Representación hecha al Rey Ntro. Sor. por D. Francisco Carrasco... sobre amortización : real orden con que fué remitida al Consejo Pleno de Castilla : dictamen que en él ha dado en calidad de fiscal y última satisfacción à los reparos que se han opuesto

Copia digital : Biblioteca de Asturias "Ramón Pérez de Ayala" : Biblioteca Pública Estatal de Oviedo, 2010Fecha y lugar al final del texto: Madrid, 16 de noviembre de 1765Sign.: A5, B-E4, F

Data Deluge in Astrophysics: Photometric Redshifts as a Template Use Case

Astronomy has entered the big data era and Machine Learning based methods have found widespread use in a large variety of astronomical applications. This is demonstrated by the recent huge increase in the number of publications making use of this new approach. The usage of machine learning methods, however is still far from trivial and many problems still need to be solved. Using the evaluation of photometric redshifts as a case study, we outline the main problems and some ongoing efforts to solve them.Comment: 13 pages, 3 figures, Springer's Communications in Computer and Information Science (CCIS), Vol. 82

Visual Performance Fields: Frames of Reference

Performance in most visual discrimination tasks is better along the horizontal than the vertical meridian (Horizontal-Vertical Anisotropy, HVA), and along the lower than the upper vertical meridian (Vertical Meridian Asymmetry, VMA), with intermediate performance at intercardinal locations. As these inhomogeneities are prevalent throughout visual tasks, it is important to understand the perceptual consequences of dissociating spatial reference frames. In all studies of performance fields so far, allocentric environmental references and egocentric observer reference frames were aligned. Here we quantified the effects of manipulating head-centric and retinotopic coordinates on the shape of visual performance fields. When observers viewed briefly presented radial arrays of Gabors and discriminated the tilt of a target relative to homogeneously oriented distractors, performance fields shifted with head tilt (Experiment 1), and fixation (Experiment 2). These results show that performance fields shift in-line with egocentric referents, corresponding to the retinal location of the stimulus

Inhibition of the sodium-dependent HCO₃ - transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype

\ua9 2022, eLife Sciences Publications Ltd. All rights reserved. Bicarbonate secretion is a fundamental process involved in maintaining acid-base homeostasis. Disruption of bicarbonate entry into airway lumen, as has been observed in cystic fibrosis, produces several defects in lung function due to thick mucus accumulation. Bicarbonate is critical for correct mucin deployment and there is increasing interest in understanding its role in airway physiology, particularly in the initiation of lung disease in children affected by cystic fibrosis, in the absence of detectable bacterial infection. The current model of anion secretion in mammalian airways consists of CFTR and TMEM16A as apical anion exit channels, with limited capacity for bicarbonate transport compared to chloride. However, both channels can couple to SLC26A4 anion exchanger to maximise bicarbonate secretion. Nevertheless, current models lack any details about the identity of the basolateral protein(s) responsible for bicarbonate uptake into airway epithelial cells. We report herein that the electrogenic, sodium-dependent, bicarbonate cotransporter, SLC4A4, is expressed in the basolateral membrane of human and mouse airways, and that it’s pharmacological inhibition or genetic silencing reduces bicarbonate secretion. In fully differentiated primary human airway cells cultures, SLC4A4 inhibition induced an acidification of the airways surface liquid and markedly reduced the capacity of cells to recover from an acid load. Studies in the Slc4a4-null mice revealed a previously unreported lung phenotype, characterized by mucus accumulation and reduced mucociliary clearance. Collectively, our results demonstrate that the reduction of SLC4A4 function induced a CF-like phenotype, even when chloride secretion remained intact, highlighting the important role SLC4A4 plays in bicarbonate secretion and mammalian airway function

Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability

Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening

Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

BACKGROUND: The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. METHODS: We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. RESULTS: Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. CONCLUSION: Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found

Impact of the Covid-19 pandemic on perinatal mental health (Riseup-PPD-COVID-19): protocol for an international prospective cohort study

Background: Corona Virus Disease 19 (COVID-19) is a new pandemic, declared a public health emergency by the World Health Organization, which could have negative consequences for pregnant and postpartum women. The scarce evidence published to date suggests that perinatal mental health has deteriorated since the COVID-19 outbreak. However, the few studies published so far have some limitations, such as a cross-sectional design and the omission of important factors for the understanding of perinatal mental health, including governmental restriction measures and healthcare practices implemented at the maternity hospitals. Within the Riseup-PPD COST Action, a study is underway to assess the impact of COVID-19 in perinatal mental health. The primary objectives are to (1) evaluate changes in perinatal mental health outcomes; and (2) determine the risk and protective factors for perinatal mental health during the COVID-19 pandemic. Additionally, we will compare the results between the countries participating in the study. Methods: This is an international prospective cohort study, with a baseline and three follow-up assessments over a six-month period. It is being carried out in 11 European countries (Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom), Argentina, Brazil and Chile. The sample consists of adult pregnant and postpartum women (with infants up to 6 months of age). The assessment includes measures on COVID-19 epidemiology and public health measures (Oxford COVID-19 Government Response Tracker dataset), Coronavirus Perinatal Experiences (COPE questionnaires), psychological distress (BSI-18), depression (EPDS), anxiety (GAD-7) and post-traumatic stress symptoms (PTSD checklist for DSM-V). Discussion: This study will provide important information for understanding the impact of the COVID-19 pandemic on perinatal mental health and well-being, including the identification of potential risk and protective factors by implementing predictive models using machine learning techniques. The findings will help policymakers develop suitable guidelines and prevention strategies for perinatal mental health and contribute to designing tailored mental health interventions. Trial registration: ClinicalTrials.gov Identifier: NCT04595123.The project is part of the COST Action Riseup-PPD CA 18138 and was supported by COST under COST Action Riseup-PPD CA18138; also, by the Spanish Ministry of Health, the Institute of Health Carlos III, and the European Regional Development Fund «Una manera de hacer Europa» by the Prevention and Health Promotion Research Network ‘redIAPP’ (RD16/0007). Raquel Costa is supported by the FSE and FCT under an individual Post-Doctoral Grant SFRH/BPD/117597/2016. Rena Bina and Drorit Levy received funding from the Bar-Ilan Dangoor Centre for Personalized Medicine, Israel. Ana Mesquita is supported from the Portuguese Foundation for Science and Technology (FCT) and from EU through the European Social Fund and from the Human Potential Operational Program - IF/00750/2015. Ana Osório received financial support from CAPES/Proex no. 0653/2018 and CAPES/PrInt grant no. 88887.310343/2018-00.The funders of the study had no role in the study design or the writing the protocol. The corresponding author had final responsibility for the decision to submit for publication