Effect of the β-amyloid peptide on microglia activation: ATP release

Previous studies have shown a key role of microglial cells in the neuroinflammatory processes associated with some neurodegenerative diseases, such as Alzheimer’s disease (AD). Microglia sense several types of diffusible molecules that regulate the multiple repertoire of microglial functions. Among them, extracellular nucleotides, acting on microglial P2 receptors, have central roles. In this sense, the ionotropic P2X7 receptor has gained recognition as a key regulator of microglial-mediated inflammatory responses.It is known that microglia releases ATP and other nucleotides to the extracellular medium. Although several mechanisms, such as release trough conexins or panexins, has been proposed, a vesicular origin for this released nucleotides, relying on the activity of the vesicular nucleotide transporter (VNUT), cannot be ruled out.In this work we evaluated whether the expression of VNUT and the P2X7 receptor, as well as the ATP release, could be modified in the reactive microglia. To achieve microglia activation we stimulated the cells with the lipopolysaccharide (LPS). Moreover, we analyzed the effect of the b-amyloid peptide b1-42, which is also able to activate the microglial cells, on the expression of VNUT and the ATP release in the microglia.Previous studies have shown a key role of microglial cells in the neuroinflammatory processes associated with some neurodegenerative diseases, such as Alzheimer’s disease (AD). Microglia sense several types of diffusible molecules that regulate the multiple repertoire of microglial functions. Among them, extracellular nucleotides, acting on microglial P2 receptors, have central roles. In this sense, the ionotropic P2X7 receptor has gained recognition as a key regulator of microglial-mediated inflammatory responses.It is known that microglia releases ATP and other nucleotides to the extracellular medium. Although several mechanisms, such as release trough conexins or panexins, has been proposed, a vesicular origin for this released nucleotides, relying on the activity of the vesicular nucleotide transporter (VNUT), cannot be ruled out.In this work we evaluated whether the expression of VNUT and the P2X7 receptor, as well as the ATP release, could be modified in the reactive microglia. To achieve microglia activation we stimulated the cells with the lipopolysaccharide (LPS). Moreover, we analyzed the effect of the b-amyloid peptide b1-42, which is also able to activate the microglial cells, on the expression of VNUT and the ATP release in the microgli

El transportador vesicular de nucleótidos (VNUT). Relevancia en tejidos neurales y neuroendocrinos. Nuevas perspectivas farmacológicas

Vesicular storage of neurotransmitters, which allows their subsequent exocytotic release, is essential for chemical transmission in neurons and endocrine cells. Neurotransmitter uptake to secretory vesicles is carried out by vesicular transporters, which use the electrochemical gradient of protons generated by a vacuolar proton-ATPase as transport driving force. ATP and other nucleotides and dinucleotides are relevant signaling molecules that participate in a variety of biological process. Although the active transport of nucleotides has been pharmacologically and biochemically characterized in a diversity of secretory vesicles, the protein responsible for such vesicular accumulation remained unidentified for some time. In 2008, SLC17A9, the last identified member of the SLC17 transporter family, was found to encode the vesicular nucleotide transporter (VNUT). VNUT is expressed in various ATP-secreting cells and is able to transport several nucleotides in a vesicular membrane potential- dependent fashion. VNUT knockout mice lack vesicular storage and release of ATP from neurons and neuroendocrine cells, resulting in blockage of the purinergic chemical transmission. This review summarizes the current studies on VNUT and analyzes the relevance of vesicular nucleotide transport in different cells types and tissues. The possible use of VNUT inhibitors and interference RNA to reduce VNUT gene expression for therapeutic purposes is also discussed.El almacenamiento vesicular de los neurotransmisores, que permite su subsecuente liberación exocitótica, es un proceso esencial para la transmisión química en neuronas y células endocrinas. La acumulación de los neurotransmisores en vesículas de secreción se lleva a cabo por medio de transportadores vesiculares, que utilizan el gradiente electroquímico de protones generado por una ATPasa vacuolar como fuerza impulsora del transporte. El ATP, así como otros nucleótidos y dinucleótidos, son importantes moléculas señalizadoras que intervienen en una gran variedad de procesos biológicos. Aunque el transporte activo de nucleótidos se ha caracterizado desde el punto de vista bioquímico y farmacológico en una variedad de vesículas de secreción, la proteína responsable de esta acumulación vesicular permaneció durante mucho tiempo desconocida. En 2008, se demostró que SLC17A9, el último miembro identificado de la familia de transportadores SLC17, codifica el transportador vesicular de nucleótidos (VNUT). VNUT se expresa en una variedad de células que liberan ATP y ha mostrado ser capaz de transportar varios nucleótidos de manera dependiente del potencial de membrana vesicular. Ratones deficientes en VNUT pierden la capacidad de almacenar y liberar ATP de neuronas y células neuroendocrinas, lo que resulta en un bloqueo de la transmisión química purinérgica. En esta revisión se pretende resumir los estudios llevados a cabo hasta la fecha sobre VNUT y analizar la relevancia del transporte vesicular de nucleótidos en distintos tipos celulares y tejidos. Asimismo, se discute el posible uso de inhibidores de VNUT, así como de ARNs de interferencia que reduzcan su expresión, con fines terapéuticos

Wavelength calibration for OSIRIS/GTC* tunable filters

OSIRIS (Optical System for Imaging and low Resolution Integrated Spectroscopy) is the first light instrument of the Gran Telescopio Canarias (GTC). It provides a flexible and competitive tunable filter (TF). Since it is based on a Fabry-Perot interferometer working in collimated beam, the TF transmission wavelength depends on the position of the target with respect to the optical axis. This effect is non-negligible and must be accounted for in the data reduction. Our paper establishes a wavelength calibration for OSIRIS TF with the accuracy required for spectrophotometric measurements using the full field of view (FOV) of the instrument. The variation of the transmission wavelength $\lambda(R)$ across the FOV is well described by $\lambda(R)=\lambda(0)/\sqrt{1+(R/f_2)^2}$, where $\lambda(0)$ is the central wavelength, $R$ represents the physical distance from the optical axis, and $f_2=185.70\pm0.17\,$mm is the effective focal length of the camera lens. This new empirical calibration yields an accuracy better than 1\,\AA\ across the entire OSIRIS FOV ($\sim$8\arcmin$\times$8\arcmin), provided that the position of the optical axis is known within 45 $\mu$m ($\equiv$ 1.5 binned pixels). We suggest a calibration protocol to grant such precision over long periods, upon re-alignment of OSIRIS optics, and in different wavelength ranges. This calibration differs from the calibration in OSIRIS manual which, nonetheless, provides an accuracy $\lesssim1$\AA\, for R\lesssim 2\arcmin.Comment: 22 pages, 7 figures, accepted for publication in PAS

New GTC spectroscopic data and a statistical study to better constrain the redshift of the BL Lac RGB J2243 + 203

We present new spectroscopic data of the BL Lac RGB 2243 + 203, and its surroundings, obtained with the OSIRIS Multi Object Spectrograph (MOS) mounted in the Gran Telescopio Canarias (GTC). The spectra of neither the BL Lac nor its host galaxy show any spectral feature, thus hindering direct determination of its redshift. The spectroscopic redshift distribution of objects in the MOS field of view shows four galaxies with redshift between 0.5258 and 0.5288. We make use of a statistical analysis to test the possibility that the targeted BL Lac may be a member of that group. By using the spectroscopic redshifts obtained with our GTC observations, we found that this probability is between 86 and 93 per cent.Fil: Rosa González, D. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Muriel, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Mayya, Y. D.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Aretxaga, I.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Becerra González, J.. Instituto de Astrofisica de Canarias; EspañaFil: Carramiñana, Alberto. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Méndez-Abreu, J.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Vega, O. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Terlevich, E-. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Coutiño de León, S.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Furniss, A.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Longinotti, A. L.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Terlevich, R. J.. Instituto Nacional de Astrofísica, Optica y Electrónica; MéxicoFil: Pichel, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Donzelli, Carlos Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentin

Could giardiasis be a risk factor for low zinc status in schoolchildren from northwestern Mexico? A cross-sectional study with longitudinal follow-up

<p>Abstract</p> <p>Background</p> <p>Both giardiasis and zinc deficiency are serious health problems worldwide. In Mexico, the prevalence of <it>G. intestinalis </it>was estimated at 32% in 1994. It remains a health problem in northwestern Mexico. Recent surveys (1987, 1995, and 1999) reported zinc deficiency in the Mexican population. The association of giardiasis and malabsorption of micronutrients has been well documented, although the association with zinc remains controversial. This study investigated the association between giardiasis and zinc deficiency in schoolchildren from northwestern Mexico.</p> <p>Methods</p> <p>We combined a cross-sectional design with a longitudinal follow-up six months after parasite treatment. The baseline sample consisted of 114 schoolchildren (mean age 8.8 yr) from seven suburban public schools, grouped as <it>Giardia</it>-free (<it>n </it>= 65, 57%) and <it>Giardia</it>-infected (<it>n </it>= 49, 43%). Three stool analyses per child were done using Faust's method. Children with giardiasis received secnidazole. Serum zinc was determined by atomic absorption spectrophotometry. Height and weight were measured. Socioeconomic information was obtained in an oral questionnaire, and daily zinc intake was assessed using 24 hour-recalls. Pearson's correlation and ANCOVA and paired t-test analyses were used to determine the association between giardiasis and zinc status.</p> <p>Results</p> <p>Longitudinal analysis demonstrated a significant increase of the mean serum zinc levels in the <it>Giardia</it>-infected group six months after treatment (13.78 vs. 19.24 μmol/L μmol/L; p = 0.001), although no difference was found between the <it>Giardia</it>-free and the <it>Giardia</it>-infected groups (p = 0.86) in the baseline analysis. Z scores for W/A and H/A were lower in the <it>Giardia</it>-infected than in the <it>Giardia</it>-free group (p < 0.05). No difference was observed in the socioeconomic characteristics and mean daily intakes of zinc between the groups (p > 0.05).</p> <p>Conclusions</p> <p>Giardiasis may be a risk factor for zinc deficiency in schoolchildren from northwestern Mexico.</p

Prevalence of anemia and deficiency of iron, folic acid, and zinc in children younger than 2 years of age who use the health services provided by the Mexican Social Security Institute

<p>Abstract</p> <p>Background</p> <p>In Mexico, as in other developing countries, micronutrient deficiencies are common in infants between 6 and 24 months of age and are an important public health problem. The objective of this study was to determine the prevalence of anemia and of iron, folic acid, and zinc deficiencies in Mexican children under 2 years of age who use the health care services provided by the Mexican Institute for Social Security (IMSS).</p> <p>Methods</p> <p>A nationwide survey was conducted with a representative sample of children younger than 2 years of age, beneficiaries, and users of health care services provided by IMSS through its regular regimen (located in urban populations) and its Oportunidades program (services offered in rural areas). A subsample of 4,955 clinically healthy children was studied to determine their micronutrient status. A venous blood sample was drawn to determine hemoglobin, serum ferritin, percent of transferrin saturation, zinc, and folic acid. Descriptive statistics include point estimates and 95% confidence intervals for the sample and projections for the larger population from which the sample was drawn.</p> <p>Results</p> <p>Twenty percent of children younger than 2 years of age had anemia, and 27.8% (rural) to 32.6% (urban) had iron deficiency; more than 50% of anemia was not associated with low ferritin concentrations. Iron stores were more depleted as age increased. Low serum zinc and folic acid deficiencies were 28% and 10%, respectively, in the urban areas, and 13% and 8%, respectively, in rural areas. The prevalence of simultaneous iron and zinc deficiencies was 9.2% and 2.7% in urban and rural areas. Children with anemia have higher percentages of folic acid deficiency than children with normal iron status.</p> <p>Conclusion</p> <p>Iron and zinc deficiencies constitute the principal micronutrient deficiencies in Mexican children younger than 2 years old who use the health care services provided by IMSS. Anemia not associated with low ferritin values was more prevalent than iron-deficiency anemia. The presence of micronutrient deficiencies at this early age calls for effective preventive public nutrition programs to address them.</p

Spatially resolved properties of the ionized gas in the H II galaxy J084220+115000

We present a spatially resolved spectroscopic study for the metal poor H II galaxy J084220+115000 using MEGARA Integral Field Unit observations at the Gran Telescopio Canarias. We estimated the gas metallicity using the direct method for oxygen, nitrogen, and helium and found a mean value of 12 + log (O/H) = 8.03 ± 0.06, and integrated electron density and temperature of ∼161 cm−3 and ∼15400 K, respectively. The metallicity distribution shows a large range of Δ(O/H) = 0.72 dex between the minimum and maximum (7.69 ± 0.06 and 8.42 ± 0.05) values, unusual in a dwarf star-forming galaxy. We derived an integrated log (N/O) ratio of −1.51 ± 0.05 and found that both N/O and O/H correspond to a primary production of metals. Spatially resolved maps indicate that the gas appears to be photoionized by massive stars according to the diagnostic line ratios. Between the possible mechanisms to explain the starburst activity and the large variation of oxygen abundance in this galaxy, our data support a possible scenario where we are witnessing an ongoing interaction triggering multiple star-forming regions localized in two dominant clumps. © 2023 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society.DFA work is funded by a Consejo Nacional de Ciencia y Tecnología (CONACyT, Mexico) grant through project A1-S-22784. This publication is based on data obtained with the MEGARA instrument at the GTC, installed in the Spanish Observatorio del Roque de los Muchachos, in the island of La Palma. MEGARA has been built by a Consortium led by the Universidad Complutense de Madrid (Spain) and that also includes the Instituto de Astrofísica, Optica y Electrónica (INAOE, Mexico), Instituto de Astrofísica de Andalucía (CSIC, Spain), and the Universidad Politécnica de Madrid (Spain). This work is based on data obtained with the MEGARA instrument, funded by European Regional Development Funds (ERDF), through the Programa Operativo Canarias FEDER 2014–2020. YDM thanks CONACYT for the research grant CB-A1-S-25070 and DRG for the research grant CB-A1-S-22784 from which the postdoctoral grant that supported DFA was obtained. RC also thanks CONACyT for the research grant CF2022-320152. RA acknowledges support from ANID Fondecyt Regular 1202007. ALGM acknowledges support from the Spanish Ministry of Science and Innovation, project PID2019-107408GB-C43 (ESTALLIDOS), and from Gobierno de Canarias through EU FEDER funding, project PID2020010050. JMA acknowledges the support of the Viera y Clavijo Senior program funded by ACIISI and ULL. JIP acknowledges financial support from projects Estallidos6 AYA2016-79724-C4 (Spanish Ministerio de Economia y Competitividad), Estallidos7 PID2019-107408GB-C44 (Spanish Ministerio de Ciencia e Innovacion), grant P18-FR-2664 (Junta de Andalucía), and grant SEV-2017-0709 ‘Center of Excellence Severo Ochoa Program’ (State Agency for Research of the Spanish MCIU).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe

MEGARA, the new intermediate-resolution optical IFU and MOS for GTC: getting ready for the telescope

MEGARA (Multi-Espectrógrafo en GTC de Alta Resolución para Astronomía) is an optical Integral-Field Unit (IFU) and Multi-Object Spectrograph (MOS) designed for the GTC 10.4m telescope in La Palma that is being built by a Consortium led by UCM (Spain) that also includes INAOE (Mexico), IAA-CSIC (Spain), and UPM (Spain). The instrument is currently finishing AIV and will be sent to GTC on November 2016 for its on-sky commissioning on April 2017. The MEGARA IFU fiber bundle (LCB) covers 12.5x11.3 arcsec2 with a spaxel size of 0.62 arcsec while the MEGARA MOS mode allows observing up to 92 objects in a region of 3.5x3.5 arcmin2 around the IFU. The IFU and MOS modes of MEGARA will provide identical intermediate-to-high spectral resolutions (RFWHM~6,000, 12,000 and 18,700, respectively for the low-, mid- and high-resolution Volume Phase Holographic gratings) in the range 3700-9800ÅÅ. An x-y mechanism placed at the pseudo-slit position allows (1) exchanging between the two observing modes and (2) focusing the spectrograph for each VPH setup. The spectrograph is a collimator-camera system that has a total of 11 VPHs simultaneously available (out of the 18 VPHs designed and being built) that are placed in the pupil by means of a wheel and an insertion mechanism. The custom-made cryostat hosts a 4kx4k 15-μm CCD. The unique characteristics of MEGARA in terms of throughput and versatility and the unsurpassed collecting are of GTC make of this instrument the most efficient tool to date to analyze astrophysical objects at intermediate spectral resolutions. In these proceedings we present a summary of the instrument characteristics and the results from the AIV phase. All subsystems have been successfully integrated and the system-level AIV phase is progressing as expected