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Los microRNA (miRNA) son pequeños ARN que regulan postranscripcionalmente la expresión génica eucariota, y que participan en una amplia gama de procesos fisiológicos. Se han observado cambios temporales y regionales en la expresión de los miRNA, así como una correlación entre la expresión de estos y la población microbiana del tubo digestivo en las primeras etapas de vida en becerros. Esta revisión sintetiza y analiza el conocimiento actual de los miRNA como reguladores de la función de las células inmunes, así como su papel como biomarcadores de salud. Además de revisar información sobre la relación hospedador­microbiota y sus impactos sobre el sistema inmune y la salud de becerros.

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.

This article is based on the following assumption: to be or not to be on the stage. However, if the stage is real life, part of a public space, this situation is a very complex one. Thus, everyday urban life becomes an artistic and performance event. In this way, citizens become active spectators. Urban interventions change the usual way of regarding the city, and propose a blurs the line between the roles of the person who looks and the person who acts. The example to discuss this game of presences will be A veces creo que te veo (Sometimes I think I can see you), a performance work done in Buenos Aires by Mariano Pensotti, in 2010., Cet article a pour point de départ le paradoxe théâtral: être ou ne pas être sur scène. Mais que se passe-t-il lorsque cette dernière intervient dans le cadre de la vie quotidienne? Les citoyens deviennent alors des spectateurs actifs devant reconnaître, momentanément, la scène comme un récit fictionnel. Ces interventions urbaines changent le regard habituel sur la ville et proposent une inversion des rôles entre regardants et regardés, dans un jeu de présences. Pour réfléchir sur cette question, nous prendrons l’exemple de la performance urbaine A veces creo que te veo (Parfois je crois que je te vois) réalisée par Mariano Pensotti en 2010., El artículo parte de la paradoja teatral: ser o no ser en la escena. Pero ¿qué ocurre cuando ésta sucede dentro de un ámbito de la vida cotidiana? Los ciudadanos se vuelven parte de ella y se convierten, a la vez, en espectadores activos que deben reconocer momentáneamente, la instancia de relato ficcional. Este tipo de teatralidad propone cambiar la mirada habitual sobre la ciudad y mezclar los roles entre quienes miran y quienes son mirados, como un juego de presencias. Para analizar esta cuestión tomaremos la performance urbana de Mariano Pensotti, A veces creo que te veo realizada en 2010.

Deschampsia P. Beauv. is a cosmopolitan grass genus, which grows in cold and temperate regions, including about 15 species growing in South America and Antarctica. The species delimitation is difficult due to the high phenotypic plasticity and the likely occurrence of hybridization which generates species complexes with high morphological affinity. This work aims to describe the cytogenetic traits of the South American species of Deschampsia, highlighting similarities and differences in a phylogenetic context. We report the chromosome number of seven species of Deschampsia and Deyeuxia eminens for the first time, verifying that basic chromosome number x = 13 is shared by all the species. We found that the phylogenetic relationships are in agreement with the morphological affinities described in the species revisions, and the species of Deschampsia and Deyeuxia Sect. Stylagrostis form a well-supported clade. Despite the variation from x = 13 reported for populations of Deschampsia in the northern hemisphere, all the South American and Antarctic taxa studied here have a conserved basic chromosome number. Polyploids were found in several species, which suggests that genomic duplication is a recurrent process in the evolutionary history of Deschampsia. In contrast with the conserved chromosome morphology, the rDNA pattern showed high intra- and inter-specific variability and it is related to the phylogeny. Particularly, the complex of D. cespitosa is polymorphic for the distribution pattern of rDNA, as was also seen for molecular and morphological traits. Our results suggest that the common ancestor between Deschampsia and Deyeuxia sec. Stylagrostis could have had chromosomal characteristics currently shared by both. The incorporation of new chromosomal, molecular, and morphological data in Deyeuxia species will allow clarification of the close phylogenetic relationship with Deschampsia, in which reticulation and hybridization events cannot be excluded.

Chia seeds (CS) and sprouts are rich in bioactive compounds. This study aimed to assess the effects of germination and chemical elicitation (salicylic acid [SA]; hydrogen peroxide [H

Endometriosis is defined as the presence of endometrial glands in extrauterine sites. Intestinal deep infiltrating endometriosis is considered when the endometriotic lesion is located more than 5 mm below the peritoneum. Intestinal obstruction due to endometriosis is rare, occurring in approximately 1% of cases. We present three cases with intestinal occlusion as deep infiltrating endometriosis debut. Its symptomatic presentation can mimic multiple gastroenterological entities, mainly irritable bowel syndrome or inflammatory bowel disease so its diagnosis can be difficult. However, suspecting this pathology and diagnosing it is important to define therapeutic behavior and improve the quality of life of our patients.

Diverse families of satellite DNA (satDNA) were detected in heterochromatin regions of Deschampsia. This kind of repetitive DNA consists of tandem repeat sequences forming big arrays in genomes, and can contribute to lineages differentiation. The differentiation between types of satDNA is related to their sequence identity, the size and number of monomers forming the array, and their chromosomal location. In this work, four families of satDNA (D2, D3, D12, D13), previously isolated by genomic analysis, were studied on chromosomal preparations of 12 species of Deschampsia (D. airiformis, D. antarctica, D. cespitosa, D. cordillerarum, D. elongata, D. kingii, D. laxa, D. mendocina, D. parvula, D. patula, D. venustula, and Deschampsia sp) and one of Deyeuxia (D. eminens). Despite the number of satDNA loci showing interspecific variation, the general distribution pattern of each satDNA family is maintained. The four satDNA families are AT-rich and associated with DAPI + heterochromatin regions. D2, D3, and D12 have mainly subterminal distribution, while D13 is distributed in intercalary regions. Such conservation of satDNA patterns suggests a not random distribution in genomes, where the variation between species is mainly associated with the array size and the loci number. The presence of satDNA in all species studied suggests a low genetic differentiation of sequences. On the other hand, the variation of the distribution pattern of satDNA has no clear association with phylogeny. This may be related to high differential amplification and contraction of sequences between lineages, as explained by the library model.

In the first few weeks of a calf's life, the early colonization of microbes throughout the gastrointestinal tract (GIT) is critical in its digestive system and immunity development. Analyses of data generated from next-generation sequencing platforms have revolutionized the understanding of host-associated microbial communities; these analyses can be done through a variety of bioinformatics pipelines. This study aimed to describe the diversity and evolution of gastrointestinal tract microbial communities in the first days of life of calves; for which we used the USEARCH and KRAKEN2 algorithms, in terms of alpha and beta diversity analysis in the rumen and jejunum contents of calves from 0, 7, 28, 42 days-born in the Mexican Tropic and its changes. The two pipelines detected similar abundance distributions in the three most abundant taxa Proteobacteria, Firmicutes, and Bacteroidetes. The present study revealed the changes occurring in the rumen and jejunum ecosystem in the first week of life, reflected by a decline in the phylum Proteobacteria and an increase in phylum Bacteroidetes in rumen and Firmicutes in the jejunum. We observed an increase in the similarity in the phylum taxa with age, suggesting a homogeneous and specific mature community, compared with the primary community.

Los festejos del Bicentenario nacional argentino −Mayo de 2010− y el espacio público intervenido artísticamente para la ocasión nos permiten reflexionar sobre las narrativas visuales expandidas por la ciudad en esos días. La puerta del Grupo de Arte Callejero (GAC) problematiza la condición material del recuerdo, en tanto artefacto efímero, entablando una correlación con el contexto sociopolítico en el que tuvo lugar. De esta manera, en las siguientes páginas nos proponemos pensarla como una práctica de memoria contemporánea mediante la cual las categorías de lo monumental/contramonumental resultarían convergentes con una percepción de la ciudad interpeladora y performática.

The Cestrum genus is karyotypically exceptional in Solanaceae. It is characterised by a basic number x = 8, a large chromosomal and genomic size, complex heterochromatin patterns, B-chromosomes (Bs) with particular heterochromatin and distribution of 18?5.8?26S and 5S rDNA. Cestrum nocturnum L. has a diploid number of 2n = 16 plus a variable number of B-chromosomes. The aims of work was to analyse their numerical variation, structure and behaviour of C. nocturnum B-chromosomes by classical and molecular cytogenetics. The individuals analysed had 2n = 16 + 0−13 B-chromosomes. All B-chromosomes were metacentric and smaller than A-chromosomes. The number of B-chromosomes showed a great variability between and within individuals, thereby denoting the occurrence of events that promote mitotic and meiotic instability. Cytogenetic techniques made it possible to observe that B-chromosomes are rich in heterochromatin, probably with AT- and GC-rich regions. In addition, molecular techniques allowed to detect homologous sequences of transposable element conserved domains of Ty1-Copia and Ty3-Gypsy superfamilies. These sequences were located by FISH in all B-chromosomes and some A-chromosomes. Our results showed that repetitive DNA could play an important role in chromosomal evolution as well as in the stability of B-chromosomes in C. nocturnum. Fil: Montechiari, Keisy Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: González, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Yañez Santos, Anahi Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentina Fil: Hajduczyk Rutz, Jésica Lidiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Urdampilleta, Juan Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

Deschampsia antarctica is one of the two native vascular plants present in the Antarctic continent. More than half of its genome is composed of repetitive DNA. The present work aims to study the amount, composition and chromosomal localization of the main retroelements in the genome of D. antarctica, via a bioinformatic analysis and cytogenetic approach in two Antarctic localities. The retroelements are the largest fraction of genomic repetitive DNA. Ty3-Gypsy superfamily was more abundant than Ty1-Copia in D. antarctica´s genome. However, Ty1-Copia was more diverse. Angela, SIRE, TatV and Tekay families were the most abundant in the studied genome. The hybridization signals showed that the four retrotransposon families have dispersal distributions in both Antarctic localities studied. However, some differences in the chromosomal distribution were observed among families and between localities. This study contributes to the understanding of the diversity and distribution of repetitive DNA in D. antarctica.

Deschampsia antactica E. Desv. is one of the only two native vascular plants of Antarctica, having a disjunct distribution with South America. Its presence in different environmental conditions turn it into an interesting evolution model, particularly for genomic evolutionary studies. The repetitive DNA is a genome component, that cause important changes in genome size and chromosome organization, and therefore its variation is very important in group?s delimitation. Some tandem repetitive DNA sequences, known as satellite DNA (satDNAs) are shared between many groups of Poaceae (e.g. of these are the CON1, CON2, COM1 and COM2 sequences) highlighting its evolutionary component. This study aims to identify, classify and characterize repetitive elements in the D. antarctica genome by clustering analysis of genome sequences, focusing on the CON1, CON2, COM1 and COM2. Repetitive DNA represented about 73.3% of the D. antarctica genome. All studied populations presented loci for the studied satDNAs but the distribution pattern showed differences than seem to be related to the geographic distribution. The analysis of CON/COM sequences in D. antarctica contributes with the understanding of these elements in Poaceae genomes and highlights the importance of changes in chromosome organization of repetitive DNA in populations with fragmented geographical distribution. The distribution of such chromosome changes may both reflect the process of colonization of D. antarctica in Antarctica and explain some evolutionary processes of differentiation in Deschampsia species complex in the Patagonia, still unresolved with other DNA sequences. Fil: González, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Chiapella, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad de Viena; Austria Fil: Urdampilleta, Juan Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

To find novel P-gp-inhibitors, a library of pregnane X receptor (PXR) ligands and the ZINC DrugsNow library were superimposed on the P-gp inhibitor (+)-pinoresinol (1) used as a query for a three-dimensional similarity search. After determining the TanimotoCombo index of similarity with 1, eight compounds from the PXR library and two ZINC compounds were selected for biological evaluation. The P-gp inhibition study showed that compounds 7, 8, and 9 successfully increased intracellular doxorubicin (DOX) accumulation in the P-gp overexpressed Lucena 1 cells from 25, 12.5, and 6.25 μM, respectively. Among a series of analogues of 9, compounds 26–30 were shown to be active, with 26 and 27 causing a significant increase in DOX accumulation from 1.56 μM and rendering Lucena 1 sensitive to DOX from 1.56 and 0.78 μM, respectively. Molecular modeling studies showed that both compounds bind to the P-gp at transmembrane helices (TMH) 4, 5, and 6, with 27 also showing contacts with TMH 3. Fil: Laiolo, Jerónimo. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Tomasič, Tihomir. University of Ljubljana; Eslovenia Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: González, María L.. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Lanza Castronuovo, Priscila Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: Gancedo, Samanta Nerea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: Hodnik, Žiga. University of Ljubljana; Eslovenia Fil: Peterlin Masic, Lucija. University of Ljubljana; Eslovenia Fil: Kikelj, Danijel. University of Ljubljana; Eslovenia Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina

El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes)MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p

Unlike the Arctic flora, with many floweringplant species offering opportunities to study evolutionaryprocesses, the Antarctic flora offers only two. One of themis the Antarctic grass Deschampsia antarctica E. Desv.,whose distribution spans from northern Patagonia (ca.38S) down to Alamode Island (ca. 68S), in the west sideof the Antarctic Peninsula. While some aspects of Antarcticplants have been extensively studied (e.g., anatomy,physiology, genetics), little is known about the relatedPatagonian populations. Particularly in cytogenetics, nosingle study has focused on continental populations and itsrelationships with the Antarctic plants. The combination oftraditional fluorescent in situ hybridization (FISH) with aphylogenetic framework highlights the importance ofcytogenetics in plant evolutionary studies, by allowingcomparison of chromosome characters in phylogeneticallyrelated individuals. Most used characters for this purposeare the chromosome number, karyotype morphology andpatterns of repetitive DNA. These were used to comparedistant populations of D. antarctica in a phylogeneticframework, to obtain a first view of the cytogeneticstructure of the species along its distribution. Patagonianpopulations have greater variability in the chromosomaland molecular characters, while Antarctic populations arevery alike, hinting at a South American origin hypothesis.A polyploid population is reported for the first time,located on Central Patagonia populations, close to thenorthern limit of distribution range. Cytogenetic characteristicssuggest that hybridization processes could haveplayed an important role in the evolution of the genome ofD. antarctica. Fil: González, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Urdampilleta, Juan Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Fasanella, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Reg.universidad Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Laboratorio de Ecotono; Argentina Fil: Premoli Il'grande, Andrea Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Reg.universidad Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Laboratorio de Ecotono; Argentina Fil: Chiapella, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

Plants are a significant reservoir of cytotoxic agents, including compounds with the ability to interfere with multidrug resistant (MDR) cells. With the aim of finding promising candidates for chemotherapy, 91 native and naturalized plants collected from the central region of Argentina were screened for their cytotoxic effect toward sensitive and MDR P-glycoprotein (P-gp) over-expressing human leukemia cells by means of MTT assays. The ethanol extracts obtained from Aldama tucumanensis, Ambrosia elatior, Baccharis artemisioides, Baccharis coridifolia, Dimerostemma aspilioides, Gaillardia megapotamica and Vernonanthura nudiflora presented outstanding antiproliferative activity at 50 ug/mL, with inhibitory values from 93 to 100%, when tested on the acute lymphoblastic leukemia (ALL) cell line CCRF-CEM and the resistant derivative CEM-ADR5000, while 70-90% inhibition was observed against the chronic myelogenous leukemia (CML) cell K562 and its corresponding resistant subline, Lucena 1. Subsequent investigation showed these extracts to possess marked cytotoxicity with IC50 values ranging from 0.37 to 29.44 ug/mL, with most of them below 7 ug/mL, and with ALL cells, including the drug-resistant phenotype, being the most affected. G. megapotamica extract was found to be one of the most effective, and bioguided fractionation yielded helenalin (1). The sesquiterpene lactone displayed IC50 values of 0.63, 0.19, 0.74 and 0.16 ug/mL against K562, CCRF-CEM, Lucena 1 and CEM/ADR5000, respectively. These results support the potential of these extracts as a source of compounds for treating sensitive and multidrug-resistant leukemia cells, and support compound 1 as a lead for developing effective anticancer agents. Fil: González, María Laura. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Joray, Mariana Belén. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Laiolo, Jerónimo. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Crespo, Maria Ines. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Palacios, Sara Maria. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina Fil: Ruiz, Gustavo Miguel. Universidad Católica de Córdoba. Facultad de Ciencias Agropecuarias; Argentina Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; Argentina

The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2′,4′-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4′-dihydroxy-3′-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 g/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1-5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6-9.9 M) and a lower effect against CML cells (IC50 = 27.5-30.0 M). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound. Fil: Joray, Mariana Belén. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Trucco, Lucas Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: González, María Laura. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Diaz Napal, Georgina Natalia. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Palacios, Sara Maria. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Deschampsia antarctica is the only grass naturally occurring in Antarctica, and it is also indigenous to southern South America. We aimed to evaluate patterns of within-population genetic diversity and between the focal areas Patagonia and Antarctica by using 144 sequences of nuclear internal transcribed spacer and non-coding plastid regions. We analysed phylogenetic relationships between these two main areas and performed demographic and landscape analysis. To test the divergence time between Antarctic and Patagonian populations we used approximate Bayesian computation. We found 17 nuclear and eight plastid haplotypes. For both molecular markers, Patagonia was the most genetically variable area in the range of D. antarctica. The divergence time between populations from Antarctica and Patagonia was dated to the mid to late Pleistocene. The large number of private haplotypes found in Patagonia and the great genetic variability support the hypothesis of a South American origin of the Antarctic populations of D. antarctica. Finally, we suggest that D. antarctica probably survived the Last Glacial Maximum and possibly earlier glaciations in ice-free refugia in Patagonia and Antarctica. Dispersal to Antarctica possibly occurred in the mid to late Pleistocene through bird-aided long-distance transport from South America. Fil: Fasanella, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina Fil: Premoli Il'grande, Andrea Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina Fil: Urdampilleta, Juan Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: González, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Chiapella, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

Plants are a significant reservoir of cytotoxic agents, including compounds with the ability to interfere with multidrug-resistant (MDR) cells. With the aim of finding promising candidates for chemotherapy, 91 native and naturalized plants collected from the central region of Argentina were screened for their cytotoxic effect toward sensitive and MDR P-glycoprotein (P-gp) overexpressing human leukemia cells by means of MTT assays. The ethanol extracts obtained from Aldama tucumanensis, Ambrosia elatior, Baccharis artemisioides, Baccharis coridifolia, Dimerostemma aspilioides, Gaillardia megapotamica, and Vernonanthura nudiflora presented outstanding antiproliferative activity at 50 μg/mL, with inhibitory values from 93 to 100%, when tested on the acute lymphoblastic leukemia (ALL) cell line CCRF-CEM and the resistant derivative CEM-ADR5000, while 70–90% inhibition was observed against the chronic myelogenous leukemia (CML) cell K562 and its corresponding resistant subline, Lucena 1. Subsequent investigation showed these extracts to possess marked cytotoxicity with IC50 values ranging from 0.37 to 29.44 μg/mL, with most of them being below 7 μg/mL and with ALL cells, including the drug-resistant phenotype, being the most affected. G. megapotamica extract found to be one of the most effective and bioguided fractionation yielded helenalin (1). The sesquiterpene lactone displayed IC50 values of 0.63, 0.19, 0.74, and 0.16 μg/mL against K562, CCRF-CEM, Lucena 1, and CEM/ADR5000, respectively. These results support the potential of these extracts as a source of compounds for treating sensitive and multidrug-resistant leukemia cells and support compound 1 as a lead for developing effective anticancer agents.

P-glycoprotein (P-gp) is a membrane protein associated with multidrug resistance (MDR) due to its key role in mediating the traffic of chemotherapeutic drugs outside cancer cells, leading to a cellular response that hinders efforts toward successful therapy. With the aim of finding agents that circumvent the MDR phenotype mediated by P-gp, 15 compounds isolated from native and naturalized plants of Argentina were screened. Among these, the non-cytotoxic lignan (±) pinoresinol successfully restored sensitivity to doxorubicin from 7 μM in the P-gp overexpressed human myelogenous leukemia cells, Lucena 1. This resistance-reversing effect was confirmed by competitively increasing the intracellular doxorubicin accumulation and by significantly inhibiting the efflux of doxorubicin and, to a lesser extent, that of rhodamine 123. The activity obtained was similar to that observed with verapamil. No such results were observed in the sensitive parental K562 cell line. To gain deeper insight into the mode of action of pinoresinol, its effect on P-gp function and expression was examined. The docking simulations indicated that the lignan bound to P-gp at the apex of the V-shaped transmembrane cavity, involving transmembrane helices 4, 5, and 6, and partially overlapped the binding region of tariquidar, which was used as a positive control. These results would shed some light on the nature of its interaction with P-gp at molecular level and merit further mechanistic and kinetic studies. In addition, it showed a maximum 29% activation of ATP hydrolysis and antagonized verapamil-stimulated ATPase activity with an IC50 of 20.9 μM. On the other hand, pinoresinol decreased the presence of P-gp in the cell surface. Derivatives of pinoresinol with improved activity were identified by docking studies. The most promising one, the non-cytotoxic 1-acetoxypinoresinol, caused a reversion of doxorubicin resistance from 0.11 μM and thus higher activity than the lead compound. It also caused a significant increase in doxorubicin accumulation. Results were similar to those observed with verapamil. The results obtained positioned these compounds as potential candidates for effective agents to overcome P-gp-mediated MDR, leading to better outcomes for leukemia chemotherapy. Fil: González, María Laura. Universidad Católica de Córdoba; Argentina Fil: Vera, Domingo Mariano Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: Laiolo, Jerónimo. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Joray, Mariana Belén. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Maccioni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Palacios, Sara Maria. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Molina, Gabriela. Universidad Católica de Córdoba; Argentina Fil: Lanza Castronuovo, Priscila Ailin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; Argentina Fil: Gancedo, Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Rumjanek, Vivian. Universidade Federal do Rio de Janeiro; Brasil Fil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Gonzales Pereyra M.L., Chiacchiera S.M., Rosa C.A. da R., Sager R., Dalcero A.M. & Cavaglieri L.R. Fungal and mycotoxin contamination in mixed feeds: Evaluating risk in cattle intensive rearing operations (Feedlots). [Contaminação por fungos e micotoxinas em rações para bovinos: Avaliação de risco em operações de criação intensiva de gado (confinamento)]. Revista Brasileira de Medicina Veteriná- ria, 34(4):311-318, 2012. Departamento de Microbiología e Inmunología, Universidad Nacional de Río Cuarto, Ruta 36 Km, 601, (5800) Río Cuarto, Córdoba, Argentina. E-mail: lcavaglieri@exa.unrc.edu.ar Argentina is the fourth global beef producer. Exposure to mycotoxins through contaminated feed is a major hazard for ruminants. In the present study we assess mycobiota, aflatoxin B1 (AFB1 ), fumonisin B1 (FB1 ), deoxynivalenol (DON) and zearalenone (ZEA) levels in total mixed rations (TMRs) during two consecutive years. Total fungal counts were evaluated and fungal species were identified. Also, ability of A. flavus isolates to produce AFB1 in vitro was tested. Natural contamination with AFB1 and FB1 was quantified by HPLC. Deoxynivalenol and zearalenone were analysed by immunochromatography and TLC, respectively. Fungal counts varied from ND to 2.10 x 108 CFU/g. The prevalent genera were Aspergillus spp. (60%) and Fusarium spp. (66.7%), respectively. The prevalent species was Aspergillus fumigatus. Fifty percent of A. flavus strains produced 75 to 112.5 µg/g AFB1 . Forty- six percent of 2007 samples were contaminated with 4 to 10 µg/ kg AFB1 . Deoxynivalenol was detected in 33.3 % of the samples (≥ 1. 25 µg/g). Fumonisin B1 and ZEA were not detected. This study can be useful to estimate the mycotoxicological risk of cattle TMRs in this region and to compare results with studies from other beef-producing countries., A Argentina é a quarta maior produtora mundial de carne. Com isso, a exposição às micotoxinas através de alimentos contaminados é um grande risco para o gado. No presente estudo a micobiota e a contaminação natural com aflatoxina B1 (AFB1 ), fumonisina B1 (FB1 ), deoxinivalenol (DON) e zearalenona (ZEA) em rações completas mistas (TMRs) para bovinos foram avaliadas durante dois anos consecutivos. As contagens totais de fungos (UFC/g) foram avaliadas e as espéciesfúngicas foram identificadas. A capacidade dos A. flavus isolados para produzir AFB1 in vitro e a contaminação das rações com AFB1 , FB1 , DON e ZEA foram testadas. As contagens totais de fungos variaram entre não detectado (ND) e 2,10x108 UFC/g. Aspergillus spp. (60%) e Fusarium spp. (66,7%) foram os gêneros prevalentes, enquanto A. fumigatus foi à espécie isolada com maior frequencia. Cinquenta por cento dos A. flavus isolados foram produtores de 75 a 112,5 µg/g de AFB1 . Quarenta e seis por cento das amostras coletadas em 2007 estavam contaminadas com 4 a 10 µg/ kg AFB1 . Deoxinivalenol foi detectado em 33,3% das amostras (≥ 1,25 µg/g), enquanto FB1 e ZEA não foram detectadas. Este estudo é útil para estimar o risco de micotoxicológico das TMRs usadas na produção intensiva de gado numa das regiões produtoras de carne bovina mais importante e comparar os resultados com estudos de outros países.

Landa M.F., González Pereyra M.L., Pena G., Bagnis G., Cavaglieri L.R., Rosa C.A.R. & Dalcero A.M. Chronic exposure to aflatoxigenic fungi related to liver damage in pelt chinchillas (Chinchilla lanigera). [Exposição crônica a fungos produtores de aflatoxinas relacionada a danos hepáticos em chinchilas (Chinchilla lanigera) de pele]. Revista Brasileira de Medicina Veterinária, 34(4):303-310, 2012. Departamento de Microbiología e Inmunología, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta N 36 Km 601 (5800), Río Cuarto, Córdoba, Argentina. E.mail: adalcero@exa.unrc.edu.ar Chinchilla pelt is a rare and expensive fur. Therefore, breeding these animals is a profitable activity. Confirmed acute cases of aflatoxin intoxication have been reported in Argentinean farms. The aims of this study were i) to evaluate mycobiota and AFB1- -producing species in chinchilla feeds ii) to investigate their natural AFB1 contamination and iii) to analyze histopathological lesions in chinchilla livers. Feed samples (A: fur, B: mother, C: lucerne cubes) were collected from a factory and a farm. Livers of sacrificed chinchilla from the farm were macroscopically and microscopically examined. Total fungal counts of feed C exceeded 1x104 CFU/g. Aspergillus, Fusarium and Penicillium were the prevalent genera, while A. flavus, A. fumigatus, F. verticillioides and F. proliferatum were the prevalent species. Fifty % of A. flavus strains from factory samples and 69.7% from farm samples were able to produce 2.78 to 8.64µg/g and 0.66 to 58.8µg/g AFB1, respectively. Aflatoxin B1 was detected only in feeds from the farm, finding the highest incidence in feed C. Toxin levels varied between 1.90 and 97.34 µg/ kg AFB1 . Mean levels in feed A and C exceeded 20 µg/kg. Macroscopic examination of livers revealed normal appearance, size and color. However, histopathological examination indicated 63.3% showed slight to moderate lipid degeneration with diffuse cytoplasm vacuolation, 9% intense lipid cytoplasm vacuolation and 27.3% hydropic degeneration and nuclear vacuolation in hepatocytes. A periodic monitoring of aflatoxins in feeds and their ingredients can prevent acute outbreaks and economic losses caused by chronic exposure., A pele de chinchila é uma das mais exóticas e caras. Portanto, a criação destes animais é uma atividade rentável. Casos agudos de intoxicação por aflatoxinas têm sido informados em fazendas Argentinas. Os objetivos deste estudo foram: i) Avaliar a micobiota e os fungos produtoresde Aflatoxina B1 (AFB1 ) presente em rações para chinchilas ii) analisar a contaminação natural com AFB1 destas rações e iii) pesquisar lesões histopatológicas nos fígados das chinchilas. As amostras de diferentes rações (A: pele, B: mãe, C: cubos de alfafa) foram coletadas numa fábrica e uma fazenda localizadas na cidade de Rio Cuarto, na região central da Argentina. Os fígados das chinchilas eutanasiadas, na fazenda, foram analisados macroscó- pica e microscopicamente. As contagens totais de fungos das rações foram superiores a 1x104 UFC/g. Aspergillus, Fusarium e Penicillium foram os gê- neros prevalentes, enquanto A. flavus, A. fumigatus, F. verticillioides e F. proliferatum foram às espé- cies isoladas com maior freqüência. Cinquenta por cento dos A. flavus isolados da fábrica e 69,7% dos isolados da fazenda foram produtores de 2,78 a 8,64 µg/g e 0,66 a 58,8 µg/g de AFB1 , respectivamente. A AFB1 foi detectada só nas amostras coletadas na fazenda, com maior incidência na ração C. Os ní- veis de toxina variaram entre 1,90 e 97,34 µg/kg. Os níveis médios na ração A e C foram superiores a 20 µg/kg. Analise macroscópica dos fígados revelou aparência, tamanho e cor normais. No entanto, o exame histopatológico indicou que 63,3% dos fí- gados apresentaram leve a moderada degeneração lipídica com vacuolização difusa do citoplasma, 9% apresentaram vacuolização lipídica intensa do citoplasma e 27,3% apresentaram degeneração hidrópica e vacuolização nuclear nos hepatócitos. O monitoramento periódico da qualidade das rações e ingredientes usados na alimentação de chinchilas pode evitar intoxicações agudas e perdas econômicas causadas pela exposição crônica as aflatoxinas.

The present study investigated the antibacterial activity of two plant-derived compounds, 23-methyl-6-O-desmethylauricepyrone (1) and (Z,Z)-5-(trideca-4,7-dienyl)resorcinol (2), and their synergistic effects with erythromycin and gentamicin against methicillin-susceptible (MSSA) and gentamicin- and methicillin-resistant Staphylococcus aureus (MRSA). Studies of the individual antibacterial activity of each plant-derived compound and synergy experiments were carried out, by the microdilution test in agar and by the checkerboard method, respectively. Compound 1 showed minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 2 and 8 μg/mL, respectively, against both strains of S. aureus, while compound 2 exhibited anti-MSSA and anti-MRSA activity with MICs and MBCs of 4 and 8 and 2 and 8 μg/mL, respectively. Time-kill curves showed that, while compound 1 produced complete killing of both strains at 24 h from the beginning of the experiment, 2 produced the same effect in the first hour. Combinations of 1 with erythromycin or gentamicin showed a notable synergism against MSSA, which enabled the antibiotic concentration to decrease by up to 300 or 260 times, respectively. When the aminoglycoside was placed together with compound 2, only an additive effect was observed. The assayed compounds did not produce erythrocyte hemolysis or genotoxicity and they did not affect macrophage viability at the effective or higher concentrations. These results suggest that both compounds could be considered as promising antibacterial agents while compound 1 could be used in combinatory therapies with erythromycin and gentamicin.

Minthostachys verticillata (Griseb.) Epling is a South American traditional medicinal herb used as digestive, anti-spasmodic, anti-inflammatory and bronchial dilator agent among other uses. Its anti-microbial activity against staphylococcal strains and its anti-viral properties against HVS-1 and strain RC/79 of PrV have been demonstrated.To determine the immunomodulating ability of M. verticillata decoction and essential oil. As a complementary study, the main constituents of the essential oil were identified.Lymphocyte-proliferating activity of both vegetal derivatives was tested and compared with cellular expansion induced by PHA, Pokeweed, CGB in cytomorphological study. A non-stimulate culture was used as control reference. The score of lymphocyte clusters and colonies was performed using the method described by Lange. Among proliferated cells, LT CD8+ subpopulation was characterized by direct immunofluorescence. The in vitro degranulant ability of the vegetal fractions was tested on basophils from allergic and non-allergic individuals sensitized to environmental fungi. Essential oil components of M. verticillata were identified by gas chromatography technique.M. verticillata derivatives reached higher proliferation levels compared to non-stimulated cultures, showed mitogenic activity and induced cluster and colony formation similar to PHA, Pokeweed and CGB. Cells that proliferated after stimulation with derivatives showed 40% of LT CD8+. Tested concentrations of decoction and essential oil did not reach minimum degranulation indexes over basophils, from both allergic and non-allergic individuals. Gas chromatography analysis revealed the presence of pulegone and menthone as the main constituents.M. verticillata derivatives were mitogenic over LT, inducing significant cluster and colony formation. There was no evidence of degranulating ability over basophils at the concentrations tested. We assume that the derivatives from M. verticillata would induce Th1 deviation in cellular cultures from allergic patients, which would diminish hypersensitivity reactions. Some of the compounds of the essential oil revealed by gas chromatography analysis may be responsible of the biological activity of these products.