Open data on Covid-19 in the Spanish autonomous communities: reutilization in spatial epidemiology studies

The Covid-19 pandemic has highlighted the need for governments and health administrations at all levels to have an open data registry that facilitates decision-making in the planning and management of health resources and provides information to citizens on the evolution of the epidemic. The concept of “open data” includes the possibility of reutilization by third parties. Space and time are basic dimensions used to structure and interpret the data of the variables that refer to the health status of the people themselves. Hence, the main objective of this study is to evaluate whether the autonomous communities’ data files regarding Covid-19 are reusable to analyze the evolution of the disease in basic spatial and temporal analysis units at the regional and national levels. To this end, open data files containing the number of diagnosed cases of Covid-19 distributed in basic health or administrative spatial units and temporal units were selected from the portals of the Spanish autonomous communities. The presence of infection-related, demographic, and temporal variables, as well as the download format and metadata, were mainly evaluated. Whether the structure of the files was homogeneous and adequate for the application of spatial analysis techniques was also analyzed. The results reveal a lack of standardization in the collection of data in both spatial and temporal units and an absence of, or ambiguity in, the meaning of the variables owing to a lack of metadata. An inadequate structure was also found in the files of seven autonomous communities, which would require subsequent processing of the data to enable their reuse and the application of analysis and spatial modeling techniques, both when carrying out global analyses and when comparing patterns of evolution between different regions

Sex differences in constitutive autophagy

Sex bias has been described nowadays in biomedical research on animal models, although sexual dimorphism has been confirmed widely under pathological and physiological conditions. The main objective of our work was to study the sex differences in constitutive autophagy in spinal cord and skeletalmuscle tissue fromwild type mice. To examine the influence of sex on autophagy, mRNA and proteins were extracted from male and female mice tissues.The expressions of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), markers to monitor autophagy, were analyzed at 40, 60, 90, and 120 days of age.We found significant sex differences in the expression of LC3 and p62 in both tissues at these ages. The results indicated that sex and tissue specific differences exist in constitutive autophagy.These data underlined the need to include both sexes in the experimental groups to minimize any sex bias

Intradomain confinement of disulfides in the folding of two consecutive modules of the LDL receptor

The LDL receptor internalizes circulating LDL and VLDL particles for degradation. Its extracellular binding domain contains ten (seven LA and three EGF) cysteine-rich modules, each bearing three disulfide bonds. Despite the enormous number of disulfide combinations possible, LDLR oxidative folding leads to a single native species with 30 unique intradomain disulfides. Previous folding studies of the LDLR have shown that non native disulfides are initially formed that lead to compact species. Accordingly, the folding of the LDLR has been described as a "coordinated nonvectorial" reaction, and it has been proposed that early compaction funnels the reaction toward the native structure. Here we analyze the oxidative folding of LA4 and LA5, the modules critical for ApoE binding, isolated and in the LA45 tandem. Compared to LA5, LA4 folding is slow and inefficient, resembling that of LA5 disease-linked mutants. Without Ca++, it leads to a mixture of many two-disulfide scrambled species and, with Ca++, to the native form plus two three-disulfide intermediates. The folding of the LA45 tandem seems to recapitulate that of the individual repeats. Importantly, although the folding of the LA45 tandem takes place through formation of scrambled isomers, no interdomain disulfides are detected, i.e. the two adjacent modules fold independently without the assistance of interdomain covalent interactions. Reduction of incredibly large disulfide combinatorial spaces, such as that in the LDLR, by intradomain confinement of disulfide bond formation might be also essential for the efficient folding of other homologous disulfide-rich receptors

Versatilidad de las toxinas en la investigación biomédica

El fragmento C de la toxina tetánica (TTC) se caracteriza por ser no tóxico y poseer untransporte retrogrado y transináptico. Gracias a estas cualidades, se presenta como un candidatomuy interesante tanto como trazador neuronal para el mapeo de las conexiones anatómicas entrelas distintas estructuras del Sistema Nervioso Central (SNC) como vector de posibles moléculasterapéuticas para dicho sistema. Se ha demostrado que la unión a moléculas biológicas comogenes reporteros o proteínas (de hasta 150 kDa) y moléculas potencialmente terapéuticas noimplican la perdida de su actividad biológica. Al fusionarse a distintas moléculas, TTC ha sidousado como una herramienta molecular para el estudio de procesos neuronales como laendocitosis, el transporte retrogrado o el análisis de sinapsis por ser diana de moto neuronastanto in vivo como in vitro. Por otra parte, estudios realizados por nuestro laboratorio con elDNA desnudo que codifica para el fragmento C de la toxina tetánica han demostrado que por simismo es capaz de proteger a neuronas de la degeneración en distintos modelos animales quecursan con neurodegeneracion como son la Esclerosis Lateral Amiotrófica, la Atrofia MuscularEspinal o la isquemia cerebral. Este último hecho nos ha permitido patentar y licenciar TTC auna empresa farmaceútica como posible medicamento neuroprotector en el tratamiento de laEsclerosis Lateral Amiotrófica

Intradomain confinement of disulfides in the folding of two consecutive modules of the LDL receptor

© 2015 Martínez-Oliván et al. The LDL receptor internalizes circulating LDL and VLDL particles for degradation. Its extracellular binding domain contains ten (seven LA and three EGF) cysteine-rich modules, each bearing three disulfide bonds. Despite the enormous number of disulfide combinations possible, LDLR oxidative folding leads to a single native species with 30 unique intradomain disulfides. Previous folding studies of the LDLR have shown that non native disulfides are initially formed that lead to compact species. Accordingly, the folding of the LDLR has been described as a >coordinated nonvectorial> reaction, and it has been proposed that early compaction funnels the reaction toward the native structure. Here we analyze the oxidative folding of LA4 and LA5, the modules critical for ApoE binding, isolated and in the LA45 tandem. Compared to LA5, LA4 folding is slow and inefficient, resembling that of LA5 disease-linked mutants. Without Ca++, it leads to a mixture of many two-disulfide scrambled species and, with Ca++, to the native form plus two three-disulfide intermediates. The folding of the LA45 tandem seems to recapitulate that of the individual repeats. Importantly, although the folding of the LA45 tandem takes place through formation of scrambled isomers, no interdomain disulfides are detected, i.e. the two adjacent modules fold independently without the assistance of interdomain covalent interactions. Reduction of incredibly large disulfide combinatorial spaces, such as that in the LDLR, by intradomain confinement of disulfide bond formation might be also essential for the efficient folding of other homologous disulfide-rich receptors.Peer Reviewe

Light yield determination in large sodium iodide detectors applied in the search for dark matter

Application of NaI(Tl) detectors in the search for galactic dark matter particles through their elastic scattering off the target nuclei is well motivated because of the long standing DAMA/LIBRA highly significant positive result on annual modulation, still requiring confirmation. For such a goal, it is mandatory to reach very low threshold in energy (at or below the keV level), very low radioactive background (at a few counts/keV/kg/day), and high detection mass (at or above the 100 kg scale). One of the most relevant technical issues is the optimization of the crystal intrinsic scintillation light yield and the efficiency of the light collecting system for large mass crystals. In the frame of the ANAIS (Annual modulation with NaI Scintillators) dark matter search project large NaI(Tl) crystals from different providers coupled to two photomultiplier tubes (PMTs) have been tested at the Canfranc Underground Laboratory. In this paper we present the estimates of the NaI(Tl) scintillation light collected using full-absorption peaks at very low energy from external and internal sources emitting gammas/electrons, and single-photoelectron events populations selected by using very low energy pulses tails. Outstanding scintillation light collection at the level of 15~photoelectrons/keV can be reported for the final design and provider chosen for ANAIS detectors. Taking into account the Quantum Efficiency of the PMT units used, the intrinsic scintillation light yield in these NaI(Tl) crystals is above 40~photoelectrons/keV for energy depositions in the range from 3 up to 25~keV. This very high light output of ANAIS crystals allows triggering below 1~keV, which is very important in order to increase the sensitivity in the direct detection of dark matter

Background analysis and status of the ANAIS dark matter project

ANAIS (Annual modulation with NaI Scintillators) is a project aiming to set up at the new facilities of the Canfranc Underground Laboratory (LSC), a large scale NaI(Tl) experiment in order to explore the DAMA/LIBRA annual modulation positive result using the same target and technique. Two 12.5 kg each NaI(Tl) crystals provided by Alpha Spectra took data at the LSC in the ANAIS-25 set-up. The comparison of the background model for the ANAIS-25 prototypes with the experimental results is presented. ANAIS crystal radiopurity goals have been achieved for Th-232 and U-238 chains, but a Pb-210 contamination out-of-equilibrium was identified, whose origin has been studied. The high light collection efficiency obtained with these prototypes allows to anticipate an energy threshold of the order of 1 keVee. A new detector, with improved performances, was received in March 2015 and very preliminary results are shown.Comment: 6 pages, 7 figure