Estudios sefardíes dedicados a la memoria de Iacob M. Hassán (ź"l)

Elena Romero y Aitor García Moreno son los editores de este volumen.[EN] This work aims to honour Iacob. M. Hassán, who set up, promoted, and for decades maintained, the CSIC's School of Sephardic studies (Escuela de Estudios Sefardíes) in Madrid. It comprises a collection of articles on the Jews in the medieval Spanish kingdoms, along with other articles on a wide variety of language issues, and the study and publication of literary works produced or handed down by the Sephardim of the Balkans and Morocco between the sixteenth and the twentieth centuries, such as biblical commentaries and lexicons, liturgical poetry, rabbinic literature, biographies, folk tales, popular folk songs, ballads, and modern songs ... These studies also include an article by Iacob. M. Hassán published here for the first time in the form of a facsimile of his original typed manuscript. The work is preceded by a foreword and an unpublished text of one of his lectures, which contains a wealth of autobiographical information, as well as his views on the vicissitudes of Sephardic Studies as an academic discipline.[ES] Con esta obra se quiere honrar al creador, impulsor y mantenedor durante decenios de la llamada Escuela de Estudios Sefardíes del CSIC (Madrid). Se recogen en ella artículos relativos a los judíos en los reinos hispanos medievales, y otros dedicados a muy variados temas de lengua, y al estudio y edición de obras literarias producidas o transmitidas por los sefardíes de los Balcanes y de Marruecos entre el siglo XVI y el XX: comentarios y léxicos bíblicos, poesía litúrgica, literatura rabínica, biografías, cuentos tradicionales, coplas, romances, cancionero moderno, etc., etc. Entre los estudios se incluye además, como primicia, un artículo mecanografiado de Iacob. M. Hassán que se publica por primera vez en edición facsímil. La obra va precedida de un Prólogo y del texto inédito de una de sus conferencias, en la que aporta numerosos datos autobiográficos, así como su visión sobre los avatares de los Estudios Sefardíes como disciplina académica

Glutathione S-transferase P1 mRNA expression in plasma cell disorders and its correlation with polymorphic variants and clinical outcome

BACKGROUND: Glutathione S-transferase P1 (GSTP1) is an important phase II enzyme involved in detoxification of carcinogens. GSTP1 gene overexpression has been observed in a variety of human cancers but there are no studies in plasma cell disorders. The aim of this study was to examine GSTP1 mRNA expression level in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). In addition, we have determined GSTP1 polymorphic variants in order to estimate MM risk and their relationship with the expression level. Results were also correlated with laboratory parameters and clinical outcome. METHODS: Bone marrow mononuclear cells from 125 patients with plasma cell disorders were studied. Peripheral blood samples of 110 age and sex matched healthy controls were also evaluated. Real-Time Quantitative RT-PCR and PCR-RFLP assays were used. RESULTS: Upregulation of GSTP1 was observed in 37.7% MM and in 22.6% MGUS patients. A significant increase of GSTP1 expression in MM with respect to MGUS was detected (p=0.0427). Most MM patients that achieved complete remission had low transcription levels (77.8%) compared to those who did not reach this condition (44.4%) (p=0.0347). GSTP1 heterozygous carriers showed reduced expression compared to those with homozygous wild type genotype (p=0.0135). CONCLUSION: Our findings suggest, for the first time, a role for GSTP1 expression in development and/or progression of plasma cell disorders, and a probable influence of functional capacity of the enzyme on clinical outcome. These results and those of the literature support GSTP1 as an interesting tumor marker and a potential therapeutic target.Fil: Stella, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fantl, Dorotea Beatriz. Hospital Italiano; ArgentinaFil: Schutz, Natalia. Hospital Italiano; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Glutathione S-transferase gene polymorphisms in celiac disease and their correlation with genomic instability phenotype

Background and objective: Genomic instability and reduced glutathione S-transferase (GST) activity have been identified as potential risk factors for malignant complications in celiac disease (CD). In this study, we assessed the possible influence of GST polymorphisms on genome instability phenotypes in a genetically characterised group of celiac patients from previous studies. Methods: The deletion polymorphisms in GSTM1 and GSTT1 genes and the single-nucleotide polymorphism GSTP1 c.313A>G were genotyped using PCR in a set of 20 untreated adult patients with a known genomic instability phenotype and 69 age- and sex-matched healthy individuals. Results: The frequencies of variant genotypes in patients were GSTM1-null (30%), GSTT1-null (5%), GSTP1-AG (60%) and GSTP1-GG (15%), and they showed no differences from controls. No significant differences were found in the genotype distribution based on telomere length. Cases with GSTM1-null genotype (83%) and microsatellite stability were more frequent than those with genomic instability. Moreover, carriers of GSTP1-variant genotype (73%) and stable phenotype were significantly increased compared to unstable patients (27%) (P=0.031). No differences were found according to the clinical-pathological characteristics of celiac cases. Conclusions: No association between GST polymorphic variants and celiac-associated genomic instability was proven in our cohort. Future studies should explore the usefulness of other biomarkers to distinguish celiac patients who are susceptible to cancer development.Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Crivelli, Adriana. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: La Motta, Graciela. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

GSTM1 and GSTP1, but not GSTT1 genetic polymorphisms are associated with chronic myeloid leukemia risk and treatment response

Background: Chronic myeloid leukemia (CML) is associated to the BCR-ABL1 oncogene and can successfully be treated with tyrosine kinase inhibitors (TKIs). However, it remains still under investigation which molecular factors may influence CML risk or varying responses to TKIs. The aim of this study was to assess the role of Glutathione-S- transferases (GSTs) genetic polymorphisms in CML susceptibility and TKI clinical outcome.Materials: Deletion polymorphisms in GSTM1 and GSTT1 genes and the single nucleotide polymorphism in GSTP1 c.319A>G (rs1695; p.105Ile>Val) were genotyped by PCR methods in 141 CML treated patients and 141 sex- and age-matched healthy individualsResults: Individual analysis of each GST gene showed no association with CML risk. A trend toward significance (p=0.07) for a recessive model was found for GSTP1 (OR: 2.04; IC: 0.94-4.4). However, the combined analysis showed that GSTM1-null/GSTP1- GG as well as GSTT1-null/GSTP1- GG were associated with CML development (p= 0.03; OR: 3.54 IC: 1.2-14.57; p= 0.05; OR: 12.65; IC: 1.17-21.5). The relationship with treatment outcome showed that the presence of GSTM1 gene was significantly linked with an inferior rate of major molecular response (p=0.048) and poor event free-survival (EFS)(p=0.02).Furthermore, a group of patients with GSTP1-GG genotype were significantly associated with reduced EFS comparing to those carrying other GSTP1 genotypes (p=0.049). GSTP1-GG genotypes had short time to treatment failure in a group of patients unresponsive to TKIs comparing to other GSTP1 genotypes (p=0.03).Conclusions: This study highlights the significance of GSTs polymorphisms on CML susceptibility and response to TKIs in the Argentinean population.Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Bengio, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Giere, Isabel. Fundaleu; ArgentinaFil: Pavlovsky, Carolina. Fundaleu; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome

BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G > C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G > C polymorphism may be involved in CML development considering a recessive model (p = 0.01; OR: 0.19; CI: 0.06–0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50 years (p = 0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p = 0.04) and shorter event free survival (p = 0.04). Moreover, a trend toward significance was found for failure free survival (p = 0.06) and time to imatinib failure (p = 0.08). In conclusion, our data suggest that a; TP53 c.213 G > C may be a potential biomarker of CML susceptibility and clinical outcome.Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Moiraghi, Elena Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Giere, Isabel. Fundaleu; ArgentinaFil: Pavlovsky, Carolina. Fundaleu; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

A FLI1-KLF6 Axis Regulates Aging in Human Hematopoietic Stem and Progenitor Cells and Normalization of KLF6 Levels in Aged Cells Leads to Their Rejuvenation

Abstract Aging causes a gradual decline in hematopoietic stem cell (HSC) function, which increases the risk for hematological malignancies. While much has been done in murine models, human HSC aging impairment is less understood. We recently showed that Krüppel-like transcription factor 6 (KLF6) is among the top downregulated genes during human HSC aging, which correlates with H3K27ac loss at several upstream putative enhancers. Moreover, loss of KLF6 in human CD34 + cells resulted in impaired in vitro differentiation, increased colony-forming potential and a transcriptional profile similar to that of aged CD34 + CD38 - cells. We hypothesized that age-acquired deregulation of KLF6 may be a key player in age-related HSC dysfunction and sought to fully characterize this. Thus, we isolated CD34 + cells from young (65 y.o.) healthy donors and performed CRISPR-Cas9 genome editing and transcriptional activation of KLF6, respectively, followed by epigenetic and transcriptional reprogramming, in vivo hematopoietic reconstitution, and analysis of DNA damage, apoptosis, and reactive oxygen species (ROS) levels. KLF6 knock-out (KO) and non-targeting control (NTC) cells from young healthy donors were engrafted into immunodeficient NSGS mice. Hematopoietic reconstitution analysis showed that KLF6 KO cells led to increased myeloid and reduced lymphoid reconstitution in peripheral blood (PB; p<1.62 -7) and an increase in immunophenotypically defined HSC and CD34 + CD38 - progenitor fractions in the bone marrow (BM; p=0.02, and p=0.04, respectively). H3K27ac analysis of KLF6 KO cells revealed a loss of 3,390 ChIP-seq peaks (FDR < 0.05) and 285 peaks gained. Functional annotation using ChIP-Enrich showed that H3K27ac loss associates with myeloid homeostasis, erythroid differentiation and oxidative stress (FDR < 0.05). Three putative enhancer (E) regions upstream of the KLF6 locus showed loss of H3K27ac with aging. Depletion of the E1 but not E2 or E3 regions phenocopied in vitro and in vivo findings of KLF6 KO. Transcription factor (TF) ChIP-seq data analysis revealed FLI1, ERG, and RUNX1 binding overlapping the E1 region. Knockdown of FLI1 but not ERG or RUNX1 led to an increase in KLF6. Notably, FLI1 mRNA levels, but not ERG or RUNX1, are increased during normal aging. We next performed in vitro KLF6 activation in aged CD34 + (KLF6a) cells using a dCas9-VP64 system to test if we could rejuvenate these cells. KLF6a cells exhibited a decrease in their in vitro myeloid differentiation potential, compared to aged NTC CD34 + cells (p<0.0041), and behaved instead similar to young controls. ChIP-seq analysis of KLF6a showed marked decrease of H3K4me1 (n=3,273 peaks) with relatively few regions with increased H3K4me1 (n=602) (FDR < 0.05). In contrast, we observed an increase in H3K27ac (n=3,361 peaks) with only 71 peaks lost compared to aged NTC (FDR < 0.05). Regions that gained H3K27ac in KLF6a were associated with platelet activation, cell junction and adhesion. In vivo analysis of KLF6a cells injected into NSGS mice revealed a significant reduction in the PB myeloid fraction compared to NTC (p<1.2-8), with a concomitant expansion in the lymphoid compartment (p<4.4 -11). BM composition analysis at week 16 showed a decrease in the HSC fraction in KLF6a cells (p=0.0029) as well as a reduction in CD34 +CD38 -, CD34 +CD38 + and MEPs (p=0.036, p<0.0001 and p=0.041, respectively). We next examined the impact of KLF6 modulation on DNA damage and observed that young human KLF6 KO cells had a significant increase in gH2AX and 53BP1 (p<0.0001, for both) whereas KLF6a in aged CD34 + cells exhibited reduced gH2AX and 53BP1 foci in comparison to aged NTC (p<0.0001, for both). In addition, apoptotic levels in KLF6 KO cells were higher than in NTC cells (p=0.006) whereas aged KLF6a cells showed a reduction in the incidence of apoptotic cells compared to NTC (p=0.019). Finally, ROS analysis in young KLF6 KO showed increased levels of total and mitochondrial ROS compared to NTC (p=0.0008 and p<0.0001, respectively) whereas both ROS fractions were reduced in KLF6a cells (p=0.0002 and p<0.0001, respectively). In summary, these results show that the FLI1-KLF6 axis plays a key role in regulating HSPC aging and that KLF6 is required for normal HSPC function and differentiation. In addition, normalization of KLF6 levels in aged HSPCs resulted in reprogramming and rejuvenation HSPCs, confirming the central role of this TF in aging HSPC biology. Disclosures No relevant conflicts of interest to declare

Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer

RING1B, a core Polycomb repressive complex 1 subunit, is a histone H2A ubiquitin ligase essential for development. RING1B is overexpressed in patients with luminal breast cancer (BC) and recruited to actively transcribed genes and enhancers co-occupied by the estrogen receptor α (ERα). Whether ERα-induced transcriptional programs are mediated by RING1B is not understood. We show that prolonged estrogen administration induces transcriptional output and chromatin landscape fluctuations. RING1B loss impairs full estrogen-mediated gene expression and chromatin accessibility for key BC transcription factors. These effects were mediated, in part, by RING1B enzymatic activity and nucleosome binding functions. RING1B is recruited in a cyclic manner to ERα, FOXA1, and GRHL2 cobound sites and regulates estrogen-induced enhancers and ERα recruitment. Last, ChIP exo revealed multiple binding events of these factors at single-nucleotide resolution, including RING1B occupancy approximately 10 base pairs around ERα bound sites. We propose RING1B as a key regulator of the dynamic, liganded-ERα transcriptional regulatory circuit in luminal BC

Single nucleotide polymorphism in PTEN-Long gene: a risk factor in chronic myeloid leukemia

The BCR-ABL1 oncogene is associated with chronic myeloid leukemia (CML) pathogenesis, but the molecular mechanisms that initiate leukemogenesis are still unclear. Cancer pathogenesis has been associated with genetic alterations that may lead to inactivation of tumor suppressor genes. Phosphatase and tensin homolog (PTEN) is frequently deleted or inactivated in various tumors. A recently discovered variant of PTEN, PTEN-Long (PTEN-L), results from an alternative translation initiation site located upstream of the canonic AUG and generates a protein of 576 amino acids instead the expected protein of 403 amino acids. A 16 bp perfect palindromic motif centered on the PTEN-L CUG 513 start codon is required for translation initiation. A single nucleotide polymorphism (SNP) of PTEN-L gene rs12573787 is located on the first exon respect to the CUG initiation site. In this case-control study we evaluated the association of genetic variants in PTEN-L with CML risk and therapy response in the Argentine population. The allele A of SNP rs12573787 was found to be associated with CML risk OR (95% CI) 1.71 (1.11–2.63) p = 0.016, which resulted consistent by multivariate analysis adjusted by gender and age. According to previous evidence that CML is more frequent in males, we found that the genetic risk of CML was confined to this gender. Unexpectedly, we also found this association confined to CML patients older than 45 years old. To our knowledge, this is the first time that PTEN-L rs1257378 was studied in CML suggesting that the variant A allele is a risk factor for CML development but, no association with the failure to TKIs treatment was found.Fil: Ferri, Cristian Alberto. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Miami University; Estados UnidosFil: Gutiérrez, L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bengió, M. R.. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; ArgentinaFil: Zapata, Pedro Dario. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Departamento de Bioquímica Clínica. Laboratorio de Biotecnología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Gene polymorphism profiles of drug-metabolising enzymes GSTM1, GSTT1 and GSTP1 in an Argentinian population

Background: Glutathione S-transferases (GSTs) are drug-metabolising enzymes involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free radicals. Polymorphisms of GST genes contribute to inter-individual and population variability in the susceptibility to environmental risk factors, cancer predisposition and pharmacotherapy responses. However, data about GST variability in Argentina are lacking. Aim: The purpose was to determine the prevalence of GSTM1, GSTT1 and GSTP1 polymorphisms in the general population from a central region of Argentina and to perform inter-population comparisons. Subjects and methods:GSTM1 and GSTT1 gene deletions and GSTP1 c.313A > G were genotyped by PCR assays in 609 healthy and unrelated Argentinians. Results: The frequencies of variant genotypes in Argentinians were GSTM1-null (45%), GSTT1-null (17%) and GSTP1-GG (11%). GSTM1-present genotype was significantly associated with GSTP1-AG or GSTP1-GG variants (p = 0.037; p = 0.034, respectively). Comparison with worldwide populations demonstrated that the GST distributions in Argentina are similar to those reported for Italy and Spain, whereas significant differences were observed regarding Asian and African populations (p < 0.001). Conclusion: This study has determined, for the first time, the normative profile of three pharmacogenetically relevant polymorphisms (GSTM1, GSTT1 and GSTP1) in the largest Argentinian cohort described to date, providing the basis for further epidemiological and pharmacogenetic studies in this country.Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Cerliani, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Aráoz, Hilda V.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Chertkoff, Lilien Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Richard, Silvina Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin