Spectroscopic and functional investigations of the AMPA subtype of ionotropic glutamate receptors

Ion channels play a crucial role in the functioning of different systems of the body because of their ability to bridge the cell membrane and allow ions to pass in and out of the cell. Ionotropic glutamate receptors are one class of these important proteins and have been shown to be critical in propagating synaptic transmission in the central nervous system and in other diverse functions throughout the body. Because of their wide-ranging effects, this family of receptors is an important target for structure-function investigations to understand their mechanism of action. ^ α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one subtype of glutamate receptors and have been shown to be the primary receptors involved in rapid excitatory signaling in the central nervous system. Agonist binding to the extracellular ligand binding domain of these receptors causes various conformational changes that culminate in formation of the ion channel. Previous structural investigations have provided important information about their mechanism of action, including uncovering a relationship between the degree of cleft closure in the binding domain and activation of the receptor. However, what question remains unanswered is how specific interactions between the agonist and the protein interplay with cleft closure to mediate receptor activation. ^ To investigate this question, I applied a multiscale approach to investigate the effects of agonist binding on various levels. Vibrational spectroscopy was utilized to investigate molecular-level interactions in the binding pocket, and fluorescence resonance energy transfer (FRET) was employed to measure cleft closure in the isolated ligand binding domain. The results of these studies in the isolated binding domain were then correlated to activation of the full receptor. These investigations showed a relationship between the strength of the interaction at the α-amine group of the agonist and extent of receptor activation, where a stronger interaction correlated to a larger activation, which was upheld even when the extent of cleft closure did not correlate to activation. These results show that this interaction at the α-amine group is critical in mediating the allosteric mechanism of activation and provide a bit more insight into how agonist binding is coupled to channel gating in AMPA receptors. ^

Macromolecular interaction studies on FF1-3 of human CA150 and STAT1-importin alpha5 using biophysical and biochemical methods

Macromolecular interactions, such as protein-protein interactions and protein-DNA interactions, play important roles in executing biological functions in cells. However the complexity of such interactions often makes it very challenging to elucidate the structural details of these subjects. In this thesis, two different research strategies were applied on two different two macromolecular systems: X-ray crystallography on three tandem FF domains of transcription regulator CA150 and electron microscopy on STAT1-importin α5 complex. The results from these studies provide novel insights into the function-structure relationships of transcription coupled RNA splicing mediated by CA150 and the nuclear import process of the JAK-STAT signaling pathway. ^ The first project aimed at the protein-protein interaction module FF domain, which often occurs as tandem repeats. Crystallographic structure of the first three FF domains of human CA150 was determined to 2.7 Å resolution. This is the only crystal structure of an FF domain and the only structure on tandem FF domains to date. It revealed a striking connectivity between an FF domain and the next. Peptide binding assay with the potential binding ligand of FF domains was performed using fluorescence polarization. Furthermore, for the first time, FF domains were found to potentially interact with DNA. DNA binding assays were also performed and the results were supportive to this newly proposed functionality of an FF domain. ^ The second project aimed at understanding the molecular mechanism of the nuclear import process of transcription factor STAT1. The first structural model of pSTAT1-importin α5 complex in solution was built from the images of negative staining electron microscopy. Two STAT1 molecules were observed to interact with one molecule of importin α5 in an asymmetric manner. This seems to imply that STAT1 interacts with importin α5 with a novel mechanism that is different from canonical importin α-cargo interactions. Further in vitro binding assays were performed to obtain more details on the pSTAT1-importin α5 interaction. ^

Evidence for the role of agonist binding frequency in receptor -mediated activation of adenylate cyclase

$\beta$-adrenergic receptor-mediated activation of adenylate cyclase exhibits an agonist-specific separation between the dose/response curve (characterized by the EC$\sb{50}$) and the dose/binding curve (characterized by the K$\sb{\rm d}$). Cyclase activity can be near-maximal when receptor occupancy is quite low (EC$\sb{50}$ $\ll$ K$\sb{\rm d}$). This separation between the binding and response curves can be explained by the assumption that the rate of cyclase activation is proportional to the concentration of agonist-bound receptors, since the receptor is mobile and can activate more than one cyclase (the Collision Coupling Model of Tolkovsky and Levitzki). Here it is established that agonist binding frequency plays an additional role in adenylate cyclase activation in S49 murine lymphoma cells. Using epinephrine (EC$\sb{50}$ = 10 nM, K$\sb{\rm d}$ = 2 $\mu$M), the rate of cyclase activation decreased by 80% when a small (1.5%) receptor occupancy was restricted (by addition of the antagonist propranolol) to a small number (1.5%) of receptors rather than being proportionally distributed among the cell's entire population of receptors. Thus adenylate cyclase activity is not proportional to receptor occupancy in all circumstances. Collisions between receptor and cyclase pairs apparently occur a number of times in rapid sequence (an encounter); the high binding frequency of epinephrine ensures that discontiguous regions of the cell surface experience some period of agonist-bound receptor activity per small unit time minimizing "wasted" collisions between activated cyclase and bound receptor within an encounter. A contribution of agonist binding frequency to activation is thus possible when: (1) the mean lifetime of the agonist-receptor complex is shorter than the mean encounter time, and (2) the absolute efficiency (intrinsic ability to promote cyclase activation per collision) of the agonist-receptor complex is high. These conclusions are supported by experiments using agonists of different efficiencies and binding frequencies. These results are formalized in the Encounter Coupling Model of adenylate cyclase activation, which takes into explicit account the agonist binding frequency, agonist affinity for the $\beta$-adrenergic receptor, agonist efficiency, encounter frequency and the encounter time between receptor and cyclase. ^

Modulation of cytochrome P450 enzyme activity and PAH -induced skin carcinogenesis by naturally occurring coumarins

The present study was designed to determine the potential anticarcinogenic activity of naturally occurring coumarins and their mechanism of action. The results indicated that several naturally occurring coumarins including bergamottin, coriandrin, imperatorin, isopimpinellin, and ostruthin, to which humans are routinely exposed in the diet, were effective inhibitors and/or inactivators of CYP1A1-mediated ethoxyresorufin-O-dealkylase (EROD) or CYP2B1-mediated pentoxyresorufin-O-dealkylase (PROD) in mouse liver microsomes. In addition, bergamottin and corandrin were also found to be inhibitors of purified human P450 1A1 in vitro. Further studies with coriandrin revealed that this compound was a mechanism-based inactivator of P450 1A1 and covalently bound to the P450 1A1 apoprotein. In cultured mouse keratinocytes, bergamottin and coriandrin effectively inhibited the B(a) P metabolism and significantly decreased covalent binding of B(a) P and DMBA to keratinocyte DNA and anti-diol-epoxide-DNA adducts derived from both B(a) P and DMBA in keratinocytes. The data from in vivo experiments showed that bergamottin and coriandrin were potent inhibitors of covalent binding of B (a) P to epidermal DNA and the formation of (+) anti BPDE-DNA adduct, whereas imperatorin and isopimpinellin were more potent inhibitors of covalent binding of DMBA to epidermal DNA. The ability of coumarins to inhibit covalent binding of B (a) P to DNA in mouse epidermis was positively correlated with their inhibitory effect P450 1A1 in vitro, while the inhibitory effect of coumarins on covalent binding of DMBA to epidermal DNA was positively correlated with their inhibitory effects on P450 2B1 and negatively to their inhibitory activity toward P450 1A1. The data from tumor experiments indicated that bergamottin, ostruthin, and coriandrin inhibited tumor initiation by B (a) P in a two-stage carcinogenesis protocol. Bergamottin was most effective in this regard and produced a dose dependent inhibition of papilloma formation in these experiments. In addition, imperatorin was an effective inhibitor of skin tumorigenesis induced by DMBA in SENCAR mouse skin using both a two-stage and a complete carcinogenesis protocol. At dose levels higher than those effective against DMBA, imperatorin also inhibited tumor initiation by B (a) P. The results to date demonstrate that several naturally occurring coumarins possess the ability to block tumor initiation and tumorigenesis by PAHs such as B (a) P and DMBA through inhibition of the P450s involved in the metabolic activation of these hydrocarbons. A working model for the involvement of specific P450s in the metabolic activation of these two PAHs was proposed. ^

NMR structural analysis of cardiac troponin C: Monitoring conformational changes induced by binding calcium, troponin I, and calcium -sensitizing drugs

Contraction of cardiac muscle is regulated through the Ca2+ dependent protein-protein interactions of the troponin complex (Tn). The critical role cardiac troponin C (cTnC) plays as the Ca2+ receptor in this complex makes it an attractive target for positive inotropic compounds. In this study, the ten Met methyl groups in cTnC, [98% 13C ϵ]-Met cTnC, are used as structural markers to monitor conformational changes in cTnC and identify sites of interaction between cTnC and cardiac troponin I (cTnI) responsible for the Ca2+ dependent interactions. In addition the structural consequences that a number of Ca2+-sensitizing compounds have on free cTnC and the cTnC·cTnI complex were characterized. Using heteronuclear NMR experiments and monitoring chemical shift changes in the ten Met methyl 1H-13C correlations in 3Ca2+ cTnC when bound to cTnI revealed an anti-parallel arrangement for the two proteins such that the N-domain of cTnI interacts with the C-domain of cTnC. The large chemical shifts in Mets-81, -120, and -157 identified points of contact between the proteins that include the C-domain hydrophobic surface in cTnC and the A, B, and D helical interface located in the regulatory N-domain of cTnC. TnI association [cTnI(33–80), cTnI(86–211), or cTnI(33–211)] was found also to dramatically reduce flexibility in the D/E central linker of cTnC as monitored by line broadening in the Met 1H- 13C correlations of cTnC induced by a nitroxide spin label, MTSSL, covalently attached to cTnC at Cys 84. TnI association resulted in an extended cTnC that is unlike the compact structure observed for free cTnC. The Met 1H-13C correlations also allowed the binding characteristics of bepridil, TFP, levosimendan, and EMD 57033 to the apo, 2Ca2+, and Ca2+ saturated forms of cTnC to be determined. In addition, the location of drug binding on the 3Ca2+cTnC·cTnI complex was identified for bepridil and TFP. Use of a novel spin-labeled phenothiazine, and detection of isotope filtered NOEs, allowed identification of drug binding sites in the shallow hydrophobic cup in the C-terminal domain, and on two hydrophobic surfaces on N-regulatory domain in free 3Ca2+ cTnC. In contrast, only one N-domain drug binding site exists in 3Ca2+ cTnC·cTnI complex. The methyl groups of Met 45, 60 and 80, which are grouped in a hydrophobic patch near site II in cTnC, showed the greatest change upon titration with bepridil or TFP, suggesting that this is a critical site of drug binding in both free cTnC and when associated with cTnI. The strongest NOEs were seen for Met-60 and -80, which are located on helices C and D, respectively, of Ca2+ binding site II. These results support the conclusion that the small hydrophobic patch which includes Met-45, -60, and -80 constitutes a drug binding site, and that binding drugs to this site will lead to an increase in Ca2+ binding affinity of site II while preserving maximal cTnC activity. Thus, the subregion in cTnC makes a likely target against which to design new and selective Ca2+-sensitizing compounds. ^

Dual role of interleukin-12 on ultraviolet -induced immune suppression

Skin cancer is the most prevalent form of neoplasia, with over one million newcases diagnosed this year. UV radiation is a ubiquitous environmental agent that induces skin cancer. In addition to its carcinogenic effect, UV radiation also suppresses cell-mediated immune responses. This immune suppression is not only observed at the site of irradiation, but UV radiation also induces systemic immune suppression. Since UV radiation has a limited ability to penetrate the skin, the question of the mechanism of this systemic immune suppression arises. A number of studies have suggested that UV radiation induce systemic effects through the production of immunoregulatory cytokines, such as IL-4 and IL-10. These cytokines affect the immune response by altering systemic antigen presentation, specifically by suppressing the activation of Th1 cells while allowing the activation of Th2 cells. Because IL-12 is an important regulator of Th1 cell activation, we tested the hypothesis that administration of IL-12 could overcome UV-induced immune suppression. ^ The studies presented here are divided into dime specific aims. In the first specific aim, the ability of IL-12 to overcome UV-induced immune suppression was examined. IL-12 could overcome UV-induced immune suppression as well as prevent the generation of and neutralize the activity of preformed suppressor cells induced by UV radiation. In the second specific aim, the mechanism by which IL-12 overcomes UV-induced immune suppression was examined. IL-12 overcame UV-induced immune suppression by blocking the production of immunoregulatory cytokines such as IL-4, IL-10 and TNF-α. In the third specific aim, the effect of UV radiation on antigen presentation was investigated. UV radiation was found to decrease the production of biologically active IL-12. In addition, UV also increased the production of IL-12p40 homodimer, an antagonist of IL-12p70 heterodimer. This result suggests that IL-12 may have a dual role in the immune suppression induced by, UV radiation. On one hand the biologically active IL-12p70 heterodimer blocks UV-induced immune suppression. In contrast, IL-12p40 homodimer may mediate the suppressive effect of UV radiation. This paradox indicates that IL-12 may have a greater regulatory role in the immune response than was previously suspected. ^

Regulation of p53 antiproliferative function by transactivation domain phosphorylation at threonine 18 and serine 20

We investigated the induction and physiological role of Thr18 and Ser20 phosphorylation of p53 in response to DNA damage caused by treatment with ionizing (IR) or ultraviolet (UV) radiation. Polyclonal antibodies specifically recognizing phospho-Thr18 and phospho-Ser20 were used to detect p53 phosphorylation in vivo. Analyses of five wild-type (wt) p53 containing cell lines revealed lineage specific differences in phosphorylation of Thr18 and Ser20 after treatment with IR or UV. Importantly, the phosphorylation of p53 at Thr18 and Ser20 correlated with induction of the p53 downstream targets p21Waf1/Cip1 (p21) and Mdm-2, suggesting a transactivation enhancing role for Thr18 and Ser20 phosphorylation. Whereas Thr18 phosphorylation appears to abolish side-chain hydrogen bonding between Thr18 and Asp21, Ser20 phosphorylation may introduce charge attraction between Ser20 and Lys24. Both of these interactions could contribute to stabilizing α-helical conformation within the p53 transactivation domain. Mutagenesis-derived phosphorylation mimicry of p53 at Thr18 and Ser20 by Asp substitution (p53T18D/S20D) altered transactivation domain conformation and significantly reduced the interaction of p53 with the transactivation repressor Mdm-2. Mdm-2 interaction was also reduced with p53 containing a single site Asp substitution at Ser20 (p53S20D) and with the Thr18/Asp21 hydrogen bond disrupting p53 mutants p53T18A, p53T18D and p53D21A. In contrast, no direct effect was observed on the interaction of p53T18A, p53T18D and p53D21A with the basal transcription factor TAF II31. However, prior incubation of p53T18A, p53T18D and p53D21A with Mdm-2 modulated TAFII31 interaction, suggesting Mdm-2 blocks the accessibility of p53 to TAFII31. Consistently, p53-null cells transfected with p53S20D and p53T18A, p53T18D and p53D21A demonstrated enhanced endogenous p21 expression; transfection with p53T18D/S20D most significantly enhanced p21 and fas/APO-1 (fas ) expression. Expression of p53T18A, p53T18D and p53D21A in p53/Mdm-2-double null cells exhibited no discernible differences in p21 expression. Cell proliferation was also significantly curtailed in p53-null cells transfected with p53T18D/S20D relative to cells transfected with wt p53. We conclude the irradiation-induced phosphorylation of p53 at Thr18 and Ser20 alters the α-helical conformation of its transactivation domain. Altered conformation reduces direct interaction with the transrepressor Mdm-2, enhancing indirect recruitment of the basal transcription factor TAFII31, facilitating sequence-specific transactivation function resulting in proliferative arrest. ^

Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity using ROS -generating agents

A major goal of chemotherapy is to selectively kill cancer cells while minimizing toxicity to normal cells. Identifying biological differences between cancer and normal cells is essential in designing new strategies to improve therapeutic selectivity. Superoxide dismutases (SOD) are crucial antioxidant enzymes required for the elimination of superoxide (O2·− ), a free radical produced during normal cellular metabolism. Previous studies in our laboratory demonstrated that 2-methoxyestradiol (2-ME), an estradiol derivative, inhibits the function of SOD and selectively kills human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The present work was initiated to examine the biochemical basis for the selective anticancer activity of 2-ME. Investigations using two-parameter flow cytometric analyses and ROS scavengers established that O2·− is a primary and essential mediator of 2-ME-induced apoptosis in cancer cells. In addition, experiments using SOD overexpression vectors and SOD knockout cells found that SOD is a critical target of 2-ME. Importantly, the administration of 2-ME resulted in the selective accumulation of O 2·− and apoptosis in leukemia and ovarian cancer cells. The preferential activity of 2-ME was found to be due to increased intrinsic oxidative stress in these cancer cells versus their normal counterparts. This intrinsic oxidative stress was associated with the upregulation of the antioxidant enzymes SOD and catalase as a mechanism to cope with the increase in ROS. Furthermore, oxygen consumption experiments revealed that normal lymphocytes decrease their respiration rate in response to 2-ME-induced oxidative stress, while human leukemia cells seem to lack this regulatory mechanism. This leads to an uncontrolled production of O2·−, severe accumulation of ROS, and ultimately ROS-mediated apoptosis in leukemia cells treated with 2-ME. The biochemical differences between cancer and normal cells identified here provide a basis for the development of drug combination strategies using 2-ME with other ROS-generating agents to enhance anticancer activity. The effectiveness of such a combination strategy in killing cancer cells was demonstrated by the use of 2-ME with agents/modalities such as ionizing radiation and doxorubicin. Collectively, the data presented here strongly suggests that 2-ME may have important clinical implications for the selective killing of cancer cells. ^

La odisea de un concepto nómada : el desarrollo sustentable en la órbita de la Geografía

Nuevo paradigma para algunos, o simple eslogan político-mediático para otros, el concepto de desarrollo sustentable levanta reacciones contradictorias en el mundo científico. Existen notables diferencias en el acercamiento al desarrollo sustentable entre los representantes de las ciencias naturales y los de las ciencias humanas. El carácter nómada del concepto (Stengers, 1987) de desarrollo sustentable es percibido por ciertos investigadores en geografía como una verdadera tara genética, cuando otros piensan por el contrario que puede servir de palanca para renovar el acercamiento geográfico a los grandes problemas contemporáneos. ¿Para la investigación en geografía, qué postura es conveniente adoptar? ¿El desarrollo sustentable, como concepto nómada, puede convertirse en una herramienta eficaz e innovadora? ¿O bien su incertidumbre semántica nos conduce de manera inexorable hacia un vagabundeo de las ideas? El objetivo central de esta reflexión es intentar situar el concepto de desarrollo sustentable en la órbita del pensamiento geográfico, en una óptica comparativa con disciplinas vecinas y cuestionando a su vez su interés para la investigación en nuestro campo disciplinario. Para ello, es necesario en primer lugar acercarse sin tabúes a los problemas planteados por este concepto: ¿Debe considerarse el nomadismo conceptual del desarrollo sustentable como una especie de pecado original que lo convertiría en un instrumento inoperante para la geografía? En segundo lugar, desmitificando la novedad aparente del concepto, conviene analizar cuáles son sus filiaciones con la geografía y otras disciplinas. Y finalmente, plantear casos concretos de utilización del concepto en la investigación geográfica (ciudad sustentable; bosques sustentables), subrayando sus aportes, pero también poniendo a la luz sus límites.

Otra Patagonia Austral es posible : proyectos de territorio entre la emergencia y la urgencia

Nuevo paradigma para algunos, o simple eslogan político-mediático para otros, el concepto de desarrollo sustentable levanta reacciones contradictorias en el mundo científico. Existen notables diferencias en el acercamiento al desarrollo sustentable entre los representantes de las ciencias naturales y los de las ciencias humanas. El carácter nómada del concepto (Stengers, 1987) de desarrollo sustentable es percibido por ciertos investigadores en geografía como una verdadera tara genética, cuando otros piensan por el contrario que puede servir de palanca para renovar el acercamiento geográfico a los grandes problemas contemporáneos. ¿Para la investigación en geografía, qué postura es conveniente adoptar? ¿El desarrollo sustentable, como concepto nómada, puede convertirse en una herramienta eficaz e innovadora? ¿O bien su incertidumbre semántica nos conduce de manera inexorable hacia un vagabundeo de las ideas? El objetivo central de esta reflexión es intentar situar el concepto de desarrollo sustentable en la órbita del pensamiento geográfico, en una óptica comparativa con disciplinas vecinas y cuestionando a su vez su interés para la investigación en nuestro campo disciplinario. Para ello, es necesario en primer lugar acercarse sin tabúes a los problemas planteados por este concepto: ¿Debe considerarse el nomadismo conceptual del desarrollo sustentable como una especie de pecado original que lo convertiría en un instrumento inoperante para la geografía? En segundo lugar, desmitificando la novedad aparente del concepto, conviene analizar cuáles son sus filiaciones con la geografía y otras disciplinas. Y finalmente, plantear casos concretos de utilización del concepto en la investigación geográfica (ciudad sustentable; bosques sustentables), subrayando sus aportes, pero también poniendo a la luz sus límites.

La literatura de viajes y la mirada antropológica

La antropología como ciencia ha sido considerada hija del colonialismo europeo. En este sentido comparte un destino similar al de la literatura de viajes e incluso puede ser considerada como el vástago más cercano a las ciencias naturales de esta última. En la conformación de su programa de investigación -que también puede comprenderse como la aplicación de la teoría evolucionista a la historia de la cultura humana-, la literatura de viajes. con su vocación referencial y su insistencia en la descripción de la diversidad humana y geográfica, ha jugado un papel fundamental. En este trabajo se intenta realizar aportes, desde algunos textos de Alexander von Humboldt, como viajero y autor de textos que pueden ser considerados parte de la literatura de viajes, a la distinción de ambos ámbitos, el literario y el más definidamente antropológico.

La epistemología : estudio y validación del conocimiento científico : aclaraciones y reflexiones en el ámbito de la Facultad de Odontología

Hablar de Epistemología en el ámbito de nuestra Facultad nos traslada a la discusión de algo que, en general, y a simple vista, aparece como alejado de la cotidiana actividad en nuestro espacio de trabajo. Desde la cátedra de “Epistemología y Metodología de la Investigación Científica" queremos efectuar algunas aclaraciones. Nuestro propósito es llevar algo de luz sobre esta disciplina, en especial para contribuir a esclarecer conceptos que se utilizan desde la filosofía y las ciencias sociales en general, y que recuperados por científicos ligados a las ciencias naturales posteriormente en su etapa fragmentada, tornaron su significación a posiciones inamovibles donde se pretendió establecer una misma mirada para todo el quehacer científico, hecho equívoco que, como veremos, la ciencia actual ya no discute. Debido a lo extenso del tema, hemos preferido realizar una primera parte en esta oportunidad a modo de introducción, y así irnos introduciendo en el apasionante mundo de la ciencia.

Construyendo nuevas miradas pedagógicas en pos de la accesibilidad académica en la universidad

Durante el primer cuatrimestre del año 2012 la asignatura Patrimonio Natural Regional de la carrera Tecnicatura de Empresas de Servicios Turísticos — Facultad de Turismo — Universidad Nacional del Comahue; contó con la presencia de un estudiante en situación de discapacidad (motora). A partir de la iniciativa de los docentes de la asignatura, se solicita apoyo institucional y se toma contacto con la Comisión Universitaria sobre Accesibilidad al Medio Físico y Social, para consensuar estrategias a implementar en la evaluación parcial del alumno en situación de discapacidad en relación al resto del curso. Este trabajo tiene por objetivos: reflexionar acerca de la evaluación parcial con estudiantes en situación de discapacidad y proponer cambios en la evaluación parcial de la asignatura Patrimonio Natural Regional en relación a estudiantes en situación de discapacidad motora. La metodología usada por el equipo de cátedra fue de un estudio de diseño para las asignaturas del área de concurso Recursos Naturales, contextualizado para el estudiante en situación de discapacidad con el asesoramiento de la comisión sobre accesibilidad y también de la comunicación con el alumno. Algunas conclusiones a las que se arribó tienen relación con los ejes 1. Necesidad de evaluaciones con nuevas estrategias pedagógicas contextuales particulares; 2.Necesidad de un acompañamiento institucional ante la presencia de estudiantes en situación de discapacidad en las aulas.

La escritura en la enseñanza y el aprendizaje de la historia : Aproximaciones desde una investigación didáctica

La lectura y la escritura, potentes herramientas para aprender, se han constituido en temas relevantes para la investigación didáctica como respuesta a las dificultades confrontadas por los alumnos de diferentes niveles educativos al leer y producir textos. El presente trabajo se enmarca en una investigación inter-didácticas desarrollada desde el año 2000 -a través de sucesivos proyectos UBACyT-, que se centró originalmente en el estudio de las situaciones de lectura para aprender contenidos de ciencias sociales y ciencias naturales y en la actualidad aborda también el análisis del papel de la escritura en el aprendizaje de estos contenidos. Sintetizaremos aquí avances recientes vinculados con el estudio del desarrollo en el aula de situaciones de escritura para aprender contenidos históricos, considerando los resultados de varios trabajos de campo centrados en la enseñanza de un contenido específico: la catástrofe demográfica de la población aborigen durante la conquista de América

Aproximación metodológica para la identificación del perfil y patrones de colaboración de dominios científicos universitarios

La diversidad temática y complejidad estructural de las universidades nacionales argentinas hacen que la identificación de sus perfiles científicos no resulte sencilla. En este estudio se realiza una aproximación metodológica para el análisis del perfil temático y patrones de colaboración de estos dominios científicos, a partir del estudio bibliométrico de las contribuciones científicas de las facultades que las conforman, sin perder de vista sus posicionamientos relativos respecto de la universidad de la que son parte y del país en su conjunto. Como ejemplo de aplicación de la metodología propuesta se estudia el caso de una facultad, la Facultad de Ciencias Naturales y Museo (FCNyM) de la Universidad Nacional de La Plata (UNLP), Argentina. Se realiza un análisis bibliométrico de sus contribuciones científicas recogidas en el Science Citation Index versión CD-ROM para el período 1991-2000, identificando y comparando su perfil, patrones y posicionamiento científico relativo en los contextos de la UNLP y de Argentina. Los resultados muestran que la metodología propuesta es una alternativa válida tanto para relevar las fortalezas científicas de una universidad como para aportar información cuantitativa y cualitativa de apoyo a la toma de decisiones en materia de planificación y evaluación de sus actividades de investigación