Lobster eye optics for nano-satellite x-ray monitor

The Lobster eye design for a grazing incidence X-ray optics provides wide field of view of the order of many degrees, for this reason it would be a convenient approach for the construction of space X-ray monitors. In this paper, we compare previously reported measurements of prototype lobster eye X-ray optics called P-25 with computer simulations and discuss differences between the theoretical end experimentally obtained results. Usability of this prototype lobster eye and manufacturing technology for the nano-satellite mission is assessed. The specific scientific goals are proposed

Tau-dependent HDAC1 nuclear reduction is associated with altered VGluT1 expression

During AD pathology, Tau protein levels progressively increase from early pathological stages. Tau altered expression causes an unbalance of Tau subcellular localization in the cytosol and in the nuclear compartment leading to synaptic dysfunction, neuronal cell death and neurodegeneration as a consequence. Due to the relevant role of epigenetic remodellers in synaptic activity in physiology and in neurodegeneration, in particular of TRIM28 and HDAC1, we investigated the relationship between Tau and these epigenetic factors. By molecular, imaging and biochemical approaches, here we demonstrate that Tau altered expression in the neuronal cell line SH-SY5y does not alter TRIM28 and HDAC1 expression but it induces a subcellular reduction of HDAC1 in the nuclear compartment. Remarkably, HDAC1 reduced activity modulates the expression of synaptic genes in a way comparable to that observed by Tau increased levels. These results support a competitive relationship between Tau levels and HDAC1 subcellular localization and nuclear activity, indicating a possible mechanism mediating the alternative role of Tau in the pathological alteration of synaptic genes expression

Fetal Tracheal Occlusion Increases Lung Basal Cells via Increased Yap Signaling

Basal cell; Fetal tracheal occlusion; MechanotransductionCélula basal; Oclusión traqueal fetal; MecanotransducciónCèl·lula basal; Oclusió traqueal fetal; MecanotransduccióFetal endoscopic tracheal occlusion (FETO) is an emerging surgical therapy for congenital diaphragmatic hernia (CDH). Ovine and rabbit data suggested altered lung epithelial cell populations after tracheal occlusion (TO) with transcriptomic signatures implicating basal cells. To test this hypothesis, we deconvolved mRNA sequencing (mRNA-seq) data and used quantitative image analysis in fetal rabbit lung TO, which had increased basal cells and reduced ciliated cells after TO. In a fetal mouse TO model, flow cytometry showed increased basal cells, and immunohistochemistry demonstrated basal cell extension to subpleural airways. Nuclear Yap, a known regulator of basal cell fate, was increased in TO lung, and Yap ablation on the lung epithelium abrogated TO-mediated basal cell expansion. mRNA-seq of TO lung showed increased activity of downstream Yap genes. Human lung specimens with congenital and fetal tracheal occlusion had clusters of subpleural basal cells that were not present in the control. TO increases lung epithelial cell nuclear Yap, leading to basal cell expansion.Funding was obtained from NIH/NHLBI R01HL141229 (to BV)

Del orden de las milicias al orden de las instituciones: agencias de control y nuevas disciplinas en Santa Fe y Entre Ríos entre 1860 y 1880

El presente artículo se propone reseñar los principales hallazgos del proyecto en el que investigamos las nuevas configuraciones del orden jurídico durante la segunda mitad del siglo XIX en el territorio santafesino y entrerriano, período durante el cual la región participó de un acelerado proceso de institucionalización de su estructura estatal en tanto progresaba la formación de un régimen moderno de dominación y su incorporación plena al sistema capitalista.Con el objeto de aproximarnos a aquel régimen de gobierno y modernización estatal que subyace en las formas institucionales y en las prácticas sociales de las nuevas agencias estatales, analizaremos comparativamente la instrumentación jurídica y práctica de aquellas agencias que capilarmente constituyen a los nuevos órdenes provinciales en Santa Fe y Entre Ríos entre 1860 y 1880, antes de la definitiva consolidación de la dominación en la forma moderna del estado nacional. Y en un apartado final, a modo de conclusión, reflexionaremos sobre la experiencia de investigación desde una perspectiva teórico-metodológica

An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ.

Passive immunization against β-amyloid (Aβ) has become an increasingly desirable strategy as a therapeutic treatment for Alzheimer's disease (AD). However, traditional passive immunization approaches carry the risk of Fcγ receptor-mediated overactivation of microglial cells, which may contribute to an inappropriate proinflammatory response leading to vasogenic edema and cerebral microhemorrhage. Here, we describe the generation of a humanized anti-Aβ monoclonal antibody of an IgG4 isotype, known as MABT5102A (MABT). An IgG4 subclass was selected to reduce the risk of Fcγ receptor-mediated overactivation of microglia. MABT bound with high affinity to multiple forms of Aβ, protected against Aβ1-42 oligomer-induced cytotoxicity, and increased uptake of neurotoxic Aβ oligomers by microglia. Furthermore, MABT-mediated amyloid plaque removal was demonstrated using in vivo live imaging in hAPP((V717I))/PS1 transgenic mice. When compared with a human IgG1 wild-type subclass, containing the same antigen-binding variable domains and with equal binding to Aβ, MABT showed reduced activation of stress-activated p38MAPK (p38 mitogen-activated protein kinase) in microglia and induced less release of the proinflammatory cytokine TNFα. We propose that a humanized IgG4 anti-Aβ antibody that takes advantage of a unique Aβ binding profile, while also possessing reduced effector function, may provide a safer therapeutic alternative for passive immunotherapy for AD. Data from a phase I clinical trial testing MABT is consistent with this hypothesis, showing no signs of vasogenic edema, even in ApoE4 carriers

The thin and medium filters of the EPIC camera on-board XMM-Newton: measured performance after more than 15 years of operation

After more than 15 years of operation of the EPIC camera on board the XMM-Newton X-ray observatory, we have reviewed the status of its Thin and Medium filters. We have selected a set of Thin and Medium back-up filters among those still available in the EPIC consortium and have started a program to investigate their status by different laboratory measurements including: UV/VIS transmission, Raman scattering, X-Ray Photoelectron Spectroscopy, and Atomic Force Microscopy. Furthermore, we have investigated the status of the EPIC flight filters by performing an analysis of the optical loading in the PN offset maps to gauge variations in the optical and UV transmission. We both investigated repeated observations of single optically bright targets and performed a statistical analysis of the extent of loading versus visual magnitude at different epochs. We report the results of the measurements conducted up to now. Most notably, we find no evidence for change in the UV/VIS transmission of the back-up filters in ground tests spanning a 2 year period and we find no evidence for change in the optical transmission of the thin filter of the EPIC-pn camera from 2002 to 2012. We point out some lessons learned for the development and calibration programs of filters for X-ray detectors in future Astronomy missions

Children with Kawasaki disease or Kawasaki-like syndrome (MIS-C/PIMS) at the time of COVID-19: are they all the same? Case series and literature review.

Since the coronavirus disease 2019 (COVID-19) outbreak started, children have been considered marginally involved compared to adults, with a quite significant percentage of asymptomatic carriers. Very recently, an overwhelming inflammatory activation, which shares clinical similarities with Kawasaki disease (KD), has been described in children exposed to COVID-19. We report three KD-like cases that occurred during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a highly affected area of Northern Italy. The clinical presentation was characterized by the presence of unremitting fever, diarrhea and elevated inflammatory markers. Case #1 and Case #2 occurred one week apart and shared other clinical features: laboratory tests confirmed COVID-19 exposure and high inflammatory activation with myocardial involvement. Case #3 followed a more typical pattern for KD. Interestingly, this patient showed lower levels of procalcitonin, C-reactive protein, D-dimers, and ferritin compared to the other two cases, whereas platelet count was higher. We hypothesize that SARS-CoV-2 might act in children as a trigger, either inducing a classical KD phenotype or causing a systemic inflammatory response leading to a severe KD-like phenotype, eventually characterized by myocardial impairment. We think that bringing these cases and their differences to the attention of the rheumatology community during the COVID-19 pandemic will be beneficial in order to highlight the importance of early diagnosis and to increase awareness of this new phenomenon

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project

Background: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. Methods: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. Discussion: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. Trial registration: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380