Altered inflammasome machinery as a key player in the perpetuation of Rett syndrome oxinflammation

Rett syndrome (RTT) is a progressive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene. RTT patients show multisystem disturbances associated with an oxinflammatory status. Inflammasomes are multi-protein complexes, responsible for host immune responses against pathogen infections and redox-related cellular stress. Assembly of NLRP3/ASC inflammasome triggers pro-caspase-1 activation, thus, resulting in IL-1β and IL-18 maturation. However, an aberrant activation of inflammasome system has been implicated in several human diseases. Our aim was to investigate the possible role of inflammasome in the chronic subclinical inflammatory condition typical of RTT, by analyzing this complex in basal and lipopolysaccharide (LPS)+ATP-stimulated primary fibroblasts, as well as in serum from RTT patients and healthy volunteers. RTT cells showed increased levels of nuclear p65 and ASC proteins, pro-IL-1β mRNA, and NLRP3/ASC interaction in basal condition, without any further response upon the LPS + ATP stimuli. Moreover, augmented levels of circulating ASC and IL-18 proteins were found in serum of RTT patients, which are likely able to amplify the inflammatory response. Taken together, our findings suggest that RTT patients exhibited a challenged inflammasome machinery at cellular and systemic level, which may contribute to the subclinical inflammatory state feedback observed in this pathology

Tele-Psychiatry Assessment of Post-traumatic Stress Symptoms in 100 Patients With Bipolar Disorder During the COVID-19 Pandemic Social-Distancing Measures in Italy

The acute phase of the COrona VIrus Disease-19 (COVID-19) emergency determined relevant stressful burdens in psychiatric patients, particularly those with chronic mental disorders such as bipolar disorder (BD), not only for the threat of being infected but also for the strict lock-down and social-distancing measures adopted, the economic uncertainty, and the limited possibilities to access psychiatric services. In this regard, telepsychiatry services represented a new important instrument that clinicians could adopt to monitor and support their patients. The aim of the present study was to investigate acute post-traumatic stress symptoms (PTSS) reported by patients with BD followed in the framework of a telepsychiatry service, set up in the acute phase of the COVID-19 outbreak at the psychiatric clinic of the University of Pisa (Italy). A sample of 100 patients were consecutively enrolled and assessed by the IES-r, GAD-7, HAM-D, and YMRS. Patients reported a mean (±SD) IES-r total score of 18.15 ± 13.67. Further, 17% of the sample reported PTSS (IES-r > 32), 17% depressive symptoms (HAM-D > 17), and 26% anxiety symptoms (GAD-7 > 10). Work and financial difficulties related to the COVID-19 pandemic and anxiety symptoms appeared to be positively associated with the development of acute PTSS. Acute manic symptoms appeared to be protective. The data of the present study suggest the relevance of monitoring patients with BD exposed to the burden related to the COVID-19 outbreak for prompt assessment and treatment of PTSS

Spatial-Related Community Structure and Dynamics in Phytoplankton of the Ross Sea, Antarctica

The Ross Sea exhibits the largest continental shelf and it is considered to be the most productive region in Antarctica, with phytoplankton communities that have so far been considered to be driven by the seasonal dynamics of the polynya, producing the picture of what is considered as the classical Antarctic food web. Nevertheless, the Ross Sea is made up of a complex mosaic of sub-systems, with physical, chemical, and biological features that change on different temporal and spatial scales. Thus, we investigated the phytoplankton community structure of the Ross Sea with a spatial scale, considering the different ecological sub-systems of the region. The total phytoplankton biomass, maximum quantum efficiency (Fv/Fm), size classes, and main functional groups were analyzed in relation to physical–chemical properties of the water column during the austral summer of 2017. Data from our study showed productivity differences between polynyas and other areas, with high values of biomass in Terra Nova Bay (up to 272 mg chl a m–2) and the south-central Ross Sea (up to 177 mg chl a m–2) that contrast with the HNLC nature of the off-shore waters during summer. Diatoms were the dominant group in all the studied subsystems (relative proportion ≥ 50%) except the southern one, where they coexisted with haptophytes with a similar percentage. Additionally, the upper mixed layer depth seemed to influence the level of biomass rather than the dominance of different functional groups. However, relatively high percentages of dinoflagellates (∼30%) were observed in the area near Cape Adare. The temporal variability observed at the repeatedly sampled stations differed among the sub-systems, suggesting the importance of Long-Term Ecological Research (L-TER) sites in monitoring and studying the dynamics of such an important system for the global carbon cycle as the Ross Sea. Our results provide new insights into the spatial distribution and structure of phytoplankton communities, with different sub-systems following alternative pathways for primary production, identifiable by the use of appropriate sampling scales

Subsurface life can modify volatile cycling on a planetary scale

The past decade of environmental microbiology has revealed that subsurface environments, both marine and continental, harbor one of the largest ecosystems of our planet, with diversity and biomass rivaling those of the surface. In addition, subsurface life has been recently shown to contribute significantly to the planet’s biogeochemistry, with microbial activity potentially playing an important role in controlling the flux and composition of volatiles recycled between the Earth’s surface and interior, which has broad implications for the search for life beyond our planet. Current efforts to discover extraterrestrial life are focused on planetary bodies with largely inhospitable surfaces, such as Mars, Venus, Europa, Titan, and Enceladus. In these locations, subsurface environments might provide niches of habitability, making the study of deep microbial life a priority for future astrobiological missions. Understanding how volatile elements are exchanged between planetary surfaces and interiors and the role of a subsurface biosphere in altering their composition and flux might provide a tractable target for defining planetary habitability and the detection of subsurface life forms.Fil: Giovanelli, D.. Università degli Studi di Napoli Federico II; Italia. Tokyo Institute of Technology; Japón. Rutgers University; Estados Unidos. Consiglio Nazionale delle Ricerche; Italia. Woods Hole Oceanographic Institution; Estados UnidosFil: Barry, P. H.. Woods Hole Oceanographic Institution; Estados UnidosFil: Bekaert, D. V.. Woods Hole Oceanographic Institution; Estados UnidosFil: Chiodi, Agostina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Cordone, A.. Università degli Studi di Napoli Federico II; ItaliaFil: Covone, G.. Università degli Studi di Napoli Federico II; Italia. Istituto Nazionale di Astrofisica; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Jessen, G.. Universidad Austral de Chile; ChileFil: Lloyd, K.. University of Tennessee; Estados UnidosFil: de Moor, J. M.. Universidad Nacional; Costa RicaFil: Morrison, S. M.. Carnegie Institution For Science; Estados UnidosFil: Schrenk, M. O.. Michigan State University; Estados UnidosFil: Vitale Brovarone, A.. Alma Mater Studiorum Universit`a Di Bologna; Italia. Sorbonne University; Francia. Museum National d’Histoire Naturelle; Franci

Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an “endothelial hyperglycemic memory” model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo

Speeding-Up Expensive Evaluations in High-Level Synthesis Using Solution Modeling and Fitness Inheritance

High-Level Synthesis (HLS) is the process of developing digital circuits from behavioral specifications. It involves three interdependent and NP-complete optimization problems: (i) the operation scheduling, (ii) the resource allocation, and (iii) the controller synthesis. Evolutionary Algorithms have been already effectively applied to HLS to find good solution in presence of conflicting design objectives. In this paper, we present an evolutionary approach to HLS that extends previous works in three respects: (i) we exploit the NSGA-II, a multi-objective genetic algorithm, to fully automate the design space exploration without the need of any human intervention, (ii) we replace the expensive evaluation process of candidate solutions with a quite accurate regression model, and (iii) we reduce the number of evaluations with a fitness inheritance scheme. We tested our approach on several benchmark problems. Our results suggest that all the enhancements introduced improve the overall performance of the evolutionary search

Dynamics of hydration water in deuterated purple membranes explored by neutron scattering

The function and dynamics of proteins depend on their direct environment, and much evidence has pointed to a strong coupling between water and protein motions. Recently however, neutron scattering measurements on deuterated and natural-abundance purple membrane (PM), hydrated in H2O and D2O, respectively, revealed that membrane and water motions on the ns–ps time scale are not directly coupled below 260 K (Wood et al. in Proc Natl Acad Sci USA 104:18049–18054, 2007). In the initial study, samples with a high level of hydration were measured. Here, we have measured the dynamics of PM and water separately, at a low-hydration level corresponding to the first layer of hydration water only. As in the case of the higher hydration samples previously studied, the dynamics of PM and water display different temperature dependencies, with a transition in the hydration water at 200 K not triggering a transition in the membrane at the same temperature. Furthermore, neutron diffraction experiments were carried out to monitor the lamellar spacing of a flash-cooled deuterated PM stack hydrated in H2O as a function of temperature. At 200 K, a sudden decrease in lamellar spacing indicated the onset of long-range translational water diffusion in the second hydration layer as has already been observed on flash-cooled natural-abundance PM stacks hydrated in D2O (Weik et al. in J Mol Biol 275:632–634, 2005), excluding thus a notable isotope effect. Our results reinforce the notion that membrane-protein dynamics may be less strongly coupled to hydration water motions than the dynamics of soluble proteins