150 research outputs found

    Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

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    Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

    Epidemiological and clinical features of rotavirus among children younger than 5 years of age hospitalized with acute gastroenteritis in Northern Italy

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    BACKGROUND: Rotavirus is the major cause of acute gastroenteritis and severe dehydrating diarrhea in young children. METHODS: To estimate the proportion of hospital admissions for rotavirus acute gastroenteritis and identify the circulating G and P genotypes among children under five years of age, we conducted a prospective observational study from January to December 2008, recruiting children consecutively admitted to six hospitals in Milan and nearby towns in northern Italy. Typing was done on stool samples by reverse transcriptase polymerase chain reaction amplification. RESULTS: Of the 521 stool samples from children with acute gastroenteritis, 34.9% (95%CI, 30.8 to 39.2%) were rotavirus-positive. Two thirds (67.6%) were under two years of age, and 13.2% were under six months. The predominant G type was G1 (40.7%), followed by G9 (22.5%), G2 (13.2%), G3 (5.5%), G4 (3.8%) and G10 (1.6%). Twenty-one (11.7%) mixed-G infections were identified: G1+G10 (8.8%); G1+G9 (1.6%); and G2+G10 (1.2%). Only P[8] (67.6%) and P[4] (12.6%) types were P genotyped. The predominant single G/P combination was G1P[8] (39.7%), followed by G9P[8] (25.3%), G2P[4] (14.3%), and G3P[8] (4.1%). All G-mixed types combined with P[8]. CONCLUSIONS: These findings show an high prevalence of rotavirus infections among children admitted to hospital for acute gastroenteritis caused by different rotavirus strains circulating in the area studied

    The SSDC Role in the LICIACube Mission: Data Management and the MATISSE Tool

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    Light Italian Cubesat for Imaging of Asteroids (LICIACube) is an Italian mission managed by the Italian Space Agency (ASI) and part of the NASA Double Asteroid Redirection Test (DART) planetary defense mission. Its main goals are to document the effects of the DART impact on Dimorphos, the secondary member of the (65803) Didymos binary asteroid system, characterizing the shape of the target body and performing dedicated scientific investigations on it. Within this framework, the mission Science Operations Center will be managed by the Space Science Data Center (ASI-SSDC), which will have the responsibility of processing, archiving, and disseminating the data acquired by the two LICIACube onboard cameras. In order to better accomplish this task, SSDC also plans to use and modify its scientific webtool Multi-purpose Advanced Tool for Instruments for the solar system Exploration (MATISSE), making it the primary tool for the LICIACube data analysis, thanks to its advanced capabilities for searching and visualizing data, particularly useful for the irregular shapes common to several small bodies

    C/EBPβ-Thr217 Phosphorylation Signaling Contributes to the Development of Lung Injury and Fibrosis in Mice

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    mice are refractory to Bleomycin-induced lung fibrosis the molecular mechanisms remain unknown. Here we show that blocking the ribosomal S-6 kinase (RSK) phosphorylation of the CCAAT/Enhancer Binding Protein (C/EBP)-β on Thr217 (a RSK phosphoacceptor) with either a single point mutation (Ala217), dominant negative transgene or a blocking peptide containing the mutated phosphoacceptor ameliorates the progression of lung injury and fibrosis induced by Bleomycin in mice. mice with a cell permeant, C/EBPβ peptide that inhibits phosphorylation of C/EBPβ on Thr217 (40 µg instilled intracheally on day-2 and day-6 after the single Bleomycin dose) also blocked the progression of lung injury and fibrosis induced by Bleomycin. Phosphorylation of human C/EBPβ on Thr266 (human homologue phosphoacceptor) was induced in collagen-activated human lung fibroblasts in culture as well as in activated lung fibroblasts in situ in lungs of patients with severe lung fibrosis but not in control lungs, suggesting that this signaling pathway may be also relevant in human lung injury and fibrosis.These data suggest that the RSK-C/EBPβ phosphorylation pathway may contribute to the development of lung injury and fibrosis

    TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis

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    Abstract Background We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice. Results We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis. This was not associated with increased viral load in TLR-9-/- mice or with major alterations in T helper (Th)1 and Th2 cytokines. We examined alveolar epithelial-cell apoptosis in both strains, but this could not explain the altered fibrotic outcomes. As expected, TLR-9-/- mice had a defect in the production of interferon (IFN)-β after viral infection. Balb/c fibroblasts infected with γHV68 in vitro produced more IFN-β than did infected TLR-9-/- fibroblasts. Accordingly, in vitro infection of Balb/c fibroblasts resulted in reduced proliferation rates whereas infection of TLR-9-/- fibroblasts did not. Finally, therapeutic administration of CpG oligodeoxynucleotides ameliorated bleomycin-induced fibrosis in wild-type mice. Conclusions These results show a protective role for TLR-9 signaling in murine models of lung fibrosis, and highlight differences in the biology of TLR-9 between mice and humans.http://deepblue.lib.umich.edu/bitstream/2027.42/112877/1/13069_2011_Article_57.pd

    Role of host genetics in fibrosis

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    Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function

    Anticipated Geological Assessment of the (65803) Didymos–Dimorphos System, Target of the DART–LICIACube Mission

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    On 2022 September 26, the DART spacecraft will impact the surface of Dimorphos, the ∼160 m size satellite of the binary near-Earth asteroid (NEA) (65803) Didymos. What will be observed on the surfaces of both asteroids and at the DART impact site is largely unknown, beyond the details of Didymos revealed by previous Arecibo and Goldstone radar observations. We present here the expected DART and LICIACube observations of the Didymos system and discuss the planned mapping strategies. By searching similar geological features and processes identified on other NEAs, we constrain the impact conditions that DART might encounter at Dimorphos, assessing both the asteroid's surface and interior structure
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