Biology subjects

Figueroa, T.

Publications and source records attributed to Figueroa, T..

12 recordsLinked to original sources

bioRxiv2026

Multiomic and Spatial Profiling of Colorectal Tissue Reveals Viral Persistence and Immune Dysregulation in Long COVID

Long COVID (LC) - a chronic condition characterized by persistent, debilitating symptoms following SARS-CoV-2 infection - has emerged as a major public health challenge. Although many interrelated mechanisms have been proposed as drivers of LC, the root causes have yet to be identified, posing significant challenges for therapeutic development. While many blood-based studies have been conducted, they have not yielded conclusive mechanistic insights into LC pathogenesis. Attention has therefore turned toward direct tissue investigation, with the gastrointestinal (GI) tract becoming a major focus due to evidence that virus or viral components can persist at this site for months to years following an episode of COVID-19. Here, we performed a high-dimensional characterization of colorectal tissue and peripheral blood in a highly characterized cohort of 44 people with LC and 13 recovered controls. We profiled SARS-CoV-2 persistence, host immune responses, and tissue inflammation using bulk and single-cell RNA sequencing, nCounter RNA probe hybridization, quantitative PCR, metagenomic next-generation sequencing, plasma proteomics, high-dimensional spectral flow cytometry, in situ-hybridization/immunohistochemistry, and single-cell digital spatial omics. Our results support a model in which LC is driven by long-term immune dysregulation and perturbations of the regulatory gut immune environment which imply ongoing viral persistence, although direct viral detection was only observed in a subset of participants. Specifically, we identify a tissue-based transcriptional environment in which SARS-CoV-2 activates innate myeloid immune signaling, driving chronic inflammation while simultaneously downregulating pathways responsible for immune-mediated clearance of infected cells, including antigen presentation, phagocytosis, cytotoxic immune cell trafficking, and granzyme production. Importantly, signatures in peripheral blood are considerably weaker than those observed in tissue. Together, these findings provide a direct biological rationale for therapeutic strategies in LC aimed at enhancing or redirecting cytotoxic immune function to overcome immune dysregulation and clear persistent viral reservoirs.

immunology↗

bioRxiv2026

Early immune responses anticipate HIV rebound and precede viral control

Sustained viral suppression following antiretroviral treatment (ART) cessation is a major goal of HIV cure research1. Rare individuals mount immune responses able to control viral rebound without intervention2,3, however, the earliest moments in which these responses form remain poorly defined. We performed an intensively sampled, prospective analytical treatment interruption (ATI) to study the initial immune response to rebound and to understand its role in defining subsequent virus control. Profiling of peripheral blood mononuclear cells and plasma revealed consistent immune activation prior to systemic rebound, including upregulation of antiviral transcriptional pathways, expansion of CD16++ non-classical monocytes, and increases of inflammatory and antiviral soluble plasma proteins. Individuals with prior viral control (controllers) diverged from non-controllers with a slower slope of rebound, a longer period of immune activity prior to rebound, and engagement of a multifaceted immune program with less systemic inflammation. An intermediate immune signature emerged in a separate ATI cohort of individuals who experienced delayed rebound after receiving broadly neutralizing antibodies4, suggesting that immunotherapy can induce a potentially protective pre-rebound immune response. Together, these data resolve the earliest systemic host immune responses to HIV rebound and demonstrate broad immune differences associated with HIV control phenotypes.

immunology↗

bioRxiv2026

Abstract Encoding of Sounds in the Frontopolar Cortex

The frontopolar cortex has been linked to higher-order cognition, including analogical reasoning, cost-benefit analysis, and semantic associations, primarily based on neuroimaging studies in humans rather than from direct single-neuron recordings. Notably, sensory input to this region originates from auditory cortical areas. To investigate the role of the frontopolar cortex in auditory perception, we recorded single neurons in nonhuman primates trained to discriminate between various sounds, including monkey calls and human words. We found that individual neurons form abstract, nonlinear representations of learned and novel sounds, collectively encoding all sound categories and generating decision-making signals. Our findings suggest that the frontopolar cortex integrates auditory information into behaviorally relevant signals, thereby providing insights regarding its role in cognition.

neuroscience↗

bioRxiv2025

Use of ANCHOR viruses to validate radiative, physical and chemical decontamination systems in operational conditions.

ANCHOR tagged viruses provide a high-performance platform for the rapid evaluation of disinfection methods across chemical, radiative, and physical modalities. This study highlights the robustness of Vaccinia virus (VACV) and human Adenovirus type 5 (hAdV5) as environmental persistence models, demonstrating their suitability for testing disinfection protocols. ANCHOR imaging capability allows real-time visualization of disinfection efficacy, enabling rapid calibration and cost-effective validation of new disinfection systems. This technology provides essential support for the development and optimization of disinfection solutions in public areas up to the improvement of safety protocols in high-containment laboratories. The increasing number of BSL-4 laboratories worldwide underscores the critical needs for efficient and reliable decontamination systems and methods to test them in operational conditions to ensure biohazard safety. HighlightsO_LIANCHOR-tagged viruses provide a rapid and cost-effective platform for evaluating disinfection methods across chemical, physical, and radiative modalities. C_LIO_LIHuman Adenovirus type 5 (hAdV5) and Vaccinia virus (VACV) serve as robust environmental persistence models for testing viral decontamination protocols. C_LIO_LIThe use of ANCHOR viruses enables rapid real-time visualization of disinfection efficacy, improving safety validation in high-containment laboratories and public health applications. C_LI

microbiology↗

bioRxiv2024

Invariant crossmodal equivalence between objects in rhesus monkeys

After hearing the words Little Red Riding Hood, many humans instantly visualize a girl wearing a red hood in the woods. However, whether nonhuman primates also evoke such visual imagery from sounds remains an open question. We explored this from direct behavioral measurements from two rhesus macaques trained in a delayed crossmodal equivalence task. In each trial, they listened to a sound, such as a monkey vocalization or a word, and three seconds later, selected a visual equivalent out of a pool of 2 to 4 pictures appearing on a touchscreen. We show that monkeys can be trained to discriminate perceptual objects of numerous properties and furthermore that they perceive as invariant different versions of the learned sounds. We propose two potential mechanisms for the brain to solve this task: acoustic memory or visual imagery. After analyzing the monkeys choice accuracies and reaction times in the task, we find that they experience visual imagery when listening to sounds. Therefore, the ability of rhesus monkeys to perceive crossmodal equivalences between learned categories poses rhesus monkeys as an ideal model organism for studying high-order cognitive processes like semantics and conceptual thinking at the single-neuron level.

animal behavior and cognition↗

bioRxiv2023

Crossmodal correspondence of natural amplitude modulations

Crossmodal correspondence is the ability to recognize objects from different sensory modalities to be similar. Here, we investigated the capacity of humans to perform crossmodal discriminations between visual, acoustic, and tactile stimuli modulated in amplitudes of low-pass filtered envelopes obtained from natural sounds. We found that the perception of crossmodal correspondence emerged from the number of amplitude prominences in each stimulus rather than from temporal variations. Therefore, we propose saliency as the supramodal trade coin of temporal modulations.

neuroscience↗

bioRxiv2021

The strength of the innate immune response drives the within-host competition between highly and low pathogenic avian influenza viruses

Highly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8LP increased H5N8HP replication and pathogenesis. By contrast, the H5N8LP antagonized H5N8HP replication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8LP, which correlated with H5N8HP inhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variants interactions in viral evolution.

microbiology↗

bioRxiv2021

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN- starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN- starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatments are beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease. One Sentence SummaryThe timing of type I interferon treatment is a critical determinant of its efficacy against SARS-CoV-2 infection.

microbiology↗

bioRxiv2020

Neuronal Correlates of the Perceptual Invariance of Words and Other Sounds in the Supplementary Motor Area of Macaques

The supplementary motor area (SMA) of the brain is critical for integrating memory and sensory signals into perceptual decisions. For example, in macaques, SMA activity correlates with decisions based on the comparison of sounds.1 In humans, functional MRI shows SMA activation during the invariant recognition of words pronounced by different speakers.2 Nevertheless, the neuronal correlates of perceptual invariance are unknown. Here we show that the SMA of macaques associates novel sounds with behaviors triggered by similar learned categories when recognizing sounds such as words. Notably, the neuronal activity at single and population levels correlates with the monkeys behaviors (e.g. hits and false alarms). Our results demonstrate that invariant recognitions of complex sounds involve premotor computations in areas other than the temporal and parietal speech areas. Therefore, we propose that perceptual invariance depends on motor predictions and not only sensory representations. We anticipate that studies on speech will observe sensory-motor transformations of acoustic information into motor skills.

neuroscience↗

bioRxiv2020

Auditory Decisions in the Supplementary Motor Area

In human speech and communication across various species, recognizing and categorizing sounds is fundamental for the selection of appropriate behaviors. But how does the brain decide which action to perform based on sounds? We explored whether the premotor supplementary motor area (SMA), responsible for linking sensory information to motor programs, also accounts for auditory-driven decision making. To this end, we trained two rhesus monkeys to discriminate between numerous naturalistic sounds and words learned as target (T) or non-target (nT) categories. We demonstrated that the neural population is organized differently during the auditory and the movement periods of the task, implying that it is performing different computations in each period. We found that SMA neurons perform acoustic-decision-related computations that transition from auditory to movement representations in this task. Our results suggest that the SMA integrates sensory information while listening to auditory stimuli in order to form categorical signals that drive behavior.

neuroscience↗

bioRxiv2019

Invariant recognition of words and naturalistic sounds in non-human primates

The ability to invariably identify spoken words and other naturalistic sounds in different temporal modulations and timbres requires perceptual tolerance to numerous acoustic variations. However, the mechanisms by which auditory information is perceived to be invariant are poorly understood, and no study has explicitly tested the perceptual constancy skills of nonhuman primates. We investigated the ability of two trained rhesus monkeys to learn and then recognize multiple sounds that included multisyllabic words. Importantly, we tested their ability to group unexperienced sounds into corresponding categories. We found that the monkeys adequately categorized sounds whose formants were at close Euclidean distance to the learned sounds. Our results indicate that macaques can attend and memorize complex sounds such as words. This ability was not studied or reported before and can be used to study the neuronal mechanisms underlying auditory perception.

neuroscience↗

bioRxiv2019

The Intestinal Microbiota Contributes To The Control Of Highly Pathogenic H5N9 Influenza Virus Replication In Ducks

Ducks usually show little or no clinical signs following highly pathogenic avian influenza virus infection. In order to analyze if the gut microbiota could contribute to the control of influenza virus replication in ducks, we used a broad-spectrum oral antibiotic treatment to deplete the gut microbiota before infection with a highly pathogenic H5N9 avian influenza virus. Antibiotic-treated ducks and non-treated control ducks did not show any clinical signs following H5N9 virus infection. We did not detect any difference in virus titers neither in the respiratory tract, nor in the brain and spleen. However, we found that antibiotic-treated H5N9 virus infected ducks had significantly increased intestinal virus excretion at day 3 and 5 post-infection. This was associated with a significantly decreased antiviral immune response in the intestine of antibiotic-treated ducks. Our findings highlight the importance of an intact microbiota for an efficient control of avian influenza virus replication in ducks.\n\nIMPORTANCEDucks are frequently infected with avian influenza viruses belonging to multiple subtypes. They represent an important reservoir species of avian influenza viruses, which can occasionally be transmitted to other bird species or mammals, including humans. Ducks thus have a central role in the epidemiology of influenza virus infection. Importantly, ducks usually show little or no clinical signs even following infection with a highly pathogenic avian influenza virus. We provide evidence that the intestinal microbiota contributes to the control of influenza virus replication in ducks by modulating the antiviral immune response. Ducks are able to control influenza virus replication more efficiently when they have an intact intestinal microbiota. Therefore, maintaining a healthy microbiota by limiting perturbations to its composition should contribute to prevention of avian influenza virus spread from the duck reservoir.

microbiology↗