Zircon U-Pb and Hf isotopic constraints on the genesis of a post-kinematic S-type Variscan tin granite: the Logrosán cupola (Central Iberian Zone)

The Variscan orogeny produced widespread granites along the European Variscan belt. In relation to crustal thickening, post-collisional multiple tin-bearing highly fractionated S-type leucogranites were emplaced. The Logrosán granite represents one of those granitic bodies and is a focus of this study. The Logrosán granite is located in the Central Extremadura Batholith (CEB), within the Central Iberian Zone (CIZ) and was emplaced during post kinematic stages of the Variscan orogeny at ca. 308 Ma, as determined by combined ID-TIMS U–Pb and LA-ICPMS geochronology. The granitic body intruded the metasedimentary Schist Greywacke Complex (SGC) of Neoproterozoic age. A moderately evolved medium- to coarse-grained two mica leucogranite (Main unit) and some highly evolved aplitic or microporphyritic units (evolved units) are distinguishable on the basis of their petrography and whole rock geochemistry.  Initial 87Sr/86Sr ratios vary from 0.7134 to 0.7311, whereas initial εNd shows a restricted range from -4.3 to -4.0 and εHf(t) ranges from  +2.0 to -4.6 for Variscan-age zircons. Inherited zircons exhibit mostly Neoproterozoic ages and juvenile Hf-isotope composition (eHf up to +14.6), analogous to that of zircons from the SGC metasediments. The available geological, geochronological, geochemical and isotopic data allow to propose the partial melting of heterogeneous Neoproterozoic metasedimentary material, similar to the outcropping SGC, for the genesis of the Logrosán granite.La orogenia Varisca produjo una gran cantidad de granitos a lo largo del Cinturón Varisco Europeo. En relación con el engrosamiento cortical se emplazaron tardíamente granitos de tipo-S, muy fraccionados y ricos en Sn. El presente estudio se centra en uno de esos cuerpos graníticos, el granito de Logrosán. El plutón de Logrosán forma parte del Batolito de Extremadura Central (BEC), en la Zona Centroibérica (ZCI), y se emplazó durante las etapas tardías de la orogenia Varisca, a los ca. 308 Ma, según los datos combinados de geocronología de U-Pb por ID-TIMS y por LA-ICPMS. El cuerpo granítico intruyó los metasedimentos del Complejo Esquisto Grauváquico (CEG) de edad fundamentalmente Neoproterozoica. En el plutón se distinguen, de acuerdo a la petrografía y a la geoquímica de roca total, un leucogranito de dos micas de tamaño de grano medio-grueso moderadamente evolucionado (Main Unit) y varias unidades aplíticas o microporfídicas altamente evolucionadas (Evolved Units). Las relaciones isotópicas iniciales de 87Sr/86Sr varían de 0.7125 a 0.7286, mientras que el εNd inicial muestra un rango restringido de -4.3 a -4.0 y el εHf(t) en circones variscos oscila de +5.7 a -10.5. Los circones heredados del granito de Logrosán muestran edades principalmente Neoproterozoicas y composiciones isotópicas de Hf juveniles (εHf > +14.7), análogas a las encontradas en los circones del CEG. Los datos geológicos, geoquímicos, geocronológicos e isotópicos de los que se dispone sugieren que el granito de Logrosán se originó por la fusión parcial de materiales metasedimentarios Neoproterozoicos similares a los del CEG

Validation of a DNA methylation microarray for 285,000 CpG sites in the mouse genome

Mouse has been extensively used as a model organism in many studies to characterize biological pathways and drug effects and to mimic human diseases. Similar DNA sequences between both species facilitate these types of experiments. However, much less is known about the mouse epigenome, particularly for DNA methylation. Progress in delivering mouse DNA methylomes has been slow due to the currently available time-consuming and expensive methodologies. Following the great acceptance of the human DNA methylation microarrays, we have herein validated a newly developed DNA methylation microarray (Infinium Mouse Methylation BeadChip) that interrogates 280,754 unique CpG sites within the mouse genome. The CpGs included in the platform cover CpG Islands, shores, shelves and open sea sequences, and loci surrounding transcription start sites and gene bodies. From a functional standpoint, mouse ENCODE representative DNase hypersensitivity sites (rDHSs) and candidate cis-Regulatory Elements (cCREs) are also included. Herein, we show that the profiled mouse DNA methylation microarray provides reliable values among technical replicates; matched results from fresh frozen versus formalin-fixed samples; detects hemimethylated X-chromosome and imprinted CpG sites; and is able to determine CpG methylation changes in mouse cell lines treated with a DNA demethylating agent or upon genetic disruption of a DNA methyltransferase. Most important, using unsupervised hierarchical clustering and t-SNE approaches, the platform is able to classify all types of normal mouse tissues and organs. These data underscore the great features of the assessed microarray to obtain comprehensive DNA methylation profiles of the mouse genome.We thank the CERCA Programme/Generalitat de Catalunya for institutional support. This work was supported by the Health Department PERIS-project no. SLT/002/16/00374 and AGAUR-project no. 2017SGR1080 of the Catalan Government (Generalitat de Catalunya); Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI), and European Regional Development Fund (ERDF) project no. RTI2018-094049-B-I00 and PID2020-117284RB-I00; the Cellex Foundation; Marie Sklodowska-Curie Fellowship no. 895979 from the European Commission (BNV); and ‘la Caixa’ Banking Foundation (LCF/PR/GN18/51140001).Peer ReviewedPostprint (published version

Sleep quality among inpatients of Spanish public hospitals

Sleep is a complex process and is needed both in health and illness. Deprivation of sleep is known to have multiple negative physiological effects on people's bodies and minds. Despite the awareness of these harmful effects, previous studies have shown that sleep is poor among hospitalised patients. We utilized an observational design with 343 patients recruited from medical and surgical units in 12 hospitals located in nine Spanish regions. Sociodemographic and clinical characteristics of patients were collected. Sleep quality at admission and during hospitalisation was measured by the Pittsburgh Sleep Quality Index. Sleep quantity was self-reported by patients in hours and minutes. Mean PSQI score before and during hospitalisation were respectively 8.62 ± 4.49 and 11.31 ± 4.04. Also, inpatients slept about an hour less during their hospital stay. Lower educational level, sedative medication intake, and multi-morbidity was shown to be associated with poorer sleep quality during hospitalisation. A higher level of habitual physical activity has shown to correlate positively with sleep quality in hospital. Our study showed poor sleep quality and quantity of inpatients and a drastic deterioration of sleep in hospital versus at home. These results may be helpful in drawing attention to patients' sleep in hospitals and encouraging interventions to improve sleep.This project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2018 call under the Health Strategy Action 2013–2016, with reference PI18/00732, PI18/00743, PI18CIII/0012, co-funded with the European Union ERDF funds (European Reginal Development Fund “a way to make Europe) and the Predoctoral staff in training program from the University of Lleida, Jade Plus and La Caixa Bank Foundation 2019.S

Use of an NIR MEMS spectrophotometer and visible/NIR hyperspectral imaging systems to predict quality parameters of treated ground peppercorns

peer-reviewedThe aim of this study was to investigate the potential of a micro-electromechanical NIR spectrophotometer (NIR-MEMS) and visible (Vis)/NIR hyperspectral imaging (HSI) systems to predict the moisture content, antioxidant capacity (DPPH, FRAP) and total phenolic content (TPC) of treated ground peppercorns. Partial least squares (PLS) models were developed using spectra from peppercorns treated with hot-air, microwave and cold plasma. The spectra were acquired using three spectroscopy systems: NIR-MEMS (1350–1650 nm), Vis-NIR HSI (450–950 nm) and NIR HSI (957–1664 nm). Very good predictions of TPC (RPD > 3.6) were achieved using NIR-MEMS. The performance of models developed using Vis-NIR HSI and NIR HSI were good or very good for DPPH (RPD > 3.0), FRAP (RPD >2.9) and TPC (RPD > 3.8). This study demonstrated the potential of NIR-MEMS and Vis-NIR/NIR HSI to predict the moisture content, antioxidant capacity and total phenolic content of peppercorns. The spectroscopy technologies investigated are suitable for use as in-line PAT tools to facilitate improved process control and understanding during peppercorn processing

In vivo computer-aided diagnosis of colorectal polyps using white light endoscopy

Background and study aims Artificial intelligence is currently able to accurately predict the histology of colorectal polyps. However, systems developed to date use complex optical technologies and have not been tested in vivo. The objective of this study was to evaluate the efficacy of a new deep learning-based optical diagnosis system, ATENEA, in a real clinical setting using only high-definition white light endoscopy (WLE) and to compare its performance with endoscopists. Methods ATENEA was prospectively tested in real life on consecutive polyps detected in colorectal cancer screening colonoscopies at Hospital Clínic. No images were discarded, and only WLE was used. The in vivo ATENEA's prediction (adenoma vs non-adenoma) was compared with the prediction of four staff endoscopists without specific training in optical diagnosis for the study purposes. Endoscopists were blind to the ATENEA output. Histology was the gold standard. Results Ninety polyps (median size: 5 mm, range: 2-25) from 31 patients were included of which 69 (76.7 %) were adenomas. ATENEA correctly predicted the histology in 63 of 69 (91.3 %, 95 % CI: 82 %-97 %) adenomas and 12 of 21 (57.1 %, 95 % CI: 34 %-78 %) non-adenomas while endoscopists made correct predictions in 52 of 69 (75.4 %, 95 % CI: 60 %-85 %) and 20 of 21 (95.2 %, 95 % CI: 76 %-100 %), respectively. The global accuracy was 83.3 % (95 % CI: 74%-90 %) and 80 % (95 % CI: 70 %-88 %) for ATENEA and endoscopists, respectively. Conclusion ATENEA can accurately be used for in vivo characterization of colorectal polyps, enabling the endoscopist to make direct decisions. ATENEA showed a global accuracy similar to that of endoscopists despite an unsatisfactory performance for non-adenomatous lesions

Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy

Synucleinopathies represent a group of neurodegenerative disorders which are characterized by intracellular accumulation of aggregated α-synuclein. α-synuclein misfolding and oligomer formation is considered a major pathogenic trigger in these disorders. Therefore, targeting α-synuclein species represents an important candidate therapeutic approach. Our aim was to analyze the biological effects of passive immunization targeting α-synuclein and to identify the possible underlying mechanisms in a transgenic mouse model of oligodendroglial α-synucleinopathy. We used PLP-α-synuclein mice overexpressing human α-synuclein in oligodendrocytes. The animals received either antibodies that recognize α-synuclein or vehicle. Passive immunization mitigated α-synuclein pathology and resulted in reduction of total α-synuclein in the hippocampus, reduction of intracellular accumulation of aggregated α-synuclein, particularly significant in the spinal cord. Lowering of the extracellular oligomeric α-synuclein was associated with reduction of the density of activated iba1-positive microglia profiles. However, a shift toward phagocytic microglia was seen after passive immunization of PLP-α-synuclein mice. Lowering of intracellular α-synuclein was mediated by autophagy degradation triggered after passive immunization in PLP-α-synuclein mice. In summary, the study provides evidence for the biological efficacy of immunotherapy in a transgenic mouse model of oligodendroglial synucleinopathy. The different availability of the therapeutic antibodies and the variable load of α-synuclein pathology in selected brain regions resulted in differential effects of the immunotherapy that allowed us to propose a model of the underlying mechanisms of antibody-aided α-synuclein clearance

Palimpsestos y cambios culturales en el límite Pleistoceno-Holoceno: el conjunto lítico de Picamoixons (Alt Camp, Tarragona)

This paper presents the technological and typological study of the lithic assemblage recovered at Picamoixons during the field season carried out in 1993. Its technotypological features, the differential conservation of the assemblage, the spatial distribution of lithic remains and the radiometric dates allow us to divide the assemblage into two different sets and suggest that they belong to different chronological and cultural periods. The items included in the first one (CP) show a strong patina and should be included in the macrolithic Mesolithic, while the second one’s items (CNP) are not patinated and belong to the final part of upper Palaeolithic.En este artículo se presenta el análisis tecnológico y tipológico de la industria lítica recuperada en el año 1993 en el yacimiento de Picamoixons. Dadas sus características, su estado de conservación diferencial, su distribución espacial y las dataciones radiométricas disponibles, podemos concluir la existencia de dos conjuntos líticos pertenecientes a dos momentos cronológicos y culturales diferentes. El primero es el conjunto patinado (CP) que debería incluirse dentro del Mesolítico macrolítico, y el segundo conjunto es el no patinado (CNP) perteneciente a los momentos finales del Paleolítico superior

Zrsr2 and functional U12-dependent spliceosome are necessary for follicular development

SUMMARY ZRSR2 is a splicing factor involved in recognition of 30 -intron splice sites that is frequently mutated in myeloid malignancies and several tumors; however, the role of mutations of Zrsr2 in other tissues has not been analyzed. To explore the bio logical role of ZRSR2,we generated threeZrsr2 mutantmouse lines. AllZrsr2 mutant lines exhibited blood cell anomalies, and in two lines, oogenesis was blocked at the secondary follicle stage. RNA-seq of Zrsr2mu secondary follicles showed aberrations in gene expression and showed altered alternative splicing (AS) events involving enrichment of U12-type intron retention (IR), supporting the functional Zrsr2 action in minor spliceosomes. IR events were preferentially associated with centriole repli cation, protein phosphorylation, and DNA damage checkpoint. Notably, we found alterations in AS events of 50 meiotic genes. These results indicate that ZRSR2 mu tations alter splicing mainly in U12-type introns, which may affect peripheral blood cells, and impede oogenesis and female fertility

Long term outcome of adolescent and adult patients with pineal parenchymal tumors treated with fractionated radiotherapy between 1982 and 2003 -- a single institution's experience

Background: To evaluate the effectivity of fractionated radiotherapy in adolescent and adult patients with pineal parenchymal tumors (PPT). Methods: Between 1982 and 2003, 14 patients with PPTs were treated with fractionated radiotherapy. 4 patients had a pineocytoma (PC), one a PPT with intermediate differentiation (PPTID) and 9 patients a pineoblastoma (PB), 2 of which were recurrences. All patients underwent radiotherapy to the primary tumor site with a median total dose of 54 Gy. In 9 patients with primary PB treatment included whole brain irradiation (3 patients) or irradiation of the craniospinal axis (6 patients) with a median total dose of 35 Gy. Results: Median follow-up was 123 months in the PC patients and 109 months in the patients with primary PB. 7 patients were free from relapse at the end of follow-up. One PC patient died from spinal seeding. Among 5 PB patients treated with radiotherapy without chemotherapy, 3 developed local or spinal tumor recurrence. Both patients treated for PB recurrences died. The patient with PPTID is free of disease 7 years after radiotherapy. Conclusion: Local radiotherapy seems to be effective in patients with PC and some PPTIDs. Diagnosis and treatment of patients with more aggressive variants of PPTIDs as well as treatment of PB need to be further improved, since local and spinal failure even despite craniospinal irradiation (CSI) is common. As PPT are very rare tumors, treatment within multi-institutional trials remains necessary