Mecp2-null mice provide new neuronal targets for Rett syndrome

BACKGROUND: Rett syndrome (RTT) is a complex neurological disorder that is one of the most frequent causes of mental retardation in women. A great landmark in research in this field was the discovery of a relationship between the disease and the presence of mutations in the gene that codes for the methyl-CpG binding protein 2 (MeCP2). Currently, MeCP2 is thought to act as a transcriptional repressor that couples DNA methylation and transcriptional silencing. The present study aimed to identify new target genes regulated by Mecp2 in a mouse model of RTT. METHODOLOGY/PRINCIPAL FINDINGS: We have compared the gene expression profiles of wild type (WT) and Mecp2-null (KO) mice in three regions of the brain (cortex, midbrain, and cerebellum) by using cDNA microarrays. The results obtained were confirmed by quantitative real-time PCR. Subsequent chromatin immunoprecipitation assays revealed seven direct target genes of Mecp2 bound in vivo (Fkbp5, Mobp, Plagl1, Ddc, Mllt2h, Eya2, and S100a9), and three overexpressed genes due to an indirect effect of a lack of Mecp2 (Irak1, Prodh and Dlk1). The regions bound by Mecp2 were always methylated, suggesting the involvement of the methyl-CpG binding domain of the protein in the mechanism of interaction. CONCLUSIONS: We identified new genes that are overexpressed in Mecp2-KO mice and are excellent candidate genes for involvement in various features of the neurological disease. Our results demonstrate new targets of MeCP2 and provide us with a better understanding of the underlying mechanisms of RTT

Pharmacological Interactions of Nintedanib and Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis in Times of COVID-19 Pandemic

The discovery of antifibrotic agents have resulted in advances in the therapeutic management of idiopathic pulmonary fibrosis (IPF). Currently, nintedanib and pirfenidone have become the basis of IPF therapy based on the results of large randomized clinical trials showing their safety and efficacy in reducing disease advancement. However, the goal of completely halting disease progress has not been reached yet. Administering nintedanib with add-on pirfenidone is supposed to enhance the therapeutic benefit by simultaneously acting on two different pathogenic pathways. All this becomes more important in the context of the ongoing global pandemic of coronavirus disease 2019 (COVID-19) because of the fibrotic consequences following SARS-CoV-2 infection in some patients. However, little information is available about their drug-drug interaction, which is important mainly in polymedicated patients. The aim of this review is to describe the current management of progressive fibrosing interstitial lung diseases (PF-ILDs) in general and of IPF in particular, focusing on the pharmacokinetic drug-drug interactions between these two drugs and their relationship with other medications in patients with IPF

Impact of prevalence ratios of chondroitin sulfate (CS)- 4 and -6 isomers derived from marine sources in cell proliferation and chondrogenic differentiation processes

[Abstract] Osteoarthritis is the most prevalent rheumatic disease. During disease progression, differences have been described in the prevalence of chondroitin sulfate (CS) isomers. Marine derived-CS present a higher proportion of the 6S isomer, offering therapeutic potential. Accordingly, we evaluated the effect of exogenous supplementation of CS, derived from the small spotted catshark (Scyliorhinus canicula), blue shark (Prionace glauca), thornback skate (Raja clavata) and bovine CS (reference), on the proliferation of osteochondral cell lines (MG-63 and T/C-28a2) and the chondrogenic differentiation of mesenchymal stromal cells (MSCs). MG-G3 proliferation was comparable between R. clavata (CS-6 intermediate ratio) and bovine CS (CS-4 enrichment), for concentrations below 0.5 mg/mL, defined as a toxicity threshold. T/C-28a2 proliferation was significantly improved by intermediate ratios of CS-6 and -4 isomers (S. canicula and R. clavata). A dose-dependent response was observed for S. canicula (200 µg/mL vs 50 and 10 µg/mL) and bovine CS (200 and 100 µg/mL vs 10 µg/mL). CS sulfation patterns discretely affected MSCs chondrogenesis; even though S. canicula and R. clavata CS up-regulated chondrogenic markers expression (aggrecan and collagen type II) these were not statistically significant. We demonstrate that intermediate values of CS-4 and -6 isomers improve cell proliferation and offer potential for chondrogenic promotion, although more studies are needed to elucidate its mechanism of action.Xunta de Galicia; IN607A 2017/11Xunta de Galicia; IN607B 2018/19European Commission; 0245_IBEROS_1_

Shape-invariant quantum Hamiltonian with position-dependent effective mass through second order supersymmetry

Second order supersymmetric approach is taken to the system describing motion of a quantum particle in a potential endowed with position-dependent effective mass. It is shown that the intertwining relations between second order partner Hamiltonians may be exploited to obtain a simple shape-invariant condition. Indeed a novel relation between potential and mass functions is derived, which leads to a class of exactly solvable model. As an illustration of our procedure, two examples are given for which one obtains whole spectra algebraically. Both shape-invariant potentials exhibit harmonic-oscillator-like or singular-oscillator-like spectra depending on the values of the shape-invariant parameter.Comment: 16 pages, 5 figs; Present e-mail of AG: [email protected]

Conductance oscillations of a spin-orbit stripe with polarized contacts

We investigate the linear conductance of a stripe of spin-orbit interaction in a 2D electron gas; that is, a 2D region of length $\ell$ along the transport direction and infinite in the transverse one in which a spin-orbit interaction of Rashba type is present. Polarization in the contacts is described by means of Zeeman fields. Our model predicts two types of conductance oscillations: Ramsauer oscillations in the minority spin transmission, when both spins can propagate, and Fano oscillations when only one spin propagates. The latter are due to the spin-orbit coupling with quasibound states of the non propagating spin. In the case of polarized contacts in antiparallel configuration Fano-like oscillations of the conductance are still made possible by the spin orbit coupling, even though no spin component is bound by the contacts. To describe these behaviors we propose a simplified model based on an ansatz wave function. In general, we find that the contribution for vanishing transverse momentum dominates and defines the conductance oscillations. Regarding the oscillations with Rashba coupling intensity, our model confirms the spin transistor behavior, but only for high degrees of polarization. Including a position dependent effective mass yields additional oscillations due to the mass jumps at the interfaces.Comment: 8.5 pages, 9 figure

The INT Search for Metal-Poor Stars. Spectroscopic Observations and Classification via Artificial Neural Networks

With the dual aims of enlarging the list of extremely metal-poor stars identified in the Galaxy, and boosting the numbers of moderately metal-deficient stars in directions that sample the rotational properties of the thick disk, we have used the 2.5m Isaac Newton Telescope and the Intermediate Dispersion Spectrograph to carry out a survey of brighter (primarily northern hemisphere) metal-poor candidates selected from the HK objective-prism/interference-filter survey of Beers and collaborators. Over the course of only three observing runs (15 nights) we have obtained medium-resolution (resolving power ~ 2000) spectra for 1203 objects (V ~ 11-15). Spectral absorption-line indices and radial velocities have been measured for all of the candidates. Metallicities, quantified by [Fe/H], and intrinsic (B-V)o colors have been estimated for 731 stars with effective temperatures cooler than roughly 6500 K, making use of artificial neural networks (ANNs), trained with spectral indices. We show that this method performs as well as a previously explored Ca II K calibration technique, yet it presents some practical advantages. Among the candidates in our sample, we identify 195 stars with [Fe/H] <= -1.0, 67 stars with [Fe/H] <= -2.0, and 12 new stars with [Fe/H] <= -3.0. Although the EFECTIVE YIELD of metal-poor stars in our sample is not as large as previous HK survey follow-up programs, the rate of discovery per unit of telescope time is quite high.Comment: 27 pages (including 13 figures) + 6 tables (20 pages); uses aastex, lscape and graphicx; to appear in A

Metodología para la evaluación del error de medición de un parque de contadores

[ES] El rendimiento volumétrico de un abastecimiento es quizás uno de los parámetros más importantes a la hora de analizar la eficiencia de un sistema de distribución de agua. Sin embargo para realizar una estimación correcta del mismo se debe conocer una serie de factores como son: el volumen no medido, el no contabilizado debido al subcontaje de los contadores domiciliarios o el perdido en fugas. El presente artículo propone una metodología para estimar la porción de volumen no registrado que corresponde al subcontaje de contadores. Se estructura en dos partes. La primera se centra en la obtención de la forma de consumir de los abonados. En la segunda se lleva a cabo un análisis estadístico del parque de contadores para, en función de la forma de consumir de los abonados, calcular la precisión media del mismo y, en consecuencia, el volumen no registrado en los contadores domiciliarios.El presente trabajo ha sido parcialmente financiado por la CICYT, a través del proyecto de investigación "Monitorización de redes de distribución de agua y su aplicación a la detección de fugas" Ref. AMB95-0869.Arregui De La Cruz, F.; García-Serra García, J.; López Patiño, G.; Martínez Solano, J. (1998). Metodología para la evaluación del error de medición de un parque de contadores. Ingeniería del Agua. 5(4):55-66. https://doi.org/10.4995/ia.1998.2772SWORD556654Amirola Camps J. J. (1997) Control de pérdidas de agua. Análisis de pérdidas y fugas en redes de abastecimiento. Curso 4/1997. A.S.A.Andrés M. (1995) Mejora del Rendimiento y de la Fiabilidad en Sistemas de Distribución de Agua. Ed. Grupo Mecánica de Fluidos. U.P.V.Arregui F. (1998) Propuesta de una Metodología para el Análisis y Gestión del Parque de Contadores de Agua en un Abastecimiento. Tesis Doctoral. Universidad Politécnica de Valencia.AWWA (1986) Water Meters-Selection. Installation. Testing and Maintenance. AWWA 3rd Ed.; Denver, COAWWA (1966) Determination of Economic Period for Water meter Replacement. J. of AWWA. Junio 1966; pp 642-650.Bowen P.T., Harp J.F., Baxter J.W., Shull R.D. (1993) Residential Water Use Patterns. Ed American Water Works Association Research Foundation. Denver, COBrittain, R.L. (1974) Small Meter Periodic Test Limit Extension Study. Unpublished Report, Philadelphia Suburban Water Company.Daniel W.W., Terriel J.C. (1994) Business Statistics for Management and Economics. Houghton Mifflin Company. BostonGraeser, H.J. (1958) Detecting Lost Water at Dallas. L of AWWA. Juho 1958; pp 925-932Hudson, W.D. (1964) Reduction of Unaccounted-for Water. J. ofAWWA. Febrero 1964; pp 143-148Male J.W., Noss R.R., Moore I.C. (1985) Identifying and Reducing Losses in Water Distribution Systems. Noyes Publications.Nielsen, N. (1969) Determination of Proper Age for 5/8 Inch Meters in the Hacken sack and Spring Valley Systems. Report for the Hackensack Water Company, Harrington Park, NJ.Planells F., Antolí A., López V., Sanz F., García-Serra J. (1987) Diagnóstico de la gestión óptima de contadores en un sistema de distribución de agua. Tecnología del Agua N°38 1987.Siseo, R.J. (1967) The case for Meter Replacement Programs J. of AWWA ,Nov. 1967; pp 1149-1455.Skarda, B.C. (1987) The Swiss Experience with Performance Indicators and Special Viewpoints on Water Networks. IWSA Workshop on Performance Indicators and Distributions Systems. LNEC. Lisboa. Mayo 1997Yanov, D.A., Koch, R.N. (1987) A Modern Residential Flow Demand Study. Session 27 of AWWA Annual Conference. Kansas City, KS

Complex organic molecules in protostellar environments in the SKA era

Molecular complexity builds up at each step of the Sun-like star formation process, starting from simple molecules and ending up in large polyatomic species. Complex organic molecules (COMs; such as methyl formate, HCOOCH$_3$, dymethyl ether, CH$_3$OCH$_3$, formamide, NH$_2$CHO, or glycoaldehyde, HCOCH$_2$OH) are formed in all the components of the star formation recipe (e.g. pre-stellar cores, hot-corinos, circumstellar disks, shocks induced by fast jets), due to ice grain mantle sublimation or sputtering as well as gas-phase reactions. Understanding in great detail the involved processes is likely the only way to predict the ultimate molecular complexity reached in the ISM, as the detection of large molecules is increasingly more difficult with the increase of the number of atoms constituting them. Thanks to the recent spectacular progress of astronomical observations, due to the Herschel (sub-mm and IR), IRAM and SMA (mm and sub-mm), and NRAO (cm) telescopes, an enormous activity is being developed in the field of Astrochemistry, extending from astronomical observatories to chemical laboratories. We are involved in several observational projects providing unbiased spectral surveys (in the 80-300 and 500-2000 GHz ranges) with unprecedented sensitivity of templates of dense cores and protostars. Forests of COM lines have been detected. In this chapter we will focus on the chemistry of both cold prestellar cores and hot shocked regions, (i) reviewing results and open questions provided by mm-FIR observations, and (ii) showing the need of carrying on the observations of COMs at lower frequencies, where SKA will operate. We will also emphasize the importance of analysing the spectra by the light of the experimental studies performed by our team, who is investigating the chemical effects induced by ionising radiation bombarding astrophysically relevant ices.Comment: 18 pages, 8 figure

Ecological correlates of Golden eagle (Aquila chrysaetos) breeding occurrence in Sardinia (Italy).

Capsule Golden Eagles Aquila chrysaetos in Sardinia are clustered across the main mountain ranges of the island, with a preference for undisturbed and homogeneous inland habitats. Aims To analyse habitat preferences of the Golden Eagle in Sardinia, Italy, at the landscape and home range spatial scales. Methods Landscape scale habitat preferences were analysed using the 10 × 10 km Universal Transverse Mercator grid and the home range scale was based on the spatial distribution of breeding territories. Generalized linear models were fitted with three different sets of environmental predictors (topographic, bioclimatic and land use variables) to analyse the spatial distribution of Golden Eagles with a case-control design. Results Eagles showed a preference for rugged and elevated areas, characterized by a certain degree of humidity and surrounded by areas of forest. The distribution of Golden Eagles on this Mediterranean island was negatively affected by the occurrence of arable farmland and coastal areas, as well as by the effects of habitat fragmentation. Conclusions The results of this study could contribute to future management strategies and conservation projects aimed to protect this species, and may be used to identify the most suitable conservation areas for this and other competing species, such as the Bonelli's Eagle Aquila fasciata, which is currently the subject of a reintroduction project in Sardinia

Ocular related emergencies in Spain during the COVID-19 pandemic, a multicenter study

Purpose: To evaluate ophthalmological emergencies (OE) during the COVID-19 pandemic comparing them with the same period of the previous year. Methods: Retrospective observational study of all OE visits in four tertiary hospitals in Spain comparing data from March 16th to April 30th, 2020 (COVID-19 period) and the same period of 2019 (pre-COVID-19 period). Severity of the conditions was assessed following Channa et al. publication. Data on demographics, diagnosis and treatments were collected from Electronic Medical Records. Results: During lockdown, OE significantly declined by 75.18%, from 7, 730 registered in the pre-COVID-19 period to 1, 928 attended during the COVID-19 period (p < 0.001). In 2019, 23.86% of visits were classified as emergent, 59.50% as non-emergent, and 16.65% could not be determined. In 2020, the percentage of emergent visits increased up to 29.77%, non-emergent visits significantly decreased to 52.92% (p < 0.001), and 17.31% of the visits were classified as “could not determine”. During the pandemic, people aged between 45 and 65 years old represented the largest attending group (37.89%), compared to 2019, where patients over 65 years were the majority (39.80%). In 2019, most frequent diagnosis was unspecified acute conjunctivitis (11.59%), followed by vitreous degeneration (6.47%), and punctate keratitis (5.86%). During the COVID-19 period, vitreous degeneration was the first cause for consultation (9.28%), followed by unspecified acute conjunctivitis (5.63%) and punctate keratitis (5.85%). Conclusions: OE visits dropped significantly during the pandemic in Spain (75.18%), although more than half were classified as non-urgent conditions, indicating a lack of understanding of the really emergent ocular pathologies among population. © 2021, The Author(s)