Contextual influences on Italian university students during the COVID-19 lockdown: Emotional responses, coping strategies and resilience

Based on an ecological perspective on the COVID-19 lockdown experience, this study describes psychological responses among Italian university students. Our study considers three zones of the country that have differed in the intensity of the COVID-19 pandemic. Specifically, this research explores whether differences in pandemic conditions can account for their divergent psychological outcomes. The participants were 792 university students from seven different Italian universities. Students were asked to express their emotions and describe meaningful events during the lockdown in writing. Based on the grounded theory approach, this study conducted qualitative data analysis using ATLAS.ti 8.0. The core emerged categories are emotions, emotional moods and state of mind, coping strategies, and resilience. The results describing these emergent factors in relation to environmental variables highlight differences in the feeling of anxiety among individuals: anxiety was more self-focused in zones that were more affected by the lockdown, while such anxiety was more related to family and friends in less-affected zones. In addition to identifying the negative repercussions that this emergency has had, this study describes some positive outcomes, such as the elaboration of new personal perspectives that help foster individual growth and allow individuals to gain new awareness of themselves and others. The confinement due to the COVID-19 emergency measures has been a very unique experience for people, and further research is needed to understand the long-term effects of the different coping responses activated by participants during and after the lockdown

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Una Giornata per la scienza aperta: ‘Viaggiatori in Toscana: personaggi e testimonianze’

La relazione ricostruisce gli interventi tenutisi il 9 aprile 2021 in occasione della giornata per la scienza aperta dedicata a Viaggiatori in Toscana: personaggi e testimonianze, organizzata nell’ambito del Festival di Pasqua del Comune di Montepulciano. Tema centrale è stato quello del ‘viaggio’ inteso come esperienza di formazione, educazione culturale e socialità e in particolare del viaggio in Toscana, luogo d’elezione per numerosi grandtouristi italiani e stranieri. Il testo è frutto della collaborazione delle relatrici dell’evento: Elisabetta Angrisano, Biancamaria Brumana, Silvia Calamandrei, Cinzia Cardinali, Laura Giambastiani, Annantonia Martorano e Fiammetta Sabba (alla quale si deve la curatela complessiva del testo)

Una Giornata per la scienza aperta: ‘Viaggiatori in Toscana: personaggi e testimonianze’

The report reconstructs the lectures held on April 9 2021 during the open science day dedicated to Viaggiatori in Toscana: personaggi e testimonianze, organized by the ‘Festival di Pasqua’ of the Municipality of Montepulciano. The main theme was the ‘journey’ as social, formative and cultural education experience, and in particular the journey in Tuscany, place of choice for many Italian and foreign grandtourists. The speeches show the results of research that has seen the examination of library, archival, artistic and musicological sources and experiences that are so different from each other but which, in a harmonious and interconnected way, give back the image of a social and cultural phenomenon based on the exchange and contamination of ideas. All of this is done through a new form of divulgation, intended for a non-academic public and in line with the principles of the Third Mission of the universities.La relazione ricostruisce gli interventi tenutisi il 9 aprile 2021 in occasione della giornata per la scienza aperta dedicata a Viaggiatori in Toscana: personaggi e testimonianze, organizzata nell’ambito del Festival di Pasqua del Comune di Montepulciano. Tema centrale è stato quello del ‘viaggio’ inteso come esperienza di formazione, educazione culturale e socialità e in particolare del viaggio in Toscana, luogo d’elezione per numerosi grandtouristi italiani e stranieri. Gli interventi mostrano i risultati di ricerche che hanno visto il vaglio di fonti ed esperienze bibliotecarie, archivistiche, artistiche e musicologiche così diverse tra loro ma che, in modo armonico e interconnesso, restituiscono l’immagine di un fenomeno sociale e culturale fondato sullo scambio e sulla contaminazione delle idee. Il tutto attraverso una forma divulgativa nuova, destinata ad un pubblico non accademico e rispondente ai principi della Terza missione delle università

Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10. © 2007 Elsevier Inc. All rights reserved

UVB-induced activation and internalization of keratinocyte growth factor receptor

Ultraviolet irradiation of mammalian cells induces several events that include activation of growth factor receptors and triggering of signal transduction pathway. Most of the UV responses are mediated by the production of reactive oxygen species (ROS) and can be blocked by antioxidants. In this study, we analysed the effect of UVB irradiation at physiologic doses and that of the prooxidant agent cumene hydroperoxide (CUH) on the activation of the receptor for keratinocyte growth factor (KGF), a key mediator of epithelial growth and differentiation. Exposure to both UVB (30-150 mJ/cm(2)) and CUH (200 muM of NIH3T3 KGFR (KGF receptors) transfectants caused a rapid tyrosine phosphorylation and activation of KGFR similar to that induced by KGF, and internalization of the activated receptor. The KGFR expression appeared unmodified by the treatments. Ultrastructural observations of both UVB- and CUH-treated cells showed a normal morphology of the plasma membranes and intracellular organelles. The antioxidant N-acetylcysteine inhibited UVB-induced receptor phosphorylation. The generation of an intracellular oxidative stress was detected as a decrease of catalase activity and of vitamin E, and reduced glutathione levels, whereas superoxide dismutase activity was not significantly modified. A peroxidation of polyunsaturated fatty acids of cell membranes was observed after both treatments, associated with the intracellular oxidative stress. Similar biochemical events were observed on NIH3T3 untransfected control cells, suggesting that KGFR activation follows intracellular generation of ROS and is not associated with a scavenging effect. Taken together our results demonstrate that exposure to UVB and to oxidant stimuli induces a rapid intracellular production of ROS, which in turn are capable of triggering KGFR activation and internalization, similar to those induced by KGF

Up-modulation of the expressin of functional keratinocyte growth factor receptors induced by high cel density in he human keratinocyte HaCaT cell line.

Keratinocyte growth factor (KGF) is involved in the control of proliferation and differentiation of human keratinocytes. It binds to, and activates, the tyrosine kinase KGF receptor (KGFR), a splicing transcript variant of the fibroblast growth factor receptor 2. We have previously shown (C. Marchese et al., Cell Growth Differ., 8: 989-997, 1997) that differentiation of primary cultured keratinocytes triggered by high Ca2+ concentrations in the growing medium induced up-regulation of KGFR expression, which suggested that KGFR may play a crucial role in the control of the proliferative/differentiative program during transition from basal to suprabasal cells. Here we analyzed the process of modulation of the expression of KGFRs in the human keratinocyte cell line HaCaT, widely used as a model to study keratinocyte differentiation. Western blot and double immunofluorescence for KGFR and the K1 differentiation marker showed that cell differentiation and stratification induced by confluence and high cell density correlated with an increase in KGFR expression. KGFRs, present on suprabasal differentiated cells, appeared to be efficiently tyrosine-phosphorylated by KGF, which indicated that the receptors up-regulated by differentiation can be functionally activated by ligand binding. Bromodeoxyuridine incorporation assay revealed that a significant portion of suprabasal differentiated cells expressing KGFR seemed to be still able to synthesize DNA and to proliferate in response to KGF, which suggested that increased KGFR expression may be required for retention of the proliferative activity

Endocytic pathways and biological effects induced by UVB-dependent or ligand-dependent activation of the keratinocyte growth factor receptor.

ABSTRACT UVB exposure of epidermal cells is known to trigger early and late molecular pathways dependent on receptor tyrosine kinases and reactive oxygen species (ROS). We have recently reported that UVB irradiation induces tyrosine phosphorylation, kinase activation, and internalization of the receptor for the keratinocyte growth factor (KGFR), a paracrine mediator of epithelial growth, differentiation, and survival. Here we analyzed in more detail the UVB-induced endocytic pathway of KGFR and the role of KGFR activation and internalization in regulating UVB-promoted apoptosis and cell cycle arrest. Immunogold electron microscopy and confocal analysis revealed that the UVB-induced endocytosis of KGFR occurs through clathrin-coated pits and that the internalized receptors are sorted to the degradative route and reach the lysosomal compartment with a timing similar to that induced by their ligand KGF. Treatment with the anti-oxidant Nacetylcysteine inhibited KGFR endocytosis, suggesting that the receptor internalization is mediated by the intracellular production of ROS. The ligand-independent KGFR endocytic pathway induced by UVB requires receptor kinase activity and tyrosine phosphorylation and involves transient receptor ubiquitination. Inhibition of KGFR activity reduces both the KGF-mediated proliferative response and the UVB-promoted apoptotic cell death, indicating a different effect of ligand-induced and UVB-induced KGFR triggering. In addition, receptor internalization leads to protection from apoptosis caused by UVB exposure. Finally, we compared directly the behavior of KGFR with that of the epidermal growth factor receptor (EGFR) upon UVB exposure. Surprisingly, biochemical and immunofluorescence analysis showed that EGFR, differently from KGFR, does not undergo UVB-induced tyrosine phosphorylation and internalization. Taken together, our results suggest a differential role of KGFR and EGFR in the response of epidermal cells to UVB possibly because KGFR endocytosis could be crucial for attenuation of survival signals in the suprabasal layers of human skin