Extracellular Vesicle Signatures and Post-Translational Protein Deimination in Purple Sea Urchin (<i>Strongylocentrotus purpuratus</i>) Coelomic Fluid—Novel Insights into Echinodermata Biology

The purple sea urchin (Strongylocentrotus purpuratus) is a marine invertebrate of the class Echinoidea that serves as an important research model for developmental biology, cell biology, and immunology, as well as for understanding regenerative responses and ageing. Peptidylarginine deiminases (PADs) are calcium-dependent enzymes that mediate post-translational protein deimination/citrullination. These alterations affect protein function and may also play roles in protein moonlighting. Extracellular vesicles (EVs) are membrane-bound vesicles that are released from cells as a means of cellular communication. Their cargo includes a range of protein and RNA molecules. EVs can be isolated from many body fluids and are therefore used as biomarkers in physiological and pathological responses. This study assessed EVs present in the coelomic fluid of the purple sea urchin (Strongylocentrotus purpuratus), and identified both total protein cargo as well as the deiminated protein cargo. Deiminated proteins in coelomic fluid EVs were compared with the total deiminated proteins identified in coelomic fluid to assess putative differences in deiminated protein targets. Functional protein network analysis for deiminated proteins revealed pathways for immune, metabolic, and gene regulatory functions within both total coelomic fluid and EVs. Key KEGG and GO pathways for total EV protein cargo furthermore showed some overlap with deimination-enriched pathways. The findings presented in this study add to current understanding of how post-translational deimination may shape immunity across the phylogeny tree, including possibly via PAD activity from microbiota symbionts. Furthermore, this study provides a platform for research on EVs as biomarkers in sea urchin models

A Large Family with p.Arg554His Mutation in ABCD1: Clinical Features and Genotype/Phenotype Correlation in Female Carriers

X-linked adrenoleukodystrophy (X-ALD, OMIM #300100) is the most common peroxisomal disorder clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the cerebral demyelinating form of X-ALD (cerebral ALD). The disease is caused by defects in the gene for the adenosine triphosphate (ATP)-binding cassette protein, subfamily D (ABCD1) that encodes the peroxisomal transporter of very-long-chain fatty acids (VLCFAs). The defective function of ABCD1 protein prevents β-oxidation of VLCFAs, which thus accumulate in tissues and plasma, to represent the hallmark of the disease. As in many X-linked diseases, it has been routinely expected that female carriers are asymptomatic. Nonetheless, recent findings indicate that most ABCD1 female carriers become symptomatic, with a motor disability that typically appears between the fourth and fifth decade. In this paper, we report a large family in which affected males died during the first decade, while affected females develop, during the fourth decade, progressive lower limb weakness with spastic or ataxic-spastic gait, tetra-hyperreflexia with sensory alterations. Clinical and genetic evaluations were performed in nine subjects, eight females (five affected and three healthy) and one healthy male. All affected females were carriers of the c.1661G>A (p.Arg554His, rs201568579) mutation. This study strengthens the relevance of clinical symptoms in female carriers of ABCD1 mutations, which leads to a better understanding of the role of the genetic background and the genotype-phenotype correlation. This indicates the relevance to include ABCD1 genes in genetic panels for gait disturbance in women

A Pyrazolo[3,4-d]pyrimidine compound inhibits Fyn phosphorylation and induces apoptosis in natural killer cell leukemia

Natural killer (NK) cell neoplasms are characterized by clonal proliferation of cytotoxic NK cells. Since there is no standard treatment to date, new therapeutic options are needed, especially for NK aggressive tumors. Fyn tyrosine kinase has a key role in different biological processes, such as cell growth and differentiation, being also involved in the pathogenesis of hematologic malignancies. Our previous studies led us to identify 4c pyrazolo[3,4-d]pyrimidine compound capable of inhibiting Fyn activation and inducing apoptosis in different cancer cell lines. Here we investigated the presence of Fyn and the effect of its inhibitor in NK malignant cells. Firstly, we showed Fyn over-expression in NK leukemic cells compared to peripheral blood mononuclear cells from healthy donors. Subsequently, we demonstrated that 4c treatment reduced cell viability, induced caspase 3-mediate apoptosis and cell cycle arrest in NK cells. Moreover, by inhibiting Fyn phosphorylation, 4c compound reduced Akt and P70 S6 kinase activation and changed the expression of genes involved in cell death and survival in NK cells. Our study demonstrated that Fyn is involved in the pathogenesis of NK leukemia and that it could represent a potential target for this neoplasm. Moreover, we proved that Fyn inhibitor pyrazolo[3,4-d]pyrimidine compound, could be a started point to develop new therapeutic agents

Decipher non-canonical SPAST splicing mutations with the help of functional assays in patients affected by spastic paraplegia 4 (SPG4)

Flowchart showing the molecular approach used to decipher the non-canonical splicing mutations

Macchine del Tempo/Time Machines Concept per la realizzazione di una grande mostra INAF nella città di Roma

La Mostra “Macchine del Tempo/Time Machines” sarà inaugurata a fine 2023, si chiuderà a Primavera del 2024 e verrà ospitata nel secondo piano del Palazzo delle Esposizioni di Roma, in Via Nazionale, gestito dall’Azienda Speciale Palaexpo, una partecipata del Comune di Roma, con cui sarà siglata una specifica convenzione. Il progetto ha un duplice obiettivo, da un lato realizzare una mostra pop che parli a tutti e che metta al centro l’Istituto Nazionale di Astrofisica, le sue persone e le sue ricerche, dall’altro dar vita a qualcosa di unico, che faccia parlare di sé e che incentivi il pubblico a informarsi sulle tematiche affrontate per ampliare il proprio sapere e conoscere INAF e i suoi osservatori distribuiti sul territorio italiano. Un percorso che vuole giocare tra il vecchio e il nuovo, con uno stile anni ’80, ma con contenuti che parlano dell’oggi e del domani e che usa il gioco come meccanismo per suscitare interesse ed emozione positiva. Le “Macchine del Tempo” sono strumenti dell’ingegno italiano, frutto della ricerca condotta negli osservatori dell’Istituto Nazionale di Astrofisica dalle donne e dagli uomini che ogni giorno mettono impegno e passione per portare le conoscenze umane sempre più distanti. Questa mostra vuole diffondere la conoscenza attuale facendo però vedere chi c’è “dietro l’oculare”. Un’esperienza immersiva che comincia da noi stessi e subito passa a Galileo, l’italiano che - inventando il cannocchiale - posò l’occhio sulla nostra prima “macchina del tempo”. Sarà importante realizzare un catalogo della mostra e sono stati avviati contatti per rendere l’esposizione fruibile al pubblico in modo quanto più possibile inclusivo. Nel corso del periodo in cui sarà visitabile la mostra saranno organizzati incontri scientifici di alto livello, con nomi di primo piano della Ricerca astrofisica e spaziale mondiale, ma anche aperitivi scientifici più informali, durante i quali i cittadini potranno conversare direttamente con i ricercatori. Verranno proposti dei progetti di public engagement che utilizzano format nuovi come il Poetry Slam abbinato a uno stage scientifico o rassegne cinematografiche che propongono film nei quali sono presenti strutturei INAF. Si intende inoltre realizzare uno show per planetario, in collaborazione con il Planetario di Roma, sul tema “Macchine del Tempo”, da programmare in un periodo vicino a quello della della mostra e da diffondere in seguito, anche sotto forma di film per planetario, sia in italiano che in altre lingue, per la fruizione da parte di un pubblico internazionale. La mostra “Macchine del Tempo” ha per INAF molteplici aspetti di ritorno in campo sociale, comunicativo e relazionale. La mostra vuole stimolare le giovani generazioni allo studio di materie STEM, ma con “contaminazioni” anche di altre discipline non solo scientifiche. Questo determinerà in futuro per INAF anche la possibilità di avere giovani risorse da inserire nell’organico di ricerca. L’astrofisica italiana è un'eccellenza internazionalmente riconosciuta e deve essere maggiormente valorizzata anche in Italia, per potenziare l’immagine che INAF trasmette ai cittadini, alle istituzioni e agli stakeholders, attraverso i finanziamenti pubblici rivolti alla ricerca, incentivando ad esempio le collaborazioni, o anche le donazioni, con altre realtà pubbliche o private. Questa mostra vuole essere un mezzo per offrire alle scuole del territorio, e non solo, la possibilità di accedere a un patrimonio culturale che unisce scienza, tecnologia e storia. Un patrimonio davvero unico nel suo genere. L’ambizione è di riuscire a realizzare un contenitore di eventi e di dibattiti che ruotino attorno ai temi più attuali dell’astrofisica, ma che non temono e che anzi cercano forti legami con l’arte tutta, dal teatro alla pittura, dalla musica alla letteratura

IAU Office of Astronomy for Education OAE Center Italy - Quarterly Report 1 January-March 2022

The IAU O!ce of Astronomy for Education Center Italy (I-OAE) is a joint project of a consortium of Italian partners led and represented by Istituto Nazionale di Astrofisica (INAF, National Institute for Astrophysics), the International Astronomical Union (IAU) and the IAU O!ce of Astronomy for Education. The Italian consortium is constituted by: INAF, the Italian Astronomical Society (SAIt) and the University of Rome Tor Vergata (ToV). I-OAE HQ are hosted by the INAF - Rome Astronomical Observatory, in Monteporzio. Personnel is selected on voluntary bases according to their interests and competence, in agreement with the Institutes they work for. Brochure of the 2021 activities: https://www.flipsnack.com/eduinaf/oaei-brochure.htmlQuarterly Report 1 January-March 2022 is the report of the activities from January to March 2022 of the IAU Office of Astronomy for Education OAE Center Italy Attachment: brochure of the activities and project 202

Report EduINAF anno 2021/2022

Il periodo a cui fa riferimento questo Report (Anno scolastico 2021/2022: Settembre 2021-Agosto 2022) è stato caratterizzato dal protrarsi dell’emergenza COVID in Italia con conseguenti difficoltà delle scuole e periodi di ricorso alla Didattica a Distanza (DaD). Il 2021/2022 è stato anche il terzo anno di attività della testata registrata EduINAF, il magazine di Didattica e Divulgazione dell’Istituto Nazionale di Astrofisica. In questo periodo, la redazione di EduINAF, oltre a pubblicare risorse didattiche e contenuti informativi sul mondo della Didattica e Divulgazione della scienza, ha organizzato e contribuito a organizzare numerose iniziative a sostegno della scuola e della società, come le dirette osservative della Serie “Il Cielo in Salotto”, i concorsi per le scuole e altre campagne di engagement. In questo Report si presentano le attività svolte nell’arco di tempo indicato e si analizzano i risultati ottenuti in termini di audience, di comportamento e di gradimento del pubblico. L’obiettivo è quello di fornire il contesto per strutturare il Piano Editoriale 2022/2023 che conterrà le linee guida per la programmazione del prossimo anno scolastico

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation