Biology subjects

Rivera, D.

Publications and source records attributed to Rivera, D..

10 recordsLinked to original sources

bioRxiv2026

Cell autonomous inflammation in VEXAS is mediated by cGAS-STING

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a severe adult-onset inflammatory disease caused by somatic mutations that reduce cytoplasmic activity of UBA1, the primary initiating enzyme for ubiquitylation. How this hypomorphic state drives cell-intrinsic immune activation in mature myeloid cells is unknown. Using unbiased multi-omic, biochemical, and cell biological analyses of model systems and patient-derived cells, we show that loss of cytoplasmic UBA1 activity convergently disrupts endoplasmic reticulum- associated degradation (ERAD) and mitochondrial homeostasis. ERAD failure arises from preferential under-charging of ERAD E2 enzymes, explaining hallmark VEXAS features, including ER-derived vacuoles and unfolded protein response activation, and promotes accumulation of the ERAD substrate STING. Simultaneously, mitochondrial dysfunction drives cytosolic leakage of mitochondrial DNA, inducing cGAS-dependent STING signaling and inflammatory cytokine production. STING inhibition or reversal of mitochondrial DNA leakage resolves multi-cytokine inflammation in VEXAS models and patient myeloid cells, establishing the cGAS-STING pathway as a therapeutically actionable vulnerability.

genetics↗

bioRxiv2025

Psilocybin Prolongs the Neurovascular Coupling Response in Mouse Visual Cortex

Psilocybin has profound therapeutic potential for various mental health disorders, but its mechanisms of action are unknown. Functional MRI studies have reported the effects of psilocybin on brain activity and connectivity; however, these measurements rely on neurovascular coupling to infer neural activity changes and assume that blood flow responses to neural activity are not altered by psilocybin. Using two-photon excited fluorescence imaging in the visual cortex of awake mice to simultaneously measure neural activity and capillary blood flow dynamics, we found that psilocybin administration prolonged the increase in visual stimulus-evoked capillary blood flow - an effect which was reduced by pretreatment with a 5-HT2AR antagonist - despite not causing changes in the stimulus-evoked neural response. Multi-modal widefield imaging also showed that psilocybin extends the stimulus-evoked vascular responses in surface vessels with no observed effect on the population neural response. Computational simulation with a whole-brain neural mass model showed that prolonged neurovascular coupling responses can lead to spurious increases in BOLD-based measures of functional connectivity. Together, these findings demonstrate that psilocybin broadens neurovascular responses in the brain and highlights the importance of accounting for these effects when interpreting human neuroimaging data of psychedelic drug action.

neuroscience↗

bioRxiv2022

The AI Neuropsychologist: Automatic scoring of memory deficits with deep learning

BackgroundMemory deficits are a hallmark of many different neurological and psychiatric conditions. The Rey-Osterrieth complex figure (ROCF) is the state-of-the-art assessment tool for neuropsychologists across the globe to assess the degree of non-verbal visual memory deterioration. To obtain a score, a trained clinician inspects a patients ROCF drawing and quantifies deviations from the original figure. This manual procedure is time-consuming, slow and scores vary depending on the clinicians experience, motivation and tiredness. MethodsHere, we leverage novel deep learning architectures to automatize the rating of memory deficits. For this, we collected more than 20k hand-drawn ROCF drawings from patients with various neurological and psychiatric disorders as well as healthy participants. Unbiased ground truth ROCF scores were obtained from crowdsourced human intelligence. This dataset was used to train and evaluate a multi-head convolutional neural network. ResultsThe model performs highly unbiased as it yielded predictions very close to the ground truth and the error was similarly distributed around zero. The neural network outperforms both online raters and clinicians. The scoring system can reliably identify and accurately score individual figure elements in previously unseen ROCF drawings, which facilitates explainability of the AI-scoring system. To ensure generalizability and clinical utility, the model performance was successfully replicated in a large independent prospective validation study that was pre-registered prior to data collection. ConclusionsOur AI-powered scoring system provides healthcare institutions worldwide with a digital tool to assess objectively, reliably and time-efficiently the performance in the ROCF test from hand-drawn images.

neuroscience↗

bioRxiv2022

RNA fluorescence in situ hybridization (FISH) to visualize microbial colonization and infection in the Caenorhabditis elegans intestines

The intestines of wild Caenorhabditis nematodes are inhabited by a variety of microorganisms, including gut microbiome bacteria and pathogens, such as microsporidia and viruses. Because of the similarities between Caenorhabditis elegans and mammalian intestinal cells, as well as the power of the C. elegans system, this host has emerged as a model system to study host intestine-microbe interactions in vivo. While it is possible to observe some aspects of these interactions with bright-field microscopy, it is difficult to accurately classify microbes and characterize the extent of colonization or infection without more precise tools. This protocol introduces RNA fluorescence in situ hybridization (FISH) as a tool used for the identification, visualization, and quantification of the microbes within the intestines of C. elegans. FISH probes that label the highly abundant small subunit ribosomal RNA can produce a bright signal for bacteria and microsporidian cells, and similar probes can be used to label viral RNA. FISH probes can be ordered from a commercial source as single-stranded DNA end-labeled with fluorophores. One limitation is that FISH may not provide robust signal against low copy targets, although signal can be boosted by using multiple probes (so-called single-molecule FISH). FISH staining involves collecting colonized or infected animals, washing to eliminate external contamination, followed by fixation in either paraformaldehyde or acetone. After fixation, FISH probes are incubated with samples to allow for the hybridization of probes to the desired target. To remove excess background, the animals are washed again, and then examined on microscope slides or using automated approaches. Overall, this protocol enables detection, identification, and quantification of the microbes that inhabit the C. elegans intestine, including microbes for which there are no genetic tools available. SUMMARYGut microbiome bacteria and intestinal intracellular pathogens, like the Orsay virus and microsporidia, are often found associated with wild Caenorhabditis nematodes. This protocol presents RNA FISH as a method for the detection, quantification, and identification of colonizing or infectious microbes within the context of intact C. elegans nematodes.

microbiology↗

bioRxiv2022

Red harvester ant (Order: Hymenoptera) preference for cover crop seeds in South Texas

Harvester ants are known to selectively forage seeds, potentially impacting nearby plant community composition. In agricultural areas, harvester ants may be viewed as pests by foraging on crop seeds or as beneficials by preferentially removing weed seeds. However, little work has been done on harvester ant preferences for cover crop seeds. Local observations suggest that ants may take cover crop seeds, but no studies have evaluated ant agricultural impacts or seed preferences in the Lower Rio Grande Valley (LRGV). We examined red harvester ant (Pogonomyrmex barbatus Smith) preferences for commonly used cover crop seeds in the LRGV (vetch, oat, fescue, sunn hemp, and radish with wheatgrass as a control) and a commonly used bacterial seed inoculation treatment meant to increase root nodulation. We tested seed sets using choice tests housed in seed depots located within the foraging range of ant colonies with no prior exposure to the selected seeds. Of the evaluated cover crop seeds, wheatgrass and oat were the first to be removed entirely from the depot, with vetch remaining after 24 h. When we inoculated the two most preferred seeds to determine if there was a preference for non-inoculated seeds, we found no difference between inoculated and non-inoculated seeds. There were also significant changes in activity over time for both trials. These data indicate that harvester ant foraging preferences and activity can inform grower management recommendations regarding the risks of using certain cover crops and months sowing should be conducted in fields with known harvester ant presence.

ecology↗

bioRxiv2020

Evolutionary and homeostatic changes in morphology of visual dendrites of Mauthner cells in Astyanax blind cavefish

Mauthner cells are the largest neurons in the hindbrain of teleost fish and most amphibians. Each cell has two major dendrites thought to receive segregated streams of sensory input: the lateral dendrite receives mechanosensory input while the ventral dendrite receives visual input. These inputs, which mediate escape responses to sudden stimuli, may be modulated by the availability of sensory information to the animal. To understand the impact of the absence of visual information on the morphologies of Mauthner cells during development and evolutionary time scales, we examined Astyanax mexicanus. This species of tetra is found in two morphs: a seeing surface fish and a blind cavefish. We compared the structure of Mauthner cells in surface fish raised under daily light conditions, surface fish that raised in constant darkness, and two independent lineages of cave populations. The length of ventral dendrites of Mauthner cells in dark-raised surface larvae were longer and more branched, while in both cave morphs the ventral dendrites were smaller or absent. The absence of visual input in surface fish with normal eye development leads to a homeostatic increase in dendrite size, whereas over evolution, the absence of light led to the loss of eyes and a phylogenetic reduction in dendrite size. Consequently, homeostatic mechanisms are under natural selection that provide adaptation to constant darkness.

neuroscience↗

bioRxiv2019

Evolutionary increases in catecholamine signaling may underlie the emergence of adaptive traits and behaviors in the blind cavefish, Astyanax mexicanus

Evolutionary changes in catecholamine neurotransmitters such as dopamine and noradrenaline can lead to habitat specific behaviors. We used tyrosine hydroxylase, a conserved precursor to the biosynthesis of dopamine and noradrenaline, to compare catecholaminergic neurons in the brain of a species undergoing allopatric speciation. The teleost fish Astyanax mexicanus is extant in two readily available forms, an ancestral river dwelling form (surface) and various derived blind cave forms (cavefish). Adaptation to nutrient poor cave life without predation has led to marked differences in the behavior of this species. The cavefish has lost defensive responses, such as stimulus aversion, found in the ancestral surface fish and instead displays enhanced food seeking behaviors. This is reflected by an increase in catecholamine immunoreactivity in the cavefish brain in regions associated with non-visual sensory perception, motor control pathways, attention, and endocrine release. These neuroanatomical regions include the olfactory system, the basal telencephalon, the preoptic nuclei, the posterior tuberculum, caudal hypothalamus, and isthmus. These results indicate that the evolutionary shift from aversive defensive responses to attractive exploratory behaviors was driven by increases in the size and/or quantity of catecholaminergic neurons in the cavefish brain.

neuroscience↗

bioRxiv2018

Hyperconnectivity of the default mode network in multiorgan dysfunction syndrome

Multiple Organ Dysfunction Syndrome (MODS) is a systemic physiological disorder affecting two or more body organs triggered after an insult complication. Beyond the systemic failure, patients who survive MODS present cognitive and neurological impairments that remain stable even several years after Intensive Care Unit (ICU) discharge. Here, we focus on the specific situation of MODS patients with no apparent brain damage (NABD), where the mechanisms driving cognitive impairment at long term are not well-understood. We recruit N1 = 13 MODS patients with NABD at 6 months after ICU discharge, together with N2 = 13 healthy controls (matched by age, sex and years of education), and acquire functional magnetic resonance imaging at rest to find that, as compared to control, MODS patients with NABD present an overall increase of the functional connectivity (FC) at rest. In particular, we find that the default mode network (DMN) hyperconnects (increasing the node strength of the FC matrix) to three classes of networks: primary sensory (such as auditory, sensory-motor and visual), multimodal integration (such as dorsal attention and salience) and higher order cognition networks (such as fronto-parietal, language and executive control). Therefore, although these patients do not have an apparent structural damage after MODS, at the functional level, we found brain network alterations coexisting with hyperconnectivity of the DMN, that similar to what happens at the onset of other pathologies, might indicate a possible mechanism for brain compensation occurring after MODS.

neuroscience↗

bioRxiv2018

Improved localizers and anatomical images to enable phosphorus magnetic resonance spectroscopy of liver metastasis at 7T

Phosphorus spectroscopy (31P) at 7T (300 MHz) enables clinically-relevant spatial resolutions and time scales with high potential for monitoring response to cancer treatment. However, at 7T collecting a radiological-grade anatomical image of the liver--which is required for performing localized 31P spectroscopy--presents a challenge. Unlike lower field-strength scanners, there is no body coil in the bore of the 7T and despite inadequate penetration depth (<10 cm), surface coils are the current state-of-the-art for acquiring anatomical (1H) images. Therefore, thus far, high field 31P spectroscopy has been limited to diffuse liver disease. However, the use of antennas enable improved penetration depths at 300 MHz, and when combined with parallel transmit, can enable body imaging at 7T. We have developed a protocol for imaging liver metastases of patients using parallel transmit and 31P spectroscopy at 7T. We used a custom-made liver coil consisting of eight 30-cm dipole antennas tuned to the proton (300 MHz) frequency, and two partially overlapping 20-cm-diameter loops tuned for 31P (120 MHz). The field of view afforded by the two antennas underneath the 31P loops is not sufficient to image the complete boundaries of the liver for chemical shift imaging (CSI) planning and region-of-interest-based B0 shimming. The liver and full axial slice of the abdomen was imaged with eight transmit/receive antennas using parallel transmit B1-shimming to overcome image voids. Through the use of antennas we overcome the challenges for multi-parametric body imaging, and can begin to explore the possibility of monitoring the response of patients with liver metastasis to cancer treatments.\n\nABBREVIATIONS

bioengineering↗

bioRxiv2018

Genus-wide sequencing supports a two-locus model for sex-determination in Phoenix

The date palm tree is a commercially important member of the genus Phoenix whose 14 species are all dioecious with separate male and female individuals. Previous studies identified a multi-megabase region of the date palm genome linked to sex and showed that dioecy likely developed in Phoenix prior to speciation. To identify genes critical to sex determination we sequenced the genomes of 28 Phoenix trees representing all 14 species. Male-specific sequences were identified and extended using phased single molecule sequencing or BAC clones to distinguish X and Y alleles.\n\nHere we show that only four genes contain sequences conserved in all analyzed males, likely identifying the changes foundational to dioecy in Phoenix. The majority of these sequences show similarity to a single genomic locus in the closely related oil palm. CYP703 and GPAT3, two genes critical to male flower development in other monocots, appear fully deleted in females while maintained as single copy in males. A LOG-like gene appears translocated into the Y chromosome and a cytidine deaminase-like appears at the border of a chromosomal rearrangement. Our data supports a two-mutation model for the evolution from hermaphroditism to dioecy through a gynodioecious intermediate.

genomics↗