Biology subjects

Santoni, A.

Publications and source records attributed to Santoni, A..

6 recordsLinked to original sources

bioRxiv2025

Spatial grouping modulates the link between individual alpha frequency and temporal integration windows in crowding

Previous research has linked endogenous alpha oscillations ([~]7-13 Hz) to temporal integration windows in visual perception, with higher individual alpha frequency (IAF) predicting improved temporal segregation. Here, we investigated whether alpha-rhythmic temporal integration is a factor in visual crowding and whether this relationship is mediated by spatial grouping mechanisms. 47 participants performed a Vernier discrimination task, in which we manipulated both the stimulus onset asynchrony (SOA) between flankers and targets, and the spatial configuration of the flankers. Specifically, flankers were arranged to either induce crowding or "uncrowding", through the manipulation of good-Gestalt properties. Our results show that crowding has a temporal integration period of around 170 ms but this varies substantially across individuals. Importantly, resting-state IAF predicted individual variance in temporal integration windows: individuals with faster endogenous alpha rhythms could begin to segregate targets from distractors at shorter SOAs. Crucially, this effect was specific for crowding-inducing flankers and disappeared when flankers led to uncrowding. These results suggest that top-down spatial grouping can overwrite the temporal integration constraint imposed by alpha oscillations, highlighting both the relevance of alpha for understanding limits on peripheral visual processing as well as the flexible and context-dependent role of alpha in temporal integration. SIGNIFICANCE STATEMENTThe frequency of alpha-band activity varies across individuals and has previously been linked to temporal integration windows for low-level stimulus properties (e.g., flashes). However, the relevance of individual alpha frequency (IAF) for everyday perception is less clear. We tested whether IAF predicts temporal integration in spatial crowding, a phenomenon that strongly limits perceptual abilities. We found that individuals with higher IAF were better able to spatially segregate targets from flankers at shorter flanker-target offsets, indicating that they spatially integrated the flankers over a smaller temporal window. Interestingly, this effect disappeared when crowding was alleviated by flanker configurations following good-Gestalt principles. Our results suggest that bottom-up mediated spatio-temporal constraints on perception are linked to alpha oscillations but can be overridden by top-down spatial cues.

neuroscience↗

bioRxiv2025

Temporal windows of perceptual organization: Evidence from crowding and uncrowding

Organizing visual input into coherent percepts requires dynamic grouping and segmentation mechanisms that operate across both spatial and temporal domains. While crowding disrupts target perception when nearby elements fall within the same spatial pooling window, specific flanker configurations can alleviate this effect through Gestalt-based grouping, a phenomenon known as uncrowding. Here, we examined the temporal dynamics underlying these spatial organization processes using a Vernier discrimination task. In Experiment 1, we varied stimulus duration and found that uncrowding emerged only after 160 ms, suggesting a time-consuming process. In Experiment 2, we manipulated the stimulus onset asynchrony (SOA) between the target and flankers. We found that presenting good-Gestalt flankers briefly before the target (as little as 32 ms) significantly boosted uncrowding, even in the absence of temporal overlap between the two stimuli. This effect was specific to conditions in which flankers preceded the target, ruling out pure temporal integration and masking accounts. These findings suggest that spatial segmentation can be dynamically facilitated when the temporal order of presentation allows grouping mechanisms to engage prior to target processing. Moreover, the observed time course indicates that segmentation is not purely feedforward, particularly for stimuli that are likely to recruit higher-level visual areas, pointing instead to the involvement of recurrent or feedback processes.

neuroscience↗

bioRxiv2023

Targeting DNA2 Overcomes Metabolic Reprogramming in Multiple Myeloma

DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover novel mechanisms through which MM cells overcome DNA damage, we investigated how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting ILF2, a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo an adaptive metabolic rewiring and rely on oxidative phosphorylation to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identified the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells ability to overcome ILF2 ASO-induced DNA damage, as being essential to counteracting oxidative DNA damage and maintaining mitochondrial respiration. Our study revealed a novel vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation. STATEMENT OF SIGNIFICANCEMetabolic reprogramming is a mechanism through which cancer cells maintain survival and become resistant to DNA-damaging therapy. Here, we show that targeting DNA2 is synthetically lethal in myeloma cells that undergo metabolic adaptation and rely on oxidative phosphorylation to maintain survival after DNA damage activation.

cancer biology↗

bioRxiv2022

Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature.

Although the prime/boost interval can impact vaccine responses, the criteria for deciding its time length are poorly defined. To address this, we examined CD8 T cell responsiveness to boost in a BALB/c mouse model of intramuscular (i.m.) vaccination by priming with HIV-1 gag-encoding Chimpanzee adenovector, and boosting with HIV-1 gag-encoding Modified Vaccinia virus Ankara. We found that boost was more effective at day(d)100 than at d30 post-prime, as evaluated at d45 post-boost by multi-lymphoid organ assessment of gag-specific CD8 T cell frequency, CD62L-expression (as a guide to memory status) and in vivo killing. RNA-sequencing of splenic gag-primed CD8 T cells at d100 revealed a quiescent, but highly responsive signature, that trended toward a central memory (CD62L+) phenotype. Interestingly, gag-specific CD8 T cell frequency selectively diminished in the blood at d100, relative to the spleen, lymph nodes and bone marrow. These results move forward the rational design of prime/boost intervals.

immunology↗

bioRxiv2020

NK cells acquire PD-1 from the membrane of tumor cells.

Leucocytes often perform trogocytosis, the process by which cells acquire parts of the plasma membrane from interacting cells. Accumulating evidence indicates that trogocytosis modulates immune responses, but the underlying molecular mechanisms are unclear. Here, using two mouse models of leukemia, we found that cytotoxic lymphocytes perform trogocytosis at high rates with tumor cells. While performing trogocytosis, both Natural Killer and CD8+ T cells acquire the checkpoint receptor PD-1 from leukemia cells. In vitro and in vivo investigation revealed that PD-1 protein found on the surface of Natural Killer cells, rather than being endogenously expressed, was derived entirely from leukemia cells. Mechanistically, SLAM receptors were essential for PD-1 trogocytosis. PD-1 acquired via trogocytosis actively suppressed anti-tumor immunity, as revealed by the positive outcome of PD-1 blockade in PD-1-deficient mice. PD-1 trogocytosis was corroborated in patients with clonal plasma cell disorders, where Natural Killer cells that stained for PD-1 also stained for tumor cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on Natural Killer and cytotoxic T cells, reveal the immune-regulatory effect of membrane transfer occurring when immune cells contact tumor cells. Once sentence summaryNatural Killer cells are inhibited by PD-1 acquired from the surface of tumor cells via trogocytosis.

immunology↗

bioRxiv2018

A previously missed population of antigen-specific CD8 T cells divides in the blood after vaccination

Although clonal expansion is a hallmark of adaptive immunity, the location(s) where antigen-responding T cells enter cell cycle and complete it have been poorly explored. This lack of knowledge stems partially from the limited experimental approaches available. By using Ki67 plus DNA staining and a novel data analysis technique, we distinguished antigen-specific CD8 T cells in G0, in G1, and in S-G2-M phases after intramuscular vaccination of BALB/c mice with antigen-expressing viral vectors. We discovered an entire population of cycling cells that are usually missed. This \"extra\" population was present early after vaccination in lymph nodes, spleen and, surprisingly, also in the blood, which is not expected to be a site for mitosis of normal non-leukemic cells. These results have implications for previous and future immunological studies in animal models, and potentially in humans. They might also inspire hematologists to seek for other missed populations of dividing cells in blood.

immunology↗