Regulation of transforming growth factor β- and activin-induced transcription by mammalian Mad proteins

Members of the transforming growth factor β (TGF-β) superfamily are involved in diverse physiological activities including development, tissue repair, hormone regulation, bone formation, cell growth, and differentiation. At the cellular level, these functions are initiated by the interaction of ligands with specific transmembrane receptors with intrinsic serine/threonine kinase activity. The signaling pathway that links receptor activation to the transcriptional regulation of the target genes is largely unknown. Recent work in Drosophila and Xenopus signaling suggested that Mad (Mothers against dpp) functions downstream of the receptors of the TGF-β family. Mammalian Mad1 has been reported to respond to bone morphogenetic protein (BMP), but not to TGF-β or activin. We report here the cloning and functional studies of a novel mammalian Mad molecule, Mad3, as well as a rat Mad1 homologue. Overexpression of Mad3 in a variety of cells stimulated basal transcriptional activity of the TGF-β/activin-responsive reporter construct, p3TP-Lux. Furthermore, expression of Mad3 could potentiate the TGF-β- and activin-induced transcriptional stimulation of p3TP-Lux. By contrast, overexpression of Mad1 inhibited the basal as well as the TGF-β/activin induced p3TP-Lux activity. These findings, therefore, support the hypothesis that Mad3 may serve as a mediator linking TGF-β/activin receptors to transcriptional regulation.

Contrasting roles for Myc and Mad proteins in cellular growth and differentiation.

The positive effects of Myc on cellular growth and gene expression are antagonized by activities of another member of the Myc superfamily, Mad. Characterization of the mouse homolog of human mad on the structural level revealed that domains shown previously to be required in the human protein for anti-Myc repression, sequence-specific DNA-binding activity, and dimerization with its partner Max are highly conserved. Conservation is also evident on the biological level in that both human and mouse mad can antagonize the ability of c-myc to cooperate with ras in the malignant transformation of cultured cells. An analysis of c-myc and mad gene expression in the developing mouse showed contrasting patterns with respect to tissue distribution and developmental stage. Regional differences in expression were more striking on the cellular level, particularly in the mouse and human gastrointestinal system, wherein c-Myc protein was readily detected in immature proliferating cells at the base of the colonic crypts, while Mad protein distribution was restricted to the postmitotic differentiated cells in the apex of the crypts. An increasing gradient of Mad was also evident in the more differentiated subcorneal layers of the stratified squamous epithelium of the skin. Together, these observations support the view that both downregulation of Myc and accumulation of Mad may be necessary for progression of precursor cells to a growth-arrested, terminally differentiated state.

El color como recurso expresivo: análisis de las series de televisión Mad Men y Breaking Bad

La presente investigación tiene como objetivo reconocer y aprender a utilizar el color en el medio audiovisual, es decir, conocer sus cualidades, técnicas y estrategias para, de esta forma, dar justa dimensión a su gran capacidad expresiva. El mirar y, posteriormente, observar permite saber el tipo de atmósferas que son necesarias para sugerir determinados estados. Estas atmósferas se generan gracias a los elementos que las componen, cada uno de ellos con sus formas, colores, ubicación en el espacio, más la interrelación global entre ellos. La composición visual se da a partir del conjunto de elementos distribuidos en el espacio. Que se ven “envueltos” con la luz planteada. Toda esta suma, es la que consigue expresar una emoción por parte del creador y, si se sabe “leer”, una correcta interpretación por parte del espectador. Esta “alfabetización visual” establece nexos entre el creador y el receptor, lo que lleva a unos y otros a un mayor conocimiento en la utilización de las reglas. Ello permite reforzar el texto narrativo, que “se articula en dos niveles: la historia —lo narrado, el qué— y el discurso —el modo de narrarlo, el cómo—, es decir, el plano del contenido y el plano de la expresión” (García, F., 2011, p.12). El creador de la obra audiovisual guía al espectador por los caminos de la historia que está desarrollando, mientras que el espectador, al saber “leer”, puede conocer el camino por donde tiene que transitar para disfrutarlo y entenderlo en su totalidad. Comprender la información que proporciona el color parecería innato al ser humano del siglo XXI, dominado por un entorno netamente visual. Pero no es así. Por lo tanto, si se aprende a conocer los parámetros sobre los que se desarrolla la información que se presenta visualmente, se conseguirá hacer más eficaz la comunicación, a la vez que se fomentará la creatividad, por un lado, y el disfrute visual, por otro...

al- Hamzīyah al-ramzīyah fī madḥ khayr man la-hu al-mazīyah

taʼlīf Aḥmad al-Ḥuṭānī.

al- Azhār al-ʻāṭirah al-anfās bi-dhikr baʻḍ maḥāsin quṭb al-Maghrib wa-tāj madīnat Fās

li-Abī Abd ʻAllāh Muḥammad ibn Jaʻfar ibn Idrīs al-Ḥasanī al-Idrīsī al-Kattānī.

Hādhihi Ṭabaqāt al-ʻallāmah al-Shaykh Aḥmad al-Shurnūbī yadhkuru fīhā manāqib al-awliyāʼ al-arbaʻah wa-karāmāt aṣḥāb al-ashāyir al-arbaʻ

[Muḥammad al-Bulqīnī].

Kitāb al-Nafaḥāt al-hudāʼīyah ʻalá wird al-sādāt al-Aḥmadīyah

taʼlīf Muḥammad Nūrī al-Arīḥāwī al-Rifāʻī.

al- ʻAḍb al-Yamānī fī al-radd ʻan Shaykhinā Sīdī Aḥmad al-Tijānī

li-Abī al-ʻAbbās Aḥmad ibn Muḥammad ibn ʻAbd Allāh ibn Muḥammad ibn al-Qāḍī al-ʻAlawī nasaban al-Tijānī ṭarīqan al-Shinjīṭī ; bi-taṣḥīḥ Abī ʻAbd Allāh Muḥammad Jannūn.

Risālat Bulūgh al-amānī fī manāqib al-Shaykh Sīdī Aḥmad al-Tijānī

Aḥmad Adīb al-Makkī.

Nawādir Mawlānā al-ʻālim al-ʻallāmah al-ḥibr al-baḥr al-qudwah al-fahhāmah al-ustādh Aḥmad Shihāb al-Dīn al-Qalyūbī

Date and imprint taken from colophon.