Biology subjects

Manuel, S.

Publications and source records attributed to Manuel, S..

5 recordsLinked to original sources

bioRxiv2026

Phagocytosis Events Shift the Activation Trajectory of Neutrophils towards Serial Eating of S. aureus

Neutrophil recruitment and activation are essential for the control of microbial infections, yet how these cells adapt functionally upon entry into inflamed tissues remains incompletely understood. In particular, how temporal cues and direct interaction with the pathogen differentially shape neutrophil heterogeneity and effector functions remains poorly defined. Here, we employed in vivo time-stamping of tissue entry to disentangle time-dependent versus pathogen interaction-specific drivers of neutrophil heterogeneity during S. aureus skin infection. We show that canonical aging and activation markers progressively accumulated with increasing time since arrival in the inflamed tissue. Strikingly, however, phagocytic activity at the single-cell level was uncoupled from tissue dwell time and instead strictly correlated with each neutrophil's history of prior uptake of S. aureus. Furthermore, pathogen engagement induced an immediate shift towards a maximally activated phenotype. Therefore, neutrophil functional heterogeneity in infected tissues is governed less by residence time and more by discrete pathogen encounters which act as a key instructive event for subsequently enhanced phagocytosis. This suggests that the balance of microenvironmental and pathogen-derived cues tailors neutrophil activation in order to optimize antimicrobial clearance.

immunology↗

bioRxiv2025

BC-Predict Database: A Curated Resource of Experimentally Validated Markers in Multidrug Resistance in Breast Cancer

BackgroundIn this study, we aim to develop a yearly updatable database that could predict chemotherapeutic drug resistance and overall survival probability in breast cancer patients. Existing drug sensitivity databases depend on correlation-based predictions. In our study, candidates involved in drug resistance are chosen based on cell line validation (overexpression or downregulation or inhibition of candidates) studies, curated manually. Method28,773 mRNA expression signatures from 914 breast cancer patients were extracted from cProsite. 106 of these patients had clinical information and log2 fold change information required for this study. We categorized these patients into deceased and surviving groups from TCGA. To prepare a database that can predict drug resistance and overall survival, we included mRNAs that were over-expressed in at least 80% of the breast cancer patients and mRNAs over-expressed in deceased and surviving groups. In addition, we also reported breast cancer-associated drug resistance candidates which have been reported in cell-line based studies. The database matrix preparation involved an approximate of 15000 manual searches of cell validated studies. (750 candidates x 20 drugs). The database was validated using a publicly available breast cancer patient proteomics data. ResultsOur analysis identified a list of top priority candidates associated with multidrug resistance, categorized based on their resistance to >15 drugs, 5-15 drugs, and 2-4 drugs. Analysis of patient profiles in the database revealed that the number of proteins contributing to drug resistance was high in the poor prognosis category compared to the good prognosis category. ConclusionsOur study highlights the probable gaps in breast cancer drug resistance research, as only a small subset of overexpressed mRNA candidates found in patients are studied in vitro or in vivo experiments focusing on drug resistance. We also identified candidates involved in multidrug resistance, whose role in drug resistance has not been studied in more than 15 drugs. After further validations, this will benefit the clinicians and upcoming CRISPR gene therapeutics.

cancer biology↗

bioRxiv2024

Temperature drives seagrass recovery across the Western North Atlantic

Climate-driven shifts in herbivores, temperature and nutrient runoff threaten coastal ecosystem resilience. However, our understanding of ecological resilience, particularly for foundation species, remains limited due to a rarity of field experiments that are conducted across appropriate spatial and temporal scales and that investigate multiple stressors. This study aimed to evaluate the resilience of a widespread tropical marine plant (turtlegrass) to disturbances across its geographic range and how this is impacted by environmental gradients in (a)biotic factors. We assessed the resilience (i.e. recovery) of turtlegrass to a simulated disturbance (complete above- and belowground biomass removal) over a year. Contrary to temperate studies, higher temperature generally enhanced seagrass recovery. While nutrients and light availability had minimal impact, combined high levels of nutrients and herbivore grazing (meso and megaherbivore) reduced aboveground recovery. Our results suggest that the resilience of some tropical species, especially in cooler subtropical waters, may initially increase with warming.

ecology↗

bioRxiv2023

Modulating Subjective Pain Perception with Decoded MNI-space Neurofeedback

Pain is a complex emotional experience that still remains challenging to manage. Previous functional magnetic resonance imaging (fMRI) studies have associated pain with distributed patterns of brain activity (i.e., brain decoders), but it is still unclear whether these observations reflect causal mechanisms. To address this question, we devised a new neurofeedback approach leveraging real-time decoding of fMRI data to test if modulating pain-related multivoxel fMRI patterns could lead to changes in subjective pain experience. We first showed that subjective pain ratings can indeed be accurately predicted using a real-time decoding approach based on the stimulus intensity independent pain signature (SIIPS) and the neurologic pain signature (NPS). Next, we trained participants in a double-blinded decoded fMRI neurofeedback experiment to up- or down-regulate the SIIPS. Our results indicate that participants can learn to down-regulate the expression of SIIPS independently from NPS expression. Importantly, the success of this neurofeedback training was associated with the perceived intensity of painful stimulation following the intervention. Taken together, these results indicate that closed-loop brain imaging can be efficiently conducted using a priori fMRI decoders of pain, potentially opening up a new range of applications for decoded neurofeedback, both for clinical and basic science purposes.

neuroscience↗

bioRxiv2023

Interaction Between the Prefrontal and Visual Cortices Supports Subjective Fear

It has been reported that threatening and non-threatening visual stimuli can be distinguished based on the multi-voxel patterns of hemodynamic activity in the human ventral visual stream. Do these findings mean that there may be evolutionarily hardwired mechanisms within early perception, for the fast and automatic detection of threat, and maybe even for the generation of the subjective experience of fear? In this human neuroimaging study, we presented participants (Fear group: N=30; No Fear group: N = 30) with 2700 images of animals that could trigger subjective fear or not as a function of individuals idiosyncratic "fear profiles" (i.e., fear ratings of animals reported by a given participant). We provide evidence that the ventral visual stream may represent affectively neutral visual features that are statistically associated with fear ratings of participants, without representing the subjective experience of fear itself. More specifically, we show that patterns of hemodynamic activity predictive of a specific "fear profile" can be observed in the ventral visual stream whether a participant reports being afraid of the stimuli or not. Further, we found that the multivariate information synchronization between ventral visual areas and prefrontal regions distinguished participants who reported being subjectively afraid of the stimuli from those who did not. Together, these findings support the view that the subjective experience of fear may depend on the relevant visual information triggering implicit metacognitive mechanisms in the prefrontal cortex.

neuroscience↗