Archivio istituzionale della Ricerca - Scuola Normale Superiore
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Mapping Memory Encoding and Recall Using Translation-Dependent Reporters of Synaptic Potentiation in Physiological and Pathological Conditions
The mechanisms underlying the formation and retention of memory have been long sought after questions in Neuroscience. These central topics in research on the brain are tightly linked with the postulated existence of an “engram”, defined as an enduring modification of the neural tissue, which can remain latent, reactivated only when necessary to obtain the recall of a specific memory. This field has been recently revolutionized by a series of seminal studies in rodents, that have provided strong evidence that specific cell assemblies in the hippocampus, amygdala and cortex are necessary and sufficient for specific episodic memories to be recalled and behaviorally expressed. These findings support the existence of a memory engram at the cellular level. However, parallel studies on the basic mechanisms of information storage in neurons have demonstrated that selected subsets of the synaptic array of a single neuron – possibly belonging to identifiable neural circuits – undergo plastic modifications in response to stimuli inducing learning and memory. Linking these two aspects, namely memory engrams and plasticity at the synaptic resolution, has been largely hindered by a limitation in appropriate tools. This impediment has been recently overcome through the development of systems to label neurons and synapses activated by external inputs. Among these, ‘SynActive’ is a genetic toolbox which utilizes the 5’ and 3’ untranslated regions (UTRs) from the mRNA for the immediate-early gene Arc to confer to recombinant proteins (i.) transport to the base of dendritic spines in a dormant state and (ii.) activity- dependent translation upon synaptic potentiation. The focus of my work has been the in vivo use of gene constructs from the SynActive toolbox, expressed into the mouse hippocampus using adeno-associated viral vectors (AAVs). I first combined the SynActive tool with GFP Reconstitution Across Synaptic Partners (eGRASP) to obtain SA-eGRASP. eGRASP is based on splitting the GFP into two halves, which are expressed pre- and post-synaptically, respectively. Only when these two moieties are facing each other, i.e. are localized at the two sides of a synapse, reconstitution of fully functional, fluorescent GFP occurs. Therefore, SA-eGRASP allows circuit-specific labeling of potentiated synapses. This tool is based on four AAVs, allowing the expression of (i.) presynaptic neuronal label (Turquoise-2 blue fluorescent protein) and rtTA; TetON-controlled presynaptic half of eGRASP; (ii.) TetON-controlled presynaptic half of eGRASP; (iii.) postsynaptic neuronal label (tdTomato) and rtTA and (iv.) a TetON- and Synactive-controlled postsynaptic half of GRASP. By injecting AAVs (i.) and (ii.) within the CA3, and (iii.) and (iv.) to the CA1, SA-eGRASP was employed to identify and map both learning and memory-related synaptic potentiation in the Schaffer collateral pathway. Furthermore, this same method is being used to investigate learning- and memory-dependent synaptic potentiation in a transgenic mouse model of Alzheimer’s disease providing an opportunity to identify possible variations in the cartography of synaptic potentiation throughout disease progression. Moreover, I employed the SynActive approach to drive the expression of an optogenetic probe (channelrhodopsin-XXM; ChRXXM) combined with a fluorescent protein (mVenus) in a time and activity-dependent fashion. In addition, the TetON system was employed to control the time window of transcription of this construct. After careful optimization of the conditions for achieving optimal expression and for preventing ectopic localization of ChRXXM-mVenus in the CA1 region, I could identify the repertoire of synapses that undergo potentiation following induction of the formation of an associative episodic memory via exposure to contextual fear conditioning (CxFC). Notably, Notably, with further characterization, this tool has the potential to provide a method, not only for the identification and mapping of potentiated synapses following a learning- or memory-related protocol, but may allow for their subsequent manipulation through optogenetics, thus representing a stepping stone towards the demonstration of the existence of memory engram at the synaptic level.Taken together, the different sub-projects of the present thesis constitute a coordinated effort to create, validate and employ genetically encoded tools to contribute to shifting the resolution of studies on the physical substrates of memory from the whole neuron to specific subsets of its synapses. 
Completing the Spectral Mosaic of Chloromethane by Adding the CHD2Cl Missing Piece Through the Interplay of Rotational/Vibrational Spectroscopy and Quantum Chemical Calculations
Chloromethane (CH3Cl) is a key chlorinated organic compound not only in atmospheric chemistry, but also in the field of molecular astrophysics and a possible biosignature in exoplanetary atmospheres. While the spectroscopic characterization of the main isotopic species has been addressed in great detail, that of its isotopologues remains incomplete. This work aims at filling this gap by focusing on the bideuterated species, CHD2Cl, and exploiting both rotational and vibrational spectroscopy in combination with state-of-the-art quantum-chemical (QC) calculations. First, the rotational spectrum of CHD2Cl has been measured in the millimeter-wave domain, allowing the accurate determination of several spectroscopic constants for four isotopologues, namely 12CHD235Cl, 12CHD237Cl, 13CHD235Cl, and 13CHD237Cl. The newly determined rotational constants have been used to refine the semi-experimental equilibrium structure of chloromethane. Secondly, the vibrational analysis, supported by high-level QC predictions of vibrational energies, has been conducted in the 500–6200 cm−1 infrared (IR) region, enabling the identification of more than 30 bands including fundamental, overtone, and combination transitions. Finally, chloromethane’s radiative efficiency has been simulated using the QC IR absorption cross-sections, and the effects of isotopologue distribution on the predicted radiative properties have been investigated. All these findings greatly improve the comprehension of the spectroscopic properties of bideuterated chloromethane isotopologues, and of chloromethane in general, and facilitate future terrestrial and extraterrestrial studies
Anti-immigrant nativism in urban space and grassroots resistance for city-zenship
The seminar as part of the course Globalization, Social Justice, and Human Rights
Champions of Diversity Governance? City Approaches to Cultural Heterogeneity in Europe, Japan, and South Korea
In an era increasingly described as the age of diversity, societies worldwide grapple with how best to conceptualize and govern cultural heterogeneity. Amid shifts toward transnational rights discourses, rising urban influence, and evolving notions of identity, a critical question emerges: How do social structures originally rooted in assumptions of homogeneity transition to frameworks that acknowledge and embrace pluralism? This dissertation addresses this question by proposing a systematic, transdisciplinary, and translinguistic approach to understanding the rise of diversity as a governing framework in Europe, Japan, and South Korea.Drawing on insights from sociology, political science, anthropology, and related fields, the study critiques prevailing parochialisms in the scholarship – disciplinary, geographical, and linguistic – which impede comprehensive analyses of how cultural heterogeneity is understood and managed. These biases often confine research to specific national contexts, limit dialogue across linguistic frontiers, and perpetuate Western-centric narratives. By challenging methodological nationalism and linguistic fragmentation, the dissertation calls for broader, more integrative perspectives on diversity governance.Empirically, the research is based on a multi-sited comparative study of three cities – Barcelona in Spain, Hamamatsu in Japan, and Ansan in South Korea – each recognized as a pioneer in local-level policies for managing cultural diversity. Through in-depth fieldwork, the dissertation documents how municipal administrations, civil society actors, and city networks work together to forge innovative governance models. It examines the development and diffusion of interculturality in the European context, tabunka kyōsei in Japan, and damunhwa in South Korea, highlighting both the overlaps and unique national-cultural inflections among these frameworks. By tracing the flows of ideas and practices across these localities, the study illuminates how discourses and policy models are transmitted, adapted, and sometimes contested, ultimately shaping both local interventions and broader international discussions.Structured in four parts with eighteen chapters, the dissertation begins by outlining key theoretical debates around homogeneity, cultural pluralism, and “diversity governance.” It then introduces the policy diffusion theory and a multiscalar approach focusing on cities as entry points for the analysis, which, together, serve as a methodological tool for investigating how ideas travel across diverse socio-political landscapes. Subsequent sections explore the historical evolution of governance frameworks, cultural policies, and sociopolitical identities in Europe, Japan, and South Korea, carefully contextualizing each city’s approach to diversity. Finally, the concluding discussion synthesizes the findings, pointing to potential mechanisms driving a global convergence of diversity governance models and reflecting on the multiscalar interactions – local, national, and transnational – that shape them.Overall, this dissertation contributes a unified analytic lens aimed at transcending disciplinary barriers and national boundaries to examine how societies conceptualize, operationalize, and diffuse frameworks for cultural heterogeneity. Its comparative design reveals that local governance actors play a vital role in global policy innovation, often becoming the laboratories where novel discourses emerge and circulate. The study underscores the importance of language in shaping cultural boundaries and analytical biases, arguing that an overreliance on English-language paradigms can marginalize valuable insights from non- Western contexts. Ultimately, the dissertation highlights how scholarly endeavors themselves act as agents of diffusion, influencing both public debate and concrete policy design. By broadening the analytical horizons, this research aims to foster more inclusive, reflective, and context-sensitive approaches to cultural diversity in a rapidly changing global landscape
Review of Gorton, Ted J., Renaissance Emir: A Druze Warlord at the Court of the Medici, Northampton, MA: Olive Branch Press, 2014. ISBN 978-1-56656-963-7
This review critically examines the biography of Fakhr ad-Din Ma’n II, a Druze emir whose life spanned the complex geopolitical and cultural landscapes of the Early Modern Levant and Renaissance Europe. Gorton’s work offers a meticulously researched and accessible account of Fakhr ad-Din’s political career, exile in Tuscany, and enduring legacy, situating him within broader narratives of cross-cultural diplomacy, religious identity, and Mediterranean courtly culture. The review highlights the book’s strengths in contextualizing Druze history and its nuanced portrayal of Fakhr ad-Din’s strategic engagement with both Ottoman and European powers. It also reflects on the interpretive challenges posed by applying Western historiographical categories such as “Renaissance” to non-European figures
Charm CP violation measurements with KS0 final states at LHCb
The LHCb collaboration achieved the world's most precise measurement of the ACP(D0 -> KS0 KS0) parameter using data collected during Run 2 (2015–2018), reaching a precision of 1.3% and observing compatibility with the absence of CP violation at a significance of 2.4σ.Following a major Upgrade I, LHCb resumed operations in 2022 with a completely overhauled tracking system and a novel triggerless readout architecture, capable of reconstructing events at the full LHC bunch crossing rate of 30 MHz.This thesis presents the design and optimization of dedicated KS0 triggers, aimed at enhancing the LHCb online selection efficiency of D0 -> KS0 KS0 decays.The new triggers have been commissioned with early Run 3 data; performed tests confirm the feasibility of this new trigger strategy, never implemented before at a hadron collider.With the availability of larger samples, the impact on signal efficiency has been evaluated, leading to a fourfold enhancement for the target decay D0 -> KS0 KS0.These performances motivated an early ACP(D0 -> KS0 KS0) measurement performed on 6 fb-1 of data collected by LHCb in 2024, that already surpassed the precision of the previous measurement.This measurement is a remarkable result, being the most precise determination of this parameter to date, and demonstrating the effectiveness of the new triggers in enhancing the physics reach of the LHCb experiment
“No Labour, No Meal” Shifting Modalities of Wage Regulation in the Ahmedabad Textile Industry, 1935-65
Fast assembly of ‘clickable nanogels’ for drug delivery
Poly(alpha-glutamic acid) (PGA)-based nanogels (NGs) have garnered significant attention due to their biocompatibility, biodegradability, and potential to be functionalized. Recent advances in click chemistry, particularly strain-promoted azide-alkyne cycloaddition (SPAAC), enable the formation of nanogels under mild, metal-free conditions, preserving biocompatibility and avoiding contamination. In this work, we developed and optimized a protocol based on SPAAC click chemistry for the production of PGA-based NGs; moreover, we investigated their physicochemical properties, stability, and potential for drug delivery by encapsulating doxorubicin (Dox) as a model drug. The produced NGs showed high stability under various storage conditions, especially when containing the drug. We observed sustained drug release in various buffers or media, retention of drug functionality in cell cultures, and its transfer to cell nuclei with a delay of few hours with respect to the free drug. This click-chemistry-based method for NG production can be easily applied to produce different nanostructures, and the original or modified nanogels could serve as carriers not only for hydrophilic drugs, but also for proteins or other biomolecules in a variety of biomedical applications
Dalle Regulae alle Meditationes attraverso la dottrina delle verità eterne
The aim of this article is to analyze the distinction between the Regulae’s and the Meditationes’ conception of the mind in relation to the doctrine of eternal truths. To do this, after recalling and discussing the content of this doctrine in the
first paragraph, in the second I consider its application in the physics of Le Monde. Finally, in the last part, I discuss the insufficiencies of the Regulae in addressing the question of the foundation of knowledge, and I show how this question leads to the doctrine of eternal truths. Here, I also discuss the change of perspective between Regulae and Meditationes through the way in which the mind accesses truth, a problem deeply related to the doctrine of eternal truths