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The dynamic chemistry of the boron–nitrogen bond
No full textHere we report that fully reversible B←N bond formation/cleavage is a promising tool for the achievement of dynamic libraries (DLs) of rapidly interconverting compounds. The composition of a number of minimal DLs of adducts between phenylboronic acid catechol ester 1 and a series of nitrogen-based aromatic heterocycles (NArHets) is demonstrated to be predictable taking into account the association constants related to the formation processes of the single adducts involved. Furthermore, such composition can be controlled over time by the use of activated carboxylic acids (ACAs). Depending on the amount of added ACA, a B←N based DL can be either overturned in terms of composition, transiently overexpressing an adduct initially under-expressed, or transiently fully disassembled into its building blocks
Ellenismo: il Lazio in Italia e nel Mediterraneo. Forme, processi, idee
No full textNel nuovo scenario politico, economico e culturale che segue la fine dell’autonomia del nomen Latinum, la partecipazione del Lazio alla “romanizzazione” della Penisola e alla conquista del Mediterraneo si accompagna ad un profondo rinnovamento della cultura e dell’identità delle sue antiche città. Il Convegno tenutosi nel 2023, che si è avvalso del contributo di numerosi studiosi italiani e stranieri, si è proposto di chiarire quale sia stato il ruolo del Lazio antico nella formazione di uno specifico linguaggio culturale “latino” nel contesto dell’Ellenismo italico. La tematica è stata, finora, affrontata dal punto di vista di Roma, per la sua ovvia ed indiscussa egemonia e centralità, ma gli studi e le ricerche hanno da tempo dimostrato la spiccata vitalità dei centri latini durante il periodo ellenistico, con elementi di autonomia – e a volte, anche di precocità - rispetto alla stessa Roma, vitalità che, rapidamente, trasforma il Lazio in uno straordinario laboratorio di forme e modelli di grande originalità, destinati a connotare la costruzione dell’Italia romana come una vera e propria “latinizzazione” della Penisola e, di riflesso, delle regioni occidentali del Mediterraneo.
Nel complesso, i temi e i materiali qui indagati e discussi offrono un aggiornato quadro documentario e interpretativo e contribuiscono a ricostruire un quadro qualitativo e quantitativo molto articolato delle manifestazioni culturali del Lazio, tra la fine del IV e il I sec. a.C., tanto nella prospettiva storica che in quella geografica
Generative exaggeration in LLM social agents: Consistency, bias, and toxicity
No full textWe investigate how Large Language Models (LLMs) behave when simulating political discourse on social media. Leveraging 21 million interactions on X during the 2024 U.S. presidential election, we construct LLM agents based on 1186 real users, prompting them to reply to politically salient tweets under controlled conditions. Agents are initialized either with minimal ideological cues (Zero Shot) or recent tweet history (Few Shot), allowing one-to-one comparisons with human replies. We evaluate three model families — Gemini, Mistral, and DeepSeek — across linguistic style, ideological consistency, and toxicity. We find that richer contextualization improves internal consistency but also amplifies polarization, stylized signals, and harmful language. We observe an emergent distortion that we call “generation exaggeration”: a systematic amplification of salient traits beyond empirical baselines. Our analysis shows that LLMs do not emulate users, they reconstruct them. Their outputs, indeed, reflect internal optimization dynamics more than observed behavior, introducing structural biases that compromise their reliability as social proxies. This challenges their use in content moderation, deliberative simulations, and policy modeling
Development, performance and energy trade-off analyses of wind turbine precipitation-reactive control at offshore and onshore sites in Western Europe
No full textLeading edge erosion of wind turbine blades increases Annual Energy Production (AEP) losses and maintenance. Precipitation-Reactive Control (PRC) curtails rotor speed during erosive precipitation events, alleviating erosion but incurring curtailment-induced AEP losses. Using novel methods combining accurate wind and rain measurements and computationally efficient algorithms to select optimal precipitation metrics to steer PRC, the trade-offs of AEP losses for curtailment and erosion at an onshore site in England (Lancaster-Hazelrigg), and a Mediterranean and North Sea offshore site are evaluated. All analyses use time-series of wind speed from cup, sonic or lidar anemometers, and droplet size distributions from laser beam disdrometers. Varying levels of AEP losses for erosion are considered. The assessment at the Mediterranean site, with low erosivity, shows that PRC enables 25+ years of erosion-free operation with a 0.07% curtailment-induced AEP loss, against a 1% loss for moderate erosion. At Lancaster-Hazelrigg, the three-year mean AEP loss of 1.3% considering curtailment and erosion losses is lower than with standard control. The doubled erosion-free life gives a net positive contribution to cost of energy reductions. At the North Sea site, the three-year mean total AEP loss with PRC is higher than without, indicating the need for long-term cost analyses to evaluate PRC viability
Neurodegenerative and neuroinflammatory mechanisms in neurological and psychiatric disorders
No full textThe central nervous system (CNS) displays remarkable structural and functional adaptability, allowing neural circuits to respond to environmental changes, injury, or disease. However, dysregulation of these processes can lead to maladaptive changes that contribute to the development and progression of neurological disorders.
This thesis comprises three independent but conceptually related studies, each addressing a distinct pathological condition in which neuronal adaptability plays a key role.
The first project investigated the role of perineuronal nets (PNN), condensed aggregates of extracellular matrix (ECM) enwrapping neurons in general and Parvalbumin-positive interneurons in particular, in neuropathic pain. In a mouse model of unilateral chronic constriction injury (CCI) of the sciatic nerve, we observed reduced mechanical and thermal pain thresholds accompanied by increased WFA+ (Wisteria Floribunda Agglutinin) PNNs density in several pain-related brain regions, including somatosensory cortex (SSC), medial prefrontal cortex (mPFC), reticular thalamic nuclei (RTN), and insular cortex. These structural changes were associated with increased expression of the proteoglycans brevican and neurocan in the SSC and mPFC. Enzymatic degradation of PNNs with chondroitinase ABC in the contralateral SSC or RTN attenuated CCI-induced hypersensitivity, whereas siRNA of the PNN-degrading enzyme, type-9 matrix metalloproteinase (MMP-9), lowered pain thresholds only in sham-operated mice. Overall, these findings suggest that enhanced formation or reduced degradation of PNNs within the pain matrix causally contributes to nociceptive sensitization and the persistence of chronic pain (Mascio et al., 2025).
The second project explored the contribution of group II metabotropic glutamate receptors (mGlu2 and mGlu3) to methamphetamine use disorder (MUD), a condition characterized by persistent cognitive impairments and high relapse vulnerability. Repeated methamphetamine administration (1 mg/kg, i.p., once daily for 5 days) followed by a 7-day withdrawal period impaired novel object recognition (NOR) memory in wild-type mice. This effect was absent in mGlu2-/- and mGlu3-/- mice and was prevented by pharmacological blockades with selective negative allosteric modulators (NAMs) of mGlu2 (VU6001966) or mGlu3 (VU0650786) receptors. Methamphetamine upregulated the expression of mGlu2/3 receptors and presynaptic proteins involved in glutamate release, including vGlut1, Rab3A, and AGS3, in the PFC. Functionally, methamphetamine dysregulated mGlu2/3 receptor signaling: while it did not alter mGlu2/3-mediated inhibition of cAMP formation, it abolished the ability of postsynaptic mGlu3 receptors to potentiate mGlu5 receptor-mediated inositol phospholipid hydrolysis in PFC slices. Paradoxically, activation of presynaptic mGlu2/3 receptors amplified depolarization-evoked [3H]-D-aspartate release in PFC synaptosomes. These findings indicate that methamphetamine profoundly alters mGlu2/3 receptor expression and function, leading to dysregulated excitatory transmission in the PFC. Selective inhibition of these receptors may represent a promising therapeutic strategy to counteract methamphetamine-induced cognitive dysfunction (Busceti et al., 2024).
Finally, the third project examined whether disease-modifying therapies (DMTs) commonly used in multiple sclerosis (MS) influence the expression of angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2. To determine whether MS drugs (fingolimod, cladribine, dimethyl fumarate, and teriflunomide) affect ACE2 mRNA and protein levels, we used two different human lung carcinoma cell lines (Calu-3 and A549-hACE2-TMPRSS2) under basal and interleukin-1β (IL-1β)-mediated pro-inflammatory conditions. In Calu-3 cells, fingolimod significantly reduced ACE2 protein levels under inflammatory conditions, whereas dimethyl fumarate and teriflunomide increased ACE2 expression under both basal and pro-inflammatory conditions, and cladribine increased ACE2 protein levels under basal conditions. In A549-hACE2-TMPRSS2 cells, fingolimod reduced ACE2 mRNA and protein expression under both basal and pro-inflammatory conditions. Treatment with cladribine or teriflunomide followed by IL-1β challenge, led to a significant reduction in ACE2 protein expression; however, teriflunomide concurrently increased ACE2 mRNA expression under both basal and inflammatory conditions. These findings suggest that MS therapies can differentially influence ACE2 expression and that fingolimod, in particular, may exert a protective effect against SARS-CoV-2 infection in treated MS patients, by downregulating ACE2 (Ginerete et al., manuscript under review).
Together, these studies contribute to a broader understanding of the molecular and cellular mechanisms underlying CNS dysfunction across different neurological/psychiatric disorders, offering complementary perspectives that may guide the development of more targeted therapeutic strategies.
Busceti CL, Di Menna L, Castaldi S, D'Errico G, Taddeucci A, Bruno V, Fornai F, Pittaluga A, Battaglia G, Nicoletti F. Adaptive Changes in Group 2 Metabotropic Glutamate Receptors Underlie the Deficit in Recognition Memory Induced by Methamphetamine in Mice. eNeuro. 2024; 11(8):ENEURO.0523-23.2024.
Ginerete RP, Imbriglio T, Alborghetti M, Cannella M, Ceccherelli A, Castaldi S, Notartomaso S, Norma L, Battaglia G, Bruno V. Effects of Drugs for the Treatment of Multiple Sclerosis in Severe Acute Respiratory Syndrome Coronavirus 2 Infection on the Expression of Angiotensin-Converting Enzyme 2 in Vitro. Current Neuropharmacology. 2025, Manuscript under review.
Mascio G, Notartomaso S, Ginerete RP, Imbriglio T, Bucci D, Liberatore F, Ceccherelli A, Castaldi S, Zampini G, Cannella M, Nicoletti F, Battaglia G, Bruno V. Formation of perineuronal nets within a thalamocortical circuit shapes mechanical and thermal pain thresholds in mice with neuropathic pain. Pain. 2025; 166(5):1128-1142
Medico-legal features of rifled weapons discharge fatalities in Rome (Italy) and analysis of the differences in internal bullet wound paths between suicide and homicide
No full textFirearm wounds reppresent a significant cause of mortality worldwide. The differentiation between suicide, homicide, and accidental incidents can be complex, particularly in the absence of clear injuries linked to third-party involvement. Autopsy characteristics of wounds are pivotal in determining the manner of death. A review of the Institute of Legal Medicine of the University of Rome Tor Vergata's database identified 64 deaths due to rifled weapon discharge wounds, excluding accidental deaths. We recorded demographic, circumstantial, and autopsy data for homicides and suicides, with a focus on bullet intrasomatic wound paths analysis. Differences in frequencies of circumstantial data were observed, notably in the locations where victims’ bodies were discovered. Autopsy findings revealed distinct anatomical wound distribution. Bullet wound paths across three anatomical planes indicated patterns associated with the manner of death. Leftward, upward, and backward pathways were unique to suicides, while frontward and rightward pathways strongly indicated homicide. Therefore, comprehensive data integration is essential for accurate forensic diagnosis, and projectile directionality alone should not be considered a definitive criterion to distinguish between suicide and homicide, as similar wound paths may arise in both contexts depending on the circumstances
Gli spazi della poesia nella Cina odierna: versi in voce tra i ciliegi di Shanghai
No full textThis paper portrays a poetry event held in Shanghai in 2024, which I personally attended, to explore the symbolic and actual spaces poetry occupies in mainland China. During the reading I describe, poets voiced their works while walking along Yonghe East Road, together with the audience, media, and passers-by, embedding poetry into the
concrete and social cityscape. After a very brief historical overview, I frame the performance drawing on John Crespi’s analysis of huodong 活动 (activity/event) as used in the context of poetry, and Heather Inwood’s glossary of face-to-face poetry events. Introducing my level of observant participation, I interpret the reading through Michel
Foucault’s notion of performance as “counter-site”, via Zoë Skoulding, and Deirdre Osborne’s “landmark poetics”, for poems were hung on trees or printed on posters, enriching the city’s linguistic landscape. In doing so, I hope to reveal the vibrancy of Chinese poetry and its value as a community-building practice
Search for magnetic monopoles with the complete ANTARES dataset
No full textThis study presents a search for magnetic monopoles using the full ANTARES dataset collected over 14 years (2008–2022). The interaction of monopoles with matter was modeled according to the Kazama, Yang and Goldhaber cross-section, and dedicated reconstruction strategies were applied to probe velocities both above and below the Cherenkov threshold. No signal consistent with monopoles was found. We derive 90% C.L. upper limits on the flux of relativistic monopoles at the level of 10−18 cm−2 s−1 sr−1, improving upon previous ANTARES results and confirming those obtained by IceCube and other neutrino telescopes. These results constitute the final contribution of ANTARES to the search for magnetic monopoles
Structural basis of molecular recognition of pyridoxal 5′-phosphate in a bacterial periplasmic binding protein
No full textVitamin B6 and its vitamers are essential in bacteria. Many are auxotrophic for B6 vitamers and require salvage pathways and membrane uptake systems. Despite the importance of the uptake systems, very few transporters have been structurally characterized. The structure of the periplasmic binding protein (P5PA) of an ABC uptake transporter from the pathogen Actinobacillus pleuropneumoniae has been recently solved in complex with pyridoxal 5′-phosphate (PLP). Another close homolog from the same organism, AfuA, had been structurally characterized as a complex with glucose-6-phosphate (G6P). To study the molecular recognition of PLP by P5PA, a comparative approach has been applied. The heterologous complexes P5PA-G6P and AfuA-PLP have been generated by docking. Systematic molecular dynamics simulations have been applied to the native and heterologous complexes. Binding energies and molecular interactions have been compared for all the complexes. The results suggest the selective binding of the ligand is achieved by a combination of structural factors specific to each protein, including shape of the binding site, steric hindrance, hydrogen bonding, electrostatic and hydrophobic interactions. No single residue is uniquely responsible for ligand specificity although a few side chains play a significant role. Heterologous ligands are subject to destabilizing interactions that provoke the distortion of the ligand itself and the alteration of the protein dynamics. Residue Q267 appears to provide a significant stabilization contribution in the P5PA-PLP complex but not in AfuA-PLP. Likewise, D207 provides stabilization in the AfuA-G6P complex and not in AfuA-PLP. The indications obtained suggest strategies for the design of specific inhibitors
Targeting NADH homeostasis through GPD2 inhibition and metabolic stress induces tumor regression in colorectal cancer
No full textColorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide and is characterized by marked metabolic reprogramming to sustain tumor growth and survival. In this context, mitochondrial glycerol-3-phosphate dehydrogenase (GPD2), a key enzyme in the glycerophosphate shuttle, emerges as a critical regulator of redox balance. Through analysis of publicly available datasets and tumor samples from mouse models of intestinal tumorigenesis, we demonstrate that GPD2 is consistently upregulated at both the mRNA and protein levels in CRC compared to normal mucosa.
To investigate its functional role, we employed lentiviral-mediated knockdown of GPD2, which led to a marked decrease in proliferation and viability across multiple CRC cell lines. By a virtual screening of an in-house compound library, we identified a novel allosteric inhibitor of GPD2, termed G2i. Pharmacological inhibition of GPD2 using G2i significantly impaired tumor cell growth in vitro and in mouse models of CRC. Mechanistically, G2i disrupted mitochondrial NADH oxidation, leading to redox imbalance, accumulation of glycerol-3-phosphate (G3P), decreased ATP levels, and impaired mitochondrial respiration. These effects were reversible by restoring NADH oxidation capacity through LbNOX expression, pyruvate supplementation, or LOX-CAT induction, confirming that NADH accumulation and redox collapse are the primary vulnerabilities induced by GPD2 blockade.
Consistent with disrupted electron flow and increased redox imbalance, GPD2 inhibition led to elevated ROS levels and increased lipid remodelling. Notably, G2i promoted ferroptosis through redox-mediated ROS production and modulation of lipid metabolism.
Given the role of lactate dehydrogenase (LDH) as a compensatory cytosolic NADH sink, we tested the impact of GPD2 and LDH dual inhibition on CRC tumorigenesis. Co-targeting LDH and GPD2 synergistically enhanced redox stress, reduced NAD+ regeneration, and significantly suppressed CRC growth both in vitro and in vivo, potentiating G2i-mediated induction of ferroptosis. To further increase metabolic vulnerability, we implemented intermittent fasting (IF) protocols, which limit glycolytic substrate availability. IF potentiated the anti-tumor effects of G2i by amplifying NADH accumulation and energetic collapse, leading to enhanced tumor suppression through ferroptotic cell death.
Collectively, our findings position GPD2 as a druggable node in CRC redox metabolism. Its inhibition induces synthetic redox stress that compromises mitochondrial function and tumor viability. This vulnerability can be exploited through combined targeting of compensatory NADH sinks or nutrient restriction strategies, defining a therapeutic framework based on redox imbalance and opening new avenues for metabolic interventions in CRC