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Biology subjects

Dore, S.

Publications and source records attributed to Dore, S..

3 recordsLinked to original sources

Asymmetric Adaptation of Catch-up Saccades with Artificial Central Scotomas

In fully-sighted individuals, pursuit and saccadic eye movements work together to foveate moving targets; pursuit attempts to match target velocity, while catch-up saccades re-align the fovea to the target if it deviates during pursuit. Although saccade-pursuit interactions are well understood in healthy individuals, much less is known about how these mechanisms adapt in the presence of central vision loss. Here, we simulated central vision loss in healthy young adults to examine plasticity in saccade-pursuit mechanisms and investigated whether and how catch-up saccades adapted over five days of visual tracking. Twenty-five fully sighted participants performed a task in which they pursued a moving target that stepped position randomly (designed to elicit catch-up saccades) while viewing with a gaze-contingent central scotoma. The scotoma was shaped like a bitten cookie to encourage use of a specific preferred retinal locus (PRL) corresponding to the peripheral location with the highest acuity. By the end of the five days of repetition, most participants showed catch-up saccade endpoints shifted towards the PRL rather than the fovea. On average, endpoints shifted 0.5 deg towards the PRL between days 1 and 5 (range=0.3-1.5 deg), with significant shifts in 13 of the 25 participants. Adaptation was asymmetric; shifts were largest when the target moved in the direction opposite the scotoma bite and smallest when it moved towards it. In summary, we observed adaptation of saccade-pursuit interactive mechanisms through the re-referencing of catch-up saccades from the fovea to PRL. These results provide a promising avenue for rehabilitation in central vision loss aimed at improving eye movements and encouraging PRL use. Ultimately, such an approach may enhance residual visual function and quality of life.

neuroscience↗

The PTPN1 and PTPN2 phosphatases are Cooperative Regulators of Cancer Cell Immune Evasion

Immune evasion by cancer cells remains a major barrier to the success of immune checkpoint blockade (ICB). Here, we identify the phosphatases PTPN1 and PTPN2 as cooperative regulators of tumor immune resistance. Dual genetic ablation of PTPN1/2 in cancer cells enhances Type I and II interferon signaling, MHC-I and CXCL9 expression, and sensitizes tumor cells to cytotoxic T lymphocyte-mediated killing. The small-molecule inhibitor KQ791 phenocopies these effects and synergizes with anti-PD1 therapy to suppress tumor growth in murine models, including immunotherapy-refractory cancers. Mechanistically, PTPN1/2 loss augments STAT1/3/5 signaling and primes cancer cells for immunogenic cell death via IFN{gamma}/TNF-induced pathways. Moreover, PTPN1/2 inhibition enhances antigen release and cross-presentation, promoting robust antigen-specific CD8 T cell responses. These findings highlight PTPN1&2 as essential mediators of cancer immune evasion and support their inhibition as a strategy to broaden the effectiveness of immune checkpoint blockade in solid tumors.

cancer biology↗

Timing and Amplitude of Catch-up Saccades to Accelerating Targets

To track moving targets, humans move their eyes using both saccades and smooth pursuit. If pursuit eye movements fail to accurately track the moving target, catch-up saccades are initiated to rectify the tracking error. It is well known that retinal position and velocity errors determine saccade timing and amplitude, but the extent to which retinal acceleration error influences these aspects is not well quantified. To test this, 13 adult human participants performed an experiment where they pursued accelerating / decelerating targets. During ongoing pursuit, we introduced a randomly sized target step to evoke a catch-up saccade and analyzed its timing and amplitude. We observed that retinal acceleration error was a statistically significant predictor of saccade amplitude and timing. A multiple linear regression supported our hypothesis that retinal acceleration errors influence saccade amplitude in addition to the influence of retinal position and velocity errors. We also found that saccade latencies were shorter when retinal acceleration error increased the tracking error and vice versa. In summary, our findings support a model in which retinal acceleration error is used to compute a predicted position error [~]100ms into the future to trigger saccades and determine saccade amplitude. Significance statementWhen visually tracking object motion, humans combine smooth pursuit and saccadic eye movements to maintain the target image on the fovea. Retinal position and velocity errors are known to determine catch-up saccade amplitude and timing, however it is unknown if retinal acceleration error is also used to predict future target position. This study provides evidence of a small but statistically significant contribution of retinal acceleration error in determining saccade amplitude and timing.

neuroscience↗