Reactive astrocyte nomenclature, definitions, and future directions

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to search for astrophysical neutrino sources. It has so far provided compelling evidence for a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 was observed in coincidence with the high-energy neutrino IceCube-170922A detected by IceCube. The detection of very-high-energy gamma rays (VHE, E > 100 GeV) from this source helped establish the coincidence and constrained the modeling of the blazar emission at the time of the IceCube event. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) - FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program of target-of-opportunity observations of neutrino alerts sent by IceCube. This program has two main components. One are the observations of known gamma-ray sources around which a cluster of candidate neutrino events has been identified by IceCube (Gamma-ray Follow-Up, GFU). The second one is the follow-up of single high-energy neutrino candidate events of potential astrophysical origin such as IceCube-170922A. GFU has been recently upgraded by IceCube in collaboration with the IACT groups. We present here recent results from the IACT follow-up programs of IceCube neutrino alerts and a description of the upgraded IceCube GFU system

Combined dark matter searches towards dwarf spheroidal galaxies with Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS

Cosmological and astrophysical observations suggest that 85% of the total matter of the Universe is made of Dark Matter (DM). However, its nature remains one of the most challenging and fundamental open questions of particle physics. Assuming particle DM, this exotic form of matter cannot consist of Standard Model (SM) particles. Many models have been developed to attempt unraveling the nature of DM such as Weakly Interacting Massive Particles (WIMPs), the most favored particle candidates. WIMP annihilations and decay could produce SM particles which in turn hadronize and decay to give SM secondaries such as high energy \u1d6fe rays. In the framework of indirect DM search, observations of promising targets are used to search for signatures of DM annihilation. Among these, the dwarf spheroidal galaxies (dSphs) are commonly favored owing to their expected high DM content and negligible astrophysical background. In this work, we present the very first combination of 20 dSph observations, performed by the Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS collaborations in order to maximize the sensitivity of DM searches and improve the current results. We use a joint maximum likelihood approach combining each experiment’s individual analysis to derive more constraining upper limits on the WIMP DM self-annihilation cross-section as a function of DM particle mass. We present new DM constraints over the widest mass range ever reported, extending from 5 GeV to 100 TeV thanks to the combination of these five different \u1d6fe-ray instruments

Sensitivity of the Cherenkov Telescope Array to spectral signatures of hadronic PeVatrons with application to Galactic Supernova Remnants

The local Cosmic Ray (CR) energy spectrum exhibits a spectral softening at energies around 3~PeV. Sources which are capable of accelerating hadrons to such energies are called hadronic PeVatrons. However, hadronic PeVatrons have not yet been firmly identified within the Galaxy. Several source classes, including Galactic Supernova Remnants (SNRs), have been proposed as PeVatron candidates. The potential to search for hadronic PeVatrons with the Cherenkov Telescope Array (CTA) is assessed. The focus is on the usage of very high energy $\gamma$-ray spectral signatures for the identification of PeVatrons. Assuming that SNRs can accelerate CRs up to knee energies, the number of Galactic SNRs which can be identified as PeVatrons with CTA is estimated within a model for the evolution of SNRs. Additionally, the potential of a follow-up observation strategy under moonlight conditions for PeVatron searches is investigated. Statistical methods for the identification of PeVatrons are introduced, and realistic Monte--Carlo simulations of the response of the CTA observatory to the emission spectra from hadronic PeVatrons are performed. Based on simulations of a simplified model for the evolution for SNRs, the detection of a $\gamma$-ray signal from in average 9 Galactic PeVatron SNRs is expected to result from the scan of the Galactic plane with CTA after 10 hours of exposure. CTA is also shown to have excellent potential to confirm these sources as PeVatrons in deep observations with $\mathcal{O}(100)$ hours of exposure per source.Comment: 34 pages, 16 figures, Accepted for publication in Astroparticle Physic

Observations of the Crab Nebula and Pulsar with the Large-Sized Telescope Prototype of the Cherenkov Telescope Array

CTA (Cherenkov Telescope Array) is the next generation ground-based observatory for gamma-ray astronomy at very-high energies. The Large-Sized Telescope prototype (\LST{}) is located at the Northern site of CTA, on the Canary Island of La Palma. LSTs are designed to provide optimal performance in the lowest part of the energy range covered by CTA, down to $\simeq 20$ GeV. \LST{} started performing astronomical observations in November 2019, during its commissioning phase, and it has been taking data since then. We present the first \LST{} observations of the Crab Nebula, the standard candle of very-high energy gamma-ray astronomy, and use them, together with simulations, to assess the basic performance parameters of the telescope. The data sample consists of around 36 hours of observations at low zenith angles collected between November 2020 and March 2022. \LST{} has reached the expected performance during its commissioning period - only a minor adjustment of the preexisting simulations was needed to match the telescope behavior. The energy threshold at trigger level is estimated to be around 20 GeV, rising to $\simeq 30$ GeV after data analysis. Performance parameters depend strongly on energy, and on the strength of the gamma-ray selection cuts in the analysis: angular resolution ranges from 0.12 to 0.40 degrees, and energy resolution from 15 to 50\%. Flux sensitivity is around 1.1\% of the Crab Nebula flux above 250 GeV for a 50-h observation (12\% for 30 minutes). The spectral energy distribution (in the 0.03 - 30 TeV range) and the light curve obtained for the Crab Nebula agree with previous measurements, considering statistical and systematic uncertainties. A clear periodic signal is also detected from the pulsar at the center of the Nebula.Comment: Submitted to Ap

Representing the people: Latin American councilors and their pathway to power and political representation in Spain

Latin Americans are one of the most relevant migrant minorities in Spain. In this article, we analyze their political representation at the local level by describing how councilors of Latin American councilors perceive three stages on their “pathway to power”: the selection method most frequently used by them to become electoral candidates, their ranking as candidates in the Spanish closed and blocked lists system, and their view of political representation once in office. The article contributes to politics in recent immigration countries by implementing a mixed method strategy with survey data and in-depth interviews. The results show how candidates of Latin American origin are included in electoral lists following more participative ways of internal selection than their native-born counterparts, who are more frequently appointed by a party leader. Despite this, those who eventually get elected perceive that they have been ranked in “unsafe positions” of the electoral lists, and therefore with no guarantee of being appointed. Interestingly, once in office, councilors of Latin Americans perceive that they represent immigrants to a lesser degree, compared with their native-born counterparts.This article uses data from the APREPINM Project that received funding from the Spanish Ministry of Economy and Competitiveness in the framework of the Call of the National Research Program Oriented to Societal Challenges (reference CSO-2016-79540-R). We would like to thank all members and collaborators of this project for their assistance with the data collection. The article and its open access publication is also based upon work funded by COST Action 16111 EthmigSurveyData (https://www.cost.eu/actions/CA16111/), supported by COST (European Cooperation in Science and Technology) and funded by the Horizon 2020 Framework Programme of the European Union; the University of Oxford; the Universidad Autónoma de Madrid, and the Casa de Velázquez in Madrid

Increased vulnerability to 6-hydroxydopamine lesion and reduced development of dyskinesias in mice lacking CB1 cannabinoid receptors.

Motor impairment, dopamine (DA) neuronal activity and proenkephalin (PENK) gene expression in the caudate-putamen (CPu) were measured in 6-OHDA-lesioned and treated (l-DOPA+benserazide) CB1 KO and WT mice. A lesion induced by 6-OHDA produced more severe motor deterioration in CB1 KO mice accompanied by more loss of DA neurons and increased PENK gene expression in the CPu. Oxidative/nitrosative and neuroinflammatory parameters were estimated in the CPu and cingulate cortex (Cg). CB1 KO mice exhibited higher MDA levels and iNOS protein expression in the CPu and Cg compared to WT mice. Treatment with l-DOPA+benserazide (12 weeks) resulted in less severe dyskinesias in CB1 KO than in WT mice. The results revealed that the lack of cannabinoid CB1 receptors increased the severity of motor impairment and DA lesion, and reduced l-DOPA-induced dyskinesias. These results suggest that activation of CB1 receptors offers neuroprotection against dopaminergic lesion and the development of l-DOPA-induced dyskinesias.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe

Valoración del programa social de atención a personas con trastorno mental grave: un estudio Delphi

Fundamento. En enero de 2005 el Gobierno de Navarra aprobó el "Programa de Atención a Personas con Trastorno Mental Grave" (PA-TMG). El objetivo del presente trabajo es conocer la opinión de expertos acerca del PA-TMG. Identificar los elementos de acuerdo en la valoración de aspectos positivos y aspectos mejorables. Realizar recomendaciones a partir de su opinión. Material y métodos. Se diseñó un estudio Delphi con 34 expertos en la atención sanitaria o social de enfermos mentales. Mediante cuestionarios repetidos se identificaron las ideas que alcanzaran un consenso ?90%, y se asignó un nivel de prioridad. Se presentan los porcentajes de acuerdo, estadísticos descriptivos de la prioridad, y se elaboran las recomendaciones de análisis de las áreas de consenso. Resultados. De los 34 expertos participantes, finalizaron el estudio 25 (71,4%): 1 socióloga, 5 trabajadoras sociales, 3 psiquiatras, 5 psicólogos, 1 representante de las familias, 3 terapeutas ocupacionales, 1 técnico en integración social y 6 médicos de familia. Valoran positivamente el Plan el 64% y 72% opinan que se ha elaborado sin suficiente participación profesional. Todos piensan que podría mejorarse si se amplia la participación de expertos. Conclusiones. Las principales ideas consensuadas han sido que: la atención socio-sanitaria debe garantizarse por los poderes públicos; se deben establecer buenos sistemas de información y de evaluación; el Plan debe tener presupuesto propio; debe garantizar el seguimiento profesional del paciente por los diferentes dispositivos; se deben descentralizar muchas tomas de decisiones; se debe universalizar el acceso a un catálogo de prestaciones sociales para estos enfermos