Biology subjects

Ricci, G.

Publications and source records attributed to Ricci, G..

11 recordsLinked to original sources

bioRxiv2026

The interferon-gamma response pathway is a targetable driver of FSHD muscular dystrophy progression

Facioscapulohumeral muscular dystrophy (FSHD) is a leading neuromuscular disorder caused by the aberrant expression of the transcription factor double homeobox 4 (DUX4) in skeletal muscle. While DUX4 is normally restricted to early embryonic development, its reactivation in FSHD triggers chronic inflammation and progressive muscle degeneration. However, the precise molecular links between DUX4 and persistent immune activation remain poorly understood. Here, we show that DUX4 induces a viral mimicry-like pathway that is fundamentally uncoupled from canonical type I interferon (IFN) activation. Instead, DUX4 establishes a non-canonical innate immune state dominated by IFN-gamma signaling, providing a mechanistic explanation for the non-resolving inflammation characteristic of the disease. We demonstrate that while IFN-gamma treatment alone is sufficient to recapitulate key DUX4 pathogenic effects, its inhibition rescues muscle inflammation and halts disease progression in FSHD models. These findings define a skewed viral mimicry process driven by a disease-specific transcription factor and identify IFN-gamma as a primary therapeutic target for tissue-informed immunomodulation in muscular dystrophy.

genetics↗

bioRxiv2025

Interindividual variations in peak alpha frequency do not predict the magnitude or extent of secondary hyperalgesia induced by high-frequency stimulation

BackgroundPrevious studies have shown an association between interindividual variations in the frequency of alpha-band EEG oscillations such as estimates of peak alpha frequency (PAF) and pain sensitivity. Whether differences in PAF also influence the susceptibility to develop central sensitization (CS) is unknown. ObjectiveThis study aimed to determine if the PAF of vision- and sensorimotor-related alpha-band activity is associated with the magnitude and extent of secondary mechanical hyperalgesia induced by high-frequency stimulation (HFS) of the skin, a surrogate marker of CS. MethodsThe EEG was recorded in 32 healthy participants at rest during eyes open and eyes closed conditions, and during bilateral finger movements. Two methods were used to isolate vision- and sensorimotor-related alpha-band activity based on sensitivity to eye closure and movement: one based on an independent component analysis, the other on spectral subtraction. PAF was assessed using a center-of-gravity approach or the Fitting Oscillations and One-Over-F (FOOOF) method, accounting for the aperiodic EEG component. HFS was applied to the right forearm, and pinprick sensitivity was assessed at both forearms, before and 40 minutes after HFS. ResultsNeither sensorimotor-nor vision-related PAF were significantly correlated with the magnitude or extent of HFS-induced secondary hyperalgesia. Interestingly, at the non-sensitized forearm, participants with a higher vision-related PAF exhibited greater habituation to pinprick stimuli, suggesting that variations in PAF may relate to variations in sensory habituation. ConclusionInterindividual variations of PAF were not significantly associated with the susceptibility to develop HFS-induced secondary hyperalgesia. New and NoteworthyUsing several methods to estimate vision- and sensorimotor-related peak alpha frequency (PAF) in the EEG frequency spectrum, we found no significant association between interindividual variations in PAF and the susceptibility to develop secondary hyperalgesia following high-frequency stimulation (HFS) of the skin in healthy participants.

neuroscience↗

bioRxiv2025

Individualized Alpha-tACS for Modulating Pain Perception and Neural Oscillations: A Sham-Controlled Study in Healthy Participants

Pain encompasses sensory, affective, and cognitive dimensions, with neural oscillations increasingly recognized as key mechanisms in their integration. However, the underlying processes remain inadequately understood. Transcranial alternating current stimulation (tACS) offers a promising tool for modulating these oscillations, yet the widespread reliance on one-size-fits-all tACS protocols with fixed frequencies has led to limited and contradictory findings on its efficacy in pain treatment. In this study, we employed individualized tACS at individual peak alpha frequency (IAF) over the primary motor cortex (M1) contralateral to the dominant arm of 38 healthy participants, in a within-subject, sham-controlled design, to investigate its effects on pain perception and neural oscillations. Sustained and periodic 0.2 Hz thermonociceptive stimuli were applied to the dominant forearm before and after tACS. We measured participants pain perception and heat pain thresholds (HPT) before and after tACS stimulation. Scalp electroencephalography (EEG) measurements were used to measure neural activity during thermonociceptive stimuli. To calculate IAF, we used a discriminative approach based on independent component analysis (ICA) to separate sensorimotor related IAF (SM-IAF). The results revealed an overall increase in pain perception and a decrease in HPT in both sham and active conditions, with no significant interactions between conditions. However, a trend toward reduced sensitization post-tACS was observed. Exploratory analyses indicated a significant tACS effect on HPT in women. Furthermore, a significant correlation was found between SM-IAF and HPT. These findings provide a novel perspective on advancing individualized neuromodulation approaches for pain and neurobiological disorders.

neuroscience↗

bioRxiv2024

Single-particle analysis of small extracellular vesicles from the follicular fluid of women undergoing fertility treatments reveals distinct PD-L1+ populations

In some cell systems, small extracellular vesicles bearing PD-L1 (PD-L1+ sEVs) have been shown to be able to suppress T-cell immunity. We have herein investigated whether a distinct profile of PD-L1+ sEVs exists in human follicular fluid (FF). Single-particle interferometric reflectance imaging sensing combined with a single-particle antibody capture and immunofluorescence labelling were used to determine the expression and colocalization of CD63, CD81, CD9, and PD-L1 in sEVs derived from FF of women undergoing fertility treatments (n=10). In addition, the size distribution of sEVs was investigated via atomic force microscopy. Our data indicate that the bulk of tetraspanin-expressing EVs in human FF are less than 50 nm in size. Tetraspanins and PD-L1 exhibit distinct expression and colocalization profiles at sEV level across all cohort samples. A total of 42%, 46%, and 50% of all the particles captured by anti-CD63, anti-CD81, and anti-CD9 antibodies, respectively, were positive for CD81. PD-L1 was expressed at the highest level on CD9+ sEVs, with an average value of 5% within the cohort. The presence of distinct PD-L1+ sEV subpopulations suggests that they may play a role in regulating the immune response in the follicular microenvironment. Further research is needed to fully understand the functional significance of PD-L1+ sEVs in this context and their potential as biomarkers for predicting fertility outcomes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/628903v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@77e67dorg.highwire.dtl.DTLVardef@1bd1ce2org.highwire.dtl.DTLVardef@b376d8org.highwire.dtl.DTLVardef@3f6fad_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Multisensory integration in Peripersonal Space indexes consciousness states in sleep and disorders of consciousness

Conscious experience encompasses not only the awareness of external objects, but also a phenomenal representation of the embodied subject of the experience. The latter is mediated by the integration of multisensory stimuli between the body and the environment, a process mediated by the Peripersonal Space (PPS) system. Here we thus tested the hypothesis that a neural marker of PPS representation may index the presence of conscious experience. Using high-density EEG in awake participants, we identified a "PPS index", characterized by high-beta oscillations in centroparietal regions during the integration of audiotactile stimuli presented near versus far from the body. We then examined this marker across two models of altered consciousness, i.e., sleep and disorders of consciousness. The PPS index persisted during dreaming and waking conscious states but was absent during dreamless, unconscious states. Moreover, the same index predicted behavioural measures of consciousness and clinical outcome in patients recovering from disorders of consciousness. These results suggest that multisensory integration within the PPS is tightly linked to the presence of conscious experience.

neuroscience↗

bioRxiv2024

Platelet as key cells in endometriosis patients: insights from small extracellular vesicles in peritoneal fluid and endometriotic lesions analysis

Endometriosis is a chronic inflammatory condition characterized by the presence of endometrium-like tissue outside the uterus, primarily affecting pelvic organs and tissues. In this study, we explored platelet activation in endometriosis. We utilized the STRING database to analyze the functional interactions among proteins previously identified in small extracellular vesicles (EVs) isolated from the peritoneal fluid of endometriosis patients and controls. The bioinformatic analysis indicated enriched signaling pathways related to platelet activation, hemostasis, and neutrophil degranulation. Double immunohistochemistry analysis for CD61 and MPO revealed a significant presence of neutrophils and platelets infiltrating endometriotic lesions, suggesting potential cell-cell interactions. Subsequently, we isolated small EVs from the peritoneal fluid of women diagnosed with endometriosis and from women without endometriosis who underwent surgery for non-inflammatory benign diseases. We performed single-particle phenotyping analysis based on platelet biomarkers GPIIb/IIIa and PF4 using nanoflow cytometry, as well as single-particle morphological and nanomechanical characterization through atomic force microscopy. The study demonstrated that patients with endometriosis had a notably higher proportion of particles testing positive for platelet biomarkers compared to the total number of EVs. This finding implies a potential role for platelets in the pathogenesis of endometriosis. Further research is necessary to delve into the mechanisms underlying this phenomenon and its implications for disease progression.

cell biology↗

bioRxiv2024

Acute multi-level response to defective de novo chromatin assembly in S-phase

Long-term perturbation of de novo chromatin assembly during DNA replication has profound effects on epigenome maintenance and cell fate. The early mechanistic origin of these defects is unknown. Here, we combine acute degradation of Chromatin Assembly Factor 1 (CAF-1), a key player in de novo chromatin assembly, with single-cell genomics, quantitative proteomics, and live-microscopy to uncover these initiating mechanisms in human cells. CAF-1 loss immediately slows down DNA replication speed and renders nascent DNA hyper-accessible. A rapid cellular response, distinct from canonical DNA damage signaling, is triggered and lowers histone mRNAs. As a result, histone variants usage and their modifications are altered, limiting transcriptional fidelity and delaying chromatin maturation within a single S-phase. This multi-level response induces a cell-cycle arrest after mitosis. Our work reveals the immediate consequences of defective de novo chromatin assembly during DNA replication, explaining how at later times the epigenome and cell fate can be altered. HighlightsO_LIThe histone chaperone CAF-1 sustains DNA replication speed in single cells. C_LIO_LICAF-1 loss alters histone repertoire and delays chromatin maturation. C_LIO_LIH3K9me3 and H3K27me3 regions respond differently to acute CAF-1 depletion. C_LIO_LIImpaired S-phase chromatin assembly triggers an immediate response and a G0 arrest. C_LI

cell biology↗

bioRxiv2023

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis

Endometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. Incomplete surgery often results in recurring symptoms and the need for additional interventions. This study aims to explore the biological significance of PARP-1, EpCAM, and FR as potential targets for molecular imaging in endometriosis, assessing their suitability for targeted intraoperative imaging. Gene expression analysis was performed using the EndometDB. By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FR in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis image to perform a quantitative immunolocalization analysis. Additionally, double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as PARP-1 and FR, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment. The analysis of gene expression revealed that PARP-1, EpCAM, and FR exhibit higher levels of expression in endometriotic lesions compared to the peritoneum, used for control tissue. Immunohistochemical analysis also highlighted a significant increase in expression of all three biomarkers in endometriosis foci compared to surrounding tissues, as well as the quantitative analysis of immunolocalization of the signal. Furthermore, the double immunofluorescence analysis consistently revealed nuclear expression of PARP-1 and membrane and cytoplasmatic expression of EpCAM and FR, although relatively weaker. Overall, the three markers demonstrate significant potential for effective imaging of endometriosis. Particularly, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.

cell biology↗

bioRxiv2022

CAF-1 deposits newly synthesized histones during DNA replication using distinct mechanisms on the leading and lagging strands

During every cell cycle, both the genome and the associated chromatin must be accurately replicated. Chromatin Assembly Factor-1 (CAF-1) is a key regulator of chromatin replication, but how CAF-1 cooperates with the DNA replication machinery is unknown. Here, we reveal that this crosstalk differs between the leading and lagging strand at replication forks. Using biochemical reconstitution, we show that DNA and histones promote CAF-1 recruitment to its binding partner PCNA and reveal that two CAF-1 complexes are required for efficient nucleosome assembly under these conditions. Remarkably, in the context of the replisome, CAF-1 competes with the leading strand DNA polymerase epsilon (Pol{varepsilon}) for PCNA binding, but not with the lagging strand DNA polymerase Delta (Pol{delta}). Yet, in cells, CAF-1 deposits newly synthesized histones equally on both daughter strands. Thus, on the leading strand, chromatin assembly by CAF-1 cannot occur simultaneously to DNA synthesis, while on the lagging strand both processes are coupled. We propose that these differences may facilitate distinct parental histone recycling mechanisms and accommodate the inherent asymmetry of DNA replication.

biochemistry↗

bioRxiv2021

MEYE: Web-app for translational and real-time pupillometry

Pupil dynamics alterations have been found in patients affected by a variety of neuropsychiatric conditions, including autism. Studies in mouse models have used pupillometry for phenotypic assessment and as a proxy for arousal. Both in mice and humans, pupillometry is non-invasive and allows for longitudinal experiments supporting temporal specificity, however its measure requires dedicated setups. Here, we introduce a Convolutional Neural Network that performs on-line pupillometry in both mice and humans in a web app format. This solution dramatically simplifies the usage of the tool for non-specialist and non-technical operators. Because a modern web browser is the only software requirement, this choice is of great interest given its easy deployment and set-up time reduction. The tested model performances indicate that the tool is sensitive enough to detect both spontaneous and evoked pupillary changes, and its output is comparable with state-of-the-art commercial devices.

neuroscience↗

bioRxiv2020

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

The pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. This study offers an opportunity for novel therapeutic intervention in EM, a difficult to treat gynecological condition. SummaryC3 produced by the endometriotic tissue is involved in the lesion development through mast cell activation

immunology↗