Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2

Background: Endothelial dysfunction plays a central role in the pathophysiology of COVID-19 and is closely linked to the severity and mortality of the disease. The inflammatory response to SARS-CoV-2 infection can alter the capacity of the endothelium to regulate vascular tone, immune responses, and the balance between anti-thrombotic and pro-thrombotic properties. However, the specific endothelial pathways altered during COVID-19 still need to be fully understood. Objective: In this study, we sought to identify molecular changes in endothelial cells induced by circulating factors characteristic of COVID-19. Methods and results: To this aim, we cultured endothelial cells with sera from patients with COVID-19 or non-COVID-19 pneumonia. Through transcriptomic analysis, we were able to identify a distinctive endothelial phenotype that is induced by sera from COVID-19 patients. We confirmed and expanded this observation in vitro by showing that COVID-19 serum alters functional properties of endothelial cells leading to increased apoptosis, loss of barrier integrity, and hypercoagulability. Furthermore, we demonstrated that these endothelial dysfunctions are mediated by protease-activated receptor 2 (PAR-2), as predicted by transcriptome network analysis validated by in vitro functional assays. Conclusion: Our findings provide the rationale for further studies to evaluate whether targeting PAR-2 may be a clinically effective strategy to counteract endothelial dysfunction in COVID-19

A thorough analysis of the occurrence, removal and environmental risks of organic micropollutants in a full-scale hybrid membrane bioreactor fed by hospital wastewater

The recent draft of the Urban Wastewater Treatment Directive pays attention to contaminants of emerging concern including organic micropollutants (OMPs) and requires the removal of some of them at large urban wastewater treatment plants (WWTPs) calling for their upgrading. Many investigations to date have reported the occurrence of a vast group of OMPs in the raw influent and many technologies have been tested for their removal at a lab- or pilot-scale. Moreover, hospital wastewater (HWW) may contain specific OMPs at a high concentration and therefore its treatment deserves attention. In this study, a 1-year investigation was carried out at a full-scale membrane bioreactor (MBR) treating mainly HWW. To promote the removal of OMPs, powdered activated carbon (PAC) was added to the bioreactor at 0.1 g/L and 0.2 g/L which resulted in the MBR operating as a hybrid MBR. Its performance was tested for 232 target and 90 non-target OMPs, analysed by UHPLC-QTOF-MS using a direct injection method. The wastewater arriving at the WWTP was characterized and the performance of both the MBR and hybrid MBR was assessed for: key OMPs selected on the basis of their frequency, occurrence, persistence to removal, bioaccumulation and toxicity; OMP classes; and the whole list of OMPs. Finally, an environmental risk assessment of the OMP residues was conducted by means of the risk quotient approach. The results indicate that PAC addition increased the removal of most of the key OMPs (e.g., sulfamethoxazole, diclofenac, lidocaine) and OMP classes (e.g., antibiotics, psychiatric drugs and stimulants) with the highest loads in the WWTP influent. The hybrid MBR also reduced the risk in the receiving water as the PAC dosage increased mainly for spiramycin, lorazepam, oleandomycin. Finally, uncertainties and issues related to the investigation being carried out at full-scale under real conditions are discussed in depth

Carbonate factory response through the MECO (Middle Eocene Climate Optimum) event: Insight from the Apulia Carbonate Platform, Gargano Promontory, Italy

During the Eocene, shallow-water carbonate systems were significantly impacted by climate fluctuations and hyperthermal events. Following the peak temperatures of the Early Eocene Climatic Optimum (EECO), a general cooling trend began, with short-lived (⁓200 kyr) warming events occurring alongside it. In the early Bartonian (around 40.1 Ma), a warming event known as the Middle Eocene Climatic Optimum (MECO) occurred, lasting approximately 500,000 years. In this scenario, the types and calcification rates of marine organisms such as corals and larger benthic foraminifera (LBF) were influenced by global CO2 and oceanographic changes, which had a major effect on photic carbonate factories. To better understand the effects of these factors on carbonate factories, a detailed study of shallow-water facies types, distributions, and evolution was conducted. The Middle Eocene Monte Saraceno sequence, located on the eastern margin of the Apulia Carbonate Platform (Gargano Promontory, southern Italy), was selected as a case study to investigate the relationships between carbonate factory types and climatic changes around theMECO event. This study identified twodistinct intervalswith different modes of carbonate production, separated by a sharp boundary. The lower interval consists of clinostratified, thick beds of rudstone to floatstone, mostly made up of various large Nummulites tests, indicating an early Bartonian age (Shallow Benthic Zone 17). Instead, the upper interval consists of coral floatstone to rudstone with a packstone matrix, rich in branching corals in association with gastropods, bivalves, and rare small larger benthic foraminifera. The appearance of Heterostegina sp. and Glomalveolina ungaroi in this interval indicates a late Bartonian age (Shallow Benthic Zone 18). By integrating biostratigraphic and stable-isotope data, the lower interval, with abundant Nummulites, was linked to the MECO event, duringwhich higher sea-surface temperatures seem to enhance larger benthic foraminifera proliferation, as already occurred in the Early Eocene. However, in the late Bartonian, the sharp transition to a coral-dominated carbonate factory,with rare larger benthic foraminifera showing smaller sizes, could be attributed to a drop in temperature that created the conditions more favourable to corals. Overall, this study provides compelling evidence of how environmental changes can affect marine carbonate production, also highlighting the importance of investigating these relationships, to better understand climate change in the past, present and near future

Intraspecific variation in invertebrate cognition: a review

A well-established field of research in vertebrates focuses on the variability of cognitive abilities within species. From mammals to fish, numerous studies have revealed remarkable differences in the cognitive phenotype among individuals, particularly in terms of sex or personality. However, many aspects of the mechanisms, genetics, and selective pressures that underlie individual cognitive variation remain unclear. Surprisingly, intraspecific variability in cognition has received much less attention in invertebrates, despite the increasing evidence of remarkable cognitive abilities in this group and the insights that could be gained from examining simultaneously two distinct taxa, namely vertebrates and invertebrates. In this review, we provide evidence that certain invertebrate species exhibit all the key features of cognitive variation observed in vertebrates, including differences related to sex and personality. In many cases, invertebrate studies have provided insights into the genetic basis, evolvability and response to selection of cognitive variability. Moreover, we highlight evidence for caste differences in eusocial insects, which are linked to task specialisation within the colony. This makes insect eusociality a valuable system for understanding how selection influences cognitive variation. We propose that cognitive variation in invertebrates may be more widespread than currently thought, and that selection may operate in a similar manner on two distantly related cognitive systems (vertebrates and invertebrates). Finally, we suggest that invertebrates hold the potential to serve both as alternative and complementary models to vertebrates, contributing to a deeper understanding of cognitive evolution

Catalogazione e studio dei manoscritti del convento di Santa Croce conservati presso la Biblioteca Nazionale Centrale di Firenze

Questa tesi, che fa parte del Progetto di Interesse Nazionale (PRIN) Dantesco 2017, si pone come obiettivo primario lo studio e la profilazione in forma di schede catalografiche dei 130 manoscritti provenienti originariamente dalla biblioteca del convento francescano di Santa Croce a Firenze, ed ora conservati presso la Biblioteca Nazionale Centrale di Firenze (BNCF). Partendo da questa attività di catalogazione, il cui risultato si trova in appendice al testo, si è voluto completare il progetto, conducendo non solo un’analisi paleografica, codicologica, culturale, storico-intellettuale critica di tutti i 130 codici, ma anche una più accurata contestualizzazione storico-artistica dei manoscritti miniati e decorati presenti nella collezione sotto esame. La prima parte di questa tesi è caratterizzata, quindi, dalla ricostruzione storica dell’ambiente culturale e cittadino tardo-medievale ed inizio-rinascimentale in cui Santa Croce andava formandosi sia come complesso ecclesiastico che come centro di studi. In questa fase è stato, pertanto, necessario porre l’accento non solo sul particolare momento di transizione culturale e politico di Firenze, ma anche sul progressivo adattamento alla vita secolare dei Francescani. Si è dimostrato, infatti, che proprio questo progressivo adattamento alla vita secolare ed ai suoi relativi bisogni, ha favorito una sorta di apertura da parte dei Francescani verso tutti quei beni materiali necessari alla diffusione della cultura, in particolar modo verso i manoscritti e l’arte figurativa. Tale fenomeno si è potuto riscontrare ben caratterizzato all’interno di Santa Croce stessa. La relazione tra manoscritti, Arte e Francescani è stata, quindi, il fulcro di questa tesi poiché si è investigato come i testi, con le loro eventuali miniature e decorazioni, insieme alle altre forme di arti figurative presenti nel contesto del convento fiorentino, siano stati caratterizzanti per l’identità francescana e, specificamente, santacrociana. Infine, tale analisi ha permesso di valutare il ruolo della committenza nella collezione libraria di Santa Croce, partendo proprio dal presupposto che la maggior parte dei codici sotto esame presentassero spesso riferimenti visuali e testuali al mondo francescano, facendo quindi ipotizzare un’influenza sotto qualche forma di committenza o produzione diretta da parte dei Francescani stessi. Proprio questo ruolo di mediazione diretta nella creazione e nella collezione dei manoscritti di Santa Croce, ha permesso di ricostruire le connessioni culturali che questo convento fiorentino aveva con altre istituzioni francescane europee, in particolar modo francesi, ma anche inglesi e nordeuropee, dimostrando il livello di avanguardia intellettuale che Santa Croce, grazie ai propri frati studiosi e studenti, aveva raggiunto nel tardo Medioevo e agli albori del Rinascimento.This thesis, part of the 2017 Project of National Interest (PRIN) on Dante, aims to study and to profile the 130 manuscripts originally from the Franciscan convent library of Santa Croce in Florence and now held in the Biblioteca Nazionale Centrale of Florence (BNCF). The research has been based on compiling single catalogue entries for each manuscript in order to create a comprehensive catalogue, which can be found at the back of the thesis; this thorough palaeographical approach has been combined with a detailed cultural-historical analysis of the whole 130 manuscripts as well as an art-historical study of all the decorated and illuminated ones. The first part of this research is characterised by the historical contextualisation of the late-medieval and early-Renaissance cultural and social ambiance in which Santa Croce was developing not only as an ecclesiastical complex, but also as a cultural hub. Hence, this part not only focused on the social and political shifts of Florence at the time, but also on the Franciscans’ progressive adaptation to secular life. It has been demonstrated how exactly this progressive adaptation to secular life of the Franciscans has favoured among them an open-minded approach to all those goods needed for the diffusion of culture, thus specifically to manuscripts and the figurative arts. Such phenomenon has been clearly identified within Santa Croce and, consequently, the relationship among manuscripts, the Arts and the Franciscans has been further analysed. In actual fact, the second section of this research focused on how manuscripts, their possible decorations and any other form of art present in the Florentine Franciscan convent played a role in characterising a typical Franciscan and santa-crocian identity. Ultimately, such analysis allowed to evaluate the role of commissioning in the library collection of Santa Croce, especially considering how often the visual palimpsest referenced the Franciscan world, eventually, suggesting a certain degree of direct patronage from the Franciscans. Precisely this proactive role of the friars of Santa Croce in the creation and collection of manuscripts, allowed to identify the cultural connections that the Florentine convent had with other European Franciscan institutions, in particular French, but also English and, generally, Northern-European ones. Overall, all these elements combined, served to prove the extent to which Santa Croce managed to develop an impressive intellectual avant-gardism within its ambience thanks to its savant and studious friars between the late Middle Ages and the early Renaissance

Seeking temporal refugia to heat stress: Increasing nocturnal activity despite predation risk

Flexibility in activity timing may enable organisms to quickly adapt to environmental changes. Under global warming, diurnally adapted endotherms may achieve a better energy balance by shifting their activity towards cooler nocturnal hours. However, this shift may expose animals to new or increased environmental challenges (e.g. increased predation risk, reduced foraging efficiency). We analysed a large dataset of activity data from 47 ibex (Capra ibex) in two protected areas, characterized by varying levels of predation risk (presence versus absence of the wolf-Canis lupus). We found that ibex increased nocturnal activity following warmer days and during brighter nights. Despite the considerable sexual dimorphism typical of this species and the consequent different predation-risk perception, males and females demonstrated consistent responses to heat in both predator-present and predator-absent areas. This supports the hypothesis that shifting activity towards nighttime may be a common strategy adopted by diurnal endotherms in response to global warming. As nowadays different pressures are pushing mammals towards nocturnality, our findings emphasize the urgent need to integrate knowledge of temporal behavioural modifications into management and conservation planning

Stress–strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress–strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient’s stress–strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8–33.2] cmH2O versus 11.4 [10.3–14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress–strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS

Provenance of the ballast stones from the Roman Republican ship Ilovik-Paržine 1: A hypothesis about its place of construction

A substantial quantity of ballast, primarily comprising blocks and pebbles of limestones and quartzose limestones, has been recovered in Paržine Bay (Ilovik Island, Croatia) in the stern section of a sailing vessel discovered in 2016, that wrecked between the second and the third quarter of the 2nd C. BC. This research introduces an integrated methodology for investigating the provenance of ballast stones. Both the skeletal assemblages and the siliciclastic content of the rocks suggest a common source for most of the ballast. Micropalaeontological analyses (benthic and planktic foraminifera) and Sr87/Sr86 values indicate an age younger than 500 ka. Three main lithologies dominate the ballast rock assemblage: 1) tightly cemented quartzose grainstones and quartzarenites, 2) bioclastic quartzose grainstone with large mollusks and rhodoliths and 3) weakly indurated and bioturbated quartzose grainstone. An extensive field survey and samples analysis conducted in the Quaternary mixed carbonate-siliciclastic successions along the Adriatic and Ionian coast of Italy, reveal a very high degree of similarity between the ballast stones and the Middle to Upper Pleistocene terrace deposits of the region of Brindisi (Apulia, Italy). These similarities encompass palaeontological assemblages, age, lithofacies and microfacies associations, mineralogical composition, quartz grain morphology, sedimentary and diagenetic features, stable carbon and oxygen isotope compositions, as well as the morphology and alteration features of pebbles. Given the uniformity of the ballast of the Romano-Republican Ilovik-Paržine 1 wreck, the study suggests, with a reasonable degree of certainty, that it was loaded in a single operation near Brundisium, one of the major ports of the Apulian coast (Italy). The results also suggest two additional hypotheses: 1) the ballast could have served as permanent ballast transported to balance the ship after it was launched; 2) the provenance of the ballast may provide insights into the location where the ship was constructed

Osservatorio Corte di giustizia dell’UE

IMPOSSIBILITÀ DI ESAMINARE IN DIBATTIMENTO I TESTIMONI A CARICO SENTITI IN FASE PREDIBATTIMENALE SENZA CONTRADDITTORIO , TRA DIRITTO DI PRESENZIARE AL PROCESSO E DIRITTO A UN EQUO PROCESSO Corte di Giustizia UE, Sez. III, 8 dicembre 2022, C-348/21 RIFIUTO DI ESECUZIONE DEL MANDATO D’ARRESTO EUROPEO PER FUMUS DI VIOLAZIONE DEL DIRITTO FONDAMENTALE A UN GIUDICE PRECOSTITUITO PER LEGGE : ALCUNE GUIDELINES DELLA CORTE DI GIUSTIZIA Corte di Giustizia UE, Grande Sezione, 31 gennaio 2023, C-158/21 P RESUPPOSTI E LIMITI PER IL RIFIUTO DELL’ESECUZIONE DEL MANDATO D’ARRESTO EUROPEO IN RAGIONE DEL PERICOLO PER LA SALUTE DELLA PERSONA RICERCATA Corte di Giustizia UE, Grande Sezione, 18 aprile 2023, C-699/21 L EGAMI DEL CITTADINO DI UN PAESE TERZO CON LO STATO MEMBRO DI ESECUZIONE DEL MANDATO D’ARRESTO , RIFIUTO DELLA CONSEGNA ED ESECUZIONE IN LOCO DELLA PENA DETENTIVA Corte di Giustizia UE, Grande Sezione, 6 giugno 2023, C-700/2

Solvothermally Grown Oriented WO3 Nanoflakes for the Photocatalytic Degradation of Pharmaceuticals in a Flow Reactor

Contamination by pharmaceuticals adversely affects the quality of natural water, causing environmental and health concerns. In this study, target drugs (oxazepam, OZ, 17--ethinylestradiol, EE2, and drospirenone, DRO), which have been extensively detected in the effluents of WWTPs over the past decades, were selected. We report here a new photoactive system, operating under visible light, capable of degrading EE2, OZ and DRO in water. The photocatalytic system comprised glass spheres coated with nanostructured, solvothermally treated WO3 that improves the ease of handling of the photocatalyst and allows for the implementation of a continuous flow process. The photocatalytic system based on solvothermalWO3 shows much better results in terms of photocurrent generation and photocatalyst stability with respect to state-of-the-art WO3 nanoparticles. Results herein obtained demonstrate that the proposed flow system is a promising prototype for enhanced contaminant degradation exploiting advanced oxidation processes