“[For] I have been fortunate to be kinsfolk of the royal incas”: the maternal lineage, language and blood cleanliness in the works of inca Garcilaso de la Vega

Las referencias a Chimpu Ocllo, la madre del Inca Garcilaso, son el común denominador de su obra completa y aparecen en lugares estratégicos dentro de sus textos. Estas alusiones textuales a su madre, unas más largas que otras, funcionan como el hilo conductor de su narrativa histórica y cultural. Es mediante su madre que el Inca Garcilaso traza una genealogía propia, rechaza el olvido de su lengua materna para convertirse en traductor por excelencia y es capaz de negociar con los márgenes de la alteridad ontológica.The references to Chimpu Ocllo, Inca Garcilaso’s mother, are the central axis of his works as they appear in strategic places within his texts. These textual references, some longer than others, function as the unifying thread of his cultural and historic narratives. It is through his mother that the Inca Garcilaso designs his own genealogy, embraces his mother tongue, and becomes a cultural translator, able to negotiate with the margins of the ontological alterity

PEGylated graphene oxide for tumor-targeted delivery of paclitaxel.

AIM: The graphene oxide (GO) sheet has been considered one of the most promising carbon derivatives in the field of material science for the past few years and has shown excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate paclitaxel (PTX) to GO molecule and investigate its anticancer efficacy. MATERIALS & METHODS: We conjugated the anticancer drug PTX to aminated PEG chains on GO sheets through covalent bonds to get GO-PEG-PTX complexes. The tissue distribution and anticancer efficacy of GO-PEG-PTX were then investigated using a B16 melanoma cancer-bearing C57 mice model. RESULTS: The GO-PEG-PTX complexes exhibited excellent water solubility and biocompatibility. Compared with the traditional formulation of PTX (Taxol®), GO-PEG-PTX has shown prolonged blood circulation time as well as high tumor-targeting and -suppressing efficacy. CONCLUSION: PEGylated graphene oxide is an excellent nanocarrier for paclitaxel for cancer targeting

Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage

DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members

Omeprazole and aryl hydrocarbon hydroxylases: Should we be worried?

Diaz and colleagues have carefully studied the effects of omeprazole on the expression of cytochrome P-450 in primary cultures of human hepatocytes. When omeprazole was added to the culture medium in varying concentrations, there was an increase in P-450IA2 protein and mRNA concentrations, an increase in de novo synthesis of P-450IA2 protein, and an increase in microsomal catalytic activities characteristic of P-450IA2 (phenacetin deethylase and acetanilide hydroxylase). Omeprazole treatment also resulted in an increase in both enzymatic activity characteristic of P-450IA1 (ethoxyresorufin deethylase and benzpyrene hydroxylase) and concentration of P-450IA1 mRNA. In contrast, omeprazole appeared to have no significant effect on expression of other P-450s within the P-450II or P-450III families in the hepatocytes. To validate these in vitro observations, liver biopsy specimens were obtained from five patients before and after a 4-day course of pharmacological doses of omeprazole. In each patient, omeprazole treatment appeared to result in a two- to eightfold increase in P-450IA2 immunoreactive protein and P-450IA1 and P-450IA2 enzymatic activities. The authors conclude that omeprazole is an inducer of P-450IA2 and probably P-450IA1 in human liver. Induction of these enzymes could potentiate the bioactivation of carcinogens or the hepatotoxicity of some drugs such as acetaminophen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38345/1/1840130131_ftp.pd

The women of Vilcabamba

This essay examines published and unpublished documentary sources about the women who accompanied, inhabited, resisted, and negotiated the existence and legacy of Vilcabamba as an Inca refuge. The actions of the most visible women who operated between the Hispanic and the indigenous worlds, such as the coya or noblewoman Maria Cusi Huarcay, help us reveal lesser known yet important historical figures, tie up loose ends in colonial historiography, and strengthen a series of connections, such as the relationship between mining and women, polygamous alliances, and their conflicts, as well as the internal divisions within this new Inca order.Este ensayo examina fuentes documentales inéditas y publicadas referentes a las mujeres que acompañaron, poblaron, resistieron y negociaron la existencia y el legado histórico de Vilcabamba como refugio incaico. Las acciones de las mujeres más visibles que operaban entre el mundo hispano y el indígena, como es el caso de la coya María Cusi Huarcay, nos ayudan a develar personajes menos conocidos pero importantes, atar cabos sueltos en la historiografía colonial y fortalecer una serie de conexiones, como la relación entre la minería y las mujeres, las alianzas poligámicas y sus conflictos, así como las divisiones internas dentro de este nuevo orden incaico