The role of the physical structure of Spartina densiflora Brong. in structuring macroinvertebrate assemblages Sueiro, Maria Cruz; Bortolus, Alejandro; Schwindt, Evangelina In Patagonian rocky salt marshes, the presence of the austral cordgrass Spartina densiflora provide habitat for diverse faunal assemblages. Two different mechanisms may influence the distribution and abundance patterns of the associated organisms. Those generated by the biological properties of cordgrasses and those caused or mediated by the physical structure supplied by the plants. The aims of this study were: (1) to determine the effect of cordgrasses on macroinvertebrate assemblages dominating a rocky marsh; and (2) to determine how much of this effect is caused by the physical structure supply by the plants. In order to achieve these objectives we conducted two field manipulative experiments. In the first one we manipulated the presence of defaunated transplants of cordgrass, and in the second one, we did the same with plastic mimics cordgrasses simulating de architecture of Spartina densiflora. In both experiments, sessile and mobile assemblages were separately examined to evaluate whether they respond in the same way or not. Abundance and richness of mobile and sessile organisms were higher in transplant and mimic cordgrass plots compared to controls, indicating that the presence of cordgrasses, either transplanted or artificial, has a positive effect on sessile and mobile assemblages. Furthermore, we found that the composition of mobile and sessile macroinvertebrates assemblages did not differ between transplants and mimics. Therefore, the physical structure of cordgrass was found to be the major factor influencing macroinvertebrates assemblages in the studied Patagonia rocky salt marshes. Within the period of one year, mobile and sessile fauna colonized several times more abundantly transplant and artificial cordgrass than the control plots, highlighting the key role of cordgrasses in optimizing the colonization rate of macroinvertebrate communities in this rocky bottom environment. Since Spartina densiflora is invading different regions worldwide, our study may help to predict its potential effect on the invaded communities.

Biosorption of Trivalent Chromium from Aqueous Solution by Red Seaweed Polysiphonia nigrescens Blanes, Patricia Silvia; Sala, Luis Federico; García, Silvia I.; González, Juan Carlos; Fracaroli, María I.; Harada, Masafumi; Cong, Cong; Niwa, Yasuhiro; Matulewicz, Maria Cristina; Prado, Héctor Juan; Cortadi, Adriana Amalia; Gattuso, Martha This paper presents the biosorption of chromium onto red seaweed (Polysiphonia nigrescens). Batch mode experiments were performed to determine experimental parameters affecting sorption process such as pH, contact time, initial metal ion concentration and biomass dosage. The Cr(III) sorption was dependent on pH and adsorbent dosage. The adsorption kinetic data could be fitted with a pseudo-second-order model and the equilibrium data with a Langmuir model. The maximum sorption capacity was of 16.11 mg/g at pH 4 and 10 g/L of biomass dosage. 0.1 M H2SO4 showed good desorption efficiency (>80%). Spectroscopy analysis showed that Cr(III) sorption on seaweed was mainly through the ion-exchange mechanism. This report indicates that P. nigrescens is an effective and economical sorbent for removal of Cr(III) from wastewaters.

Phase solubility studies and stability of cholesterol/β-cyclodextrin inclusion complexes dos Santos, Cristina; Buera, Maria del Pilar; Mazzobre, Maria Florencia Background: Cyclodextrins (CDs) are able to enhance the solubility, stability and bioavailability of several bioactive hydrophobic compounds by complex formation. They can also be used for removal of undesired components (such as cholesterol, off-flavors or bitter components) present in foods. Although many patents account for the use of cyclodextrins for removal of cholesterol from dairy foods, there is no available information on the effect of water on encapsulation efficiency and on the stability of sterols in CDs. The aim of this work was to study the inclusion properties and the factors affecting the encapsulation and stability of cholesterol in β-cyclodextrin (BCD). The optimum encapsulation conditions (ligand-CD molar ratio, stirring time and temperature), and stability of the complexes as a function of storage time and water content were analyzed. Results: Phase solubility study pointed out the formation of 1:1 stoichiometric complexes between cholesterol and β-cyclodextrin, which was influenced by temperature variations. The process was shown to be exothermic and energetically favored. The presence of cholesterol greatly modified the BCD water sorption curves, being the amount of adsorbed water smaller in the combined systems. The principal 'driving force' for complex formation is the substitution of the high-enthalpy water molecules by an appropriate hydrophobic ligand. The freeze-dried complexes probed to be stable at different storage conditions. Conclusion: The phase solubility and stability data obtained could be essential for selecting the most suitable conditions when CDs are employed either for removing cholesterol or to incorporate functional ingredients (i.e. sitosterol) in the development of innovative food products.

Association of common variants in JAK2 gene with reduced risk of Metabolic Syndrome and related disorders Penas Steinhardt, Alberto; Tellechea, Mariana Lorena; Gomez Rosso, Leonardo Adrián; Brites, Fernando Daniel; Frechtel, Gustavo Daniel; Poskus, Edgardo Background: Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. We conducted a population cross-sectional study to explore the association between two common variants in JAK2 gene and MS related traits in 724 Argentinean healthy male subjects. Methods A total of 724 unrelated men aged 37.11 ± 10.91 yr were included in a cross-sectional study. Physical examination, anthropometric measurements and biochemical analysis were determined by a standardized protocol. rs7849191 and rs3780378 were genotyped. Analyses were done separately for each SNP and followed up by haplotype analysis. Results rs7849191 and rs3780378 were both associated with reduced risk of MS [p = 0.005; OR (95%CI) = 0.52 (0.33-0.80) and p = 0.006; OR (95% CI) = 0.59 (0.40-0.86) respectively, assuming a dominant model]. rs3780378 T allele was associated with triglyceridemia values under 150 mg/dl [p = 0.007; OR (95%CI) = 0.610 (0.429-0.868)] and TT carriers showed lower triglycerides (p = 0.017), triglycerides/HDL-C ratio (p = 0.022) and lipid accumulation product (p = 0.007) compared to allele C carriers. The two-SNPs-haplotype analysis was consistent with single locus analysis. Conclusions It was found for the first time, significant associations of JAK2 common variants and related haplotypes with reduced risk of MS. These findings could be explained by the role of JAK2 in insulin and/or leptin signaling.

Callochiton monteleonensis n. sp., First record of polyplacophora (Mollusca) from the Neogene of Argentina Urteaga, Diego Gaston; Griffin, Miguel; Pastorino, Roberto Santiago Guido A new species of chiton is described from early Miocene deposits of the Monte Len Formation, in Santa Cruz Province, Argentina. Callochiton monteleonensis n. sp. clearly differs from known fossil and Recent species of the southwestern Atlantic because the central area of its intermediate valves has a stepped appearance, in which each step is marked by a longitudinal rib. It is similar to Callochiton kapitiensis Mestayer, 1926, a Recent species from New Zealand. Biogeographic implications are discussed. This is the first record of a polyplacophoran from Neogene deposits of Argentina.

Lo agonal y lo irenéico en la filosofía Blanco Ilari, Juan Ignacio La esencia de lo que debemos entender por filosofía se encuentra más del lado del quehacer, de la tarea, que del lado de “lo hecho”. Entre el sustantivo (filosofía) y el verbo (filosofar) hay una estrecha relación. Este trabajo se aboca, primeramente, a lo que está antes del quehacer, que se encuentra en la experiencia de ruptura. Luego se propone articular las dos grandes actitudes originarias que se abren a partir de ese momento, una más combativa (lo agonal) y la otra más pacifista (lo ireneico).; A essência do que devemos entender por filosofía é mais próxima à tarefa que ao “jáfeito”. O substantivo (filosofía) e o verbo (filosofar) estão íntimamente relacionados. Este trabalho é abocado, en primeiro lugar, para o que está diante da tarefa, que acontece na experiência de ruptura. Depóis, ele se propõe articular as duas grandes actitudes originárias que se oferecem depóis desse momento, uma mais combativa (o agonal) e a outra mais pacifista (o irênico).

Coping between crises: Early Triassic-early Jurassic bivalve diversity dynamics Ros, Sonia; De Renzi, Miquel; Damborenea, Susana Ester; Márquez Aliaga, Ana The Triassic is bounded by two of the most severe biotic crises, but nevertheless this time was, for bivalves, both a recovery and a diversification period, and a moment to fully exploit some of their evolutionary novelties. Just how and when this was achieved is analyzed in this paper, which covers Induan to Sinemurian bivalve diversity, based on a newly compiled database. Taxonomic diversity and ecospace dynamics are examined separately. Diversity and evolutionary rates were assessed, extinction selectivity was tested using a resampling algorithm, and cohort analysis was used to study extinction patterns. During the Early Triassic most bivalve genera were survivors from the Permian and they were mainly cosmopolitan epifaunal and semi-infaunal endobyssate taxa. Reclined, epifaunal and semi-infaunal bivalves increased in diversity during the Triassic, but from Norian on, their diversity declined, and they were strongly affected by the T/J crisis. Although the Triassic/Jurassic extinction strongly impacted bivalve taxonomic diversity, it had little impact on bivalve ecologic diversity. Not a single bivalve life strategy was eliminated at the end of the Triassic. The present study does not support previous conclusions that infaunal bivalves suffered greater extinction than epifaunal ones during the T/J extinction. Not all life strategies were equally affected by the extinction event, being the deep infaunal burrowers positively selected. Bivalves with major energetic requirements seem to have been more affected with negative selectivity on fast shallow burrowers. The ecologic diversity changes of bivalves during the Late Triassic and several adaptations of durophagous predators reflect the effects of increasing predation pressure and support a Late Triassic origin of the Mesozoic Marine Revolution.

Auxotrophic mutant of Staphylococcus aureus interferes with nasal colonization by the wild type Barbagelata, María Sol; Álvarez, Lucía; Gordiola, Mariana Laura; Tuchscherr, Lorena Paola Nelly; von Eiff, Cristoff; Becker, Karsten; Sordelli, Daniel Oscar; Buzzola, Fernanda Roxana Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital setting. Bacterial interference was used as an alternative strategy for the prevention of upper respiratory, urogenital and gastrointestinal tract infections. This study was designed to assess if the administration of a live-attenuated aroA mutant of S. aureus is useful as a potential approach to prevent transient staphylococcal nasal carriage by virulent strains. We constructed an aroA mutant of S. aureus Newman strain by homologous recombination. The auxotrophic NK41 mutant was attenuated as determined by the increase of the LD50 after intraperitoneal challenge. In mice, previous nasal colonization with the NK41 mutant significantly reduced the number of CFU of S. aureus (HU-71 and Hde288) clinical isolates and the parental Newman strain. The NK41 mutant was unable to induce a pro-inflammatory response and to damage the invaded human respiratory epithelial cells. Moreover, the cells previously or simultaneously infected with the NK41 mutant were invaded by virulent strains in a significantly lower degree than those of the control group. In conclusion, the attenuated NK41 mutant interfered with the colonization and establishment of pathogenic strains of S. aureus, which produce severe infections. © 2011 Institut Pasteur.

Repensando la arqueología de Santiago del Estero: Construcción y análisis de una problemática Taboada, Constanza Este trabajo repiensa algunos aspectos de la arqueología santiagueña y plantea una definición problemática para el estudio de los procesos prehispánicos ocurridos en el territorio. Para ello analiza e interrelaciona dos aspectos: las circunstancias históricas que han dado lugar a la percepción, gestión e investigación de una "arqueología santiagueña", y los avances en la generación y análisis de datos y planteo de hipótesis sobre la región realizados por el proyecto de investigación. Sobre la base de ello y de ejemplos de análisis, plantea una lectura global y de síntesis de algunas de sus problemáticas.; This article rethinks some aspects of Santiagueña archaeology and proposes a critical definition for the study of prehispanic processes that occured in the region. In this aim two interrelatedthemes will be analysed: the historical circumstances that have given place to the perception,practice and investigation of a “Santiagueña archaeology”, and the results of the uncoveringand analysis of data concommitant with the hypothesis concerning the region proposed by our investigation project. Working on this basis and on examples from these analysis, we present a global revision and synthesis of some of the Santiagueña’s archaeologcial polemics.

Nutritional status and dietary habits of the population of the Calchaqui Valleys of Tucumán, Argentina Bassett, Maria Natalia; Romaguera, Dora; Samman, Norma Cristina Objective: To assess the nutritional status and dietary habits of the adult population of the Calchaqui Valleys of Tucuman. Methods: A cross-sectional nutritional survey that included one 24-h recall, a semiquantitative food-frequency questionnaire, and anthropometric measurements was conducted in a representative sample of 113 adult participants. Pregnant and lactating women were excluded. Overweight and obesity were assessed according to body mass index, and the percentage of individuals with cardiovascular risk according to waist circumference and waist-to-hip circumference ratio was determined. Dietary habits were described according to the mean nutrient and food intakes of men and women. Results: Means ± standard deviations for total energy intake of men and women were 1856 ± 859 and 1589 ± 799 kcal/d, respectively. The average body mass indices of men and women were 26.8 and 26.7 kg/m 2, respectively. Thirty-seven percent of the population was overweight and 22.8% was obese, whereas 1.8% of the population was undernourished. Central adiposity was high (mean waist circumferences 99.8 and 87.3 cm in men and women, respectively). Conclusions: Despite the low average energy intake, the population under study showed a high prevalence of overweight and obesity and a high risk of cardiovascular disease according to the central adiposity values. These findings could be explained by the introduction of new high-energy foods and a sedentary lifestyle or the possibility that the biological characteristics of these individuals make them more predisposed to a rapid increase in adiposity.

Characterization of natural zeolite membranes for H2/CO2 separations by single gas permeation Hosseinzadeh Hejazi, S.A.; Avila, Adolfo María; Kuznicki, T.M.; Weizhu, A.; Kuznicki, S.M. Natural zeolite membranes can be used as a model for the development of robust molecular sieve membranes with superior separation characteristics. We describe the characterization of natural clinoptilolite membranes made from dense mineral deposits by single gas H2 and CO2 permeation. Permeability values as a function of temperature and pressure were analyzed on the basis of mass transport fundamentals of gas permeation through zeolite and nonzeolite pathways. H2 and CO2 fluxes through the membranes were fitted with a model based on a combination of zeolitic, Knudsen, and viscous transports so that the selective and nonselective flux fractions could be quantified. An increase in feed pressure increased the total permeance especially at low temperatures. The membranes were also characterized by XRD, SEM, and EDX analysis.

Sub-THz and Hα activity during the preflare and main phases of a Goes class M2 event Kaufmann, Pierre; Marcon, Rogério; Castro, C. Guillermo Giménez de; White, Stephen M.; Raulin, Jean Pierre; Correia, Emilia; Fernandes, Luis Olavo; Souza, Rodney V. de; Godoy, Rodolfo Alfredo; Marun, Adolfo Hector; Pereyra, Pablo Florencio Radio and optical observations of the evolution of flare-associated phenomena have shown an initial and rapid burst at 0.4 THz only followed subsequently by a localized chromospheric heating producing an Hα brightening with later heating of the whole active region. A major instability occurred several minutes later producing one impulsive burst at microwaves only, associated with an M2.0 GOES X-ray flare that exhibited the main Hα brightening at the same site as the first flash.The possible association between long-enduring time profiles at soft X-rays, microwaves, Hα, and sub-THz wavelengths is discussed. In the decay phase, the Hα movie shows a disrupting magnetic arch structure ejecting dark, presumably chromospheric, material upward. The time sequence of events suggests genuine interdependent and possibly non-thermal instabilities triggering phenomena, with concurrent active region plasma heating and material ejection.

Similarity in parasite community structure may be used to trace latitudinal migrations of Odontesthes smitti along Argentinean coasts Carballo, María Cecilia; Cremonte, Florencia; Navone, Graciela Teresa; Timi, Juan Tomas The aims of this study were to determine the existence of migratory movements and to identify ecological stocks of the silverside Odontesthes smitti along its distribution in the Southern Atlantic Ocean, using metazoan parasites as biological tags. Samples were obtained from San José Gulf (SJ) (42° 25′ S; 64° 07′ W) and Nuevo Gulf (NG) (42° 47′ S; 65° 02′ W) in north Patagonia during winter and summer and in waters of Mar del Plata (MDP) (38° 03′ S; 57° 32′ W), Bonaerense region, during winter. Fifteen parasite species were collected. Multivariate statistical procedures on parasite community data showed strong effect of host size on the structure of parasite assemblages. Taking into account the variations among samples due to host size, the differential structure of parasite communities between SJ and NG suggests that fish inhabiting these localities could belong to different ecological stocks. Fish from MDP and SJ caught in summer showed similar composition in their parasite assemblages, which is congruent with a migratory cycle that implies that fish caught in MDP during winter inhabit SJ during summer. Further evidence of the Patagonian origin of MDP O. smitti is the presence of the digenean Proctotrema bartolii in fish from both regions. Proctotrema bartolii is acquired by O. smitti only in the Magellanic province, where its intermediate host, Darina solenoides, is distributed. The analyses suggest that O. smitti inhabiting north Patagonian gulfs could belong to different ecological stocks and that O. smitti caught in MDP could have come from SJ.

In vivo effect of three fractions of Larrea divaricata Cav. (jarilla) on the innate immune system: macrophage response against Candida albicans Martino, Renzo Fabricio; Davicino, Roberto Carlos; Mattar, María Aída; Casali, Yolanda A.; Correa, Silvia Graciela; Micalizzi, Blas Larrea divaricata Cav. (jarilla) is a plant with well-documented applications in folk medicine in Argentina. In this study, we aimed to evaluate functional parameters of peritoneal macrophages isolated from mice injected with three fractions (F1, F2 and F3) of L. divaricata. The response of macrophages against Candida albicans was evaluated. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, apoptosis was evaluated using Giemsa, acridine orange/ethidium bromide and ladder assay, oxidative burst was assayed using nitroblue tetrazolium test and nitrite production using Griess assay. Cell stimulation and their ability to kill C. albicans in vitro were measured. The number and cell viability were similar to controls. However, we found that F1 induces pre-activation of macrophages, and this pre-activation is enhanced by C. albicans. The effects exerted by F1 make it more important than F2 and F3 for the treatment of disseminated candidiasis in patients with immunodeficiency diseases such as AIDS and chronic granulomatous disease, among others.

"Me fui detrás de los obreros cantando": poesía, historia y revolución en Todos bailan de Raúl González Tuñón; "I went behind the workers singing": poetry, history and revolution in Todos bailan by Raúl González Tuñón Alle, María Fernanda En 1935 Raúl González Tuñón publica Todos bailan, un poemario a partir del cual se puede leer un cambio en la imagen de escritor que el autor construye en sus textos. Si bien muchos de los aspectos de esta imagen ya estaban contenidos en sus libros de la década anterior, su afiliación al Partido Comunista en 1934 y el rol de intelectual que asume, interviniendo desde diversos periódicos y revistas en los acontecimientos políticos de su tiempo, involucran un nuevo modo de pensar la poesía en relación con los imperativos revolucionarios y una imagen de escritor ligada a una moral de la escritura.; In 1935, Raúl González Tuñón published Todos bailan, a collection of poems that accounts for a new writer's image, which the author built up in his texts. Although many aspects of such an image were already present in his previous books, his affiliation to the Communist Party in 1934 and the role of intellectual he assumed when expressing his opinion about current political affairs in diverse newspapers and magazines, expose a new thinking of poetry in accordance with revolutionary essentials and a new writer's image related to a moral conception of writing.

1,n-Diamines. Part 4: synthesis of 1-aryl-2-alkyl-1,4,5,6,7,8-hexahydro-1,3-diazocines Díaz, Jimena Estela; Gruber, Nadia; Orelli, Liliana Raquel In this Letter we present the synthesis of hitherto unreported 1-aryl-2-alkyl-1,4,5,6,7,8-hexahydro-1,3-diazocines 1. Cyclic amidines 1 were synthesized by PPSE promoted ring closure of N-acyl-N0-arylpentamethylenediamines 2. The cyclodehydration reaction was performed under microwave irradiation in solvent-free conditions. Precursors 2 were prepared by selective functionalization of N-arylcadaverines 3.

An Antibody-based Multifaceted Approach Targeting the Human Transferrin Receptor for the Treatment of B-cell Malignancies Daniels, Tracy R.; Ortiz Sanchez, Elizabeth; Luria Pérez, Rosendo; Quintero, Rafaela; Helguera, Gustavo Fernando; Bonavida, Benjamin; Martinez Maza, Otoniel; Penichet, Manuel L. We previously developed an antibody-avidin fusion protein (ch128.1Av) targeting the human transferrin receptor 1 (TfR1, also known as CD71), which demonstrates direct in vitro cytotoxicity against malignant hematopoietic cells. This cytotoxicity is attributed to its ability to decrease the level of TfR1 leading to lethal iron deprivation. We now report that ch128.1Av shows the ability to bind the Fc γ receptors and the complement component C1q, suggesting that it is capable of eliciting Fcmediated effector functions such as antibody-dependent cellmediated cytotoxicity and complement-mediated cytotoxicity. In addition, in 2 disseminated multiple myeloma xenograft mouse models, we show that a single dose of ch128.1Av results in significant antitumor activity, including long-term survival. It is interesting to note that the parental antibody without avidin (ch128.1) also shows remarkable in vivo anticancer activity despite its limited in vitro cytotoxicity. Finally, we demonstrate that ch128.1Av is not toxic to pluripotent hematopoietic progenitor cells using the long-term cell-initiating culture assay suggesting that these important progenitors would be preserved in different therapeutic approaches, including the in vitro purging of cancer cells for autologous transplantation and in vivo passive immunotherapy. Our results suggest that ch128.1Av and ch128.1 may be effective in the therapy of human multiple myeloma and potentially other hematopoietic malignancies.

Aumento de los depósitos de hierro y su relación con la enfermedad cardiovascular; Increased iron store and its relationship with cardiovascular disease Meroño, Tomás; Sorroche, Patricia; Brites, Fernando Daniel En los últimos años, se ha avanzado considerablemente en el control de varios de los denominados factores de riesgo aterogénico tradicionales, a pesar de lo cual la incidencia de la enfermedad cardiovascular (ECV) continúa siendo elevada. Entre las diversas condiciones asociadas a ECV, podría ubicarse también a la sobrecarga de hierro. Su estudio ha cobrado relevancia desde que se planteó la ?hipótesis del hierro?, la cual postula que bajos niveles de hierro ejercerían un efecto protector del sistema cardiovascular. No obstante, hasta el presente, los resultados de los estudios diseñados para probar esta hipótesis han sido controversiales. Por otro lado, se lograron numerosos avances en el conocimiento del metabolismo del hierro a partir del descubrimiento de la hormona reguladora hepcidina. Los estudios sobre las funciones fisiológicas de esta hormona permitieron elaborar nuevas hipótesis que explican los resultados de los estudios clínicos anteriormente concebidos como contradictorios. El objetivo de la presente actualización es exponer, a razón de los últimos avances sobre la regulación del metabolismo del hierro y su vinculación con la inflamación, el estado actual del conocimiento sobre el posible rol del exceso de hierro como factor de riesgo de ECV.; In the last years, great advance has been achieved in the control of several of the classic atherogenic risk factors; nonetheless, the incidence of cardiovascular disease (CVD) still remains high. Among the disorders which are associated with CVD, increased iron stores have been described as one of them. Its study gained relevance since the “iron hypothesis”, which postulates that low iron levels exert a protective effect on cardiovascular system, was elaborated. In spite of the numerous studies carried out to test this hypothesis, the results have been controversial. On the other hand, much knowledge regarding iron metabolism has been gained since the description of the regulatory hormone, hepcidin. The studies on hepcidin physiologic functions allowed the elaboration of new hypothesis that could explain the results formerly conceived as inconsistent. The aim of the present review is to describe, in light of the newest advances in iron metabolism regulation and its association with inflammation, the current state of knowledge regarding the possible role of iron overload as a risk factor of CVD.

Lethal iron deprivation induced by non-neutralizing antibodies targeting transferrin receptor 1 in malignant B cells Rodríguez, José A.; Luria Pérez, Rosendo; López Valdés, Héctor E.; Casero, David; Daniels, Tracy R.; Patel, Shabnum; Avila, David; Leuchter, Richard; So, Sokuntheavy; Ortiz Sánchez, Elizabeth; Bonavida, Benjamin; Martínez Maza, Otoniel; Charles, Andrew C.; Pellegrini, Matteo; Helguera, Gustavo Fernando; Penichet, Manuel L. A number of antibodies have been developed that induce lethal iron deprivation (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing transferrin (Tf) binding, blocking internalization of the receptor and/or inducing its degradation. We have developed recombinant antibodies targeting human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are cytotoxic to certain malignant B-cells. We now show that internalization of TfR1 bound to these antibodies can lead to its sequestration and degradation, as well as reduced Tf uptake, and the induction of a transcriptional response consistent with iron deprivation, which is mediated in part by downstream targets of p53. Cells resistant to these antibodies do not sequester and degrade TfR1 after internalization of the antibody/receptor complex, and accordingly maintain their ability to internalize Tf. These findings are expected to facilitate the rational design and clinical use of therapeutic agents targeting iron import via TfR1 in hematopoietic malignancies.

Evaluation of the acute dermal exposure of the ethanolic and hexanic extracts from leaves of Schinus molle var. areira L. in rats Bras, Cristina Liliana; Gumilar, Fernanda Andrea; Gandini, Norberto Ariel; Minetti, Silvia Alejandra; Ferrero, Adriana Alicia Ethnopharmacological relevance: Schinus molle var. areira L. (Anacardiaceae) is employed in herbal medicine for many conditions, including respiratory, urinary and menstrual disorders, and as a digestive stimulant, diuretic, astringent and antidepressant. It is also known for its topical use as wound healer, antiseptic, for skin disorders and as repellent and insecticide. In the present work, the acute dermal exposure to ethanolic and hexanic extracts from leaves of Schinus molle var. areira was studied in rats. Materials and methods: A single dose of 2000 mg/kg of body weight of ethanolic and hexanic extracts from leaves was applied on the shaved skin of male and female rats. After 24 h of exposure, the patch was removed and any sign of irritation was recorded. Behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed after the exposure to the extracts. Then, after 14 days of observation, animals were retested. Finally, histopathological studies were conducted on several organs. Results: Slight signs of erythema and edema were observed in the skin site of exposure, but they disappeared after 48 h. The exposure to the hexanic extract produced an increase in parameters of activity, rearing and arousal assessed in the functional observational battery, which reversed after 14 days. On the other hand, the ethanolic extract caused an increase in locomotor activity, reflected in a higher number of rearings performed in the open field in the evaluation carried out on Day 14. No histopathological alterations were detected in the analyzed organs. Conclusions: The results show that the acute dermal exposure of the ethanolic and hexanic extracts from leaves of Schinus molle var. areira only causes a slight and reversible skin irritation, and a mild stimulatory effect in rats. All these indicate that the topical use of these extracts would be safe.