Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling

BACKGROUND: Brain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-alpha) is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs) have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation. RESULTS: Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs) that results in increased proliferation. Moreover, we demonstrate IKK-alpha/beta-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-kappaB) as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-kappaB super-repressor IkappaB-AA1. Pharmacological blockade of IkappaB ubiquitin ligase activity led to comparable decreases in NF-kappaB activity and proliferation. In addition, IKK-beta gene product knock-down via siRNA led to diminished NF-kappaB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFbeta-activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial for future regenerative and anti-tumor medicine. CONCLUSION: TNF-mediated activation of IKK-beta resulted in activation of NF-kappaB and was followed by up-regulation of the bona-fide target gene cyclin D1. Activation of the canonical NF-kappaB pathway resulted in strongly increased proliferation of NSCs.

LA ANSIEDAD Y SU RELACIÓN CON LA EXPRESIÓN ORAL EN EL APRENDIZAJE DE LENGUAS EXTRANJERAS : Una elaboración de revisión sistemática de la literatura

La importancia de la dimensión afectiva que acompaña el proceso de adquisición de lenguas extranjeras es indiscutible. Sin embargo, a pesar de esta realidad, y de la evolución de los enfoques comunicativos como métodos de enseñanza de idiomas, la literatura continúa asegurando la existencia de aprensión lingüística en el aula y su efecto debilitador en el proceso de aprendizaje de una nueva lengua. Este estudio tiene como objetivo examinar cómo el aprendiz experimenta la variable de la ansiedad al expresarse oralmente y en qué medida el profesorado de lenguas extranjeras puede lograr crear condiciones en la clase que reduzcan los niveles de ansiedad. En este trabajo utilizamos la revisión sistemática de literatura como estrategia de investigación, un método que constituye una buena herramienta, permitiéndonos sintetizar coherentemente, de forma rigurosa, los resultados de los estudios empíricos sobre el fenómeno de la ansiedad. Los análisis revelan, en primer lugar, que los síntomas experimentados por aprendices de una nueva lengua suelen manifestarse en cada uno de los niveles que integran al individuo, en un nivel emocional, psicológico, fisiológico, de comportamiento y psicopedagógico; en segundo lugar, los investigadores plantean diversas estrategias a nivel psicológico, pedagógico y socio ambiental con el objetivo principal de incrementar en el aprendiz una serie de recursos personales para hacer frente a la ansiedad. Comentamos las implicancias pedagógicas de estos resultados para una mejor comprensión de la ansiedad y del aprendizaje de una lengua extranjera.

Downregulation of nuclear factor-kappa B (NF-kappa B) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antecedentes para la identificación de gravámenes de efectos equivalentes a derechos aduaneros" y de "gravámenes vigentes" a los fines de la aplicación del Tratado de Montevideo: I. Identificación de los conceptos que deben ser considerados como "gravámenes" a los efectos del artículo 3 del Tratado de Montevideo, y su expresión equivalente en términos de derechos aduaneros "ad valorem""

Incluye Bibliografía

La participación económica de la mujer como factor estratégico del cambio en la fecundidad: los casos de México y Costa Rica (borrador para discusión interna)

Incluye Bibliografía

NF-κB Drives the Synthesis of Melatonin in RAW 264.7 Macrophages by Inducing the Transcription of the Arylalkylamine-N-Acetyltransferase (AA-NAT) Gene

We demonstrate that during inflammatory responses the nuclear factor kappa B (NF-kappa B) induces the synthesis of melatonin by macrophages and that macrophage-synthesized melatonin modulates the function of these professional phagocytes in an autocrine manner. Expression of a DsRed2 fluorescent reporter driven by regions of the aa-nat promoter, that encodes the key enzyme involved in melatonin synthesis (arylalkylamine-N-acetyltransferase), containing one or two upstream kappa B binding sites in RAW 264.7 macrophage cell lines was repressed when NF-kappa B activity was inhibited by blocking its nuclear translocation or its DNA binding activity or by silencing the transcription of the RelA or c-Rel NF-kappa B subunits. Therefore, transcription of aa-nat driven by NF-kappa B dimers containing RelA or c-Rel subunits mediates pathogen-associated molecular patterns (PAMPs) or pro-inflammatory cytokine-induced melatonin synthesis in macrophages. Furthermore, melatonin acts in an autocrine manner to potentiate macrophage phagocytic activity, whereas luzindole, a competitive antagonist of melatonin receptors, decreases macrophage phagocytic activity. The opposing functions of NF-kappa B in the modulation of AA-NAT expression in pinealocytes and macrophages may represent the key mechanism for the switch in the source of melatonin from the pineal gland to immune-competent cells during the development of an inflammatory response.

Norepinephrine activates NF-κB transcription factor in cultured rat pineal gland

AIMS: The circadian rhythm in mammalian pineal melatonin secretion is modulated by norepinephrine (NE) released at night. NE interaction with β1-adrenoceptors activates PKA that phosphorylates the transcription factor CREB, leading to the transcription and translation of the arylalkylamine-N-acetyltransferase (AANAT) enzyme. Several studies have reported the interplay between CREB and the nuclear factor-κB (NF-κB) and a circadian rhythm for this transcription factor was recently described in the rat pineal gland. In this work we studied a direct effect of NE on NF-κB activation and the role played by this factor on melatonin synthesis and Aanat transcription and activity. MAIN METHODS: Cultured rat pineal glands were incubated in the presence of two different NF-κB inhibitors, pyrrolidine-dithiocarbamate or sodium salicylate, and stimulated with NE. Melatonin content was quantified by HPLC with electrochemical detection. AANAT activity was measured by a radiometric assay and the expression of Aanat mRNA was analyzed by real-time PCR. Gel shift assay was performed to study the NF-κB activation in cultured rat pineal glands stimulated by NE. KEY FINDINGS: Our results showed that the p50/p50 homodimer of NF-κB is activated by NE and that it has a role in melatonin synthesis, acting on Aanat transcription and activity. SIGNIFICANCE: Here we present evidence that NF-κB is an important transcription factor that acts, directly or indirectly, on Aanat transcription and activity leading to a modulation of melatonin synthesis. NE plays a role in the translocation of NF-κB p50/p50 homodimer to the nucleus of pinealocytes, thus probably influencing the nocturnal pineal melatonin synthesis

Los incentivos fiscales como factor del crecimiento empresarial : análisis empírico de la reserva para inversiones en Canarias

Doctorado en Ciencias Económicas y Empresariales. Programa de Contabilidad

Efecto de la intensidad de luz en el ser humano y su expresión a través del color de la vestimenta

Asigantura. Etología de los recursos pesqueros (Licenciatura Ciencias del mar)