Ioannes Franc. Pastor et Villar Vincentius Mora et Juliá Raphael Cabrera et Omar Michael Sanchis et Caurin has de re theologica Propositiones pro doctorali laurea adsequenda publicae concertationi exponunt praeside D.D. Francisco Martinez... in Valentina Universit... MDCCXCII

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Ironía posmoderna: Michael Graves, 1934-2015

Nota necrológica sobre Micheal Graves (1934-2015)

Don Michael Angùlo Caruajal Dei & Sanctae Sedis Apostolicae gratia Episcopus coronen... iuxta dictas literas apostolicas, & dictas antiquam & nouam taxas, vt distribuantur iuxta seriem & tenorem earundem, dat [Texto impreso]

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Iglesia Catedral de Saint Michael. Coventry

Iglesia Catedral de Saint Michael. Coventry

An Evening with Michael Eric Dyson, Best Selling Author, Scholar, and Cultural Critic

Dyson, an author and scholar, has been listed by Ebony magazine as one of the 150 most powerful African Americans. His works, including Reflecting Black: African American Cultural Criticism; Come Hell or High Water: Hurricane Katrina and the Color of Disaster; and Is Bill Cosby Right? Or Has the Black Middle Class Lost Its Mind? have provoked national conversations on race and class. Written in 1994, Dyson's Making Malcolm: The Myth and Meaning of Malcolm X is considered one of the most important African-American works of the 20th century, while his I May Not Get There with You: The True Martin Luther King, Jr. is written to unveil the true radical nature of a man whom most remember or are taught was the ultimate peacemaker.

Domain-specific gene disruption reveals critical regulation of neuregulin signaling by its cytoplasmic tail

Neuregulins are a multi-isoform family of growth factors that activate members of the erbB family of receptor tyrosine kinases. The membrane-anchored isoforms contain the receptor-activating ligand in their extracellular domain, a single membrane-spanning region, and a long cytoplasmic tail. To evaluate the potential biological role of the intracellular domain of the membrane-anchored neuregulin isoforms, we used a domain-specific gene disruption approach to produce a mouse line in which only the region of the neuregulin gene encoding almost the entire intracellular domain was disrupted. Consistent with previous reports in which all neuregulin isoforms were disrupted, the resulting homozygous neuregulin mutants died at E10.5 of circulatory failure and displayed defects in neural and cardiac development. To further understand these in vivo observations, we evaluated a similarly truncated neuregulin construct after transient expression in COS-7 cells. This cytoplasmic tail-deleted mutant, unlike wild-type neuregulin isoforms, was resistant to proteolytic release of its extracellular-domain ligand, a process required for erbB receptor activation. Thus, proteolytic processing of the membrane-bound neuregulin isoforms involved in cranial ganglia and heart embryogenesis is likely developmentally regulated and is critically controlled by their intracellular domain. This observation indicates that erbB receptor activation by membrane-bound neuregulins most likely involves a unique temporally and spatially regulated “inside-out” signaling process that is critical for processing and release of the extracellular-domain ligand.

Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups

Induction of phase 2 enzymes and elevations of glutathione are major and sufficient strategies for protecting mammals and their cells against the toxic and carcinogenic effects of electrophiles and reactive forms of oxygen. Inducers belong to nine chemical classes and have few common properties except for their ability to modify sulfhydryl groups by oxidation, reduction, or alkylation. Much evidence suggests that the cellular “sensor” molecule that recognizes the inducers and signals the enhanced transcription of phase 2 genes does so by virtue of unique and highly reactive sulfhydryl functions that recognize and covalently react with the inducers. Benzylidene-alkanones and -cycloalkanones are Michael reaction acceptors whose inducer potency is profoundly increased by the presence of ortho- (but not other) hydroxyl substituent(s) on the aromatic ring(s). This enhancement correlates with more rapid reactivity of the ortho-hydroxylated derivatives with model sulfhydryl compounds. Proton NMR spectroscopy provides no evidence for increased electrophilicity of the β-vinyl carbons (the presumed site of nucleophilic attack) on the hydroxylated inducers. Surprisingly, these ortho-hydroxyl groups display a propensity for extensive intermolecular hydrogen bond formation, which may raise the reactivity and facilitate addition of mercaptans, thereby raising inducer potencies.