Rodrigo Nores

Expression and Localization of StarD7 in Trophoblast Cells

The StAR-related lipid transfer (START) domain is defined as a motif of around 200 amino acids implicated in lipid/sterol binding. In a previous study, we identified the StarD7 transcript encoding one of the 15 family members with START domain present in the human genome. This transcript was found to be overexpressed in choriocarcinoma JEG-3 cells. In addition, we demonstrated that the recombinant StarD7 protein forms stable Gibbs and Langmuir monolayers at the air-buffer interface, showing marked surface activity and interaction with phospholipid monolayers, mainly with phosphatidylserine, cholesterol and phosphatidylglycerol. This study was undertaken to evaluate the expression and localization of StarD7 protein in trophoblastic samples. Here, we show for the first time the presence of StarD7 protein in human trophoblast cells. Western blot assays revealed a unique specific 34 kDa protein in JEG-3 cell line, choriocarcinoma tissue, complete hydatidiform mole, early and normal term placenta. Immunohistochemical data from early and normal term placentas and complete hydatidiform moles showed that this protein is abundant in the syncytiotrophoblasts, mainly at the apical side of the syncytium, with a weak and focal reaction in the cytotrophoblast cells. Furthermore, an increased StarD7 mRNA and protein expression, as well as a change in its sub-cellular localization was observed in in vitro differentiating cytotrophoblast isolated from normal term placenta. Taken together, these findings support and allow future studies to explore the possibility that StarD7 protein mediates transplacental lipid transport and/or is involved in syncytialization.

Phylogeography of mitochondrial haplogroup D1: An early spread of subhaplogroup D1j from Central Argentina

We analyzed the patterns of variation of haplogroup D1 in central Argentina, including new data and published information from other populations of South America. Almost 28% (107/388) of the individuals sampled in the region belong to haplogroup D1, whereas more than 52% of them correspond to the recently described subhaplogroup D1j (Bodner et al.: Genome Res 22 (2012) 811-820), defined by the presence of additional transitions at np T152C-C16242T-T16311C to the nodal D1 motif. This lineage was found at high frequencies across a wide territory with marked geographical-ecological differences. Additionally, 12 individuals present the mutation C16187T that defines the recently named subhaplogroup D1g (Bodner et al.: Genome Res 22 (2012) 811-820), previously described in populations of Patagonia and Tierra del Fuego. Based on our results and additional data already published, we postulate that the most likely origin of subhaplogroup D1j is the region of Sierras Pampeanas, which occupies the center and part of the northwestern portion of Argentina. The extensive yet restricted geographical distribution, the relatively large internal diversity, and the absence or low incidence of D1j in other regions of South America suggest the existence of an ancient metapopulation covering the Sierras Pampeanas, being this lineage its genetic signature. Further support for a scenario of local origin for D1j in the Sierras Pampeanas stems from the fact that early derivatives from a putative ancestral lineage carrying the transitions T16311C-T152C have only been found in this region, supporting the hypothesis that it might represent an ancestral motif previous to the appearance of D1j-specific change C16242T.

Transcriptional Control of the Human Pregnancy-specific Glycoprotein 5 Gene is Dependent on Two GT-boxes Recognized by the Ubiquitous Specificity Protein 1 (Sp1) Transcription Factor

Pregnancy-specific glycoprotein 5 gene (PSG-5) belongs to the human pregnancy-specific glycoprotein family, encoded by eleven highly similar and transcriptionally active genes. High levels of PSG biosynthesis are restricted to the placenta syncytiotrophoblast and are essential for the maintenance of normal gestation in mammalian species. We have investigated here the nature of the transcription factors that recognize the FP1 (-455/-433) and the CPE (-147/-140) regulatory sequences that significantly contribute to basal PSG-5 promoter activity. Both elements bear a similar GT-box motif; and DNA-protein complex formation, as well as promoter activity, is largely dependent on the integrity of these GT-box sequences. Gel shift, super gel shift and UV-crosslinking experiments clearly demonstrate that the ubiquitous specificity protein 1 (Sp1) is the major transcription factor involved in complex formation with both cis-acting elements in normal term placenta tissue and in PSG-non-expressing COS-7 cells. Furthermore, transfection experiments indicate that Sp1 activates PSG-5 promoter constructs. In addition, we show that Sp1 is indeed co-expressed with PSG genes in the syncytiotrophoblast cells, stressing its potential role in the in vivo regulation of PSG expression.

Transcription of genes encoding pregnancy-specific glycoproteins is regulated by negative promoter-selective elements

The human pregnancy-specific glycoprotein (PSG) genes comprise a family of 11 highly conserved members whose expression is maximal in placental cells and marginal in other cell types. We have investigated here the molecular basis of PSG regulation by analysing a large regulatory region of the PSG-5 gene in cells that do and do not express these genes. The promoter region (-254 to -43), which does not contain a TATA-box, large GC-rich sequences or a classical initiator, was active in all cell types analysed. Additional upstream sequences up to position -3204 repressed promoter activity. Two independent repressor regions were identified and found to operate effectively in HeLa, COS-7 and HTR8/SVneo placental cells. More significantly, these negatively acting modules failed to repress a heterologous TATA-containing thymidine kinase promoter. Detailed transcriptional and DNA-protein analyses of the proximal repressor region (-605 to -254) revealed the presence of both negative and positive cis-acting elements. Disruption of the repressive functions resulted in an enhanced transcription of the reporter constructs. In conclusion, these results demonstrate that PSG-5 gene transcription is highly repressed by promoter-selective negative regulatory regions and the relief of repression allows enhanced PSG-5 gene transcription irrespective of the cell type. Furthermore, our findings suggest that PSG genes are expressed mainly through a derepression mechanism.

Analysis of Uniparental Lineages in Two Villages of Santiago del Estero, Argentina, Seat of Pueblos de Indios in Colonial Times

Abstract Based on the analysis of the mitochondrial control region and seven biallelic markers of the Y chromosome, we investigated the genetic composition of two rural populations of southern Santiago del Estero, Argentina, that were seats in colonial times of pueblos de indios, a colonial practice that consisted of concentrating the indigenous populations in organized and accessible settlements, to facilitate Christianizing and policing. We found the Native American Y chromosome haplogroup Q1a3a in only 11% (3 of 27) of the males. Haplogroup R, common in European populations, is the most frequent haplogroup in Santiago del Estero (55%). In contrast, the persistence of Native American maternal lineages is extremely high (95%). This finding is most likely due to the low incidence in that region of the 20thcentury European wave of migration and to the existence of pueblos de indios from 1612 to the first decades of the 19th century. In contrast to archeological records that suggest Santiago del Estero late pre-Hispanic groups were strongly influenced by the Andean world, we did not find genetic evidence in support of significant gene flow. On the other hand, these populations share many mitochondrial DNA hypervariable region I (HVRI) haplotypes with other populations from the Sierras Pampeanas (particularly with Córdoba) and the Gran Chaco regions.

Molecular polymorphisms of the ABO locus as informative markers of ancestry in Central Argentina

The aim of this study was to investigate the distribution of molecular polymorphisms of the ABO gene in four population samples from the province of Córdoba, in Central Argentina, and to compare them with other worldwide populations.

Análisis de haplogrupos mitocondriales en restos humanos de sitios arqueológicos de la provincia de Córdoba/ Analysis of mitochondrial haplogroups in human remains from archaeological sites of the province of Córdoba

RESUMEN Este trabajo se centra en el analisis de cambios osteoartrosicos observados en esqueletos del cementerio de Rincon Chico 21 (Santa Maria, Catamarca), con el objeto de intentar la reconstruccion de los habitos corporales mas probables y explorar su vinculacion con eventuales divisiones del trabajo en la poblacion que genero este cementerio precolombino. Las manifestaciones osteoartrosicas en los principales sistemas articulares de 56 individuos adultos de ambos sexos fueron registradas, analizadas y comparadas. Los resultados sugieren que en esta comunidad con una economia de subsistencia principalmente basada en la practica de agricultura de regadio y pastoreo de camelidos (Desarrollos Regionales), habria existido una division de tareas y/o actividades potencialmente relacionadas con el sexo de los individuos. Asimismo, los analisis estadisticos aplicados entre los grupos etarios considerados estarian indicando que la edad constituiria un factor determinante en la expresion final de la enfermedad degenerativa articular tanto en las articulaciones de los miembros inferiores como en las del esqueleto axial. ABSTRACT This research is centered on the skeletal analysis of osteoarthritic changes observed in individuals from Rincon Chico 21, a prehistoric burial site at Santa Maria, Catamarca, Argentina. The aim was to try the reconstruction of the most probable corporal behaviours, as well as the possible relationships with labour divisions among individuals from the population that generated the prehistoric cemetery. Osteoarthritic manifestations on the main articular systems of 56 systematically excavated adult skeletons of both sexes were registered, analyzed and compared. Results suggested that in this prehistoric community, with subsistence economy based on agriculture and pastoralism (Regional Developments Period), there may have existed a sexual division of the daily activities. In addition, the results of the statistical analysis applied among the age groups indicate that the age would be an important factor for determining the final expression of the degenerative joint disease, both in the joints of the lower extremities and in the axial skeleton.RESUMEN El estudio de las poblaciones humanas antiguas es complejo y requiere de un enfoque interdisciplinario. La arqueologia argentina esta promoviendo el desarrollo de nuevas lineas de evidencias que incluyen espacios muy activos de interaccion con la biologia. Numerosos estudios biologicos se efectuan sobre los depositos sedimentarios asociados al contexto arqueologico. Los sedimentos asociados a los restos humanos constituyen un recurso de informacion poco explorado y en general, escasamente contemplado en el diseno previo de la excavacion. El presente trabajo aborda el examen de sedimentos de foramenes sacrales de esqueletos humanos pertenecientes al Museo Regional Monsenor Fagnano, Tierra del Fuego, una clase de material arqueologico poco estudiado. La recuperacion de rotiferos, artropodos y parasitos justifica el esfuerzo de muestreo sobre materiales sin asignacion temporal y con escasa referencia espacial. Se puede concluir que el estudio de microfosiles presentes en este tipo de deposito permite maximizar la informacion obtenida del registro bioarqueologico debido a que albergan valiosa informacion paleoambiental, bioantropologica y tafonomica. Asi, el estudio exhaustivo y no destructivo de las muestras arqueologicas resulta un punto crucial en la estrategia de investigacion. ABSTRACT The study of ancient human populations is complex and requires an interdisciplinary approach. The Argentinean archaeology is promoting the development of new research fields, including areas of active interaction with biology. Numerous biological studies are conducted on the sedimentary deposits in association to the archaeological context. The sediments associated to human remains constitute an unexplored source of information. Nevertheless, this material is frequently overlook during excavations and/or insufficient number of samples are taken. The present study analyzes the sediments found in sacral foramina of human skeletons belonging to the Monsenor Fagnano Regional Museum, Tierra del Fuego this is a kind of archaeological material rarely studied. The recovery of rotifers, arthropods and parasites justified the sampling effort on this unusual sediments characterized by a low temporary and spatial reference. It can be concluded that the study of microfossils found in this type of deposit maximized the information obtained from the bioarchaeological registry because it harbors valuable palaeoenvironmental, bioanthropological and taphonomic data. Therefore, the exhaustive and non-destructive study of the archaeological samples is a crucial point in the research strategy