The Migmatitic Complex of Mundão (Viseu, northern Portugal)

A presença de rochas migmatíticas (metatexitos e diatexitos) na região de Mundão (Zona Centro-Ibérica) mostra que as condições de fusão parcial foram atingidas durante o metamorfismo regional varisco neste sector. Com base nas relações com a deformação, foi possível identificar várias gerações de leucossomas e demonstrar que o processo de anatexia começou relativamente cedo, durante os estádios finais do engrossamento crustal (D1) e continuou durante a tectónica extensional (D2) e transcorrente (D3) subsequentes.The occurrence of migmatites (metatexites and diatexites) in the Mundão region (Central Iberian Zone) shows that the Variscan regional metamorphism reached the partial melting conditions in this sector. According to the relationships with the deformation, it was possible to identify several generations of leucosomes and demonstrate that crustal anatexis started relatively early, during the last stages of crustal thickening (D1) and continued during subsequent extensional (D2) and transcurrent (D3) tectonics

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction

[EN] Understanding the nature of pathogen host interaction may help improve strawberry (Fragaria x anahassa) cultivars. Plant resistance to pathogenic agents usually operates through a complex network of defense mechanisms mediated by a diverse array of signaling molecules. In strawberry, resistance to a variety of pathogens has been reported to be mostly polygenic and quantitatively inherited, making it difficult to associate molecular markers with disease resistance genes. Colletotrichum acutaturn spp. is a major strawberry pathogen, and completely resistant cultivars have not been reported. Moreover, strawberry defense network components and mechanisms remain largely unknown and poorly understood. Assessment of the strawberry response to C. acutatum included a global transcript analysis, and acidic hormones SA and JA measurements were analyzed after challenge with the pathogen. Induction of transcripts corresponding to the SA and JA signaling pathways and key genes controlling major steps within these defense pathways was detected. Accordingly, SA and JA accumulated in strawberry after infection. Contrastingly, induction of several important SA, JA, and oxidative stress-responsive defense genes, including FaPR1-1, FaLOX2, FaJAR1, FaPDF1, and FaGST1, was not detected, which suggests that specific branches in these defense pathways (those leading to FaPR1-2, FaPR2-1, FaPR2-2, FaAOS, FaPR5, and FaPR10) were activated. Our results reveal that specific aspects in SA and JA dependent signaling pathways are activated in strawberry upon interaction with C. acutatum. Certain described defense-associated transcripts related to these two known signaling pathways do not increase in abundance following infection. This finding suggests new insight into a specific putative molecular strategy for defense against this pathogen.Authors are grateful to Dr. JM Lopez-Aranda (IFAPA-Centro de Churriana) for providing micropropagated strawberry plants and to Nicolas Garcia-Caparros for technical assistance. Authors also want to thank Kevin M. Folta for his insightful comments on the paper. This work was supported by Junta de Andalucia, Spain [Proyectos de Excelencia P07-AGR-02482/P12-AGR-2174, and grants to Grupo-BIO278].Amil-Ruiz, F.; Garrido-Gala, J.; Gadea Vacas, J.; Blanco-Portales, R.; Munoz-Merida, A.; Trelles, O.; De Los Santos, B.... (2016). Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction. Frontiers in Plant Science. 7(1036). https://doi.org/10.3389/fpls.2016.01036S71036Acosta, I. F., & Farmer, E. E. (2010). Jasmonates. The Arabidopsis Book, 8, e0129. doi:10.1199/tab.0129Al-Shahrour, F., Diaz-Uriarte, R., & Dopazo, J. (2004). 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Lymphocytic infiltration in stage II microsatellite stable colorectal tumors: A retrospective prognosis biomarker analysis

Background: Identifying stage II patients with colorectal cancer (CRC) at higher risk of progression is a clinical priority in order to optimize the advantages of adjuvant chemotherapy while avoiding unnecessary toxicity. Recently, the intensity and the quality of the host immune response in the tumor microenvironment have been reported to have an important role in tumorigenesis and an inverse association with tumor progression. This association is well established in microsatellite instable CRC. In this work, we aim to assess the usefulness of measures of T-cell infiltration as prognostic biomarkers in 640 stage II, CRC tumors, 582 of them confirmed microsatellite stable. Methods and findings: We measured both the quantity and clonality index of T cells by means of T-cell receptor (TCR) immunosequencing in a discovery dataset (95 patients with colon cancer diagnosed at stage II and microsatellite stable, median age 67, 30% women) and replicated the results in 3 additional series of stage II patients from 2 countries. Series 1 and 2 were recruited in Barcelona, Spain and included 112 fresh frozen (FF, median age 69, 44% women) and 163 formalin-fixed paraffin-embedded (FFPE, median age 67, 39% women) samples, respectively. Series 3 included 270 FFPE samples from patients recruited in Haifa, Northern Israel, as part of a large case-control study of CRC (median age 73, 46% women). Median follow-up time was 81.1 months. Cox regression models were fitted to evaluate the prognostic value of T-cell abundance and Simpson clonality of TCR variants adjusting by sex, age, tumor location, and stage (IIA and IIB). In the discovery dataset, higher TCR abundance was associated with better prognosis (hazard ratio [HR] for ≥Q1 = 0.25, 95% CI 0.10-0.63, P = 0.003). A functional analysis of gene expression on these tumors revealed enrichment in pathways related to immune response. Higher values of clonality index (lower diversity) were not associated with worse disease-free survival, though the HR for ≥Q3 was 2.32 (95% CI 0.90-5.97, P = 0.08). These results were replicated in an independent FF dataset (TCR abundance: HR = 0.30, 95% CI 0.12-0.72, P = 0.007; clonality: HR = 3.32, 95% CI 1.38-7.94, P = 0.007). Also, the association with prognosis was tested in 2 independent FFPE datasets. The same association was observed with TCR abundance (HR = 0.41, 95% CI 0.18-0.93, P = 0.03 and HR = 0.56, 95% CI 0.31-1, P = 0.042, respectively, for each FFPE dataset). However, the clonality index was associated with prognosis only in the FFPE dataset from Israel (HR = 2.45, 95% CI 1.39-4.32, P = 0.002). Finally, a combined analysis combining all microsatellite stable (MSS) samples demonstrated a clear prognosis value both for TCR abundance (HR = 0.39, 95% CI 0.26-0.57, P = 1.3e-06) and the clonality index (HR = 2.13, 95% CI 1.44-3.15, P = 0.0002). These associations were also observed when variables were considered continuous in the models (HR per log2 of TCR abundance = 0.85, 95% CI 0.78-0.93, P = 0.0002; HR per log2 or clonality index = 1.16, 95% CI 1.03-1.31, P = 0.016). Limitations: This is a retrospective study, and samples had been preserved with different methods. Validation series lack complete information about microsatellite instability (MSI) status and pathology assessment. The Molecular Epidemiology of Colorectal Cancer (MECC) study had information about overall survival instead of progression-free survival. Conclusion: Results from this study demonstrate that tumor lymphocytes, assessed by TCR repertoire quantification based on a sequencing method, are an independent prognostic factor in microsatellite stable stage II CRC

Clinical subgroups in bilateral meniere disease

Meniere disease (MD) is a heterogeneous clinical condition characterized by sensorineural hearing loss, episodic vestibular symptoms, and tinnitus associated with several comorbidities, such as migraine or autoimmune disorders (AD). The frequency of bilateral involvement may range from 5 to 50%, and it depends on the duration of the disease. We have performed a two-step cluster analysis in 398 patients with bilateral MD (BMD) to identify the best predictors to define clinical subgroups with a potential different etiology to improve the phenotyping of BMD and to develop new treatments. We have defined five clinical variants in BMD. Group 1 is the most frequently found, includes 46% of patients, and is defined by metachronic hearing loss without migraine and without AD. Group 2 is found in 17% of patients, and it is defined by synchronic hearing loss without migraine or AD. Group 3, with 13% of patients, is characterized by familial MD, while group 4, that includes 12% of patients, is associated by the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by AD. This approach can be helpful in selecting patients for genetic and clinical research. However, further studies will be required to improve the phenotyping in these clinical variants for a better understanding of the diverse etiological factors contributing to BMD

Digital Quantum Simulation with Rydberg Atoms

We discuss in detail the implementation of an open-system quantum simulator with Rydberg states of neutral atoms held in an optical lattice. Our scheme allows one to realize both coherent as well as dissipative dynamics of complex spin models involving many-body interactions and constraints. The central building block of the simulation scheme is constituted by a mesoscopic Rydberg gate that permits the entanglement of several atoms in an efficient, robust and quick protocol. In addition, optical pumping on ancillary atoms provides the dissipative ingredient for engineering the coupling between the system and a tailored environment. As an illustration, we discuss how the simulator enables the simulation of coherent evolution of quantum spin models such as the two-dimensional Heisenberg model and Kitaev's toric code, which involves four-body spin interactions. We moreover show that in principle also the simulation of lattice fermions can be achieved. As an example for controlled dissipative dynamics, we discuss ground state cooling of frustration-free spin Hamiltonians.Comment: submitted to special issue "Quantum Information with Neutral Particles" of "Quantum Information Processing

On the 12C/13C isotopic ratio at the dawn of chemical evolution

The known Mega and Hyper Metal-Poor (MMP-HMP) stars with [Fe/H]<-6.0 and <-5.0, respectively, likely belong to the CEMP-no class, i.e. carbon-enhanced stars with low or absent second peak neutron capture elements. They are likely second generation stars and the few elements measurable in their atmospheres are used to infer the properties of single or very few progenitors. The high carbon abundance in the CEMP-no stars offers a unique opportunity to measure the carbon isotopic ratio, which directly monitors the presence of mixing between the He and H-burning layers either within the star or in the progenitor(s). By means of high-resolution spectra acquired with the ESPRESSO spectrograph at the VLT we aim to derive values for the 12C/13C ratio at the lowest metallicities. A spectral synthesis technique based on the SYNTHE code and on ATLAS models is used within a Markov-chain Monte Carlo methodology to derive 12C/13C in the stellar atmospheres of five of the most metal poor stars. These are the Mega Metal-Poor giant SMS J0313-6708 ([Fe/H]<-7.1), the Hyper Metal-Poor dwarf HE1327-2326 ([Fe/H]=-5.8),the Hyper Metal-Poor giant SDSS J1313-0019 ([Fe/H] = -5.0) and the Ultra Metal-Poor subgiant HE0233-0343 ([Fe/H]=-4.7). We also revise a previous value for the Mega Metal-Poor giant SMSS J1605-1443 with ([Fe/H] = -6.2). In four stars we derive an isotopic value while for HE1327-2326 we provide a lower limit. All Measurements are in the range 39<12C/13C<100 showing that the He- and H-burning layers underwent partial mixing either in the stars or, more likely, in their progenitors. This provides evidence of a primary production of 13C at the dawn of chemical evolution. [abridged]Comment: 10 pages, 6 figure, accepted A&

Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing

Objetives The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance. Methods Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016. Results Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). Conclusions NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.Funding: M.A.M. was supported in part by: Agency for Health Technology Assessment and Research Supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (PS12/02131 and PI17/02150); Agència de Gestió d´Ajuts Universitaris I de Recerca, Generalitat de Catalunya, 2017 SGR 794; and Fundació Marató TV3 project code 201824

Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re

The national inventory of geological heritage: methodological approach and results

A existência de um inventário nacional de património geológico é fundamental para se poderem implementar estratégias de geoconservação. Este trabalho apresenta a metodologia usada no desenvolvimento do mais completo inventário de geossítios, realizado até ao momento em Portugal, assim como os principais resultados obtidos. O inventário vai integrar o Sistema de Informação do Património Natural e o Cadastro Nacional dos Valores Naturais Classificados, ambos geridos pelo Instituto de Conservação da Natureza e da Biodiversidade.The existence of a national inventory of the geological heritage is of paramount importance for the implementation of a geoconservation strategy. This paper presents the methodological approach used to produce the most complete geosites inventory in Portugal, so far, and the obtained results. This inventory will be uploaded into the National Database of Natural Heritage managed by the Portuguese authority for nature conservation.Este trabalho é apoiado pela Fundação para a Ciência e a Tecnologia, através do financiamento plurianual do CGUP e do projecto de investigação “Identificação, caracterização e conservação do património geológico: uma estratégia de geoconservação para Portugal” (PTDC/CTE-GEX/64966/2006).info:eu-repo/semantics/publishedVersio