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

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

Xrn1 influence on gene transcription results from the combination of general effects on elongating RNA pol II and gene-specific chromatin configuration

mRNA homoeostasis is favoured by crosstalk between transcription and degradation machineries. Both the Ccr4-Not and the Xrn1-decaysome complexes have been described to influence transcription. While Ccr4-Not has been shown to directly stimulate transcription elongation, the information available on how Xrn1 influences transcription is scarce and contradictory. In this study we have addressed this issue by mapping RNA polymerase II (RNA pol II) at high resolution, using CRAC and BioGRO-seq techniques in Saccharomyces cerevisiae. We found significant effects of Xrn1 perturbation on RNA pol II profiles across the genome. RNA pol II profiles at 5ʹ exhibited significant alterations that were compatible with decreased elongation rates in the absence of Xrn1. Nucleosome mapping detected altered chromatin configuration in the gene bodies. We also detected accumulation of RNA pol II shortly upstream of polyadenylation sites by CRAC, although not by BioGRO-seq, suggesting higher frequency of backtracking before pre-mRNA cleavage. This phenomenon was particularly linked to genes with poorly positioned nucleosomes at this position. Accumulation of RNA pol II at 3ʹ was also detected in other mRNA decay mutants. According to these and other pieces of evidence, Xrn1 seems to influence transcription elongation at least in two ways: by directly favouring elongation rates and by a more general mechanism that connects mRNA decay to late elongation.Ministerio de Economía y Competitividad BFU2016-77728- C3-1-P, BFU2016-77728-C3-3-P, BFU2016- 77728-C3-2-P, RED2018-102467-TJunta de Andalucía BIO271, US-1256285, BIO258, UJA 1260360Generalitat Valenciana AICO/2019/08

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