Novel tricyclic pyrrolo-quinolines as pharmacological correctors of the mutant CFTR chloride channel

2023

AbstractF508del, the most frequent mutation in cystic fibrosis (CF), impairs the stability and folding of the CFTR chloride channel, thus resulting in intracellular retention and CFTR degradation. The F508del defect can be targeted with pharmacological correctors, such as VX-809 and VX-445, that stabilize CFTR and improve its trafficking to plasma membrane. Using a functional test to evaluate a panel of chemical compounds, we have identified tricyclic pyrrolo-quinolines as novel F508del correctors with high efficacy on primary airway epithelial cells from CF patients. The most effective compound, PP028, showed synergy when combined with VX-809 and VX-661 but not with VX-445. By testing the …

Evaluation of porous asphalt hydrological performances through rainfall-runoff modelling by EPA SWMM

2023

Over the last few decades, the increase in extreme weather events has caused urban floods to become more and more frequent, with increased risks for road users. Among the different types of pavement structures, permeable pavements (PPs) can effectively increase the hydraulic resilience of the cities since they are specifically designed for reducing runoff by allowing water to infiltrate and be discharged into the soil and/or by drains. This study aims at evaluating the hydrological performance of a Porous Asphalt (PA) using numerical simulations for a case study carried out using EPA SWMM (Storm Water Management Model) software. Several simulations have been carried out, considering differe…

Treatment of aqueous solutions of oxytetracycline by different electrochemical approaches: anodic oxidation, pressurized electro-Fenton and oxidation…

2023

The tetracycline group (TCs) includes the most common antibiotics for treatment of both human and animal infections. TCs are resistant to biological degradation; hence, conventional wastewater treatments are unable to remove these contaminants. Here, the utilization of different electrochemical processes, such as electro-Fenton (EF), direct anodic oxidation (AO) and indirect oxidation by electrogenerated active chlorine (EAC), for the treatment of aqueous solutions of oxytetracycline (OTC), which is one of the TCs, was studied. The effect of various operating conditions was evaluated to optimize the selected processes. EAC gave the fastest abatement of OTC, but the lowest removal of TOC and…

Datapackage for national high-resolution conservation prioritisation of boreal forests

2023

This data package concerns the following work: Ninni Mikkonen, Niko Leikola, Joona Lehtomäki, Panu Halme, Atte Moilanen, National high-resolution conservation prioritisation of boreal forests, Forest Ecology and Management, Volume 541, 2023, 121079 ISSN 0378-1127 https://doi.org/10.1016/j.foreco.2023.121079 The overall objective of the work was to develop spatial prioritizations that can assist the forest conservation programme METSO (The Finnish Government 2008; 2014) to make well-informed decisions about acquisition of forests for protection. The results are also aimed to be useful for other actors interested in forest conservation or biodiversity friendly forest management. We focused th…

Il risarcimento del danno provocato dall’amministrazione nazionale per violazione della disciplina sulla qualità dell’aria: una questione ancora aper…

2023

La correlazione esistente tra inquinamento e godimento dei diritti umani appare, oggi giorno, chiara ed innegabile, ciò che invece appare decisamente più complesso è stabilire quali siano le conseguenze di questa correlazione sotto il profilo strettamente giuridico. Da un lato, infatti, occorre verificare se, ed eventualmente in che misura, gli effetti nocivi dell’inquinamento possano essere qualificati come violazioni dei diritti umani da sanzionare e risarcire. Dall’altro lato, è necessario chiarire se, ed eventualmente in che misura, gli effetti nocivi dell’inquinamento, in quanto qualificati come violazioni dei diritti umani, possano essere imputati allo Stato o ad altri enti pubblici c…

Genetic basis of STEM occupational choice and regional economic performance : a UK biobank genome-wide association study

2023

Abstract Background Science, technology, engineering, and mathematics (STEM) professionals are regarded as the highly skilled labor force that fosters economic productivity, enterprise innovation, and international competitiveness of a country. This study aims to understand the genetic predisposition to STEM occupations and investigate its associations with regional economic performance. We conducted a genome-wide association study on the occupational choice of STEM jobs based on a sample of 178,976 participants from the UK Biobank database. Results We identified two genetic loci significantly associated with participants’ STEM job choices: rs10048736 on chromosome 2 and rs12903858 on chrom…

Sairaala taiteen näyttämönä

2023

Suomessa on viime vuosina rakennettu useita uusia sairaaloita ja laajennettu tai peruskorjattu vanhoja. Näihin sairaaloihin on sijoitettu ja hankittu runsaasti taidetta, sillä taiteella on tutkimuksissa osoitettu olevan terveyttä ja hyvinvointia edistävä vaikutus. Sairaaloihin hankittua ja niissä esiteltyä taidetta voidaan kutsua sairaalataiteeksi. Artikkelissa esittelemme, millaista tutkimusta sairaalataiteesta on tehty, pohdimme millaisia taiteen tiloja sairaalat ovat ja millaisia mahdollisuuksia tai haasteita sairaalat tarjoavat taidehistorioitsijoille niin työskentely-ympäristöinä kuin tutkimuskohteina. Artikkelimme empiirinen osuus perustuu havainnointiin neljässä sairaal…

Miten tiede on vastannut yhteiskunnallisiin haasteisiin?

2023

Suomen Akatemia järjesti sidosryhmilleen ”Tiede ja tutkimus tulevaisuuden menestystekijöinä: Tieteen tila” -tilaisuuden Helsingissä 14.10.2022. Tilaisuuteen kutsuttua kahta tutkijaa pyydettiin pohtimaan puheessaan oman alansa näkökulmasta, miten tiede on vastannut yhteiskunnallisiin haasteisiin. Tämä teksti on puheeni, jossa pohdin tieteen vaikuttavuutta taiteen ja kulttuurin tutkimuksen näkökulmasta. nonPeerReviewed

Plant trait‐environment relationships in tundra are consistent across spatial scales

2023

Patterns and processes shaping ecosystems vary across spatiotemporal scales. As plant functional traits reflect ecosystem properties, investigating their relationships with environment provides an important tool to understand and predict ecosystem structure and functioning. This is particularly important in the tundra where a changing climate may trigger severe alterations in plant communities as both summer and winter conditions are changing. Here, we investigate the relationships between key environmental drivers including summer temperature, snow persistence, topographic position and soil pH, and species height, specific leaf area (SLA) and seed mass as plant traits. The study is carried…

Stereoselective Synthesis of New 4-Aryl-5-indolyl-1,2,4-triazole S- and N-β-Galactosides: Characterizations, X-ray Crystal Structure and Hirshfeld Su…

2023

5-(1H-Indol-2-yl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 1a and 4-(4-chlorophenyl)-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1b were galactosylated in the presence of NaHCO3 in ethanol to produce S-galactosides 3,4, whereas, in the presence of K2CO3 in acetone they produced a mixture of S- and N-galactosides 3-6 with a higher yield of S-galactosides over the respective N-galactosides. Improvement in the yields of N-galactosides was produced by thermal migration of the galactosyl moiety from sulfur to nitrogen using fusion. β-Stereoselectivity of galactosylation was determined using the coupling constant value 3J1,2, which exceeded 9.0 Hz in all prepared galactos…

Performance-related physiological changes induced by one year of endurance training in young athletes

2023

IntroductionAlthough maximal oxygen uptake (VO2max) is generally recognized as the single best indicator of aerobic fitness in youth, interpretation of this parameter and the extent to which it can be improved by training remain controversial, as does the relative importance of VO2max for performance in comparison to other factors such as power production. Here, we examined the influence of endurance training on the VO2max, muscle power and sports-related performance of cross-country skiers attending a school specializing in sports, as well as potential relationships between any changes observed to one another and/or to perceived stress scale (Cohen) and certain blood parameters.MethodsOn t…

CH vs. HC—Promiscuous Metal Sponges in Antimicrobial Peptides and Metallophores

2023

Histidine and cysteine residues, with their imidazole and thiol moieties that deprotonate at approximately physiological pH values, are primary binding sites for Zn(II), Ni(II) and Fe(II) ions and are thus ubiquitous both in peptidic metallophores and in antimicrobial peptides that may use nutritional immunity as a way to limit pathogenicity during infection. We focus on metal complex solution equilibria of model sequences encompassing Cys–His and His–Cys motifs, showing that the position of histidine and cysteine residues in the sequence has a crucial impact on its coordination properties. CH and HC motifs occur as many as 411 times in the antimicrobial peptide database, while …

Identifying the domain-wall spin structure in antiferromagnetic NiO/Pt

2023

Regimes of patriarchy and faith : reflections on challenges in interviewing women and religious minorities in Pakistan

2023

PurposeThis paper discusses the challenges that two doctoral researchers faced while researching religious minorities and women in a culturally sensitive society such as Pakistan. Their shared interest in sensitive topics related to gender and minorities in Pakistan led both researchers to collaborate in this study to provide a better understanding of issues in qualitative research in the same research context. They discuss the challenges of interviewing participants within the educational context. They also suggest some ways to overcome such challenges.Design/methodology/approachBased on Foucualt's writings on regimes of truth, discourse and systems of exclusion, the authors in this study …

Chemical Characterization and Cytotoxic and Antioxidant Activity Evaluation of the Ethanol Extract from the Bulbs of Pancratium maritimun Collected i…

2023

P. maritimum L., belonging to the Amaryllidaceae family, is a species that grows on beaches and coastal sand dunes mainly on both sides of the Mediterranean Sea and Black Sea, the Middle East, and up to the Caucasus region. It has been largely investigated due to its several interesting biological properties. With the aim of providing new insights into the phytochemistry and pharmacology of this species, the ethanolic extract of the bulbs from a local accession, not previously studied, growing in Sicily (Italy), was investigated. This chemical analysis, performed by mono- and bi-dimensional NMR spectroscopy, as well as LC-DAD-MSn, allowed to identify several alkaloids, three of which were n…

A praxis of hope: lessons from the 'untested feasibility' for twenty-first century education

2023

This article offers a contemporary interpretation of the work of global educator, Paulo Freire, inspired by the concept of 'untested feasibility' which he first expounded in his work Pedagogy of Hope. Our purpose is to pay particular attention to some relevant lessons stemming from the imagination of what has so far been untested and yet is feasible, which Freire closely associates with his views on utopia. These lessons remain fully valid for education in the twenty-first century in a globalised world characterised by tensions and uncertainties. In this sense, these pages pay homage to Paulo Freire as global educator and respond to his willingness to revive and discuss his intellectual and…

NeuronAlg: An Innovative Neuronal Computational Model for Immunofluorescence Image Segmentation

2023

Background: Image analysis applications in digital pathology include various methods for segmenting regions of interest. Their identification is one of the most complex steps and therefore of great interest for the study of robust methods that do not necessarily rely on a machine learning (ML) approach. Method: A fully automatic and optimized segmentation process for different datasets is a prerequisite for classifying and diagnosing indirect immunofluorescence (IIF) raw data. This study describes a deterministic computational neuroscience approach for identifying cells and nuclei. It is very different from the conventional neural network approaches but has an equivalent quantitative and qu…

Meltable, Glass-Forming, Iron Zeolitic Imidazolate Frameworks

2023

Vocational life : personal, communal and temporal structures

2023

AbstractThis paper offers a new philosophical account of vocations as deeply personal but at the same time also communal and generational forms of multimodal intending. It provides a reconstruction and a systematic development of Edmund Husserl’s scattered discussions on vocations. On these grounds, the paper argues that vocational life is a general human possibility and not determined by any set of material values, religious, epistemic or moral. Rather, vocations are distinguished from other complexes of intentional acts and attitudes by certain structural features of their core valuations and volitions.

Catalytic Nucleophilic and Electrophilic Functionalization of Dihydroquinoxalin‐2‐ones

2023

The functionalization at the C-3 position of 3,4-dihydroquinoxalin-2-one core has been significantly targeted over the last years. Several nucleophilic, electrophilic as well as radical catalytic functionalization of these nitrogen heterocycles have been reported. Usually, the more convenient methods are the direct photoredox functionalizations which use mild, green and sustainable conditions.

Untreated Opuntia ficus indica for the Efficient Adsorption of Ni(II), Pb(II), Cu(II) and Cd(II) Ions from Water

2023

The raw cladode of Opuntia ficus indica (OFI) was evaluated as a sustainable biosorbent for the removal of heavy metals (Ni, Pb, Cu, and Cd) from aqueous solutions. The functional groups of OFI were identified by employing DRIFT-FTIR and CP-MAS-NMR techniques before and after contact with the ions in an aqueous media, showing a rearrangement of the biomass structure due to the complexation between the metal and the functional groups. The adsorption process was studied in both single- and multi-component systems under batch conditions at different pHs (4.0, 5.0, and 6.0), different metal concentrations, and different biomass amounts. The results show that the raw OFI had a removal capacity a…

Functions of Astrocytes under Normal Conditions and after a Brain Disease

2023

In the central nervous system (CNS) there are a greater number of glial cells than neurons (between five and ten times more). Furthermore, they have a greater number of functions (more than eight functions). Glia comprises different types of cells, those of neural origin (astrocytes, radial glia, and oligodendroglia) and differentiated blood monocytes (microglia). During ontogeny, neurons develop earlier (at fetal day 15 in the rat) and astrocytes develop later (at fetal day 21 in the rat), which could indicate their important and crucial role in the CNS. Analysis of the phylogeny reveals that reptiles have a lower number of astrocytes compared to neurons and in humans this is reversed, as …

Aliens and dragons: purposefully-framed play and non-standard learning methods in teaching evolutionary processes to primary school pupils

2023

Evolutionary processes lie at the base of the entire observable biodiversity, both at present and in the geological past (i.e., in the fossil record). For this reason, the teaching of evolution should receive more recognition than it currently has (e.g., in Poland) and become accurately applied from the early formal education stages onwards. To test the possibility of effective teaching of evolution to primary school pupils, workshops using non-standard learning methods (‘purposefully-framed play’) were organised during childrens’ university (UNIKIDS) courses of one-hour sessions for 33 groups, comprising several to 20 participants, aged 7 to 12. The final task for all participants was to p…

Morbidity and mortality after anesthesia in early life in Italy. A subgroup analysis of the NECTARINE Trial

2023

Background: Recent literature on neonatal anesthesia focuses on the importance of keeping physiology within the ranges of normality to improve the long-term neurological outcome. The Neonate and Children audit of Anesthesia pRactice IN Europe (NECTARINE) showed a derangement of one or more than one physiological parameters during anesthesia needing a medical intervention in 35.2% of 6592 anesthesia procedure performed in infants up to 60 weeks postmenstrual age. Methods: Subanalysis of the Italian NECTARINE cohort providing a snapshot of anesthesia management, incidence of clinical events requiring intervention during anesthesia, and morbidity and mortality at 30 and 90 days. Secondary aim …

Bio-plastic recognition by mussels hemocytes

2023

The growing use of bio-polymers derivatives poses an increasingly pressing problem regarding their environmental sustainability. In particular, it should be still ascertained the claimed absence of direct and indirect influence on ecosystems and the health of living organisms, including humans. Our goal was about assessing the potential effects of poly-lactates and polyhydroxyalkanoates, the most widely used bio polymers classes with promising different applications for replacing conventional plastics on natural aquatic environments. We chose M. galloprovincialis as sentinel species since their extensive filter-feeding activity. When it is exposed to microparticles can bioaccumulate them in…

The multiple potentialities of anthozoans: analyses and comparisons between animal models

2023

Anthozoans are the richest class of species of the phylum Cnidaria. They are a candidate group for studying the evolution of mutualisms and immunity and despite their morphological simplicity exhibit a repertoire of immunological components with large genomes and gene families similar to those of the Bilateria. Like other invertebrates, anthozoans immunity is based on self/non-self recognition mechanisms and allorecognition responses, therefore, maintaining their integrity and responding actively to selection pressures. Highlight and investigate the link between innate immunity, homeostasis maintenance, inflammation, tissue remodelling and regeneration in Anthozoa could be useful to elucida…

Understanding "Islandness"

2023

Islandness is a contested concept, not just between disciplines but also cultures, entangled with what islands, island studies, and island identity are understood to be. The purpose of this article is to explore some of these different meanings, without necessarily unifying or reconciling them, with the aim of keeping multiple understandings of islandness in creative tension. We begin by considering islandness as smallness, recognizing that though many entry points into island studies relate to size in some way, what constitutes small is dependent on both context and worldview. Next, we consider islandness as culture, and the concept of island identity, which is expressed in varied forms. F…

Proton Structure Functions at Next-to-Leading Order in the Dipole Picture with Massive Quarks

2023

We predict heavy quark production cross sections in deep inelastic scattering at high energy by applying the color glass condensate effective theory. We demonstrate that, when the calculation is performed consistently at next-to-leading order accuracy with massive quarks, it becomes possible, for the first time in the dipole picture with perturbatively calculated center-of-mass energy evolution, to simultaneously describe both the light and heavy quark production data at small xBj. Furthermore, we show how the heavy quark cross section data provides additional strong constraints on the extracted nonperturbative initial condition for the small-xBj evolution equations.

Sensitivity of the SIMulation-EXtrapolation (SIMEX) methodology to mis-specification of the statistical properties of the measurement errors

2023

In hydrometeorological and environmental studies, it is common to seek relations between two variables (predictand and predictor), one of which (predictor) is affected by uncertainties. These errors unavoidably affect the results of the analyses by providing erroneous estimates of the parameters of the predictor-predictand model. A possible solution is represented by the SIMulation-EXtrapolation (SIMEX) methodology. This approach follows two steps: (1) perturbation of the predictor with increasing levels of uncertainties (multiples of the known error variance); and (2) finding a relation between the model's parameters and level of uncertainty, which allows their extrapolation to the error-f…

Actinins as novel broad-spectrum AMP isolated from the tentacle of Anthozoan Actinia equina (Linnaeus, 1758)

2023

Capturing activities and defense mechanisms of Cnidarian are strongly associated with toxins and peptide with antimicrobial properties. AMP are an important component of many organisms’ innate immune system with a good inhibitory or killing effect against invaders pathogens. We investigated the AMP activity of acid extracts obtained from tentacle and body of Actinia equina (Cnidaria, Anthozoa) against Gram positive (Micrococcus lysodeikticus) and Gram negative (Escherichia coli, Vibrio alginolyticus) bacteria. The peptide fractions showed interesting minimum inhibitory concentrations (MIC) values (concentrations up to 0.125 μg/ml) against tested pathogens. Tentacle acid extracts exhibiting …

B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma

2023

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells’ signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL). Using bulk RNA and single cell analysis, we found five novel pathologic-independent clusters in DLBCL based on cells’ signaling. B-cell receptor (BCR) signaling was identified as the only enriched signal in DLBCL and pSS peripheral naive B-cells or salivary gland-infiltrated cells. The evaluation of the genes in association with …

Antimicrobial and antioxidant supramolecular ionic liquid gels from biopolymer mixtures

2023

In this work, we describe the preparation and characterization of supramolecular ionic liquid gels based on binary mixtures of biopolymers, comprising chitosan, chitin, cellulose and lignin. The gels were obtained in ionic liquids differing in the cation or the anion, with no need for a cross-linking agent or acid treatment. The materials obtained were characterized for the minimum gelation concentration, porosity, swelling and rheological properties, finding a prominent influence of the nature of the ionic liquid anion. Then, we investigated the ability of the gels to scavenge free radicals, finding that the gels exhibit a higher antioxidant ability than their individual components. Moreov…

L’Ateneo non vuole dimenticare: doppia iniziativa per Livatino

2023

A Glimpse into Chromatin Organization and Nuclear Lamina Contribution in Neuronal Differentiation

2023

During embryonic development stem cells undergo the differentiation process so that they can specialise for different functions within the organism. Complex programs of gene transcription are crucial for this process to happen. Epigenetic modifications and the architecture of chromatin in the nucleus, by the formation of specific regions of active as well as inactive chromatin, allow the coordinated regulation of the genes for each cell fate. In this mini review, we discuss the current knowledge regarding the regulation of three-dimensional chromatin structure during neuronal differentiation. We also focus on the role played in neurogenesis by the nuclear lamina that ensures the tethering o…

In Silico Design of New Dual Inhibitors of SARS-CoV-2 MPRO through Ligand- and Structure-Based Methods

2023

The viral main protease is one of the most attractive targets among all key enzymes involved in the life cycle of SARS-CoV-2. Considering its mechanism of action, both the catalytic and dimerization regions could represent crucial sites for modulating its activity. Dual-binding the SARS-CoV-2 main protease inhibitors could arrest the replication process of the virus by simultaneously preventing dimerization and proteolytic activity. To this aim, in the present work, we identified two series’ of small molecules with a significant affinity for SARS-CoV-2 MPRO, by a hybrid virtual screening protocol, combining ligand- and structure-based approaches with multivariate statistical analysis. The B…

L'attuazione del regionalismo differenziato: prime impressioni sul disegno di legge S 615

2023

The paper aims to analyze the bill s 615 on differentiated regionalism in order to evaluate its consistency with the constitutional principles.