Oral Treatment with Iododiflunisal Delays Hippocampal Amyloid-β Formation in a Transgenic Mouse Model of Alzheimer's Disease: A Longitudinal in vivo Molecular Imaging Study

Transthyretin (TTR) is a tetrameric, amyloid-β (Aβ)-binding protein, which reduces Aβ toxicity. The TTR/Aβ interaction can be enhanced by a series of small molecules that stabilize its tetrameric form. Hence, TTR stabilizers might act as disease-modifying drugs in Alzheimer's disease. Objective: We monitored the therapeutic efficacy of two TTR stabilizers, iododiflunisal (IDIF), which acts as small-molecule chaperone of the TTR/Aβ interaction, and tolcapone, which does not behave as a small-molecule chaperone, in an animal model of Alzheimer's disease using positron emission tomography (PET). Methods: Female mice (AβPPswe/PS1A246E/TTR+/-) were divided into 3 groups (n=7 per group): IDIF-treated, tolcapone-treated, and non-treated. The oral treatment (100mg/Kg/day) was started at 5 months of age. Treatment efficacy assessment was based on changes in longitudinal deposition of Aβ in the hippocampus (HIP) and the cortex (CTX) and determined using PET-[18F]florbetaben. Immunohistochemical analysis was performed at age=14 months. Results: Standard uptake values relative to the cerebellum (SUVr) of [18F]florbetaben in CTX and HIP of non-treated animals progressively increased from age=5 to 11 months and stabilized afterwards. In contrast, [18F]florbetaben uptake in HIP of IDIF-treated animals remained constant between ages=5 and 11 months and significantly increased at 14 months. In the tolcapone-treated group, SUVr progressively increased with time, but at lower rate than in the non-treated group. No significant treatment effect was observed in CTX. Results from immunohistochemistry matched the in vivo data at age=14 months. Conclusion: Our work provides encouraging preliminary results on the ability of small-molecule chaperones to ameliorate Aβ deposition in certain brain regions

The WEBT campaign on the BL Lac object PG 1553+113 in 2013. An analysis of the enigmatic synchrotron emission

A multifrequency campaign on the BL Lac object PG 1553+113 was organized by the Whole Earth Blazar Telescope (WEBT) in 2013 April-August, involving 19 optical, two near-IR, and three radio telescopes. The aim was to study the source behaviour at low energies during and around the high-energy observations by the Major Atmospheric Gamma-ray Imaging Cherenkov telescopes in April-July. We also analyse the UV and X-ray data acquired by the Swift and XMM-Newton satellites in the same period. The WEBT and satellite observations allow us to detail the synchrotron emission bump in the source spectral energy distribution (SED). In the optical, we found a general bluer-when-brighter trend. The X-ray spectrum remained stable during 2013, but a comparison with previous observations suggests that it becomes harder when the X-ray flux increases. The long XMM-Newton exposure reveals a curved X-ray spectrum. In the SED, the XMM-Newton data show a hard near-UV spectrum, while Swift data display a softer shape that is confirmed by previous Hubble Space Telescope/Cosmic Origins Spectrograph and International Ultraviolet Explorer observations. Polynomial fits to the optical-X-ray SED show that the synchrotron peak likely lies in the 4-30eV energy range, with a general shift towards higher frequencies for increasing X-ray brightness. However, the UV and X-ray spectra do not connect smoothly. Possible interpretations include: (i) orientation effects, (ii) additional absorption, (iii) multiple emission components, and (iv) a peculiar energy distribution of relativistic electrons. We discuss the first possibility in terms of an inhomogeneous helical jet mode

Multimessenger Characterization of Markarian 501 during Historically Low X-Ray and γ-Ray Activity

We study the broadband emission of Mrk 501 using multiwavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi's Large Area Telescope (LAT), NuSTAR, Swift, GASP-WEBT, and the Owens Valley Radio Observatory. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wave bands, with the highest occurring at X-rays and very-high-energy (VHE) 3-rays. A significant correlation (>3σ) between X-rays and VHE 3-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between the Swift X-Ray Telescope and Fermi-LAT. We additionally find correlations between high-energy 3-rays and radio, with the radio lagging by more than 100 days, placing the 3-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE 3-rays from mid-2017 to mid-2019 with a stable VHE flux (>0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2 yr long low state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED toward the low state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock. © 2023. The Author(s). Published by the American Astronomical Society

Multi-messenger characterization of Mrk 501 during historically low X-ray and γ\gamma-ray activity

We study the broadband emission of Mrk 501 using multi-wavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi-LAT, NuSTAR, Swift, GASP-WEBT, and OVRO. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wavebands, with the highest occurring at X-rays and very-high-energy (VHE) $\gamma$-rays. A significant correlation ($>$3$\sigma$) between X-rays and VHE $\gamma$-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between Swift-XRT and Fermi-LAT. We additionally find correlations between high-energy $\gamma$-rays and radio, with the radio lagging by more than 100 days, placing the $\gamma$-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE $\gamma$-rays from mid-2017 to mid-2019 with a stable VHE flux ($>$0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2-year-long low-state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED towards the low-state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock.Comment: 56 pages, 30 figures, 14 tables, submitted. Corresponding authors are L. Heckmann, D. Paneque, S. Gasparyan, M. Cerruti, and N. Sahakya

Diferencias en el autoconcepto por sexo en la adolescencia: construcción y validación de un instrumento

The objective of this study were construct a scale to measure and evaluate the self-concept of adolescents and to determine differences in the structure of this construct in relation to sex of participants. The sample consisted in 450 students from three high schools in Mexico City (Mean= 16.65 years). Likert items were developed for four dimensions of self-concept (social, physical, athletic and academic). The results showed Four-dimensional Self-concept Scale for Adolescents (ETAA, by its Spanish acronym) is a measuring instrument with acceptable psychometric properties. There were differences regarding gender the participants only in sports dimension and the weighting of the factors in the structure of the self-concept. Derived from the results we propose the design of intervention programs created for the improvement and strengthening of self-concept, addressing the special needs of adolescents.La presente investigación tuvo como objetivos construir una escala para medir y evaluar el autoconcepto de los(as) adolescentes, así como determinar diferencias en la estructura de este constructo en relación al sexo de los(as) participantes. La muestra estuvo conformada por 450 estudiantes de tres escuelas de nivel medio superior de la Ciudad de México (MEDAD= 16.65 años). Se elaboraron reactivos tipo Likert para cuatro dimensiones del autoconcepto (social, físico, deportivo y académico). Los resultados evidenciaron que la Escala Tetradimensional de Autoconcepto para Adolescentes (ETAA) es un instrumento de medición con propiedades psicométricas aceptables. Se presentaron diferencias respecto al sexo de los(as) participantes únicamente en la dimensión deportiva, así como en la ponderación de los factores en la estructura del autoconcepto. Derivado de los resultados, se propone el diseño de programas de intervención creados para la mejora y reforzamiento del autoconcepto, atendiendo las necesidades particulares de los(as) adolescentes

Factores motivacionales y de capital cultural que inciden en el comportamiento lector en estudiantes mexicanos de nivel medio superior de diferente estrato social

The objective was to determine to what extent motivational variables and those of cultural capital influence two dimensions of reading behavior (academic and non academic) in students from two different social strata (low and medium).The sample consisted of 315 students from two senior high schools in Mexico City, aged between 15 and 20. Results of structural modeling analysis indicated that extrinsic motivational variables had more to do with academic reading behavior, whereas the combination of intrinsic and extrinsic motivational variables was more related to non-academic reading behavior. To a lesser extent, cultural capital also showed an influence on the two dimensions of reading behavior, but with discrepancies in relation to the social stratum of the school. These results suggest a different motivational disposition and of cultural capital in the participants in this study to explain reading behavior. Regarding the type of reading, the main differences are explained in motivational terms, and with respect to the school social stratum, differences are explained by the variables of cultural capital. Results are discussed with respect to theoretical implications in explaining reading behavior.O objetivo foi determinar em que grau as variáveis motivacionais e de capital cultural influem em duas dimensões do comportamento leitor (escolar e extraescolar) em estudantes de duas classes sociais diferentes (baixa e média). A mostra esteve composta por 315 estudantes de duas escolas de nível médio superior da Cidade do México, com idades entre 15 e 20 anos. Os resultados das análises de modelagem estrutural indicaram que as variáveis motivacionais extrínsecas tiveram maior relação com o comportamento leitor escolar; enquanto que uma combinação das variáveis motivacionais intrínsecas e extrínsecas apresentou uma maior relação com o comportamento leitor extraescolar. O capital cultural também influiu, em menor grau, nas duas dimensões do comportamento leitor, mas mostrando discrepâncias em relação com o nível social da escola. Estes resultados sugerem uma disposição motivacional e de capital cultural diferente nos participantes deste estudo para explicar a conduta leitora, já que com respeito ao tipo de leitura as principais diferenças se explicaram em termos motivacionais; e com respeito ao nível social da escola, as diferenças se explicaram pelas variáveis de capital cultural. Discutem-se os resultados em relação com possíveis implicações teóricas na explicação do comportamento leitor.El objetivo fue determinar en qué grado variables motivacionales y de capital cultural influyen en dos dimensiones del comportamiento lector (escolar y extraescolar) en estudiantes de dos estratos sociales diferentes (bajo y medio). La muestra estuvo compuesta por 315 estudiantes de dos escuelas de nivel medio superior de la Ciudad de México, con edades entre los 15 y 20 años. Los resultados de los análisis de modelamiento estructural indicaron que las variables motivacionales extrínsecas tuvieron mayor relación con el comportamiento lector escolar; mientras que una combinación de las variables motivacionales intrínsecas y extrínsecas presentó una mayor relación con el comportamiento lector extraescolar. El capital cultural también influyó, en menor grado, en las dos dimensiones del comportamiento lector, pero mostrando discrepancias en relación con el estrato social de la escuela. Estos resultados sugieren una disposición motivacional y de capital cultural distinta en los participantes de este estudio para explicar la conducta lectora, ya que con respecto al tipo de lectura las principales diferencias se explicaron en términos motivacionales; y con respecto al estrato social de la escuela, las diferencias se explicaron por las variables de capital cultural. Se discuten los resultados en relación con posibles implicaciones teóricas en la explicación del comportamiento lector