173,889 research outputs found
Repair of Aberrant Splicing in Growth Hormone Receptor by Antisense Oligonucleotides Targeting the Splice Sites of a Pseudoexon
No full textContext: The GH receptor (GHR) pseudoexon 6 Psi defect is a frequent cause of GH insensitivity (GHI) resulting from a non-functioning GH receptor (GHR). It results in a broad range of phenotypes and may also be present in patients diagnosed as idiopathic short stature.Objective: Our objective was to correct aberrant GHR splicing and inclusion of 6 Psi using exon-skipping antisense oligonucleotides (ASOs).Design and Setting: Three ASOs binding the 5' (ASO-5), 3' (ASO-3), and branch site (ASO-Br) of 6 Psi were tested in an in vitro splicing assay and a cell transfection system. The wild-type (wt) and mutant (mt) DNA minigenes (wt- and mtL1-GHR6 Psi-L2, respectively) were created by inserting the GHR 6 Psi in a well-characterized splice reporter (Adml-par). For the in vitro splicing assay, the wt- and mtL1-GHR6 Psi-L2 were transcribed into pre-mRNA in the presence of [alpha P-32]GTP and incubated with ASOs in HeLa nuclear extracts. For the cell transfection studies, wt-and mtL1-GHR6 Psi-L2 cloned into pcDNA 3.1 were transfected with ASOs into HEK293 cells. After 48 h, RNA was extracted and radiolabeled RT-PCR products quantified.Results: ASO-3 induced an almost complete pseudoexon skipping in vitro and in HEK293 cells. This effect was dose dependent and maximal at 125-250 nM. ASO-5 produced modest pseudoexon skipping, whereas ASO-Br had no effect. Targeting of two splice elements simultaneously was less effective than targeting one. ASO-Br was tested on the wtL1-GHR6 Psi-L2 and did not act as an enhancer of 6 Psi inclusion.Conclusions: The exon-skipping ASO approach was effective in correcting aberrant GHR splicing and may be a promising therapeutic tool. (J Clin Endocrinol Metab 95: 3542-3546, 2010
Author Alex Haley with LA County Library Staff at Library Breakfast, 1988
No full textAuthor Alex Haley with LA County Library Staff at Library Breakfast, 198
Author, Author, o la celebración del ser y del autor (Parte II)
No full textIn the last years David Lodge has been particularly concerned with the way in which both science and the humanities are challenging the traditional idea of the self as unique and
autonomous: “If the self is a fiction, it may perhaps be the supreme fiction, the greatest
achievement of human consciousness, the one that makes us human.” For Lodge the novel
is the genre that best reflects the subjectivity of human experience, thus offering us the
richest and most comprehensive record of human consciousness. His last novel, Author,
Author, like the previous one, Thinks... is a clear apology of the autonomous, individual
self, not only because its main character is a writer, Henry James, who always defended that
the subject of the novel was the whole of human consciousness, but because it allows us to
have access to his inner thoughts and feelings, precisely those that cannot be described by
science.En los últimos años David Lodge se ha interesado particularmente por el modo en que
tanto la ciencia como las humanidades han cuestionado el concepto tradicional del ser
humano como individuo único y autónomo: “If the self is a fiction, it may perhaps be the
supreme fiction, the greatest achievement of human consciousness, the one that makes us
human.” Para Lodge la novela es el género que mejor refleja la subjetividad de la experiencia
humana, ofreciéndonos la más rica y extensa descripción de la consciencia humana. Su
última novela, Author, Author, como la anterior, Thinks... es una clara apología del ser indi-
vidual y autónomo, no sólo porque su principal personaje sea un autor, Henry James, que
siempre defendió que el principal tema de la novela debía ser la totalidad de la consciencia
humana, sino también porque nos permite tener acceso a sus pensamientos y sentimientos
más íntimos, precisamente aquellos que no pueden ser descritos por la ciencia
El fomento de la contratación laboral
No full textDesde 1994 la política legislativa para fomentar el empleo ha seguido tres caminos paralelos: a) la desaparición del contrato temporal no causal y la correlativa existencia de sólo
contratos temporales causales para los que, incluso, se ha fijado una indemnización a la
finalización; b) la existencia de un nuevo contrato de trabajo llamado contrato para el
fomento de la contratación indefinida; y c) la regulación de un programa de bonificaciones
en la cotización a la Seguridad Social. En este trabajo se analizan las diferentes medidas que
tienden al fomento de la contratación laboral como un conjunto coherente. Finalmente, el
autor incluye que el régimen de bonificaciones en las cotizaciones de la Seguridad Social no
son estrictamente «ayuda pública» de acuerdo con la jurisprudencia del Tribunal de Justicia
de la Unión Europea.Since 1994, the legal policy to encourage the support and the creation of jobs has taken
three parallel ways: a) «No-causal part-time contracts» dissapear, while more requirements
to sign part-time contracts are demanded, and even an indemnization is fixed in case those
are extinguished; b) A new labor contract, named «contract to promote indefinite-time
jobs», is encouraged; c) Yearly, the law regulates a program of bonus in employer’s contributions to Social Security. In this article, all the different aspects and also the legal of such
measures to foster job creation are analised. Finally, the author concludes that the regime of
bonus in employer’s contributions does not represent «public aid», according to the doctrine of the Court of Justice of the European Unio
Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency
No full textR P Dias is a Clinical Research Fellow funded by the Medical
Research Council
Author, Author, o la celebración del ser y del autor (Parte I)
No full textEn su constante defensa de los méritos formales y estéticos del realismo literario, David
Lodge se ha centrado en dos aspectos básicos de la tradición humanista que han sido fuer-
temente cuestionados por el estructuralismo y la desconstrucción: el concepto del autor
como individuo único y origen de la obra creativa, y la idea de la literatura como acto
comunicativo. La obra literaria no surge por accidente, sino que es el resultado de las deci-
siones y elecciones intencionadas que el autor hace con el objetivo de comunicarse con sus
lectores. En los últimos años Lodge se ha interesado por otro aspecto del realismo tradicio-
nal que está siendo criticado no sólo en la esfera de las humanidades, sino también de la
ciencia: la idea de la persona como ser único y autónomo.In his constant defence of the aesthetic and formal worth of literary realism, David Lodge
has always focused on two basic premises of the tradition of liberal humanism that have
been heavily attacked by poststructuralism and deconstruction: the notion of the author as
the unique and authenticating origin of the text and the idea of literature as communica-
tion. No work of art comes into being by accident, but is the result of the intentional
choices and decisions of the author who wants to communicate something to the reader. In
the last years Lodge has paid special attention to another aspect of the realistic tradition
that has been undermined not only by the humanities but also by science in recent times:
the idea of the person as an autonomous, individual self
Libro de actas de la hermandad de la Vela Perpetua
No full textLibro de actas de la hermandad de la Vela Perpetua, 190
Libro de actas del Apostolado de la Oración. Asociación erigida canónicamente por él Sr. Luna presbítero D. E. y Martínez en la Parroquia de la Concepción de Tepecoacuilco
No full textLibro de actas del Apostolado de la Oración. Asociación erigida canónicamente por él Sr. Luna presbítero D. E. y Martínez en la Parroquia de la Concepción de Tepecoacuilco, 193
Libro de ingresos y egresos de la Asociación del Apostolado de la Oración
No full textLibro de ingresos y egresos de la Asociación del Apostolado de la Oración, 195
Libro de asientos que corresponden a la junta de mejoras de la parroquia de Tepecoacuilco
No full textLibro de asientos que corresponden a la junta de mejoras de la parroquia de Tepecoacuilco, 1931-194
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