Effect of CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor on lipid metabolism in human bronchial epithelial cells.

Cystic Fibrosis (CF) is a life-threatening hereditary disease resulting from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that encodes a chloride channel essential for ion transport in epithelial cells. Mutations in CFTR, notably the prevalent F508del mutation, impair chloride transport, severely affecting the respiratory system and leading to recurrent infections. Recent therapeutic advancements include CFTR modulators such as ETI, a combination of two correctors (Elexacaftor and Tezacaftor) and a potentiator (Ivacaftor), that can improve CFTR function in patients with the F508del mutation.

GM1 Oligosaccharide Ameliorates Rett Syndrome Phenotypes In Vitro and In Vivo via Trk Receptor Activation.

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 () gene. Despite advancements in research, no cure exists due to an incomplete understanding of the molecular effects of MeCP2 deficiency. Previous studies have identified impaired tropomyosin receptor kinase (Trk) neurotrophin (NTP) signaling and mitochondrial redox imbalances as key drivers of the pathology.

Modeling the interaction between wildfires and windthrows: A pilot case study for Italian Alps.

Wildland fires and windthrows represent relevant disturbances for forest ecosystems worldwide. In this context, especially for Italian catchments, the interaction between windthrows and changes in wildfire behaviour starting from ALS data processing is scarcely investigated. Therefore, this research aims to compute a multi-temporal analysis of the interaction between windthrows and wildfire behaviour in a forested area (Veneto region, northern Italy), recently affected by the renamed Vaia windstorm.

Novel molecular, structural and clinical findings in an Italian cohort of congenital cataract.

The current genetic diagnostic workup of congenital cataract (CC) is mainly based on NGS panels, whereas exome sequencing (ES) has occasionally been employed. In this multicentre study, we investigated by ES the detection yield, mutational spectrum and genotype-phenotype correlations in a CC cohort recruited between 2020 and mid-2022. The cohort consisted of 67 affected individuals from 51 unrelated families and included both non-syndromic (75%) and syndromic (25%) phenotypes, with extra-CC ocular/visual features present in both groups (48% and 76%, respectively).

Semi-Transparent Luminescent Solar Concentrators Based on Intramolecular Energy Transfer in Polyurethane Matrices.

Luminescent solar concentrators (LSCs) are spectral conversion devices offering interesting opportunities for the integration of photovoltaics into the built environment and portable systems. The Förster-resonance energy transfer (FRET) process can boost the optical response of LSCs by reducing energy losses typically associated to non-radiative processes occurring within the device under operation. In this work, a new class of FRET-based thin-film LSC devices is presented, in which the synthetic versatility of linear polyurethanes (PU) is exploited to control the photophysical properties and the device performance of the resulting LSCs.

Risk factors and scores for prediction of coronary artery aneurysms in Kawasaki disease: a European monocentric study.

Background: Japanese Kawasaki disease (KD) risk scores cannot be adopted in non-Japanese patients. In North American populations a baseline coronary artery Z-score > 2 and the Son score are associated with coronary artery aneurysms (CAAs) at 4 and 8 weeks from disease onset. In European populations, the Kawanet and Kawanet-echo scores are associated with intravenous immunoglobulin resistance.

GM1 structural requirements to mediate neuronal functions.

Since the 1980s, it has been known that the administration of ganglioside GM1 to cultured cells induced or enhanced neuronal differentiation. GM1 mechanism of action relies on its direct interaction and subsequent activation of the membrane tyrosine kinase receptor, TrkA, which naturally serves as NGF receptor. This process is mediated by the sole oligosaccharide portion of GM1, the pentasaccharide β-Gal-(1-3)-β-GalNAc-(1-4)-[α-Neu5Ac-(2-3)]-β-Gal-(1-4)-β-Glc.

GM1 ganglioside exerts protective effects against glutamate-excitotoxicity via its oligosaccharide in wild-type and amyotrophic lateral sclerosis motor neurons.

Alterations in glycosphingolipid metabolism have been linked to the pathophysiological mechanisms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Accordingly, administration of GM1, a sialic acid-containing glycosphingolipid, is protective against neuronal damage and supports neuronal homeostasis, with these effects mediated by its bioactive component, the oligosaccharide head (GM1-OS). Here, we add new evidence to the therapeutic efficacy of GM1 in ALS: Its administration to WT and SOD1 motor neurons affected by glutamate-induced excitotoxicity significantly increased neuronal survival and preserved neurite networks, counteracting intracellular protein accumulation and mitochondria impairment.

Planned discharge and the inter-professional relationship from the perspective of the nursing actions during the COVID-19 pandemic.

A qualitative-case study was carried out aimed at analyzing the interprofessional relationships generated by the planned discharge from the nursing actions' perspective during the COVID-19 pandemic. The study method was the participating observation by one nurse who works in a large SUS hospital in the city of São Paulo. The production of narratives and the micropolitics analysis resulted in two diverse visibility plans: beyond the planned discharge the anthropophagy of the technological arrangements for care and the ambivalence of the nursing staff in the production of interprofessional relationships; and the medical discharge and negotiated discharge: the intersecting with other professionals, with the families and with "real" life.

Modeling windthrow effects on water runoff and hillslope stability in a mountain catchment affected by the VAIA storm.

Windthrows seriously affect forest landscapes, causing several issues in hydrological and geomorphological terms. In this regard, Airborne Laser Scanning (ALS) topographic data recently increased the opportunity to investigate in detail physical processes at the catchment scale. Moreover, topographically based hydrological and geomorphological models allow quantifying runoff alteration due to windthrows-driven land cover changes and detect the occurrence of land degradative processes at the sub-catchment scale.

GM1 oligosaccharide efficacy against α-synuclein aggregation and toxicity in vitro.

Fibrillary aggregated α-synuclein represents the neurologic hallmark of Parkinson's disease and is considered to play a causative role in the disease. Although the causes leading to α-synuclein aggregation are not clear, the GM1 ganglioside interaction is recognized to prevent this process. How GM1 exerts these functions is not completely clear, although a primary role of its soluble oligosaccharide (GM1-OS) is emerging.

GM1 Oligosaccharide Efficacy in Parkinson's Disease: Protection against MPTP.

Past evidence has shown that the exogenous administration of GM1 ganglioside slowed neuronal death in preclinical models of Parkinson's disease, a neurodegenerative disorder characterized by the progressive loss of dopamine-producing neurons: however, the physical and chemical properties of GM1 (i.e., amphiphilicity) limited its clinical application, as the crossing of the blood-brain barrier is denied.

Oculocutaneous albinism: the neurological, behavioral, and neuro-ophthalmological perspective.

Unlabelled: Oculocutaneous albinism (OCA) is a group of rare, genetic disorders caused by absent/reduced melanin biosynthesis. The aim of this study was to explore the neurovisual, cognitive, adaptive, and behavioral profile of children affected by OCA, also evaluating any possible effect of the visual acuity deficit on the clinical profile and genotype-phenotype correlations. Eighteen children (9 males, mean age 84 months ± 41; range 18-181 months) with a molecular confirmed diagnosis of OCA were enrolled in the study.

Combined Inhibition of Hedgehog and HDAC6: In Vitro and In Vivo Studies Reveal a New Role for Lysosomal Stress in Reducing Glioblastoma Cell Viability.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor in adults. The invasiveness and the rapid progression that characterize GBM negatively impact patients' survival. Temozolomide (TMZ) is currently considered the first-choice chemotherapeutic agent.

An interactive web application for processing, correcting, and visualizing genome-wide pooled CRISPR-Cas9 screens.

A limitation of pooled CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes arising from copy-number-amplified genomics regions. To solve this issue, we previously developed CRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing false-positive signals while maintaining sensitivity in identifying relevant genetic dependencies.

Identification of the Lipid Antigens Recognized by rHIgM22, a Remyelination-Promoting Antibody.

Failure of the immune system to discriminate myelin components from foreign antigens plays a critical role in the pathophysiology of multiple sclerosis. In fact, the appearance of anti-myelin autoantibodies, targeting both proteins and glycolipids, is often responsible for functional alterations in myelin-producing cells in this disease. Nevertheless, some of these antibodies were reported to be beneficial for remyelination.

Alkali-labile gangliosides.

The structure and properties of a group of gangliosides modified by mild alkaline treatment are discussed. We will present the occurrence and the structure of gangliosides carrying the N-acetyneuraminic acid O-acetylated in position 9, the Neu5,9Ac, and of gangliosides carrying a sialic acid that forms a lactone ring. Starting from biochemical data we will discuss the possible biochemical role played by these gangliosides in the processes of cell signaling and maintenance of brain functions.

Iridium and Ruthenium Complexes Bearing Perylene Ligands.

The present review summarizes the work carried out mostly in the last decade on iridium and ruthenium complexes bearing various perylene ligands, of particular interest for bioimaging, photodynamic therapy, and solar energy conversion. In these complexes, the absorption spectra and the electrochemical properties are those of the perylene subunit plus those of the metal moiety. In contrast, the emissions are completely changed with respect to perylenes considered alone.

Regulation of signal transduction by gangliosides in lipid rafts: focus on GM3-IR and GM1-TrkA interactions.

The interactions between gangliosides and proteins belonging to the same or different lipid domains and their influence on physiological and pathological states have been analysed in detail. A well-known factor impacting on lipid-protein interactions and their biological outcomes is the dynamic composition of plasma membrane. This review focuses on GM1 and GM3 gangliosides because they are an integral part of protein-receptor complexes and dysregulation of their concentration shows a direct correlation with the onset of pathological conditions.

Gangliosides and Cell Surface Ganglioside Metabolic Enzymes in the Nervous System.

Gangliosides are a large group of complex lipids found predominantly in the outer layer of the plasma membrane of cells, particularly abundant in nerve endings. Their half-life in the nervous system is short, and their membrane composition and content are strictly connected to their metabolism. The neobiosynthesis of gangliosides starts in the endoplasmic reticulum and is completed in the Golgi apparatus, whereas catabolism occurs primarily in lysosomes.

Modeling Threats to AI-ML Systems Using STRIDE.

The application of emerging technologies, such as Artificial Intelligence (AI), entails risks that need to be addressed to ensure secure and trustworthy socio-technical infrastructures. Machine Learning (ML), the most developed subfield of AI, allows for improved decision-making processes. However, ML models exhibit specific vulnerabilities that conventional IT systems are not subject to.

β-Galactosylceramidase Deficiency Causes Upregulation of Long Pentraxin-3 in the Central Nervous System of Krabbe Patients and Mice.

Globoid cell leukodystrophy (GLD), or Krabbe disease, is a neurodegenerative sphingolipidosis caused by genetic deficiency of lysosomal (), characterized by neuroinflammation and demyelination of the central (CNS) and peripheral nervous system. The acute phase protein long pentraxin-3 (PTX3) is a soluble pattern recognition receptor and a regulator of innate immunity. Growing evidence points to the involvement of PTX3 in neurodegeneration.

Development of a score for early identification of children with Kawasaki disease requiring second-line treatment in multi-ethnic populations in Europe: A multicentre retrospective cohort study.

Background: Early identification of high-risk patients is essential to stratify treatment algorithms of Kawasaki disease (KD) and to appropriately select patients at risk for complicated disease who would benefit from intensified first-line treatment. Several scores have been developed and validated in Asian populations but have shown low sensitivity in predicting intravenous immunoglobulin (IVIG) resistance in non-Asian populations. We sought methods to predict the need for secondary treatment after initial IVIG in non-Asian populations.

β-Glucocerebrosidase Deficiency Activates an Aberrant Lysosome-Plasma Membrane Axis Responsible for the Onset of Neurodegeneration.

β-glucocerebrosidase is a lysosomal hydrolase involved in the catabolism of the sphingolipid glucosylceramide. Biallelic loss of function mutations in this enzyme are responsible for the onset of Gaucher disease, while monoallelic β-glucocerebrosidase mutations represent the first genetic risk factor for Parkinson's disease. Despite this evidence, the molecular mechanism linking the impairment in β-glucocerebrosidase activity with the onset of neurodegeneration in still unknown.