Measuring Column Densities in Quasar Outflows: VLT Observations of QSO 2359-1241

We present high resolution spectroscopic VLT observations of the outflow seen in QSO 2359-1241. These data contain absorption troughs from five resonance Fe II lines with a resolution of ~7 km/s and signal-to-noise ratio per resolution element of order 100. We use this unprecedented high quality data set to investigate the physical distribution of the material in front of the source, and by that determine the column densities of the absorbed troughs. We find that the apparent optical depth model gives a very poor fit to the data and greatly underestimates the column density measurements. Power-law distributions and partial covering models give much better fits with some advantage to power-law models, while both models yield similar column density estimates. The better fit of the power-law model solves a long standing problem plaguing the partial covering model when applied to large distance scale outflow: How to obtain a velocity dependent covering factor for an outflow situated at distances thousands of time greater than the size of the AGN emission source. This problem does not affect power-law models. Therefore, based on the better fit and plausibility of the physical model, we conclude that in QSO 2359-1241, the outflow covers the full extent of the emission source but in a non-homogeneous way.Comment: 27 pages, 6 figures, to appear on ApJ Jul 10. The full (online) version of figure 2 can be obtained here: http://www.phys.vt.edu/~arav/f2_online_version.p

Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.

The Hedgehog (Hh) pathway is essential for the embryonic development and homeostatic maintenance of many adult tissues and organs. It has also been associated with some functions of the innate and adaptive immune system. However, its involvement in the immune response has not been well determined. Here we study the role of Hh signalling in the modulation of the immune response by using the Ptch-1-LacZ+/- mouse model (hereinafter referred to as ptch+/-), in which the hemizygous inactivation of Patched-1, the Hh receptor gene, causes the constitutive activation of Hh response genes. The in vitro TCR stimulation of spleen and lymph node (LN) T cells showed increased levels of Th2 cytokines (IL-4 and IL-10) in ptch+/-cells compared to control cells from wild-type (wt) littermates, suggesting that the Th2 phenotype is favoured by Hh pathway activation. In addition, CD4+ cells secreted less IL-17, and the establishment of the Th1 phenotype was impaired in ptch+/- mice. Consistently, in response to an inflammatory challenge by the induction of experimental autoimmune encephalomyelitis (EAE), ptch+/- mice showed milder clinical scores and more minor spinal cord damage than wt mice. These results demonstrate a role for the Hh/ptch pathway in immune response modulation and highlight the usefulness of the ptch+/- mouse model for the study of T-cell-mediated diseases and for the search for new therapeutic strategies in inflammatory diseases.The work was sponsored by grants from Acción Estratégica en Salud (PI17CIII/00047 and PI21/00171).S

Beta interferon restricts the inflammatory potential of CD4+ cells through the boost of the Th2 phenotype, the inhibition of Th17 response and the prevalence of naturally occurring T regulatory cells

Beta-interferon (IFN-beta) is a valuable therapy for multiple sclerosis (MS) which is also effective in the animal model of experimental autoimmune encephalomyelitis (EAE). However, the accurate mechanisms to explain its anti-inflammatory activity in the disease are not fully revealed. Available data support that T lymphocytes are among the main cell targets of IFN-beta. We have found that in vitro anti-CD3 stimulation of uncommitted murine naïve T cells under IFN-beta treatment results in skewing the T cell differentiation process towards the T2 phenotype, in a prevention from apoptosis of naturally occurring CD4+ T regulatory cells (nTreg) in correlation with an increase in Bcl-XL expression, and in a decrease of IL-17 expression. Elimination of nTreg from the primary culture of naïve CD4+ cells abolished the down-regulation of IL-17 driven by IFN-beta, what suggests the interaction between Th17 and nTreg subsets. Experiments in EAE induced in SJL mice, showed in vivo evidence for the accumulation of spleen CD4+CD25+GITR+Foxp3+ cells after IFN-beta treatment. On the other hand, treated animals showed a striking decrease of IL-17 expression by peripheral CD4+ cells (Th17) and MBP-specific spinal cord cells. Both the in vivo and in vitro results point out new targets through which IFN-beta could exert its therapeutic action.This work was supported by grants from Plan Nacional de Investigación Científica y Tecnológica (SAF2003-00189), Instituto de Salud Carlos III (FIS-PI061012) and MM Foundation (MPY-1156/07). BB was supported by a grant from Instituto de Salud Carlos III, and FMMS was supported by a grant from MM Foundation.S

Coronectomy of impacted mandibular third molars: a meta-analysis and systematic review of the literature

Background: Coronectomy is an alternative to complete removal of an impacted mandibular third molar. Most authors have recommended coronectomy to prevent damage to the inferior alveolar nerve during surgical extraction of lower third molars. The present study offers a systematic review and metaanalysis of the coronectomy technique. Material and Methods: A systematic review and meta-analysis was performed based on a PubMed and Cochrane databases search for articles published from 2014 and involving coronectomy of mandibular third molars located near the inferior alveolar nerve canal, with a minimum of 10 cases and a minimum follow-up period of 6 months. After application of the inclusion and exclusion criteria, a total of 12 articles were included in the study. Results and Discussion: Coronectomy results in significantly lesser loss of sensitivity of the inferior alveolar nerve and prevents the occurrence of dry socket. No statistically significant differences were observed in the incidence of pain and infection between coronectomy and complete surgical extraction. After coronectomy, the remaining tooth fragment migrates an average of 2 mm within two years. Conclusions: Coronectomy is indicated when the mandibular third molar is in contact with the inferior alveolar nerve and complete removal of the tooth may cause nerve damage

Caminos Escolares, una nueva experiencia de movilidad a pie y en bici. Rutas existentes en Zaragoza y nueva propuesta

En el presente Trabajo se estudian los fundamentos y objetivos del Proyecto Camino Escolar en general y se recopilan y analizan los casos concretos que se han desarrollado y puesto en marcha en Zaragoza. Además, se realiza una nueva propuesta de Caminos Escolares a pie en Zaragoza para los colegios que se incorporaron al Proyecto durante el último curso escolar 2014-2015 y también se propone la ampliación del Proyecto a las rutas escolares en bici, para lo que también se realiza una propuesta concreta de posibles rutas. Por último, se realiza una propuesta de Mejora de la Accesibilidad en el entorno de uno de los centros escolares participantes

Cumulative climatic stressors strangles marine aquaculture: Ancillary effects of COVID 19 on Spanish mariculture

Marine aquaculture takes advantage of marine ecosystem services to produce goods that can be relevant from a food security point of view. However, this activity is subject to multiple stressors as the ones exerted by global climate change. Local stressed conditions due to environmental drivers may be exacerbated by the COVID19 pandemic crisis. In this paper we analyze the pre-COVID-19 situation in two Spanish regions with the highest aquaculture production, Galicia and the Valencian Community. The incidence of storms, heat waves and mussel farming closure were analyzed, and surveys were used to define the perception of producers in terms of economic problems derived from COVID-19 and synergistic environmental concerns. Also the temporal trend of mussel production was analyzed. Spanish marine aquaculture has been intensively subjected to climatic stressors that made it more vulnerable to COVID-19, showing some weakness in terms of production as can be seen in mussel production and fresh consumption. Anyway, extensive aquaculture and aquaculture developed by Integrated Multi-Trophic Aquaculture (IMTA) was reported as somewhat more resilient to the impact of COVID-19. In order to ensure the environmental and economic sustainability of marine aquaculture - under a future uncertain pandemic scenario – our outcomes underline the need for more resilient adaptation programs and recovery plans taking into account the climate change effects.M.C.M.’s research activity was supported by the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie Action (Grant agreement no. 835589, MIRROR Project)

Confined Sandwichlike Microenvironments Tune Myogenic Differentiation.

Sandwichlike (SW) cultures are engineered as a multilayer technology to simultaneously stimulate dorsal and ventral cell receptors, seeking to mimic cell adhesion in three-dimensional (3D) environments in a reductionist manner. The effect of this environment on cell differentiation was investigated for several cell types cultured in standard growth media, which promotes proliferation on two-dimensional (2D) surfaces and avoids any preferential differentiation. First, murine C2C12 myoblasts showed specific myogenic differentiation. Human mesenchymal stem cells (hMSCs) of adipose and bone marrow origin, which can differentiate toward a wider variety of lineages, showed again myodifferentiation. Overall, this study shows myogenic differentiation in normal growth media for several cell types under SW conditions, avoiding the use of growth factors and cytokines, i.e., solely by culturing cells within the SW environment. Mechanistically, it provides further insights into the balance between integrin adhesion to the dorsal substrate and the confinement imposed by the SW system

Analysis of first-line treatment in older patients with metastasic colorectal cancer

Objective: The purpose of this study was to analyse the effectiveness and safety of first-line treatment of metastatic colorectal cancer (CRCm) in older patients treated in a tertiary hospital. Material and methods: This was an observational and retrospective study, including patients aged 75 years or older, with CRCm, who received chemotherapy treatment in 2017. The main variables studied were type of treatment, Progression-Free Survival (PFS), Overall Survival (OS), dose reductions, and treatment delays due to adverse events. Results: A total of 59 patients (71.2% men) with a median age of 76 years were enrolled in this study. About 70% presented colon cancer, with the left colon being the most frequent location. They were treated with 9 different schemes, in most cases using polychemotherapy and biological agents. The median PFS and OS was 12 and 30 months, respectively. A total of 23/59 of patients started treatment at doses lower than recommended in the clinical practice guidelines. In terms of safety, 34/59 of patients had at least one dose reduction, and 30/59 suffered one treatment delay. The most frequent adverse reactions were asthenia, peripheral neuropathy, diarrhoea, and palmoplantar erythrodysesthesia. Conclusion: Our patients presented baseline clinical characteristics similar to the general adult population, with no tumour characteristics associated with advanced age. The efficacy and toxicity were similar to those in the clinical trials, although our patients had more dose reductions. Considering the heterogeneity of patients and in the absence of clinical trials in the older population, real-life studies can be very useful

La tecnología que aprende a elegir tu talla de calzado

Ballester Fernandez, A.; Gil Mora, S.; Valero, J.; Gonzalez Garcia, JC.; Remon Gomez, A. (2019). La tecnología que aprende a elegir tu talla de calzado. Innovación biomecánica en Europa. (8):1-3. http://hdl.handle.net/10251/167979S13

The TRPM8 antagonist RGM8-51 displays analgesic activity in different pain models

TRPM8 channels are overexpressed in sensory neurons after nerve injury or inflammation, resulting in enhanced sensitivity (allodynia and hyperalgesia) to physical stimulation, and have been implicated in migraine, but the interest of TRPM8 antagonists is still a matter of controversy (1,2). The aim of our work was to evaluate the analgesic activity of a TRPM8 antagonist, RGM8-51, in different pain models, looking for similarities and differences with other antagonists. To this end, we used the mouse oxaliplatin-induced peripheral neuropathy, the chronic constriction injury of the rat sciatic nerve (CCI) and mouse NTG-induced migraine-like models. Compound RGM8- 51 reduces the cold allodynia induced by oxaliplatin, from 15 to 60 min after administration (0.1-1 μg, i.pl.), decreases the nocifensive responses to cold, heat and mechanical stimuli in the CCI model (10 μg, i.pl., 30 mg/Kg, i.p.), and relief chronic pain associated to migraine in mouse, in a sex-dependent manner (10 or 30 mg/Kg, i.v.). The β–lactam derivative RGM8-51 not only has analgesic activity in all assayed animal models, but also seems to have a different mode of interaction with the TRPM8 channel than other antagonists, as suggested by docking studies