Descripción geoquímica y geocronológica de secuencias volcánicas neógenas de Trasarco, en el extremo oriental de la Cadena Volcánica Transversal del Quevar (Noroeste de Argentina)

New geochronological data (34) and 39 new geochemical analyses have been made in the Neogene backarc volcanic sequences in the “El Quevar Transversal Volcanic Chain” defined by Viramonte et al (1984a). This chain starts at the present N-S arc with WNW-ESE trend. New volcanic centres have been recognised and analysed at the eastern end of this chain. The different pulses from each volcanic centre (Aguas Calientes, Acay, El Morro - Organullo and Tocomar) are petrographically and geochemically homogeneous. This suggests that the magma chambers related in each volcano, were geochemically homogeneous and did not have crystal enriched sectors. The Acay eruptive centre is an exception of this assumption; a compositionally differentiated magmatic chamber could be inferred. The isotopic composition of the Aguas Calientes emission centre has a crust signature in its origin, related with melts generated by crustal fussion. The geochronological determinations show volcanic pulses at 17-19 Ma, 13-12 Ma, 10 Ma, 7-6 Ma, 1-0.5 Ma in this region of the Central Andes

Descripción geoquímica y geocronológica de secuencias volcánicas neógenas de Trasarco, en el extremo oriental de la Cadena Volcánica Transversal del Quevar (Noroeste de Argentina)

Se realizaron 34 nuevas dataciones K/Ar y 39 análisis geoquímicos de elementos mayoritarios, trazas y tierras raras, que implican nuevas aportaciones sobre las secuencias volcánicas neógenas de trasarco pertenecientes a la cadena volcánica transversal del Quevar. Esta cadena volcánica parte del arco volcánico actual con dirección W N W-ESE hasta las cercanías de la localidad de San Antonio de los Cobres. Se han reconocido y estudiado centros volcánicos ubicados en el extremo oriental de la misma. Los diferentes pulsos detectados en cada uno de estos centros (Aguas Calientes, Acay, El Morro-Orrganullo y Tocomar) son geoquímica y petrogr á ficamente homogéneos. Se interpreta que las cámaras magmáticas involucradas no han estado estratificadas composicionalmente ni han tenido sectores enriquecidos en cristales. Como excepción, el centro eruptivo Acay muestra un rango composicional desde términos andesíticos a riolíticos. En este caso, se interpreta un fraccionamiento de la cámara magmática en pulsos de edad similar. La composición isotópica del centro eruptivo Aguas Calientes indica una fuerte componente cortical en la formación de los magmas. Es posible explicar su origen a partir de fusión cortical. Las determinaciones geocronológicas realizadas muestran pulsos volcánicos a los 17-19 Ma, 13-12 Ma, 10 Ma, 7-6 Ma, 1-0.5 Ma en esta región de los Andes Centrales.New geochronological data (34) and 39 new geochemical analyses have been made in the Neogene backarc volcanic sequences in the “El Quevar Transversal Volcanic Chain” defined by Viramonte et al (1984a). This chain starts at the present N-S arc with WNW-ESE trend. New volcanic centres have been recognised and analysed at the eastern end of this chain. The different pulses from each volcanic centre (Aguas Calientes, Acay, El Morro - Organullo and Tocomar) are petrographically and geochemically homogeneous. This suggests that the magma chambers related in each volcano, were geochemically homogeneous and did not have crystal enriched sectors. The Acay eruptive centre is an exception of this assumption; a compositionally differentiated magmatic chamber could be inferred. The isotopic composition of the Aguas Calientes emission centre has a crust signature in its origin, related with melts generated by crustal fussion. The geochronological determinations show volcanic pulses at 17-19 Ma, 13-12 Ma, 10 Ma, 7-6 Ma, 1-0.5 Ma in this region of the Central Andes

First month prednisone dose predicts prednisone burden during the following 11 months: An observational study from the RELES cohort

Aim: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2–12). Methods: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2–12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2–12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2–12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2–12 dose categories (p7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of =6, the model did not change. Conclusion: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months

Regulation of Pax6 by CTCF during Induction of Mouse ES Cell Differentiation

Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited knowledge concerning how Pax6 is regulated in ES cell differentiation. We report that Pax6 expression in mouse ES cells was controlled by CCCTC binding factor (CTCF) through a promoter repression mechanism. Pax6 expression was significantly enhanced while CTCF activity was kept in the constant during ES cell differentiation to radial glial cells. Instead, the interaction of CTCF with Pax6 gene was regulated by decreased CTCF occupancy in its binding motifs upstream from Pax6 P0 promoter following the course of ES cell differentiation. Reduced occupancy of CTCF in the binding motif region upstream from the P0 promoter was due to increased DNA methylations in the CpG sites identified in the region. Furthermore, changes in DNA methylation levels in vitro and in vivo effectively altered methylation status of these identified CpG sites, which affected ability of CTCF to interact with the P0 promoter, resulting in increases in Pax6 expression. We conclude that there is an epigenetic mechanism involving regulations of Pax6 gene during ES cell differentiation to neural stem cells, which is through increases or decreases in methylation levels of Pax6 gene to effectively alter the ability of CTCF in control of Pax6 expression, respectively

The HOXB4 Homeoprotein Promotes the Ex Vivo Enrichment of Functional Human Embryonic Stem Cell-Derived NK Cells

Human embryonic stem cells (hESCs) can be induced to differentiate into blood cells using either co-culture with stromal cells or following human embryoid bodies (hEBs) formation. It is now well established that the HOXB4 homeoprotein promotes the expansion of human adult hematopoietic stem cells (HSCs) but also myeloid and lymphoid progenitors. However, the role of HOXB4 in the development of hematopoietic cells from hESCs and particularly in the generation of hESC-derived NK-progenitor cells remains elusive. Based on the ability of HOXB4 to passively enter hematopoietic cells in a system that comprises a co-culture with the MS-5/SP-HOXB4 stromal cells, we provide evidence that HOXB4 delivery promotes the enrichment of hEB-derived precursors that could differentiate into fully mature and functional NK. These hEB-derived NK cells enriched by HOXB4 were characterized according to their CMH class I receptor expression, their cytotoxic arsenal, their expression of IFNγ and CD107a after stimulation and their lytic activity. Furthermore our study provides new insights into the gene expression profile of hEB-derived cells exposed to HOXB4 and shows the emergence of CD34+CD45RA+ precursors from hEBs indicating the lymphoid specification of hESC-derived hematopoietic precursors. Altogether, our results outline the effects of HOXB4 in combination with stromal cells in the development of NK cells from hESCs and suggest the potential use of HOXB4 protein for NK-cell enrichment from pluripotent stem cells

Interview investigation of insecure attachment styles as mediators between poor childhood care and schizophrenia-spectrum phenomenology

Background Insecure attachment styles have received theoretical attention and some initial empirical support as mediators between childhood adverse experiences and psychotic phenomena; however, further specificity needs investigating. The present interview study aimed to examine (i) whether two forms of poor childhood care, namely parental antipathy and role reversal, were associated with subclinical positive and negative symptoms and schizophrenia-spectrum personality disorder (PD) traits, and (ii) whether such associations were mediated by specific insecure attachment styles. Method A total of 214 nonclinical young adults were interviewed for subclinical symptoms (Comprehensive Assessment of At-Risk Mental States), schizophrenia-spectrum PDs (Structured Clinical Interview for DSM-IV Axis II Disorders), poor childhood care (Childhood Experience of Care and Abuse Interview), and attachment style (Attachment Style Interview). Participants also completed the Beck Depression Inventory-II and all the analyses were conducted partialling out the effects of depressive symptoms. Results Both parental antipathy and role reversal were associated with subclinical positive symptoms and with paranoid and schizotypal PD traits. Role reversal was also associated with subclinical negative symptoms. Angry-dismissive attachment mediated associations between antipathy and subclinical positive symptoms and both angry-dismissive and enmeshed attachment mediated associations of antipathy with paranoid and schizotypal PD traits. Enmeshed attachment mediated associations of role reversal with paranoid and schizotypal PD traits. Conclusions Attachment theory can inform lifespan models of how adverse developmental environments may increase the risk for psychosis. Insecure attachment provides a promising mechanism for understanding the development of schizophrenia-spectrum phenomenology and may offer a useful target for prophylactic intervention

Decoding the regulatory network of early blood development from single-cell gene expression measurements.

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.We thank J. Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for the Runx1-ires-GFP mouse. Research in the authors' laboratory is supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, the Leukemia and Lymphoma Society, Microsoft Research and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute. V.M. is supported by a Medical Research Council Studentship and Centenary Award and S.W. by a Microsoft Research PhD Scholarship.This is the accepted manuscript for a paper published in Nature Biotechnology 33, 269–276 (2015) doi:10.1038/nbt.315