreu, Cecilia; Galletti, Jeremías; Zanetti, Samanta R; Nannini, Paula; Bezares, Raimundo F; Pantano, Sergio; Dighiero, Guillermo; Oppezzo, Pablo; Gamberale, Romina; Giordano, Mirta

    2015-04-01

    Chronic lymphocytic leukemia (CLL) is the main cause of autoimmune hemolytic anemia (AHA). However, the cellular basis underlying this strong association remains unclear. We previously demonstrated that leukemic B cells from patients with CLL recognize the erythrocyte protein Band 3, a prevalent autoantigen in AHA. Here we show that the major binding site of Band 3 on leukemic cells is an extrinsic protein identified as high-mobility group nucleosome binding protein 2 (HMGN2), a nucleosome-interacting factor which has not been previously reported at the cell surface. T lymphocytes do not express HMGN2 or bind Band 3. Removal of HMGN2 from the cell membrane abrogated the capacity of Band 3-pulsed CLL cells to induce CD4 + T cell proliferation. We conclude that surface HMGN2 in leukemic B cells is involved in Band 3 binding, uptake and presentation to CD4 + T lymphocytes, and as such may favor the initiation of AHA secondary to CLL.

  7. Cognitive ability correlates positively with son birth and predicts cross-cultural variation of the offspring sex ratio.

    Science.gov (United States)

    Dama, Madhukar Shivajirao

    2013-06-01

    Human populations show remarkable variation in the sex ratio at birth which is believed to be related to the parental condition. In the present study, the global variation of sex ratio at birth (SRB, proportion of male offspring born) was analyzed with respect to indirect measure of condition, the intelligence quotient (IQ). IQ correlates strongly with lifespan across nations, which makes it a good indicator of health of the large populations. Relation between three standard measures of average national IQ and SRB was studied using multiple linear regression models. Average national IQ was positively correlated with SRB (r = 0.54 to 0.57, p wealth, son preference, latitude, low birth weight, and neonatal mortality in the regression models. These results suggest that the striking variation of offspring sex ratio across nations could be caused in part by the difference in general condition of populations.

  8. 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 were extracted from parents' descriptions of their experiences: (a) "From the place where pain and sadness was sown, a new smile was grown," relating to transforming the experience of loss into a new meaning for life; (b) "No to a child memorial," focusing on parents' awareness of the burden placed on the child who was born; and (c) "Different parenting," dealing with participant's parenting following their loss. The study's findings are discussed in the context of literature dealing with reconstructing meaning through coping and bereavement.

  9. Trajectories and Determinants of Elder Care in Rural China During an 8-Year Period: Why Having Sons Makes a Difference.

    Science.gov (United States)

    Guo, Man; Chi, Iris; Silverstein, Merril

    2016-07-01

    Using 8-year panel data for 1,355 older adults in rural Anhui province, China, this study examined the trajectories and determinants of elder care provided by adult children to their older parents. The results of two-level latent variable growth models showed that trajectories of elder care differed by the gender of children, with an increase in care from sons but a decrease in care from daughters over time. Children's life stages influenced their care provision but differed by gender. Functional impairment of parents and care provided by siblings in the family also affected the care provided by each child. The findings reflect the patrilineal nature of Chinese family systems and demonstrate the linkages between critical life events and caregiving behaviors of adult children. Findings of this study can inform the formulation of elder care policies that meet the needs of families with different structures and at different life stages.

  10. Différences inter-individuelles en latéralisation de sons basse fréquence

    OpenAIRE

    Savel, Sophie

    2010-01-01

    National audience; La plupart des études sur la localisation auditive en champ libre ou la latéralisation au casque ont été menées sur un très faible effectif d'auditeurs, sur-entraînés à la tâche. Nous avons récemment décelé d'importantes différences entre 50 individus naïfs dans la capacité à localiser un son basse fréquence en champ libre, et identifié un lien entre sexe ou latéralité manuelle et asymétrie gauche/droite de cette capacité (Savel, 2009, Hearing Research). Dans l'étude présen...

  11. Sensitive mother-to-adolescent disclosures after divorce: is the experience of sons different from that of daughters?

    Science.gov (United States)

    Koerner, Susan Silverberg; Wallace, Sara; Lehman, Stephanie Jacobs; Lee, Sun-A; Escalante, Kristine A

    2004-03-01

    This study addressed two main questions: (a) Are adolescent sons and daughters exposed to sensitive maternal disclosures after divorce with similar frequency and in similar detail? and (b) Does gender act as a moderator in the association between maternal disclosures and adolescent adjustment difficulties? Forced-choice and open-ended data were collected from 194 adolescents within 2 years after their parents' divorce. Quantitative analyses revealed that although the majority of adolescents experience some level of maternal disclosure, neither frequency nor detail of maternal disclosure differed as a function of adolescent gender. Frequent and detailed maternal disclosures were associated with adolescent adjustment difficulties, primarily psychological distress. Gender did not moderate that significant association. Qualitative analysis shed light on the link between maternal disclosures and adolescent distress, suggested the importance of how disclosures are made, and revealed several gender differences in reactions to maternal disclosures. Implications of the findings are discussed.

  12. Action audio-visual for the promotion of between mother attachment seropositivity for HIV and his son

    Directory of Open Access Journals (Sweden)

    Camila Nayane de Carvalho Lima

    2012-09-01

    Full Text Available The study aimed at evaluating the effects of the educational video use to promote the attachment between HIV positive mother and her son after six months of contact between them.This is an exploratory-descriptive study with a qualitative approach. Data was collected through semi-structured interviews. The sampling was intentional. The plan of analysis consisted of the following steps: the constitution of the corpus, definition of unit analysis, data categorization and analysis through categories. This study showed that, despite the difficulties and obstacles imposed by HIV / AIDS, by the treatment and the doubts present in daily life, HIV mothers develop strategies that enable them to live and better deal with the disease, without forgetting their role as a mother.

  13. La segregación residencial urbana en estudios latinoamericanos y bogotanos. ¿Son necesarias nuevas miradas?

    Directory of Open Access Journals (Sweden)

    Esperanza Cifuentes Ardila

    2015-12-01

    Full Text Available En América Latina, las lecturas sobre la segregación residencial urbana concluyen que las ciudades de la región son ámbitos territoriales segregados por razones económicas: las inequidades se expresan en la organización urbana. Este artículo tiene como propósito mostrar que, incluso en regiones tan desiguales como la nuestra, la estructura simbólica incide en la configuración de la segregación residencial urbana, pues la valoración que los agentes sociales dan a determinados lugares y grupos humanos es decisiva para su localización en el espacio urbano.

  14. Integrable String Models in Terms of Chiral Invariants of SU(n, SO(n, SP(n Groups

    Directory of Open Access Journals (Sweden)

    Victor D. Gershun

    2008-05-01

    Full Text Available We considered two types of string models: on the Riemmann space of string coordinates with null torsion and on the Riemman-Cartan space of string coordinates with constant torsion. We used the hydrodynamic approach of Dubrovin, Novikov to integrable systems and Dubrovin solutions of WDVV associativity equation to construct new integrable string equations of hydrodynamic type on the torsionless Riemmann space of chiral currents in first case. We used the invariant local chiral currents of principal chiral models for SU(n, SO(n, SP(n groups to construct new integrable string equations of hydrodynamic type on the Riemmann space of the chiral primitive invariant currents and on the chiral non-primitive Casimir operators as Hamiltonians in second case. We also used Pohlmeyer tensor nonlocal currents to construct new nonlocal string equation.

  15. Las matemáticas son las greguerías de la razón

    OpenAIRE

    Muñoz, José

    2007-01-01

    Las greguerías de Ramón Gómez de la Serna son frases en las que con grandes dosis de humor e ingenio se unen dos elementos del mundo que nos rodea acercándose a veces a la literatura del absurdo. Las matemáticas están presentes a nuestro alrededor y forma parte de nuestra vida cotidiana, por ello no es extraño que formen parte de nuestro lenguaje y por tanto de la literatura. En este artículo investigaremos qué matemáticas usamos normalmente en nuestro habla y haremos un repaso por las gregue...

  16. Deletion of locus D15S113 in a mother and son without features of Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Michaelis, R.C.; Tarleton, J.C.; Donlon, T.A.; Simensen, R.J. [Greenwood Gneetic Center, SC (United States)] [and others

    1994-09-01

    Deletions of the proximal long arm of chromosome 15 result in Angelman syndrome when inherited from the mother and Prader-Willi syndrome when inherited from the father. The minimal critical deletion region for Angelman syndrome has been reported to include D15S74 (B1.5), D15S10 (TD3-21), and D15S113 (LS6-1). We report a mother and son who have deletions that include D15S113 but who do not have features of Angelman syndrome. D.H. is a 10-year-old white male referred for genetic evaluation due to mental retardation. He has mild to moderate mental retardation and minor dysmorphic features, including downslanting palpebral fissures, prominent nose, broad forehead, small chin, midface hypoplasia, and large ears. His mother (B.S.) has slightly downslanting palpebral fissures and a borderline intellectual deficit. Neither individual has the seizures, excessive laughter, hand clapping, ataxia or facial dysmorphism which are characteristic of Angelman syndrome. The linear order of probes mapping to 15q11-q13 is 15cen-D15S11-D15S13-D15S10-D15S113-GABRB3-D15S12-tel. The proximal border of the deletion in our patients lies between D15S10 and D15S113. The fact that these two individuals do not have Angelman syndrome, despite deletion of D15S113, suggests that the Angelman syndrome critical deletion region should be further refined to exclude the D15S113 locus. In addition, the findings of a more severe intellectual impairment in the son than in the mother suggests that the region immediately telomeric to the critical deletion region for Angelman syndrome may contain imprintable genes that influence intellectual function.

  17. 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

  18. Asp residues of βDELSEED-motif are required for peptide binding in the Escherichia coli ATP synthase.

    Science.gov (United States)

    Ahmad, Zulfiqar; Tayou, Junior; Laughlin, Thomas F

    2015-04-01

    This study demonstrates the requirement of Asp-380 and Asp-386 in the βDELSEED-motif of Escherichia coli ATP synthase for peptide binding and inhibition. We studied the inhibition profiles of wild-type and mutant E. coli ATP synthase in presence of c-terminal amide bound melittin and melittin related peptide. Melittin and melittin related peptide inhibited wild-type ATPase almost completely while only partial inhibition was observed in single mutations with replacement of Asp to Ala, Gln, or Arg. Additionally, very little or no inhibition occurred among double mutants βD380A/βD386A, βD380Q/βD386Q, or βD380R/βD386R signifying that removal of one Asp residue allows limited peptide binding. Partial or substantial loss of oxidative phosphorylation among double mutants demonstrates the functional requirement of βD380 and βD386 Asp residues. Moreover, abrogation of wild-type E. coli cell growth and normal growth of mutant cells in presence of peptides provides strong evidence for the requirement of βDELSEED-motif Asp residues for peptide binding. It is concluded that while presence of one Asp residue may allow partial peptide binding, both Asp residues, βD380 and βD386, are essential for proper peptide binding and inhibition of ATP synthase. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Furukawa Toru

    2012-12-01

    Full Text Available Abstract Background Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK. Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. Methods A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. Results The knockdown screening revealed that knockdown of SON, the gene encoding SON, which is a large serine/arginine-rich protein involved in RNA processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. Conclusion These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic

  20. The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin gamma chains in integrin binding by laminins.

    Science.gov (United States)

    Ido, Hiroyuki; Nakamura, Aya; Kobayashi, Reiko; Ito, Shunsuke; Li, Shaoliang; Futaki, Sugiko; Sekiguchi, Kiyotoshi

    2007-04-13

    Laminins are the major cell-adhesive proteins in the basement membrane, consisting of three subunits termed alpha, beta, and gamma. The putative binding site for integrins has been mapped to the G domain of the alpha chain, although trimerization with beta and gamma chains is necessary for the G domain to exert its integrin binding activity. The mechanism underlying the requirement of beta and gamma chains in integrin binding by laminins remains poorly understood. Here, we show that the C-terminal region of the gamma chain is involved in modulation of the integrin binding activity of laminins. We found that deletion of the C-terminal three but not two amino acids within the gamma1 chain completely abrogated the integrin binding activity of laminin-511. Furthermore, substitution of Gln for Glu-1607, the amino acid residue at the third position from the C terminus of the gamma1 chain, also abolished the integrin binding activity, underscoring the role of Glu-1607 in integrin binding by the laminin. We also found that the conserved Glu residue of the gamma2 chain is necessary for integrin binding by laminin-332, suggesting that the same mechanism operates in the modulation of the integrin binding activity of laminins containing either gamma1 or gamma2 chains. However, the peptide segment modeled after the C-terminal region of gamma1 chain was incapable of either binding to integrin or inhibiting integrin binding by laminin-511, making it unlikely that the Glu residue is directly recognized by integrin. These results, together, indicate a novel mechanism operating in ligand recognition by laminin binding integrins.

  1. 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.

  2. Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics.

    Science.gov (United States)

    Manikandan, Mayakannan; Munirajan, Arasambattu Kannan

    2014-02-01

    Cancer, a complex genetic disease involving uncontrolled cell proliferation, is caused by inactivation of tumor suppressor genes and activation of oncogenes. A vast majority of these cancer causing genes are known targets of microRNAs (miRNAs) that bind to complementary sequences in 3' untranslated regions (UTR) of messenger RNAs and repress them from translation. Single Nucleotide Polymorphisms (SNPs) occurring naturally in such miRNA binding regions can alter the miRNA:mRNA interaction and can significantly affect gene expression. We hypothesized that 3'UTR SNPs in miRNA binding sites of proto-oncogenes could abrogate their post-transcriptional regulation, resulting in overexpression of oncogenic proteins, tumor initiation, progression, and modulation of drug response in cancer patients. Therefore, we developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 30 high-confidence SNPs that may impair miRNA target sites in the 3' UTR of 54 mRNA transcripts of 24 proto-oncogenes. Further, 8 SNPs amidst them had the potential to determine therapeutic outcome in cancer patients. Functional annotation suggested that altogether these SNPs occur in proto-oncogenes enriched for kinase activities. We provide detailed in silico evidence for the functional effect of these candidate SNPs in various types of cancer.

  3. Evaluation of binding strength depending on the adhesive binding methods

    Directory of Open Access Journals (Sweden)

    Suzana Pasanec Preprotić

    2015-05-01

    Full Text Available A book with a personal value is worth remembering since it represents specific interests of an individual - author of the book. Therefore the original is the first issue of a book which is always bound manually. Due to cost-effectiveness, adhesive binding is most commonly used in author’s edition in paperback and hardback. Adhesive binding methods differ only if a paper leaf is a binding unit in adhesive binding form. The subject of the research is the quality of book block binding for two binding methods with/without mull fabric. The assumption is that double-fan adhesive binding method shows an extraordinary binding quality as compared to the rough spine method. For the needs of this research book block parameters remained unaltered: paper type, size and book volume. The results related to strength were obtained by using an experimental method of tensile strength for individual paper leaves. The rating of book block quality was conducted in accordance with FOGRA Nr.71006 guidelines for page pull-test. Furthermore, strength results for both methods were compared in order to evaluate the importance of changing the quality of adhesive binding. Statistical method ANOVA analysis of variance and Fisher’s F-test were used to evaluate the quality of book block binding.

  4. 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.

  5. ‘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.

  6. Pan-HER - an antibody mixture targeting EGFR, HER2, and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers

    DEFF Research Database (Denmark)

    Ellebaek, Sofie; Pedersen, Susanne Brix; Grandal, Michael

    2016-01-01

    Abs is development of acquired resistance through mechanisms such as alterated receptor dimerization patterns and dependencies. Pan-HER is a mixture of six mAbs simultaneously targeting epidermal growth factor receptor (EGFR), HER2, and HER3 with two mAbs against each receptor. Pan-HER has previously demonstrated....... The effect of Pan-HER on cell proliferation and HER-family receptor degradation was superior to treatment with single mAbs targeting either single receptor, and similar to targeting a single receptor with two non-overlapping antibodies. Furthermore, changes in EGFR-dimerization patterns after treatment......-HER and the EGFR-targeting mAb mixture also blocked EGF-binding and thereby ligand-induced changes in EGFR-dimerization levels. These results suggest that Pan-HER reduces the cellular capability to switch HER-dependency and dimerization pattern in response to treatment and thus hold promise for future clinical...

  7. 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.

  8. Construction and validation of the SON-R 5 1/2-17, the Snijders-Oomen non-verbal intelligence test

    NARCIS (Netherlands)

    Laros, Jacob Arie; Tellegen, Peter Johannes

    1991-01-01

    In this thesis the construction and validation of the SON-R 5,5-17 is described, the recent revision of the Snijders-Oomen non-verbal intelligence test. The SON-R is an individual test of (non-verbal) intelligence for children in the ages of 51/2 to 17 years. The test was published in 1989 with an e

  9. Hydrological changes in western Central Asia (Kyrgyzstan) during the Holocene as inferred from a palaeolimnological study in lake Son Kul

    Science.gov (United States)

    Huang, Xiangtong; Oberhänsli, Hedi; von Suchodoletz, Hans; Prasad, Sushma; Sorrel, Philippe; Plessen, Birgit; Mathis, Marie; Usubaliev, Raskul

    2014-11-01

    The hydrology of western Central Asia is highly sensitive to climatic perturbations. In order to understand its long-term variability and to infer linkages between precipitation and atmospheric and oceanic systems, we conducted a thorough sedimentary and geochemical study on a composite core retrieved in lake Son Kul (central Kyrgyzstan). A multi-proxy approach was conducted on lake sediments based on grain size analyses, magnetic susceptibility, total organic carbon (TOC), total nitrogen (TN) and carbon and oxygen isotope analyses on bulk and biogenic materials (ostracoda and molluscs shells) at a resolution equivalent to ca 40 years, aiming to characterise the sequence of palaeolimnological changes in Son Kul. As indicated by δ18O record of bulk carbonates, mainly consisting of aragonite, the Holocene hydrological balance was negative during most of time, suggesting an excess of evaporation (E) over precipitation (P). Limnological conditions fluctuated rapidly before 5000 cal yr BP indicating significant changes in regional hydrology and climate. In particular, the long-term negative hydrological balance was impeded by several short stages with marked increase of precipitation, lasting several decades to a few centuries (e.g., 8300-8200, 6900-6700, 6300-6100, 5500-5400, 5300-5200 and 3100-3000 cal yr BP). Precipitation changes as inferred from δ18O data are also documented by increased minerogenic detritus and higher TOC. We propose that the seasonal pattern of precipitation varied transiently in western Central Asia during the Holocene, although evaporation changes may also account for the rapid changes observed in δ18O data. When the annual water balance was less critical (P ≤ E), the excess of water might be ascribed to increased precipitation during cold seasons mainly because winter precipitation has more negative δ18O than its summer equivalent. Conversely, when the annual water balance is negative (P ≪ E), the moisture was mainly delivered during

  10. SON68 nuclear glass dissolution kinetics: Current state of knowledge and basis of the new GRAAL model

    Energy Technology Data Exchange (ETDEWEB)

    Frugier, P.; Gin, S.; Minet, Y.; Chave, T. [CEA Marcoule, DTCD SECM LCLT, 30 (France)

    2009-06-15

    Complete text of publication follows: Based on a review of the current state of knowledge concerning the aqueous alteration of SON68 nuclear glass GRAAL (Glass Reactivity with Allowance for the Alteration Layer) mechanistic model has been proposed [1]: An amorphous layer at the glass/solution interface gradually reorganized by hydrolysis and condensation mechanisms constitutes a barrier against the transport of water toward the glass and of solvated glass ions into solution [2]. The existence of this transport-inhibiting effect rapidly causes this layer to control glass alteration. The reaction affinity responsible for the glass alteration rate drop is expressed with respect to this passivating reactive interphase (PRI). Some glass constituent elements precipitate as crystallized secondary phases on the external surface and can sustain glass alteration. Correctly modeling the seat of recondensation (PRI or secondary crystallized phases) of elements is a key point for understanding their effect on glass alteration. Describing not only (1) solution chemistry but also ion transport (2) in solution by at a macroscopic scale and (3) by reactive interdiffusion in the PRI at a nanometer scale by means of a single model at each point in space and time is a complex task. Most existing models describe only one or two of these aspects. GRAAL describes a simple and still effective manner of coupling theses three phenomena using a calculation code coupling chemistry and transport HYTEC [3]. 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, glass surface area in contact with solution, and solution renewal rate. Interdiffusion through the PRI cannot be disregarded under most experimental conditions - if only to predict the solution p

  11. False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: a source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies.

    Science.gov (United States)

    Jethwa, H S; Nachman, P H; Falk, R J; Jennette, J C

    2000-09-01

    Anti-myeloperoxidase antibodies (anti-MPO) are a major type of anti-neutrophil cytoplasmic antibody (ANCA). While evaluating anti-MPO monoclonal antibodies from SCG/Kj mice, we observed several hybridomas that appeared to react with both MPO and DNA. Sera from some patients with systemic lupus erythematosus (SLE) also react with MPO and DNA. We hypothesized that the MPO binding activity is a false-positive result due to the binding of DNA, contained within the antigen binding site of anti-DNA antibodies, to the cationic MPO. Antibodies from tissue culture supernatants from 'dual reactive' hybridomas were purified under high-salt conditions (3 M NaCl) to remove any antigen bound to antibody. The MPO and DNA binding activity were measured by ELISA. The MPO binding activity was completely abrogated while the DNA binding activity remained. The MPO binding activity was restored, in a dose-dependent manner, by the addition of increasing amount of calf-thymus DNA (CT-DNA) to the purified antibody. Sera from six patients with SLE that reacted with both MPO and DNA were treated with DNase and showed a decrease in MPO binding activity compared with untreated samples. MPO binding activity was observed when CT-DNA was added to sera from SLE patients that initially reacted with DNA but not with MPO. These results suggest that the DNA contained within the antigen binding site of anti-DNA antibodies could bind to the highly cationic MPO used as substrate antigen in immunoassays, resulting in a false-positive test.

  12. Lipoxin A4 inhibits immune cell binding to salivary epithelium and vascular endothelium.

    Science.gov (United States)

    Chinthamani, Sreedevi; Odusanwo, Olutayo; Mondal, Nandini; Nelson, Joel; Neelamegham, Sriram; Baker, Olga J

    2012-04-01

    Lipoxins are formed by leukocytes during cell-cell interactions with epithelial or endothelial cells. Native lipoxin A(4) (LXA(4)) binds to the G protein-coupled lipoxin receptors formyl peptide receptor 2 (FPR2)/ALX and CysLT1. Furthermore, LXA(4) inhibits recruitment of neutrophils, by attenuating chemotaxis, adhesion, and transmigration across vascular endothelial cells. LXA(4) thus appears to serve as an endogenous "stop signal" for immune cell-mediated tissue injury (Serhan CN; Annu Rev Immunol 25: 101-137, 2007). The role of LXA(4) has not been addressed in salivary epithelium, and little is known about its effects on vascular endothelium. Here, we determined that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) receptor activation in vascular endothelium and salivary epithelium upregulated the expression of adhesion molecules that facilitates the binding of immune cells. We hypothesize that the activation of the ALX/FPR2 and/or CysLT1 receptors by LXA(4) decreases this cytokine-mediated upregulation of cell adhesion molecules that enhance lymphocyte binding to both the vascular endothelium and salivary epithelium. In agreement with this hypothesis, we observed that nanomolar concentrations of LXA(4) blocked IL-1β- and TNF-α-mediated upregulation of E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). Binding of Jurkat cells to stimulated HUVECs was abrogated by LXA(4). Furthermore, LXA(4) preincubation with human submandibular gland cell line (HSG) also blocked TNF-α-mediated upregulation of vascular cell adhesion molecule-1 (VCAM-1) in these cells, and it reduced lymphocyte adhesion. These findings suggest that ALX/FPR2 and/or CysLT1 receptor activation in endothelial and epithelial cells blocks cytokine-induced adhesion molecule expression and consequent binding of lymphocytes, a critical event in the pathogenesis of Sjögren's syndrome (SS).

  13. 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.

  14. Analytic QCD Binding Potentials

    CERN Document Server

    Fried, H M; Grandou, T; Sheu, Y -M

    2011-01-01

    This paper applies the analytic forms of a recent non-perturbative, manifestly gauge- and Lorentz-invariant description (of the exchange of all possible virtual gluons between quarks ($Q$) and/or anti-quarks ($\\bar{Q}$) in a quenched, eikonal approximation) to extract analytic forms for the binding potentials generating a model $Q$-$\\bar{Q}$ "pion", and a model $QQQ$ "nucleon". Other, more complicated $Q$, $\\bar{Q}$ contributions to such color-singlet states may also be identified analytically. An elementary minimization technique, relevant to the ground states of such bound systems, is adopted to approximate the solutions to a more proper, but far more complicated Schroedinger/Dirac equation; the existence of possible contributions to the pion and nucleon masses due to spin, angular momentum, and "deformation" degrees of freedom is noted but not pursued. Neglecting electromagnetic and weak interactions, this analysis illustrates how the one new parameter making its appearance in this exact, realistic formali...

  15. 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.

  16. Tectonomagnetic study in the seismoactive area of Narmada–Son lineament, central India: Preliminary results on repeat field observations

    Indian Academy of Sciences (India)

    S Y Waghmare; S D Pimprikar; P B Gawali; L Carlo; A G Patil

    2009-06-01

    Repeated measurements of the total geomagnetic field on the five profiles have revealed a picture of stress-induced tectonomagnetic effect in the form of secular variation of the total geomagnetic field in the tectonically and seismically active area of Jabalpur and adjoining areas of the Narmada-Son lineament (NSL),central India.For this experiment,a reference base station was established within the study area at Jabalpur.Using proton precession magnetometers with a sensitivity of 0.1 nT, simultaneous measurements of total geomagnetic field were made annually at the base and all field stations.Five cycles of repeated observations have been performed between 2003 and 2007.For data analysis,a difference method has been applied and the residuals have been calculated as secular variations of the total geomagnetic field with values ranging from ± 0.1nT to about > ± 14.6nT/yr over the different stations.The anomalies in secular variation of the total geomagnetic field may be related to anomalous accumulation of tectonic stresses and tensions on the deep fault zones and crustal blocks due to recent geodynamic processes and active geological inhomogeneities in the NSL.

  17. 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.

  18. Facies, dissolution seams and stable isotope compositions of the Rohtas Limestone (Vindhyan Supergroup) in the Son valley area, central India

    Indian Academy of Sciences (India)

    S Banerjee; S K Bhattacharya; S Sarkar

    2005-02-01

    The early Mesoproterozoic Rohtas Limestone in the Son valley area of central India represents an overall shallowing-upward carbonate succession. Detailed facies analysis of the limestone reveals outer- to inner-shelf deposition in an open marine setting. Wave-ripples, hummocky cross strat- ifications and edgewise conglomerates argue against a deep marine depositional model for the Rohtas Limestone proposed earlier. Stable isotope analysis of the limestone shows that 13C and 18O values are compatible with the early Mesoproterozoic open seawater composition. The ribbon limestone facies in the Rohtas Limestone is characterized by micritic beds, each decoupled in a lower band enriched and an upper band depleted in dissolution seams. Band-wise isotopic analysis reveals systematic short-term variations. Comparative enrichment of the heavier isotopes in the upper bands is attributed to early cementation from sea water and water derived from the lower band undergoing dissolution because of lowering of pH at depth. The short-term positive shifts in isotopic compositions in almost every upward gradational transition from a seamed band to a non-seamed band support the contention that dissolution seams here are of early diagenetic origin, although their formation was accentuated under overburden pressure.

  19. 2-D Crustal thermal structure along Thuadara–Sindad DSS profile across Narmada– Son lineament, central India

    Indian Academy of Sciences (India)

    S N Rai; S Thiagarajan

    2007-08-01

    Central India is traversed by a WSW–ENE trending Narmada–Son lineament (NSL) which is characterized by the presence of numerous hot springs, feeder dykes for Deccan Traps and seismicity all along its length. It is divided in two parts by the Barwani–Sukta Fault (BSF). To the west of this fault a graben exists, whereas to the east the basement is uplifted between Narmada North Fault (NNF) and Narmada South Fault (NSF). The present work deals with the 2-D thermal modeling to delineate the crustal thermal structure of the western part of NSL region along the Thuadara–Sindad Deep Seismic Sounding (DSS) profile which runs almost in the N–S direction across the NSL. Numerical results of the model reveal that the conductive surface heat flow value in the region under consideration varies between 45 and 47mW/m2. Out of which 23mW/m2 is the contribution from the mantle heat flow and the remaining from within the crust. The Curie depth is found to vary between 46 and 47 km and is in close agreement with the earlier reported Curie depth estimated from the analysis of MAGSAT data. The Moho temperature varies between 470 and 500°C. This study suggests that this western part of central Indian region is characterized by low mantle heat flow which in turn makes the lower crust brittle and amenable to the occurrence of deep focused earthquakes such as Satpura (1938) earthquake.

  20. ¿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.

  1. 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

  2. "Now if you have only sons you are dead": migration, gender, and family economy in twentieth century northwestern Ghana.

    Science.gov (United States)

    Abdul-Korah, Gariba B

    2011-01-01

    This article explores the interconnectedness between labor migration, gender, and the family economy in northwestern Ghana in the 20th century. It focuses specifically on the Dagaaba of the Nadowli and Jirapa administrative districts of what is now the Upper West Region (UWR). It examines how the relationships between men and women in terms of roles, status, access to productive resources and inheritance, changed in tandem with broader changes in society in the 20th century; changes that over time produced enhanced value and elevated status for women in the family. These changes in gender relations are reflected increasingly in the belief among elderly men that ‘now if you have only sons, you are dead’. By focusing on the lived experiences of ordinary women and men in the migration process, it argues that even though indigenous social structures privileged men over women in almost all spheres of life, Dagaaba women were nonetheless significantly active in shaping the history of their communities and that gender relations in Dagaaba communities were not static — they changed over time and generation. This article contributes to the ongoing discussion of the internal migration phenomenon in West Africa, which has so far attracted scant historical analysis.

  3. 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,

  4. Inhibition of factor-dependent transcription termination in Escherichia coli might relieve xenogene silencing by abrogating H-NS-DNA interactions in vivo

    Indian Academy of Sciences (India)

    Deepti Chandraprakash; Aswin Sai Narain Seshasayee

    2014-03-01

    Many horizontally acquired genes (xenogenes) in the bacterium Escherichia coli are maintained in a silent transcriptional state by the nucleoid-associated transcription regulatory protein H-NS. Recent evidence has shown that antibiotic-mediated inhibition of the transcription terminator protein Rho leads to de-repression of horizontally acquired genes, akin to a deletion of hns. The mechanism behind this similarity in outcomes between the perturbations of two distinct processes remains unclear. Using ChIP-seq of H-NS in wild-type cells, in addition to that in cells treated with bicyclomycin – a specific inhibitor of Rho, we show that bicyclomycin treatment leads to a decrease in binding signal for H-NS to the E. coli chromosome. Rho inhibition leads to RNA polymerase readthrough, which in principle could displace H-NS from the DNA, thus leading to transcriptional derepression of H-NS-silenced genes. Other possible mediators of the effect of Rho on H-NS are discussed. A possible positive feedback between Rho and H-NS might help reinforce xenogene silencing.

  5. Blocking of p53-Snail Binding, Promoted by Oncogenic K-Ras, Recovers p53 Expression and function

    Directory of Open Access Journals (Sweden)

    Sun-Hye Lee

    2009-01-01

    Full Text Available Differentially from other kinds of Ras, oncogenic K-Ras, which is mutated approximately 30% of human cancer, does not induce apoptosis and senescence. Here, we provide the evidence that oncogenic K-Ras abrogates p53 function and expression through induction of Ataxia telangiectasia-mutated and Rad3-related mediated Snail stabilization. Snail directly binds to DNA binding domain of p53 and diminishes the tumor-suppressive function of p53. Thus, elimination of Snail through si-RNA can induce p53 in K-Ras-mutated cells, whereas Snail and mutant K-Ras can suppress p53 in regardless of K-Ras status. Chemicals, isolated from inhibitor screening of p53-Snail binding, can block the Snail-mediated p53 suppression and enhance the expression of p53 as well as the transcriptional activity of p53 in an oncogenic K-Ras-dependent manner. Among the chemicals, two are very similar in structure. These results can answer why K-Ras can coexist with wild type p53 and propose the Snail-p53 binding as the new therapeutic target for K-Ras-mutated cancers including pancreatic, lung, and colon cancers.

  6. Manuka honey inhibits the development of Streptococcus pyogenes biofilms and causes reduced expression of two fibronectin binding proteins.

    Science.gov (United States)

    Maddocks, Sarah E; Lopez, Marta Salinas; Rowlands, Richard S; Cooper, Rose A

    2012-03-01

    Streptococcus pyogenes (group A Streptococcus; GAS) is always of clinical significance in wounds where it can initiate infection, destroy skin grafts and persist as a biofilm. Manuka honey has broad spectrum antimicrobial activity and its use in the clinical setting is beginning to gain acceptance with the continuing emergence of antibiotic resistance and the inadequacy of established systemic therapies; novel inhibitors may affect clinical practice. In this study, the effect of manuka honey on S. pyogenes (M28) was investigated in vitro with planktonic and biofilm cultures using MIC, MBC, microscopy and aggregation efficiency. Bactericidal effects were found in both planktonic cultures and biofilms, although higher concentrations of manuka honey were needed to inhibit biofilms. Abrogation of adherence and intercellular aggregation was observed. Manuka honey permeated 24 h established biofilms of S. pyogenes, resulting in significant cell death and dissociation of cells from the biofilm. Sublethal concentrations of manuka honey effectively prevented the binding of S. pyogenes to the human tissue protein fibronectin, but did not inhibit binding to fibrinogen. The observed inhibition of fibronectin binding was confirmed by a reduction in the expression of genes encoding two major fibronectin-binding streptococcal surface proteins, Sof and SfbI. These findings indicate that manuka honey has potential in the topical treatment of wounds containing S. pyogenes.

  7. Chromodomain helicase binding protein 8 (Chd8 is a novel A-kinase anchoring protein expressed during rat cardiac development.

    Directory of Open Access Journals (Sweden)

    Maureen O Shanks

    Full Text Available A-kinase anchoring proteins (AKAPs bind the regulatory subunits of protein kinase A (PKA and localize the holoenzyme to discrete signaling microdomains in multiple subcellular compartments. Despite emerging evidence for a nuclear pool of PKA that rapidly responds to activation of the PKA signaling cascade, only a few AKAPs have been identified that localize to the nucleus. Here we show a PKA-binding domain in the amino terminus of Chd8, and demonstrate subcellular colocalization of Chd8 with RII. RII overlay and immunoprecipitation assays demonstrate binding between Chd8-S and RIIα. Binding is abrogated upon dephosphorylation of RIIα. By immunofluorescence, we identified nuclear and perinuclear pools of Chd8 in HeLa cells and rat neonatal cardiomyocytes. We also show high levels of Chd8 mRNA in RNA extracted from post-natal rat hearts. These data add Chd8 to the short list of known nuclear AKAPs, and implicate a function for Chd8 in post-natal rat cardiac development.

  8. Identification of consensus binding sites clarifies FMRP binding determinants.

    Science.gov (United States)

    Anderson, Bart R; Chopra, Pankaj; Suhl, Joshua A; Warren, Stephen T; Bassell, Gary J

    2016-08-19

    Fragile X mental retardation protein (FMRP) is a multifunctional RNA-binding protein with crucial roles in neuronal development and function. Efforts aimed at elucidating how FMRP target mRNAs are selected have produced divergent sets of target mRNA and putative FMRP-bound motifs, and a clear understanding of FMRP's binding determinants has been lacking. To clarify FMRP's binding to its target mRNAs, we produced a shared dataset of FMRP consensus binding sequences (FCBS), which were reproducibly identified in two published FMRP CLIP sequencing datasets. This comparative dataset revealed that of the various sequence and structural motifs that have been proposed to specify FMRP binding, the short sequence motifs TGGA and GAC were corroborated, and a novel TAY motif was identified. In addition, the distribution of the FCBS set demonstrates that FMRP preferentially binds to the coding region of its targets but also revealed binding along 3' UTRs in a subset of target mRNAs. Beyond probing these putative motifs, the FCBS dataset of reproducibly identified FMRP binding sites is a valuable tool for investigating FMRP targets and function. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Asmussen, Johanne W; Lindstam, Mats;

    2007-01-01

    Accumulating evidence suggests that metallothionein (MT)-I and -II promote neuronal survival and regeneration in vivo. The present study investigated the molecular mechanisms underlying the differentiation and survival-promoting effects of MT and a peptide modeled after MT, EmtinB. Both MT...... and EmtinB directly stimulated neurite outgrowth and promoted survival in vitro using primary cultures of cerebellar granule neurons. In addition, expression and surface localization of megalin, a known MT receptor, and the related lipoprotein receptor-related protein-1 (LRP) are demonstrated in cerebellar...... granule neurons. By means of surface plasmon resonance MT and EmtinB were found to bind to both megalin and LRP. The bindings were abrogated in the presence of receptor-associated protein-1, an antagonist of the low-density lipoprotein receptor family, which also inhibited MT- and EmtinB-induced neurite...

  10. Biophysical studies on calcium and carbohydrate binding to carbohydrate recognition domain of Gal/GalNAc lectin from Entamoeba histolytica: insights into host cell adhesion.

    Science.gov (United States)

    Yadav, Rupali; Verma, Kuldeep; Chandra, Mintu; Mukherjee, Madhumita; Datta, Sunando

    2016-09-01

    Entamoeba histolytica, an enteric parasite expresses a Gal/GalNAc-specific lectin that contributes to its virulence by establishing adhesion to host cell. In this study, carbohydrate recognition domain of Hgl (EhCRD) was purified and biophysical studies were conducted to understand the thermodynamic basis of its binding to carbohydrate and Ca(++) Here, we show that carbohydrate recognition domain (CRD) of the lectin binds to calcium through DPN motif. To decipher the role of calcium in carbohydrate binding and host cell adhesion, biophysical and cell-based studies were carried out. We demonstrated that the presence of the cation neither change the affinity of the lectin for carbohydrates nor alters its conformation. Mutation of the calcium-binding motif in EhCRD resulted in complete loss of ability to bind calcium but retained its affinity for carbohydrates. Purified EhCRD significantly diminished adhesion of the amebic trophozoites to Chinese Hamster Ovary (CHO) cells as well as triggered red blood cell agglutination. The calcium-binding defective mutant abrogated amebic adhesion to CHO cells similar to the wild-type protein, but it failed to agglutinate RBCs suggesting a differential role of the cation in these two processes. This study provides the first molecular description of the role of calcium in Gal/GalNAc mediated host cell adhesion.

  11. 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.

  12. Comment Hobbes tente de rendre son matérialisme acceptable dans les appendices du Léviathan

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    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.

  13. ¿Son los errores congénitos del metabolismo causa prevenible de muerte súbita?

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    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.

  14. Clonage de l'IGF-I et de son récepteur chez le turbot (Psetta maxima

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    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.

  15. Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

    Institute of Scientific and Technical Information of China (English)

    Zhi-GangZhao; Qing-ZhengMa; Chun-XiaoXu

    2004-01-01

    Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC3m cells were treated with 0-16μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10μmol/L antisense HSP70 oligomer for 48 hr or 8μtmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10μtmol/L antisense HSP70 oligomer treatment for 48 hr or 8μtmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abro-gates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression,in turn inducing apoptosis and inhibiting cell growth in PC-3m cells. (Asian JAndro12004 Dec;6:319-324)

  16. Pan-HER-An antibody mixture targeting EGFR, HER2 and HER3 abrogates preformed and ligand-induced EGFR homo- and heterodimers.

    Science.gov (United States)

    Ellebaek, Sofie; Brix, Susanne; Grandal, Michael; Lantto, Johan; Horak, Ivan D; Kragh, Michael; Poulsen, Thomas Tuxen

    2016-11-01

    The human epidermal growth factor receptor (HER)-family is involved in development of many epithelial cancers. Therefore, HER-family members constitute important targets for anti-cancer therapeutics such as monoclonal antibodies (mAbs). A limitation to the success of single HER-targeting mAbs is development of acquired resistance through mechanisms such as alterted receptor dimerization patterns and dependencies. Pan-HER is a mixture of six mAbs simultaneously targeting epidermal growth factor receptor (EGFR), HER2 and HER3 with two mAbs against each receptor. Pan-HER has previously demonstrated broader efficacy than targeting single or dual receptor combinations also in resistant settings. In light of this broad efficacy, we decided to investigate the effect of Pan-HER compared with single HER-targeting with single and dual mAbs on HER-family cross-talk and dimerization focusing on EGFR. The effect of Pan-HER on cell proliferation and HER-family receptor degradation was superior to treatment with single mAbs targeting either single receptor, and similar to targeting a single receptor with two non-overlapping antibodies. Furthermore, changes in EGFR-dimerization patterns after treatment with Pan-HER were investigated by in situ proximity ligation assay and co-immunoprecipitation, demonstrating that Pan-HER and the EGFR-targeting mAb mixture efficiently down-regulate basal EGFR homo- and heterodimerization in two tested cell lines, whereas single mAbs had limited effects. Pan-HER and the EGFR-targeting mAb mixture also blocked EGF-binding and thereby ligand-induced changes in EGFR-dimerization levels. These results suggest that Pan-HER reduces the cellular capability to switch HER-dependency and dimerization pattern in response to treatment and thus hold promise for future clinical development of Pan-HER in resistant settings.

  17. 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.

  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. The putative effector-binding site of Leishmania mexicana pyruvate kinase studied by site-directed mutagenesis.

    Science.gov (United States)

    Hannaert, Véronique; Yernaux, Cédric; Rigden, Daniel J; Fothergill-Gilmore, Linda A; Opperdoes, Fred R; Michels, Paul A M

    2002-03-13

    The activity of pyruvate kinase of Leishmania mexicana is allosterically regulated by fructose 2,6-bisphosphate (F-2,6-P(2)), contrary to the pyruvate kinases from other eukaryotes that are usually stimulated by fructose 1,6-bisphosphate (F-1,6-P(2)). Based on the comparison of the three-dimensional structure of Saccharomyces cerevisiae pyruvate kinase crystallized with F-1,6-P(2) present at the effector site (R-state) and the L. mexicana enzyme crystallized in the T-state, two residues (Lys453 and His480) were proposed to bind the 2-phospho group of the effector. This hypothesis was tested by site-directed mutagenesis. The allosteric activation by F-2,6-P(2) appeared to be entirely abrogated in the mutated enzymes confirming our predictions.

  20. Binding Energy and Enzymatic Catalysis.

    Science.gov (United States)

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)