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Classical novae are thermonuclear explosions in stellar binary systems, and important sources of $^{26}$Al and $^{22}$Na. While gamma rays from the decay of the former radioisotope have been observed throughout the Galaxy, $^{22}$Na remains untraceable. The half-life of $^{22}$Na (2.6 yr) would allow the observation of its 1.275 MeV gamma-ray line from a cosmic source. However, the prediction of such an observation requires good knowledge of the nuclear reactions involved in the production and destruction of this nucleus. The $^{22}$Na($p,\gamma$)$^{23}$Mg reaction remains the only source of large uncertainty about the amount of $^{22}$Na ejected. Its rate is dominated by a single resonance on the short-lived state at 7785.0(7) keV in $^{23}$Mg. In the present work, a combined analysis of particle-particle correlations and velocity-difference profiles is proposed to measure femtosecond nuclear lifetimes. The application of this novel method to the study of the $^{23}$Mg states, combining magnetic and highly-segmented tracking gamma-ray spectrometers, places strong limits on the amount of $^{22}$Na produced in novae, explains its non-observation to date in gamma rays (flux < 2.5x$10^{-4}$ ph/(cm$^2$s)), and constrains its detectability with future space-borne observatories., Comment: 18 pages, 3 figures, 1 table

Resumen: Nos proponemos analizar cómo se fueron definiendo distintas y a veces contrapuestas representaciones del pasado chaqueño dentro de un espacio intelectual en formación durante la primera mitad del siglo XX. Al atender al papel de la historiografía, en su sentido amplio, para la construcción de las identidades regionales/provinciales, se pueden establecer las particulares prácticas de integración cultural a la nación que se realizaron desde este espacio. Las tres líneas interpretativas identificadas, con sus respectivos representantes, producciones y lugares de memoria instituidos, entraron en debates que enmarcarían la emergencia de una historiografía profesional en la segunda mitad del siglo. Abstract: This article analyzes how different and sometimes conflicting representations of the Chaco past were defined within an intellectual space in formation during the first half of the 20th century. By attending to the role of historiography, in its broad sense, for the construction of regional / provincial identities, can be established the particular practices of cultural integration to the nation that were carried out from this space. The three interpretive lines identified, with their respective representatives, productions and places of memory, entered into debates that would frame the emergence of a professional historiography in the second half of the century.

Background Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes. Methods and results We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants. APOA-1M, delivered as protein extracts from transgenic rice seeds, significantly reduced macrophage activation and foam cell formation in vitro in oxLDL-loaded THP-1 model. The APOA-1M delivery method and therapeutic efficacy was tested in healthy mice and in Apoe−/− mice fed with high cholesterol diet (Western Diet, WD). APOA-1M rice milk significantly reduced atherosclerotic plaque size and lipids composition in aortic sinus and aortic arch of WD-fed Apoe−/− mice as compared to wild type rice milk-treated, WD-fed Apoe−/− mice. APOA-1M rice milk also significantly reduced macrophage number in liver of WD-fed Apoe−/− mice as compared to WT rice milk treated mice. Translational impact The delivery of therapeutic APOA-1M full length proteins via oral administration of rice seeds protein extracts (the ‘rice milk’) to the disordered organism, without any need of purification, might overcome the main APOA1-based therapies' limitations and improve the use of this molecules as therapeutic agents for cardiovascular patients.

Esta bibliografía reúne lo producido en la última década (2000-2010), en distintos idiomas y espacios, sobre teoría, metodología e historia de la historiografía. Con ella se busca proporcionar una mirada de conjunto que posibilite un estado de la cuestión y que sea herramienta para los investigadores y estudiantes interesados en dichas temáticas, dada la dispersión de la producción y la dificultad de acceso a la misma.Palabras clavesTeoría de la historia, historiografía, memoria, usos públicos de la historia.AbstractThis compiled bibliography includes the last decade (2000-2010) existent literature in the subjects of theory, methodology and the history of historiography, covering different languages and geographic areas. It is intended to provide both an overview, to help to offer a state of the art, and a tool to be useful for scholars and students interested in this specific subject, given the lack of systematization and compilation of the extant literature.KeywordsTheory of History, Historiography, Memory, Public Uses of History.

Este trabajo propone trazar un recorrido reflexivo sobre la emergencia y despliegue de la historiografía referida al nordeste argentino, desde fines del siglo XIX a la década de 1970, producida tanto en vinculación con la historia “nacional” como con la historia paraguaya, atendiendo al contexto de definición de las provincias y regiones en Argentina, de los procesos de elaboración de saberes regionales y, dentro de ellos, la conformación de los campos historiográficos provinciales. Lo abordamos desde la perspectiva de una historia de la historiografía en diálogo con la antropología, la historia política, la historia cultural y de las representaciones colectivas, al considerar a la historiografía como una forma de pensar la sociedad en la dimensión espacio-temporal.

Although the low level of tuition fees and the absence of other access barriers, Italy is characterized by low educational attainments at the university level. This work models the choice of young Italians to attend university or leave education and enter the labor market, by making use of an agent-based model that reproduces the Italian higher education and policy system. The aim is to analyze the determinants behind university enrollment decisions possibly causing the low level of attainment and explore three alternative scenarios that propose the expansion of financial support and the increase in the average income gap between skilled and unskilled individuals. The model implies that the individual preference to enroll at university depends upon (i) economic motivations, represented by the expectations on future income, which are formed through interaction within individuals’ social network; (ii) influence from peers; (iii) effort of obtaining a university degree. Results show that the model can reproduce observable features of the Italian system, and highlights low income levels and the following full resort to regional scholarships. Experimented scenarios show that policies expanding financial support to education are ineffective, while an increase in the gap between average income of skilled and unskilled workers leads to an increase in enrollment in university, signaling that labor market policies may be more effective than educational policies in raising the number of students in higher education.

Fil: Leoni, María Silvia. Universidad Nacional del Nordeste. Facultad de Humanidades; Argentina. Fil: Leoni, María Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Geohistóricas; Argentina. Este artículo propone analizar el v ínculo entre historia regional y construcción de regiones en Argentina desde fines del siglo XIX hasta la actualidad, identificando sus distintos m om entos, para proporcionar finalm ente un balance de su situación actual. Los procesos de construcción de las regiones subnacionales serán estudiados con relación a la construcción del estado nacional, a las «inv enciones» y transform aciones identitarias, a la producción de m em orias y , fundam entalm ente, a la em ergencia y desarrollo de los estudios regionales en estos contextos. Cet article propose d’analy ser le lien entre histoire régionale et construction de régions en Argentine de la fin du XIXe siècle à nos jours, en identifiant leurs différents m om ents, pour fournir finalem ent un bilan de leur situation actuelle. Les processus de construction des régions infranationales seront étudiés en relation av ec la construction de l’État national, les « inv entions » et transform ations d’identité, la production de m ém oire et, fondam entalem ent, l’ém ergence et dév eloppem ent des études régionales dans ces contextes. This article analy zes the link betw een regional history and the construction of regions in Argentina from the end of the 1 9 th century to the present, identify ing their different m om ents and prov iding an assessm ent of their current situation. The construction processes of sub-national regions w ill be studied in relation to the construction of the national state, to the inv entions and transform ations of identities, to m em ory production and to the em ergence and dev elopm ent of regional studies in these contexts.

Radiative capture reactions on rare targets and prompt spectroscopy of neutron-rich nuclei produced in the neutron-capture induced-fission of 235U and 241Pu have been performed at the Institut Laue-Langevin (ILL). The high efficiency germanium (Ge) EXOGAM array has been used, complemented with Ge detectors from GASP and the ILL. LaBr3 detectors from the FATIMA collaboration have also been coupled to EXOGAM to measure lifetimes of lowlying excited states. The measured characteristics indicate very good performances of the overall setup. Some recent results will be discussed.

En la década de 1960, el gobierno nacional argentino emprendió un proceso de regionalización que definió una región Nordeste, integrada por cuatro provincias. Las posibilidades de existencia de esta región fueron debatidas por cientistas sociales radicados en dicho espacio. En este trabajo analizamos sus contribuciones a lo largo de las décadas de 1960 y 1970. In the decade of 1960, the Argentinian national government undertook a process of regionalization that defined a Northeast region, integrated by four provinces. The possibilities of existence of this region were debated by scientists residing in that space. In this paper we analyze their contributions throughout the 1960s and 1970s. Na década de 1960, o governo nacional argentino assumiu um processo de regionalização que definiu uma região Nordeste, integrada por quatro províncias. As possibilidades de existência desta região foram debatidas pelos cientistas que residiam nesse espaço. Neste artigo, analisamos suas contribuições ao longo dos anos 1960 e 1970. Fil: Leoni, María Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Investigaciones Geohistóricas. Universidad Nacional del Nordeste. Instituto de Investigaciones Geohistóricas; Argentina Fil: Solís Carnicer, María del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Investigaciones Geohistóricas. Universidad Nacional del Nordeste. Instituto de Investigaciones Geohistóricas; Argentina

Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes.We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants. APOA-1M, delivered as protein extracts from transgenic rice seeds, significantly reduced macrophage activation and foam cell formation in vitro in oxLDL-loaded THP-1 model. The APOA-1M delivery method and therapeutic efficacy was tested in healthy mice and in ApoeThe delivery of therapeutic APOA-1M full length proteins via oral administration of rice seeds protein extracts (the 'rice milk') to the disordered organism, without any need of purification, might overcome the main APOA1-based therapies' limitations and improve the use of this molecules as therapeutic agents for cardiovascular patients.

A autora comenta os artigos de Liliana Brezzo e Martha Philp, abordando os pontos comuns e divergentes apresentados, ressaltando que os mesmos permitem abordar as vinculacoes entre historia e memoria e, entre historia e politica para refletir sobre as relacoes das sociedades nacionais, mais especificamente Paraguai e Argentina, com os seus respectivos passados.

Nonalcoholic fatty liver disease (NAFLD) is an emerging disease with a broad spectrum of liver conditions. The complex molecular pathogenesis of NAFLD is still unclear. In this study, we conducted an analysis of microRNA (miRNA) expression profiles in liver of rats made NAFLD by different diets. To this aim, Sprague-Dawley rats were fed ad libitum for 3 months with different diets: standard diet (SD), diet enriched in fats and low in carbohydrates (HFD), SD with high fructose (SD-HF) and diet with high levels of fats and fructose (HFD-HF). Our results demonstrated that the treatment with different dietetic regimens caused a significant increase of the body weight and the alteration of some metabolic parameters compared with control animals, as well as various liver injuries. The miRNAs analysis showed the significant downregulation of three miRNAs (miR-122, miR-451 and miR-27) and the upregulation of miR-200a, miR-200b and miR-429 in HFD, SD-HF and HFD-HF rats. Besides, miR-21 expression was significantly decreased only in fructose-enriched diets. These miRNAs target molecules involved in the control of lipid and carbohydrate metabolism, signal transduction, cytokine and chemokine-mediated signaling pathway and apoptosis. Western blot analysis of PKCδ, LITAF, ALDOLASE-A, p38MAPK, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 showed a diet-induced deregulation of all these proteins. Interestingly, the expression pattern of LITAF, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 might be well explained by the trend of their specific mRNAs, by potentially regulatory miRNAs, or both. In conclusion, we highlight for the first time the potential involvement of novel determinants (miRNAs and proteins) in the molecular pathogenesis of diet-induced NAFLD.

The author comments on the articles by Liliana Brezzo and MarthaPhilp, discussing the similar and diverging points presented, highlighting that they make it possible to discuss the links between history and memory and between history and politics, to reflect on the relationships of national societies, more specifically those of Paraguay and Argentina, with their respective pasts.La autora comenta los artículos de Liliana Brezzo y Marta Philp, resaltando los puntos comunes y divergentes entre ambos, que permiten abordar los vínculos entre historia y memoria, y entre historia y política para así reflexionar sobre las relaciones de las sociedades nacionales, en particular, la paraguaya y la argentina, con sus respectivos pasados.A autora comenta os artigos de Liliana Brezzo e Martha Philp, abordando os pontos comuns e divergentes apresentados, ressaltando que os mesmos permitem abordar as vinculações entre história e memória e, entre história e política para refletir sobre as relações das sociedades nacionais, mais especificamente Paraguai e Argentina, com os seus respectivos passados.

Nongenomic effects of thyroid hormones on Na+-K+-ATPase activity were studied in chick embryo hepatocytes at two different developmental stages, 14 and 19 days of embryonal age, and the signal transduction pathways involved were characterized. Our data showed the following. 1) 3,5,3′-Triiodo-l-thyronine (T3) and 3,5-diiodo-l-thyronine (3,5-T2) rapidly induced a transient inhibitory effect on the Na+-K+-ATPase; the extent and duration depended on the developmental age of the cells. 2) 3,5-T2behaved as a true hormone and fully mimicked the effect of T3. 3) Thyroxine had no effect at any of the developmental stages. 4) The inhibition of Na+-K+-ATPase was mediated by activation of protein kinase A, protein kinase C, and phosphoinositide 3-kinase, suggesting several modes of modulation of ATPase activity through phosphorylation at different sites. 5) The MAPK pathway did not seem to be involved in the early phase of hormone treatment. 6) The nonpermeant analog T3-agarose inhibited Na+-K+-ATPase activity in the same way as T3, confirming that hormone signaling initiated at a receptor on the plasma membrane. From these results, it can be concluded that the cell response mechanisms change rapidly and drastically within the early phase of embryo growth. The differences found at the two stages probably reflect the different roles of thyroid hormones during development and differentiation.

TGF-β pathway is generally associated with the processes of metastasis, angiogenesis and EMT in cancer. Very little is known, however, about the role of TGF-β in cancer drug resistance. In this work, we show a specific activation of the TGF-β pathway in consequence of chemotherapeutic treatment in in vivo and in vitro models of colorectal carcinoma. 5-Fluorouracil (5FU) was able to stimulate the activation of SMAD3 and the transcription of specific genes such as ACVRL1, FN1 and TGFB1. On the other hand, the specific inhibition of TGF-βRI was able to repress the 5FU-induced genes transcription and to restore the sensitivity of chemoresistant cells to the toxic action of the drug, by decreasing the expression of BCL2L1 and ID1 genes. The role of the TGF-β molecule in the chemoresistant colon carcinoma cells' response to 5FU was further demonstrated by conditioned medium (CM) experiments: CM from 5FUtreated chemoresistant cells was able to protect chemosensitive cells against the toxic action of 5FU. In conclusion, these findings showed the pivotal role of TGF-β pathway in colon cancer mechanisms of drug resistance suggesting new possible approaches in diagnosis and treatment of colon cancer patients.

The possible nuclear compartmentalization of glutathione S-transferase (GST) isoenzymes has been the subject of contradictory reports. The discovery that the dinitrosyl-diglutathionyl-iron complex binds tightly to Alpha class GSTs in rat hepatocytes and that a significant part of the bound complex is also associated with the nuclear fraction (Pedersen, J. Z., De Maria, F., Turella, P., Federici, G., Mattei, M., Fabrini, R., Dawood, K. F., Massimi, M., Caccuri, A. M., and Ricci, G. (2007) J. Biol. Chem. 282, 6364–6371) prompted us to reconsider the nuclear localization of GSTs in these cells. Surprisingly, we found that a considerable amount of GSTs corresponding to 10% of the cytosolic pool is electrostatically associated with the outer nuclear membrane, and a similar quantity is compartmentalized inside the nucleus. Mainly Alpha class GSTs, in particular GSTA1-1, GSTA2-2, and GSTA3-3, are involved in this double modality of interaction. Confocal microscopy, immunofluorescence experiments, and molecular modeling have been used to detail the electrostatic association in hepatocytes and liposomes. A quantitative analysis of the membrane-bound Alpha GSTs suggests the existence of a multilayer assembly of these enzymes at the outer nuclear envelope that could represent an amazing novelty in cell physiology. The interception of potentially noxious compounds to prevent DNA damage could be the possible physiological role of the perinuclear and intranuclear localization of Alpha GSTs.

Fil: Leoni, María Silvia. Universidad Nacional del Nordeste. Facultad de Humanidades; Argentina. El artículo se inicia con algunas consideraciones conceptuales sobre región, regionalización y regionalismo y puntualiza algunos aspectos a considerar cuando estudiamos su construcción. Se realiza un repaso por el proceso de regionalización en la Argentina y más específicamente el caso del Nordeste. Este contexto permite explicar la situación actual de la historia regional a nivel latinoamericano y argentino, con las importantes innovaciones introducidas en las últimas décadas. Finalmente, una breve referencia a la relación de esta nueva historia con su enseñanza. The article begins with some conceptual considerations on region, regionalization and regionalism and points out some issues to consider at the study of their construction. A review of the regionalization process in Argentina and more specifically the case of the Northeast is performed. This context helps to explain the current situation of the regional Latin American and Argentine history, with important innovations in recent decades. Finally, a brief reference to the relationship of this new history with teaching

The purpose of this study was to define the distribution of the asialoglycoprotein receptor (ASGP-R) main peptide, rat hepatic lectin (RHL)-1, within the rat liver lobule and to investigate its possible modulation in physiological states characterised by marked changes of receptorial expression. In particular, we chose livers from rats partially hepatectomised or at the end of pregnancy, as models, respectively, of decreased or increased expression of the ASGP-R, and used the in situ hybridisation and immunocytochemistry techniques to analyse in parallel the lobular distributions of RHL-1 mRNA and protein. In normal rat liver, although the RHL-1 mRNA was homogeneously distributed, the RHL-1 peptide was predominantly localised on the surface of pericentral hepatocytes with a gradient of expression towards the periportal zone. This gradient of expression of RHL-1 peptide was reduced in regenerating livers, in which the positive stain was restricted to a few layers of cells around the central vein. In contrast, livers at the end of pregnancy showed an overall increase of the peptide with a concomitant flattening of the gradient across the liver plate. In all the conditions, we never observed important changes in the pattern of expression of the specific mRNA. These findings indicate that the distribution of ASGP-R is heterogeneous across the liver lobule, with a pattern of expression prevalently modulated at the posttranscriptional level.

Retinoic acid (RA), the most biologically active metabolite of vitamin A, is known to modulate cell proliferation, apoptosis and differentiation, with different effects depending on the cellular context. Retinoic acid can exert its effects by directly or indirectly influencing the expression of genes involved in the control of cell proliferation. In the present report we investigate the possible correlation between the antiproliferative, differentiative and apoptotic effects previously observed on rat hepatocytes and HepG2 cells, with a possible modulation of cell-cycle regulators. We demonstrate that RA induces growth arrest and differentiation in HepG2 cells by influencing the activities of cyclin-cdk complexes involved in the regulation of G1/S transition and S-phase progression, in particular by modifying the binding of these complexes to p21 and p27 inhibitors. In fetal cells, however, the induction of apoptosis and differentiation by RA was obtained via inhibition of cyclin D1-cdk4 activity, as result of an increased binding to the p16 inhibitor. Retinoic acid also modulates c-myc and Bcl-2 expression. In conclusion, our data suggest that RA could be useful to regulate the reversion of transformed phenotype and could also be utilized as a chemiopreventive agent in cells of hepatic origin.

Nuclei around doubly-closed shells play a crucial role in studying both a) the couplings between valence nucleons which provide information on the effective nucleon-nucleon interaction and, b) couplings of the valence nucleons with core excitations, which may be used as a unique test of various effective interactions used in mean-field based models, like Skyrme, Gogny etc. From a broader perspective, understanding the coupling of a single particle to vibrational motion in nuclei is of primary importance, as this coupling is responsible for the quenching of spectroscopic factors [1]; it is also the key process at the origin of the damping of giant resonances [2]. The vibrational phonons are best known from the spectroscopic studies of doubly-magic nuclei in which they appear, in general, as the lowest excited states. For example, in 208Pb, the lowest excitation (at 2615 keV) is the 3– octupole vibration with a large E3 transition strength of 34 W.u. We investigated the low-spin structures of 210Bi and 206Tl up to their neutroncapture states at 4.6 and 6.5 MeV, respectively, by using 209Bi(n,)210Bi and 205Tl(n,)206Tl reactions induced by cold neutrons at ILL Grenoble. The 210Bi nucleus (one proton and one neutron above the 208Pb core) was populated in the experiment performed at the PF1B and cold-neutron facility in which - coincidences were measured with the EXILL array consisting of 16 Ge detectors. It is the first time when such large array was employed for 209Bi(n,)210Bi reactions studies so the decay scheme could be revised and significantly extended. The analysis of the angular correlations of  rays provided information about transitions multipolarities and helped with the spin-parity assignments. The structure arising from the excitations of valence proton and neutron was compared to the shell-model calculations. Some of the observed states must come from the coupling of the valence particles excitations with the first excited state in 208Pb, that is 3– octupole vibration. The 206Tl nucleus was populated in the first (commissioning) experiment of FIPPS facility at ILL Grenoble. The  rays from the capture state at 6.5 MeV were measured by the array of 8 Ge clovers. We want to present the preliminary results of the -coincidence analysis which will allow to significantly extend the experimental information on the energy levels in 206Tl. The 206Tl nucleus, having just one proton-hole and one neutron-hole with respect to the best known doubly magic core 208Pb, is an ideal system for testing old and developing new shell model interactions in the south-west quadrant of the nuclear chart with respect to 208Pb.

En la segunda mitad del siglo XIX se inició la conformación de un espacio historiográfico en Corrientes impulsado por diversos factores que contribuyeron a su delineación, como el interés del Estado por reafirmar sus derechos sobre los territorios que habían pertenecido a las antiguas misiones y por reivindicar el lugar que sus elites dirigentes consideraban que debían ocupar en el orden institucional creado por la Constitución de 1853. Ambos propósitos implicaban también un creciente interés por reforzar la identidad correntina frente al inicio de un proceso de construcción de una identidad nacional que comenzaba a esbozarse en los años ochenta. En este contexto surgen figuras notables como Ramón Contreras y Manuel Florencio Mantilla, quienes se volcaron a los estudios históricos para satisfacer estas demandas. A partir de sus obras se establecieron vínculos con historiadores e instituciones de Buenos Aires y se desarrollaron debates y polémicas a través de la prensa, que permitieron ir definiendo un espacio historiográfico con sus autoridades y sus reglas de trabajo., In the second half of the nineteenth century began the conformation of a historiographical space in Corrientes driven by several factors that contributed to its delineation, like the interest of the state in reaffirm its rights on the territories that had belonged to the old missions and to vindicate the place that its elite leadership saw should occupy in institutional order created by the Constitution of 1853. Both purposes also involved a growing interest in reinforcing the Correntina identity opposite to a process of building a national identity, which began to emerge in the eighties. In this context arise notable figures such as Ramon Contreras and Manuel Florencio Mantilla, who will be drawn to the historical studies to satisfy these demands. From their works were established links with historians and institutions of Buenos Aires and developed debates and controversies through the press, which made it possible to be defining a historiographical space with its authorities and work rules., Dossier: La historia y la historiografía en América Latina en el siglo XIX. Perspectivas, configuraciones, itinerarios, Instituto de Investigaciones en Humanidades y Ciencias Sociales (IdIHCS)

We examined by Western blots the effect of variations of the heating sessions, such as duration and intensity on the following aspects: 70-kDa heat shock protein (HSP70) and HSP72 induction. Protein ubiquitination PLCγ PKCe and PKCα levels in murine liver and brain were also studied. Results demonstrated that maximal induction of HSP72 was obtained after heat shock at 43.5°C in both organs. Preconditioning at lower temperatures (either acclimation to 39°C or induction of thermotolerance to 43.5°C with a single exposure to 39°C) attenuated the heat shock response. Hepatic HSP72 induction was elicited only as a consequence of hyperthermia since either fasting or restraint were unable to trigger its synthesis. On the contrary, a ubiquitination decrease of a 31 kDa protein was obtained both after hyperthermia and fasting This indicates that the latter is a more generic response of hepatic cells to noxious stimuli. Analysis of the above mentioned enzymes showed that in liver of naive mice PKCα is barely present while PKCe is quite abundant. All hyperthermic treatments caused a general decrease of the latter, except for the heat shock at 43.5°C that caused an increase. PLCγ decreased after all heating sessions. It is known that hyperthermia in the range of 41-45°C induces apoptotic death in many cell types. Therefore we analyzed the presence of the typical apoptotic DNA ladder. Our data strongly suggest that both hyperthermia and restraint induce necrosis in liver while apoptosis and necrosis become evident in brain. All these effects are still present 24 h from the last heating session: This indicates thatin vivo, hyperthermia produces long term modifications of the hepatic cell.

OBJECTIVE To determine the incidence of antimicrobial-resistant, nonpathogenic Escherichia coli among healthy children aged 6-72 months in Camiri town and a rural village, Javillo, in south-eastern Bolivia. METHOD A community-based survey: stool samples were obtained from 296 healthy children selected by modified cluster sampling in Camiri and all 25 eligible children in Javillo. E. coli isolates were tested for antimicrobial susceptibility according to the standard disc diffusion method. By a questionnaire survey of 12 pharmacies and by using simulated patients, we investigated the antimicrobial availability and the usage patterns in Camiri town. RESULTS In Camiri, over 90%, and in Javillo over 70% of children carried E. coli resistant to ampicillin, trimethoprim-sulphamethoxazole (TMP/SMX) or tetracycline. Overall, 63% of children carried E. coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and chloramphenicol. In the simulated patients study, antimicrobials were dispensed inappropriately for 92% of adults and 40% of children with watery diarrhoea, and were under-prescribed for males with urethral discharge (67%) or females with fever and dysuria (58%). The dose and/or duration of antimicrobials dispensed was almost always too low. CONCLUSION Our study showed a disturbingly high prevalence of carriage of nonpathogenic E. coli resistant to antimicrobials. The prevalence of resistance to ampicillin and TMP/SMX was higher than that previously reported in developing countries. The existence of a large reservoir of resistance genes in healthy individuals in developing countries represents a threat to the success of antimicrobial therapy throughout the world. Programmes to improve rational and effective drug use in developing countries are urgently needed.

We investigate the effect of EGF on IP3 production, PLCγ phosphorylation, calcium transients in rat hepatocytes isolated in quiescent liver (G0 phase of cell cycle) and at 4 h (G1 phase of cell cycle) and 24 h (M phase of cell cycle) after partial hepatectomy. Our results show that EGF does not utilize IP3 and calcium as its signal transduction molecules when the hepatocytes are in vivo stimulated to entry in the cell cycle. In particular the growth factor does not phosphorylate PLCγ and induces a decrease in IP3 content. These data suggest that EGF utilizes different signal transduction to send information from receptor to nucleus during PH with respect to the quiescent liver.

International audience; The mixing ratio of the main 320-keV, M1 + E2 ground-state γ transition in 210Bi has been more precisely quantified, allowing a significant reduction in the uncertainty of measurements of the neutron-capture cross section to the ground state of 210Bi from 25% to 0.9%. Accurate values for neutron-capture cross sections to both the ground and long-lived 9− isomeric state at 271 keV in 210Bi are of particular importance as Pb-Bi finds increased usage in Accelerator Driven Systems.

γ spectroscopy of neutron-rich nuclei around 48Ca is performed by the heavy-ion transfer reaction 48Ca on 64Ni at 282 MeV, with the PRISMA-CLARA setup at Legnaro Laboratory. Angular distributions, polarizations and lifetimes analysis probe spin and parities of several excited states, shading lights on their configuration. In the one neutron transfer channels, 49Ca and 47Ca, states arising by coupling a single particle to the 3− phonon of 48Ca are observed, showing the robustness of nuclear collectivity in rather light systems. The work demonstrates the feasibility of complete in-beam γ-spectroscopy with heavy-ion transfer reactions and provides a method that can be further exploited in the future with heavy targets and radioactive beams.

Thyroid hormones (THs) have a wide variety of essential roles in vertebrates, ranging from the regulation of key metabolic processes to cell proliferation and apoptosis. The classical mechanism of action of THs is genomic; 3,5,3'-triiodothyronine (T3) binds to specific nuclear receptors (TRs) and modifies the expression of specific genes. Recently, a new category of mechanisms, termed nongenomic, has been discovered for T3. These mechanisms include, among others, the rapid activation of signal transduction pathways, such as PI3K/Akt and MAPK, which eventually lead to cell proliferation. These effects are mediated in some cell types by a plasma membrane receptor, identified as integrin αvβ3, and in other cell types by cytoplasmic TRβ1. The aim of this work was to analyze the effect of T3 on the cell growth of chick embryo hepatocytes at two different stages of development, 14 and 19 days, and to determine the activation of the signal transduction pathways, focusing on the potential involvement of a plasma membrane receptor and the possible participation of PI3K/Akt and reactive oxygen species (ROS). Our results clearly show that T3 stimulates cell proliferation at both stages of development through the activation of the PI3K/Akt pathway and the production of small amounts of ROS, which operate as effective second messengers. Moreover, we prove that these effects are not initiated at the plasma membrane receptor for T3.

High-fat and high-carbohydrate diets may predispose to simple steatosis, alone or associated with necroinflammation and fibrosis (steatohepatitis). However, there are few reports about the real effect of these nutrients on hepatocyte redox homeostasis and consequent molecular derangement. Here, we investigated whether different diets would induce oxidative damage in primary rat hepatocytes and thereby affect the activity of phosphatase and tensin homolog (PTEN). We used Sprague–Dawley rats fed, for 14 weeks, a standard diet (SD), a high-fat/low-carbohydrate diet (HFD-LC), a normal-fat/high-fructose diet (NFD-HF), or a high-fat/high-fructose diet (HFD-HF). Metabolic and histological parameters were analyzed in blood and liver samples, while oxidative stress markers and related posttranscriptional modification of PTEN were analyzed in isolated hepatocytes. Our results indicate that different dietetic hypercaloric regimens caused liver damage and a significant increase of body and liver weight, as well as elevated plasma levels of alanine aminotransferase, triglycerides and insulin. Hepatocytes from NFD-HF and HFD-HF rats displayed a decrement of cell viability and proliferation rate. Hepatocytes from animals treated with hypercaloric regimens also exhibited oxidative stress greater than SD hepatocytes. Finally, NFD-HF and HFD-HF hepatocytes showed an increased PTEN phosphorylation and decreased PTEN activity, which seem strongly correlated to an increased glutathionylation of the protein. In conclusion, we demonstrate that fructose-enriched diets cause a tissue and hepatocyte damage that might exacerbate those observed in the presence of high-fat alone and might render, via redox homeostasis imbalance, the hepatocytes more prone to posttranslational modifications and activity alteration of PTEN.

Hyperosmotic stress affects cell growth, decreasing cell volume and increasing the uptake of organic osmolytes. However, the sensitivity of embryonic cells to osmotic treatment remains to be established. We have analysed some aspects of cell-cycle control and amino-acid transport in hypertonic conditions during prenatal life. The effects of hyperosmotic stress on amino-acid uptake mediated by system A, (3)H-thymidine incorporation, and regulation of cell-cycle proteins were analysed in chick embryo hepatocytes. Hypertonic stress increased system A activity and caused cell-cycle delay. Effects on amino-acid transport involved p38 kinase activation and new carrier synthesis. Cyclin D1, cdk4 (cyclin-dependent kinase 4) and PCNA (proliferating-cell nuclear antigen) levels decreased, whereas cyclin E, p21 and p53 levels were unchanged. Incorporation of (3)H-leucine indicated decreased synthesis of cyclin D1. In contrast, analysis of mRNA by qRT-PCR (quantitative real-time PCR) showed a net increase of cyclin D1 transcripts, suggesting post-transcriptional regulation. The data show that chick embryo hepatocytes respond to hyperosmotic conditions by arresting cell growth to prevent DNA damage and increasing osmolyte uptake to regulate cell volume, indicating that the adaptive response to environmental stress exists during prenatal life.

[1-14C]-2-aminoisobutyric acid (AIB) uptake and signal transduction pattern after epidermal growth factor (EGF) stimulation were examined in freshly isolated hepatocytes from 20-day-old fetuses and 3-month-old rats. EGF induced a transient increase of AIB transport after 10 min only in adult animals; the observed unresponsiveness of fetal liver is not dependent on a lack of EGF receptors which are present though to a lesser extent on the plasma membrane in this period. As far as the production of the second messengers, inositol trisphosphate (IP3) and calcium, is concerned, substantial differences were found: EGF increased IP3 production in adult hepatocytes, whereas it had no effect in fetal ones. Moreover, the addition of EGF induced a calcium transient in hepatocytes from adult animals, while there was no increase in fetal cells. The lack of EGF effect on amino acid transport in fetal cells could be due to its inability to produce both IP3 and calcium transients, suggesting that this transduction pathway is not activated during fetal life.

Extranuclear or nongenomic effects of thyroid hormones are mediated by receptors located at the plasma membrane or inside cells, and are independent of protein synthesis. Recently the alphaVbeta3 integrin was identified as a cell membrane receptor for thyroid hormones, and a wide variety of nongenomic effects have now been shown to be induced through binding of thyroid hormones to this receptor. However, also other thyroid hormone receptors can produce nongenomic effects, including the cytoplasmic TRalpha and TRbeta receptors and probably also a G protein-coupled membrane receptor, and increasing importance is now given to thyroid hormone metabolites like 3,5-diiodothyronine and reverse T(3) that can mimick some nongenomic effects of T(3) and T(4). Signal transduction from the alphaVbeta3 integrin may proceed through at least three independent pathways (protein kinase C, Src or mitogen-activated kinases) but the details are still unknown. Thyroid hormones induce nongenomic effects on at least three important Na(+)-dependent transport systems, the Na(+)/K(+)-ATPase, the Na(+)/H(+) exchanger, and amino acid transport System A, leading to a mitogenic response in embryo cells; but modulation of the same transport systems may have different roles in other cells and at different developmental stages. It seems that thyroid hormones in many cases can modulate nongenomically the same targets affected by the nuclear receptors through long-term mechanisms. Recent results on nongenomic effects confirm the old theory that the primary role of thyroid hormones is to keep the steady-state level of functioning of the cell, but more and more mechanisms are discovered by which this goal can be achieved.

The relationship between cell proliferation and inositol lipid turnover has been studied by comparing the steady state of inositol derivative metabolism in quiescent and regenerating rat hepatocytes isolated at 4 h (G1 phase of first cell cycle) and 24 h (onset of M phase) after partial hepatectomy. The effect of two hormones able to regulate hepatic regeneration, insulin and vasopressin, has been considered, and the results can be summarized as follows: (i) at 4 h after partial hepatectomy, the precursor incorporation into inositol polyphosphates and the particulate phospholipase C activity increase with respect to quiescent hepatocytes, whereas the content of I1,4,5P3 does not change, suggesting an increased turnover of this molecule in this step of cell cycle priming; (ii) 24 h after partial hepatectomy, the radioactivity linked to IP3 and IP4, as well as soluble and particulate phospholipase C activity, and IP3 content increase, suggesting the presence, at the onset of M phase, of second messenger accumulation; (iii) only 24 h after partial hepatectomy, the inositol derivative metabolism is affected by vasopressin; and (iv) insulin exerts a modulatory role on inositol polyphosphate production without involving membrane-bound PLC activity or phosphoinositide hydrolysis. These data suggest that inositol-derived signal molecules are associated with hepatic regneration; moreover, the metabolic pathway of such compounds seems to be regulated so that only specific inositol phosphates are present in each step of the cell cycle. © 1992 Wiley-Liss, Inc.

Cadmium, a toxic heavy metal, expresses its toxicity by affecting several cellular functions, such as enzyme activities, DNA repair systems, redox state of the cell and signal transduction. Although the liver is a known target organ, the mechanisms involved in cadmium toxicity are not yet clarified, especially during prenatal development. Here we consider the effects of cadmium on viability, proliferation, adhesion and defence mechanisms in primary adult and fetal rat hepatocytes. Fetal hepatocytes are less sensitive to cadmium toxicity, they appear to be unaffected or even stimulated by treatments that strongly inhibit DNA synthesis in adult cells. The behaviour of proteins involved in cell cycle regulation also differs from adult cells, according to the proliferative state. In addition, following Cd exposure, E-cadherin/beta-catenin complex disassembles in both cell types, with fetal cells being influenced at higher doses. The beta-catenin is not found in the nucleus, ruling out a direct role on DNA synthesis stimulation. Finally, metallothionein is more easily inducible in fetal hepatocytes, while Cd intracellular concentrations and HSP protein levels are not differentially affected. In conclusion, multiple cellular targets are affected by Cd in primary hepatocytes and the adverse effects of the metal are always better counteracted by fetal cells.

The circannual behaviour of glycosylation and protein synthesis in frog liver slices was studied following the incorporation of3H-galactose and14C-glucosamine into glycolipids and glycoproteins and3H-leucine into proteins. The activity of two enzymes the galactosyl-transferase and the N-acetyl-glucosaminyl-1-P-transferase was determined. The incorporations of both sugars into the soluble fraction and into the lipid extract present a maximum during the spring-summer period. The incorporation into the protein fraction displays a different pattern:14C-Glucosamine and3H-leucine incorporation increases from winter to a maximum in autumn; the incorporation of3H-Galactose has a sharp peak during spring. The pattern of glycosyltransferase activities is similar to the pattern of incorporation of the two saccharides into proteins, indicating these enzymes as important control points for glycosylation in Anurae.

Fil: Leoni, María Silvia. Universidad Nacional del Nordeste. Facultad de Humanidades; Argentina. La cuestión de la definición regional de lo que hoy se denomina Nordeste argentino ha estado sometida a miradas contrapuestas. En esta oportunidad analizamos las propuestas de un autor cuya obra ha sido central en la historiografía chaqueña y que sólo recientemente ha merecido estudio. Guido Miranda (1912-1994), maestro y periodista incorporado a las filas del socialismo, es autor de una obra considerada un clásico: Tres ciclos chaqueños (Crónica histórica regional) (1955); a través de su producción escrita, buscó desentrañar la identidad regional. Nos proponemos interrogar al ensayo de Miranda más que como clave de interpretación, como fuente compleja de representaciones de la región, partiendo de la hipótesis de que cumple un papel fundamental en su construcción la recepción de la obra de Bernardo Canal Feijóo, con quien Miranda establece un continuo diálogo para su elaboración de una propuesta de historia regional. The issue of the regional definition of what today is named Argentina Northeast has been submitted to opposite looks. In this opportunity we analyze the propositions of an author whose work has been central in Chaco historiography: Guido Miranda (1912-1994). Teacher and journalist incorporated into the rows of the socialism, has recently deserved several studies. He is the author of Tres ciclos chaqueños (Crónica histórica regional) (1955), considered a “classic” in the regional literature, and his whole production has been related to de study of the regional identity. At this time, we propose to interrogate Miranda’s essay as a complex source of representations about the region. Our hypothesis is that the influence of Bernardo Canal Feijóo, through his written production and the continuous dialogues between them, has been a significant influence on the Miranda’s proposition of regional History.

On April 1998 a tailing dam of the Aznalcollar pyrite mine partially collapsed and released to the Guadiamar river acidic water and mud containing toxic metals threatening the Donana National Park, a Spanish wildlife reserve located near the estuary of Guadalquivir river. To assess the possible biological effects on terrestrial ecosystems, biochemical markers were assayed in the kidneys of Algerian mice (Mus spretus) collected in several areas of Donana and Guadiamar river. Biomarkers assayed are proteins involved in cell cycle regulation, in particular cyclins and their associated kinases, and some cell cycle inhibitors. Moreover Mitogen Activated Protein Kinases (MAPK), a signal transduction system involved in cell division, p53, a protein involved in growth arrest after DNA damage, and HSP70, an early stress-induced protein, were assayed. The kidneys of animals collected one year after the ecological disaster had increased levels of PCNA (proliferating cell nuclear antigen), indicating an increased number of cells in the S phase of cell cycle. This shift of cells from G0 to S phase is due to increased levels of cyclins D1, E, and A, to decreased levels of p21 and p27 cdk inhibitors, and to activation of MAPK cascade. On the other hand, p53 and HSP70 levels are not changed. These data demonstrate that the presence of toxic metals after ecological disaster provoked the induction of kidney cell proliferation interpretable as a compensatory cell growth after tissue damage and apoptosis, and that could lead to the genomic instability characteristic of cancer cell. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.

The glycosylation pattern in isolated rat hepatocytes during pre- and post-natal development and senescence has been studied by following: the [14C]glucosamine and [3H]galactose incorporation into cellular glycoproteins and glycolipids and the activity of two microsomal enzymes, N-acetyl-glucosaminyl-1-P transferase and galactosyl transferase. The data show a lowered precursor incorporation into lipids and proteins in the fetus, newborn and old rats versus the adult. Only the galactosyl transferase activity is enhanced on the 19th and 22nd day of fetal life. The glucosamine and N-acetyl-glucosamine content in both soluble and protein bound fractions was increased, while the galactose content in lipids and proteins decreased in the fetal stage. The different sugar composition of the proteins, and the decreased glucosamine and galactose incorporation into the proteins, observed in the fetus, newborn and old rat, suggest a post-translational modification which may cause alterations in functions usually mediated by glycoproteins.

The purpose of this study was to define the distribution of the asialoglycoprotein receptor (ASGP-R) main peptide, rat hepatic lectin (RHL)-1, within the rat liver lobule and to investigate its possible modulation in physiological states characterised by marked changes of receptorial expression. In particular, we chose livers from rats partially hepatectomised or at the end of pregnancy, as models, respectively, of decreased or increased expression of the ASGP-R, and used the in situ hybridisation and immunocytochemistry techniques to analyse in parallel the lobular distributions of RHL-1 mRNA and protein. In normal rat liver, although the RHL-1 mRNA was homogeneously distributed, the RHL-1 peptide was predominantly localised on the surface of pericentral hepatocytes with a gradient of expression towards the periportal zone. This gradient of expression of RHL-1 peptide was reduced in regenerating livers, in which the positive stain was restricted to a few layers of cells around the central vein. In contrast, livers at the end of pregnancy showed an overall increase of the peptide with a concomitant flattening of the gradient across the liver plate. In all the conditions, we never observed important changes in the pattern of expression of the specific mRNA. These findings indicate that the distribution of ASGP-R is heterogeneous across the liver lobule, with a pattern of expression prevalently modulated at the posttranscriptional level.

Extranuclear or nongenomic effects of thyroid hormones do not require interaction with the nuclear receptor, but are probably mediated by specific membrane receptors. This review will focus on the extranuclear effects of thyroid hormones on plasma membrane transport systems in non mammalian cells: chick embryo hepatocytes at two different stages of development, 14 and 19 days. At variance with mammals, the chick embryo develops in a closed compartment, beyond the influence of maternal endocrine factors. Thyroid hormones inhibit the Na+/K+-ATPase but stimulate the Na+/H+ exchanger and amino acid transport System A with different dose-responses: a bell-shaped curve in the case of the exchanger and a classic saturation curve in the case of System A. These effects are mimicked by the analog 3,5-diiodothyronine. Signal transduction is mediated by inter-play among kinases, mainly protein kinase C and the MAPK pathway, initially primed by second messengers such as Ca2+, IP3, and DAG as in mammalian cells. Thyroid hormones and 3,5-diiodothyronine stimulate thymidine incorporation and DNA synthesis, associated with the increased levels and activity of cyclins and cyclin-dependent kinases involved in the G1/S transition, and also these effects have their starting point at the plasma membrane. Increasing evidence now demonstrates that thyroid hormones act as growth factors for chick embryo hepatocytes and their extranuclear effects are important for prenatal development and differentiation. (c) 2005 Elsevier Inc.

In rats, various growth factors and hormones, as well as partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights the important role of thyroid hormones and thyroid status in regulating the growth of liver cells in vitro and in vivo models, the mechanism involved in the pro-proliferative effects of thyroid hormones is still unclear. Here we have investigated how in rats made hypo- and hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) and triiodothyronine (T3), the thyroid status affects liver regeneration after PH by regulating cell cycle and apoptosis proteins. Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27. On the contrary hypothyroidism induces a down-regulation of the activity of cyclin cdk complexes decreasing cyclin levels. Thyroid hormones control also p53 and p73, two proteins involved in apoptosis and growth arrest which are induced by PH. In particular, hypothyroidism increases and T3 treatment decreases p73 levels. The analysis of the phosphorylated forms of p42/44 and p38 MAPK revealed that they are induced during hepatic regeneration in euthyroid and hyperthyroid rats whereas they are negatively regulated in hypothyroid rats. In conclusion our data demonstrate that thyroid status can affects liver regeneration, altering the expression and the activity of the proteins involved in the control of cell cycle and growth arrest.

The molecular mechanism by which thyroid hormones exert their effects on cell growth is still unknown. In this study, we used chick embryo hepatocytes at different stages of development as a model to investigate the effect of the two thyroid hormones, T3 and T4, and of their metabolite T2, on the control of cell proliferation. We observed that T2 provokes increase of DNA-synthesis as well as T3 and T4, independently of developmental stage. We found that this stimulatory effect on the S phase is reverted by specific inhibitors of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (p42/44 MAPK), Ro 31-8220 or PD 98059. Furthermore, the treatment with thyroid hormones induces the activation of PKCalpha and p42/44 MAPK, suggesting their role as possible downstream mediators of cell response mediated by thyroid hormones. The increase of DNA-synthesis is well correlated with the increased levels of cyclin D1 and cdk4 that control the G1 phase, and also with the activities of cell-cycle proteins involved in the G1 to S phase progression, such as cyclin E/A-cdk2 complexes. Interestingly, the activity of cyclin-cdk2 complexes is strongly repressed in the presence of PKC and p42/44 MAPK inhibitors. In conclusion, we demonstrated that the thyroid hormones could modulate different signaling pathways that are able to control cell-cycle progression, mainly during G1/S transition.