Although the mechanism of folate uptake in the small intestine has been well characterized, very little is known about the intracellular regulation of the uptake process. Using mature confluent monolayers of the intestinal epithelial cell line IEC-6 as an in vitro intestinal epithelial cell model, we have found the uptake of folic acid to be similar to that of the native small intestine in that it is 1 ) temperature, energy, and pH dependent, 2) Na+ independent, 3) inhibited by structural analogs and anion transport inhibitors, and 4) saturable as a function of substrate concentration [apparent Michaelis constant (Km) = 0.45 +/- 0.06 microM; maximal velocity (Vmax) = 3.08 +/- 0.14 pmol x mg protein(-1) x 5 min(-1)]. Furthermore, IEC-6 cells were found by Northern blot analysis to lack the expression of the membrane folate-binding protein. Pretreatment of IEC-6 monolayers with specific protein tyrosine kinase (PTK) inhibitors genistein and tyrphostin A25 caused a significant inhibition in folic acid uptake. On the other hand, their negative controls, genistin and tyrphostin A1, respectively, had no effect. The inhibitory effect of genistein was mediated through inhibition in the Vmax of the folate uptake process with no change in the apparent Km. Pretreatment of IEC-6 monolayers with compounds that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) level (e.g., dibutyryl cAMP) also resulted in a significant (though modest) inhibition in folic acid uptake; however, specific inhibitors of protein kinase A did not affect the uptake process. Specific modulators of protein kinase C and Ca2+/calmodulin-mediated pathways did not significantly affect folic acid uptake. These results demonstrate the suitability of IEC-6 monolayers as an intestinal epithelial model to study folate transport and demonstrate for the first time that uptake of folic acid is regulated by a PTK- and a cAMP-mediated pathway.
In this article, I present some results of the archaeological study about the cultural manifestation of the Ranquels. This Indian group occupied the north part of the province of La Pampa, Argentina, from the late eighteenth century until the end of the nineteenth century. Through a perspective that links the theoretical and methodological purposes of historical archaeology of the landscape, I analyze the settlements' distributions, the access to natural resources, the methods of circulation, and the strategies of interethnic conflict with the national army and the colonists on the border area. Taking into consideration the archaeological record and its contrast with written sources, I have defined some indicators about the process of culture change. My special interest concerns changes in nineteenthcentury Ranquel material culture produced before the dissolution of the ethnic groups because of the military actions of the "desert conquest."
ResumenEl Fortín La Perra (Dpto. Loventué, La Pampa), fue uno de los asentamientos militares que se instalaron a partir de 1883 en la pampa central para ejercer la vigilancia del territorio aborigen recientemente conquistado. Las investigaciones arqueológicas realizadas en este sitio nos permitieron defi nir algunos indicadores del comportamiento de las milicias en campaña. Se registraron dos tipos de acumulaciones: una donde predominan los materiales vítreos y otra con abundantes restos faunísticos. En este trabajo se analizan los procesos de formación de esta última concentración de materiales arqueológicos. Para ello, en primer lugar utilizamos las plantas de distribución espacial de los restos faunísticos correspondientes a los diferentes niveles de excavación. En segundo lugar, evaluamos la incidencia que habrían tenido en la formación del registro diversas variables tafonómicas tales como: la pendiente del terreno, la vegetación, la dispersión de los diferentes especímenes en el área excavada, su densidad, grado de articulación, termoalteración, meteorización, marcas de carnívoros y huellas antrópicas. Según las características topográfi cas y los procesos tafonómicos identifi cados, se plantea que ese sector del asentamiento habría funcionado como un sitio destinado al descarte de residuos de comida. AbstractFort La Perra (Loventué, Department, La Pampa) was one of the military settlements established in the central pampas, since 1883, in order to watch the native territory recently conquered. The archaelogical research conducted in this site enabled us to defi ne some indicators of military behaviour in the fi eld. Two types of accumulations were recorded: there are predominantly glass materials in one of them, and abundant faunal remains in the other. This paper analyzes the formation processes of this latter concentration of bone remains. In order to attain this goal, in the fi rst place, we used
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