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TRACKING THE INVISIBLE. A SEARCH FOR SUPERSYMMETRIC HIGGSINOS WITH THE ATLAS DETECTOR.
No full textThis thesis presents two complementary searches for supersymmetric particles with compressed mass spectra using proton-proton collision data
collected by the ATLAS detector during the LHC Run 2 and Run 3. The analyses target the production of charginos and neutralinos near the electroweak scale and with mass splittings
in the range GeV. Owing to the small mass differences, the heavier neutralino and chargino are relatively long-lived and decay into low-momentum charged pions, which
are reconstructed as soft tracks displaced by a few millimeters from the proton-proton interaction point and characterised by unusually large impact parameters. The resulting final-state
signature is defined by the presence of an energetic jet, missing transverse momentum, and one or more than one soft, mildly displaced tracks. The first search
uses data collected at a center-of-mass energy of TeV, corresponding to a total integrated luminosity of . Dedicated event-level and track-level
selections are applied to define two Signal Regions maximising the overall signal-to-background ratio. No significant data excess above the Standard Model expectations
is observed, and 95\% confidence level exclusion limits are set on the chargino and neutralino masses as a function of their mass splitting. In the mass splitting range GeV,
chargino masses are excluded up to about 170 GeV, significantly extending the reach beyond the legacy LEP results for the first time. The second search uses data collected at center-of-mass energies
of and TeV, corresponding to a total integrated luminosity of . In this second analysis, an event-level binary neural network
and a track-level parameterised multi-class neural network are developed and employed in place of the cut-based approach used in the first analysis. The enhanced discriminating power
provided by the machine learning techniques, combined with the increased statistics of the Run 3 data set, is expected to further extend the LHC sensitivity into regions of parameter space
that are anticipated to remain inaccessible to future direct detection Dark Matter experiments
A molecular perspective of gelsolin amyloidosis: An old foe with new faces
No full textHereditary gelsolin amyloidosis (AGel) is a rare and often underrecognized protein misfolding disorder caused by mutations in the gelsolin (GSN) protein, leading to its aggregation in various tissues. Its rarity, combined with a heterogeneous and complex clinical presentation and the multidomain, flexible nature of GSN, has impeded research into its pathogenic mechanisms and therapeutic options. GSN comprises six homologous domains, labeled sequentially from G1 to G6. For over 40 years, AGel amyloidosis was exclusively linked to a systemic form, caused by D187N and D187Y mutations in the second domain, referred to as the Finnish and Danish variants. However, since 2013, numerous novel amyloidogenic variants have been identified in different protein regions, leading to various clinical phenotypes, characterized by distinct molecular mechanisms. This review examines these mutations and proposes a classification based on molecular and clinical features to enhance research and diagnosis. Additionally, we summarize whether elucidating the different pathogenic mechanisms aids in identifying potential druggable targets. The lack of information and biological models and limited efforts to develop pharmacological treatments highlight the need for further therapeutic exploration
¿MÁS VALE UN AÑO DE REY QUE VEINTE DE GUËY¿. GIOVANI, VIOLENZA, RECLUTAMENTO CRIMINALE E SOCIETÀ CIVILE IN MESSICO TRA VULNERABILITÀ E RESISTENZA:IL CASO DEL CENTRO JUVENIL PROMOCIÓN INTEGRAL A.C. (CEJUV, A.C.)
No full textThe thesis investigates the relationship between youth and violence in contemporary Mexico, a context marked by chronic, structural, and multifaceted forms of violence that particularly affect children and adolescents. In this scenario, the material precarization of life, exclusion from social protection systems, the erosion of rights and citizenship, and processes of stigmatization and criminalization of young people can generate specific forms of vulnerability situated between the status of victims and that of perpetrators of violence, as in the case of the criminal recruitment of minors by organized crime. Alongside these dynamics, however, practices of resistance emerge that create spaces of protection, recognition, and emancipation, opening up possibilities for escaping contexts and experiences shaped by violence. Adopting a qualitative approach, the research analyzes the narratives, practices, and strategies developed by civil associations and organizations engaged in preventing, countering, and transforming the conditions of youth overexposure to violence, while also highlighting the limits and potential of their interventions in highly vulnerable settings. The analysis focuses in particular on a case study – the work of the Centro Juvenil Promoción Integral A.C. (CEJUV A.C.) in Mexico City – through which it seeks to show how the creation of safe spaces, the building of meaningful relationships, and the promotion of opportunities for active participation can serve as central levers for generating concrete alternatives in the lives of the most vulnerable young people
Direct synthesis of phenyl isocyanate by carbonylation of nitrobenzene, catalyzed by palladium/phenanthroline complexes: promoting effect of phosphorus acids
No full textThe synthesis of aryl isocyanates by direct carbonylation of nitroarenes is the most straightforward alternative to the current technology, which involves the use of very toxic phosgene at one stage of the process. However, it faces several problems and has been little investigated in recent years. By taking advantage of our previous studies on the related carbonylation reaction yielding carbamates, we herein report that the use of phosphorus acids, diphenylphosphinic acid in particular, as promoters for the palladium/phenanthroline catalytic system, allows an improvement in activity and turnover number of almost one order of magnitude with respect to the best results previously reported. The effect of several experimental variables was investigated. Mechanistic investigations indicates that the enhanced activity is not associated with pathways involving water-assisted processes or aniline intermediates
INTEGRATED TRANSCRIPTOMIC AND TRANSLATIONAL PROFILING OF EIF6-SBDS IN SHWACHMAN-DIAMOND SYNDROM REVEALS DIFFERENT CELLULAR STATES SHAPED BY RIBOSOME COMPOSITION AND FIDELITY
No full textRibosome biogenesis is an essential and tightly regulated process that underpins cellular growth, proteostasis, and metabolic homeostasis. Disruptions in its final cytoplasmic maturation steps can profoundly alter translational output and lead to human disease. Shwachman–Diamond syndrome (SDS) exemplifies this class of disorders. Caused by biallelic loss-of-function mutations in SBDS, SDS is characterised by exocrine pancreatic dysfunction, growth impairment, bone-marrow failure, and a markedly increased risk of myelodysplastic syndrome and acute myeloid leukaemia. SBDS is required for release of the anti-association factor eIF6 from nascent 60S subunits, a prerequisite for productive 80S assembly and translational initiation. Consequently, SBDS deficiency limits the pool of functional ribosomes and constrains global protein synthesis. Recent sequencing of SDS bone marrow has revealed a striking and recurrent event: the acquisition of somatic mutations in eIF6, most frequently the missense variant N106S, arising exclusively in individuals with germline SBDS mutations. Their selective occurrence in SDS haematopoiesis has led to the hypothesis that these mutations act as a rescue event, although the underlying mechanism has remained unclear.
Here, we investigate how the eIF6 N106S mutation modifies ribosome function and interacts with SBDS depletion. Using Prime Editing, we generated isogenic HEK293T lines carrying a N106S allele in heterozygosis and established matched SBDS-depleted models via shRNAi. Polysome profiling, RNA-seq, and Ribo-seq were used to assess how each perturbation influences translational output, decoding fidelity, and stress-response pathways. Additional analyses of rRNA fragments, snoRNA dynamics, and inferred ribosomal-protein association provided complementary insight into consequences on ribosome assembly. Translation assays showed that both SBDS depletion and the N106S mutation reduce global protein synthesis. Unexpectedly, their combination further repressed translation rather than restoring it, contradicting the view that N106S simply alleviates the SBDS-dependent anti-association defect. Transcriptome profiling revealed that the double-mutant state does not recapitulate either single perturbation but instead produces a coordinated shift in stress signalling and cellular metabolism. Rather than approximating wild-type behaviour, this condition establishes a distinct regulatory environment characterised by reduced inflammatory signalling and dampened anabolic activity.
Taken together, these findings indicate that the N106S mutation does not restore the translational output impaired by SBDS deficiency but instead gives rise to a modified cellular state in which ribosome function is altered: decoding fidelity appears improved, proteotoxic stress is diminished, and transcriptional and metabolic programs diverge from both wild-type and single-mutant cells. These observations offer a plausible explanation for the selective retention of EIF6 mutations in SDS haematopoiesis and provide a foundation for future studies evaluating how modulation of the eIF6–60Scould be exploited in therapeutic treatment for SDS patients
Volunteering, Migration and Citizenship : The Role of Volunteering in Constructing Inclusive Societies
No full textVolunteering, Migration and Citizenship brings together the fields of migration studies and volunteering research to juxtapose the study of volunteering by migrants with the study of volunteering for migrants.
While in the social sciences volunteering has often been interpreted as the result of a renunciation of the transformation of society - a regression to pre-modern forms of helping the needy, or a retreat from ideals of social justice - this book takes an unconventional position by pointing to the potential of volunteering in the field of migration. Drawing on a study of volunteering for and by immigrants in Italy over the last eight years, it shows how volunteering not only responds to the logic of depoliticisation and ethical citizenship, but can also contribute to extending the social boundaries of society towards a more just and welcoming society. Crucially, it argues that volunteering in the field of migration can be situated within the domain of acts of citizenship, and that volunteering can take on a political character, enabling citizens and migrants alike to engage in micro-political acts.
Offering an innovative and unconventional look at the intersection of migration and volunteering, it crosses different themes and will appeal to an interdisciplinary audience in social movement studies, political sociology, civil society studies, cultural geography, migration studies and citizenship studies
HIV patients with poor immune recovery show exhausted CD4+ stem cell memory cells and impaired COVID-19 vaccine response
No full textVaccination triggers both humoral and cellular immune responses, generating memory T cells that ensure long-term protection. Among these, stem cell-like memory T cells (TSCM) are crucial for durable immunity due to their self-renewal and multipotency. In people with HIV (PWHIV), vaccine-induced responses can be weakened by persistent immune dysfunction. In this study, we longitudinally analyzed T cell memory responses following mRNA-1273 vaccination in PWHIV. Individuals with incomplete immune reconstitution (CD4+ < 500 cells/μL, CD4/CD8 < 0.4) showed reduced frequencies of Spike-specific CD4+ TSCM, lower levels of TCF-1 and higher expression of immune checkpoint molecules. We identified a subset of PD-1+TIGIT+ CD4+ TSCM and TCM cells that phenotypically resemble CD8+ exhausted-like progenitors (TPEX) and are enriched in PWHIV with poor immune recovery. Modulation of the Wnt/mTORs pathway via GSK3β inhibition restored TCF-1 expression and partially rescued antigen responsiveness, highlighting a potential strategy to improve vaccine efficacy in PWHIV
Genetic characterization and preliminary fusarium resistance evaluation in historical Italian rice germplasm
No full textThe conservation of traditional rice cultivars plays a crucial role in preserving agrobiodiversity and enhancing breeding programs aimed at improving resilience to climate change and disease resistance. This study presents the preliminary molecular, and phytopathological characterization of 22 historical rice accessions traditionally cultivated in the Lombardy region (Italy), now preserved in gene banks. Genetic diversity was assessed using 20 simple sequence repeats (SSR) markers, analyzed through Principal Coordinates Analysis and the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) clustering. Results highlighted the presence of genetically distinct subpopulations and confirmed the uniqueness of traditional landraces compared to modern control cultivars. To support their sustainable reintroduction into cultivation, protocols for seed sanitation and quality control were also implemented. In addition, the study provides a preliminary evaluation of the susceptibility of nine of these accessions to Fusarium fujikuroi, one of the most harmful seed-borne fungal pathogens affecting rice, associated with bakanae disease. The subset of accessions used in susceptibility assays was dictated by seed availability and infestation by nematodes that could alter the results. Pathogenicity tests revealed significant variability in susceptibility among the cultivars. Some landraces exhibited promising tolerance to Fusarium-induced bakanae, making them valuable candidates for organic and low-input farming systems. This integrated approach enhances the valorization and conservation of Italian rice germplasm and provides a foundation for breeding programs aiming at disease resistance and sustainable agriculture
Le vittime indigene della repressione della Junta militar in Argentina
No full textL’assenza nelle liste ufficiali delle vittime della Junta militar argentina di un riferimento all’eventuale loro origine indigena si manifesta come una lacuna negli studi che, sino ad ora, hanno ricostruito i molteplici aspetti della repressione di quegli anni e che hanno classificato le vittime secondo l’occupazione o la professione. Solo di recente sono state avviate ricerche per colmare questa lacuna, alle quali il saggio si propone di contribuire attraverso una sintetica ricostruzione della politica indigenista, da fine Ottocento sino agli anni del regime, che si intreccia con una sintesi della nascita, alla fine degli anni Sessanta, dell’attivismo indigeno inteso in senso ampio, cioè che comprende non solo l’impegno di indigeni per la causa indigena, ma anche quello di indigeni attivisti sindacali, politici e sociali. Ciò ha permesso di individuare alcuni indigeni vittime della repressione e di proporre, in generale, un primo profilo delle vittime d’origine indigena