Biology subjects

Vasquez, V.

Publications and source records attributed to Vasquez, V..

10 recordsLinked to original sources

bioRxiv2026

Forest fragmentation, anthropogenic land use, and climate shape sand fly community composition in central Panama.

Background: American cutaneous leishmaniasis (ACL) is endemic in central Panama, where rapid land use change is transforming tropical landscapes and potentially altering the ecology of sand fly vectors. Although researchers have widely studied environmental determinants of individual vector species, community-level responses of sand fly assemblages to landscape modification remain poorly understood. We evaluated how landscape composition, fragmentation, climate, and topography influence sand fly community structure in a rural landscape of central Panama. Methodology/Principal Findings: We combined metacommunity analyses with joint species distribution models (JSDMs) to quantify species-specific and community-level responses to climatic variables, land-cover composition, and forest configuration. We collected 1,692 individuals representing 30 species, including nine anthropportunist taxa of epidemiological importance. Sand fly assemblages had strong nestedness, low species turnover, and predominantly positive residual associations. Several anthropportunist sand fly species occurred across heterogeneous landscapes, although their responses to environmental conditions differed among taxa. Land-cover composition, forest fragmentation metrics, and elevation together explained about half of the variance in species occurrence and abundance, with the remainder attributed to climate and spatial, temporal, and community-level random effects. Grassland cover contributed most strongly to sand fly occurrence and abundance, whereas artificial surfaces consistently reduced both metrics. Fragmentation effects varied by species: edge density often increased occurrence and abundance, whereas more forest patches generally suppressed populations. Increased precipitation broadly enhanced occurrence and abundance, whereas higher temperatures negatively affected several taxa. Conclusions/significance: Landscape heterogeneity predictably structures sand fly communities, and different forms of anthropogenic disturbance exert non-uniform effects on vector assemblages. The nested organization of these assemblages and the co-occurrence of several anthropophilic species suggest that multiple potential vector species may be present across heterogeneous landscapes. These findings highlight the need for landscape-informed surveillance and control strategies that prioritize grassland-forest interfaces and other disturbed ecotones where sand fly species of epidemiological importance frequently co-occur.

ecology↗

bioRxiv2026

PIEZO1-mediated mechanosensation links aging to bladder dysfunction

Aging is accompanied by profound changes in bladder function, leading to increased urinary frequency and incontinence that impair quality of life in humans and are recapitulated in mouse models. Bladder filling and emptying rely on precise mechanosensory feedback, yet how aging alters this sensory control remains unclear. PIEZO ion channels convert mechanical forces into cellular signals essential for bladder fullness sensation. Using inducible smooth-muscle specific Piezo1 deletion, we find that loss of Piezo1 attenuates aging-related bladder dysfunction. Dietary enrichment with margaric acid, a membrane-active fatty acid previously shown to inhibit PIEZO channels, reduced urinary dysfunction in aged mice. In humans, genotype-phenotype analyses reveal an association between a PIEZO1 gain-of-function variant and early-onset neuromuscular bladder dysfunction. Together, these findings define a smooth-muscle, PIEZO1-mediated mechanosensory basis for aging-related bladder dysfunction and introduce a non-invasive strategy for targeting PIEZO channels in vivo.

physiology↗

bioRxiv2026

Imminent invasion of the chytrid fungus threatens the last naive amphibian biodiversity hotspots

While the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is driving catastrophic biodiversity loss worldwide, some amphibian communities persist seemingly unaffected despite occurring in climates conducive to pathogen establishment. These amphibian communities may remain epidemiologically naive. As mitigation of Bd is rarely successful after establishment, identifying remaining Bd-free refuges is imperative. Presently, the only known large-scale Bd-free refuge is the island of New Guinea (NG), safeguarding Australasias amphibian phylogenetic diversity otherwise devastated by Bd. Following extensive multi-year disease surveillance, we here uncover a second large-scale Bd-free refuge in the Sierra Nevada de Santa Marta (SNSM), a Neotropical biodiversity hotspot in northern Colombia. We detected no evidence of Bd in SNSM-wide screening, while we uncovered the presence of hypervirulent Bd-GPL in adjacent areas of the tropical Andes. Population genomic analyses in an SNSM-endemic anuran found no evidence for demographic bottlenecks indicative of cryptic epizootic decline. Niche modelling highlights the high risk for Bd establishment and Bd-induced declines in both the SNSM and NG, and the important role of lowland environmental barriers in restricting Bd invasion. Infection trials using three SNSM-endemic amphibians reveal varying disease susceptibility. Together, these data identify the SNSM as an epidemiologically naive refuge likely facing imminent Bd invasion, which could result in the loss of at least 25 endemic amphibian species. We highlight the urgent need for proactive conservation action and strict implementation of biosecurity to safeguard the unique and vast amphibian diversity of the worlds last major Bd-free refuges. Significance StatementAmphibian chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) has driven unprecedented global biodiversity loss. The Neotropics and Australasia comprise epicenters of declines. Identifying remaining Bd-free refuges is crucial to curb further amphibian extinctions, but so far contemporary absence of Bd has only been demonstrated for New Guinea. Here we identify the last known major Bd-free biodiversity hotspot in the Neotropics: the Sierra Nevada de Santa Marta (SNSM) in Colombia. Our results show that amphibian communities in this hotspot are immunologically naive despite occurrence of hypervirulent Bd lineages nearby and climatic conditions within the SNSM conducive to Bd-induced declines. This creates an imminent risk for Bd-driven declines and highlights the urgent need for preventive actions to avert another wave of biodiversity loss.

ecology↗

bioRxiv2025

Seeing the forest and the trees: a workflow for automatic acquisition of ultra-high resolution drone photos of tropical forest canopies to support botanical and ecological studies

Tropical forest canopies contain many tree and liana species, and foliar and reproductive characteristics useful for taxonomic identification are often difficult to see from the forest floor. As such, taxonomic identification often becomes a bottleneck in tropical forest inventories. Here we present a drone-based workflow to automatically acquire large volumes of close-up, ultra-high resolution photos of selected tree crowns (or specific locations over the canopy) to support tropical botanical and ecological studies (https://youtu.be/80goMEifpc4). Our workflow is built around the small, easy-to-use DJI Mavic 3 Enterprise (M3E) drone, which is equipped with a wide-angle and a telephoto camera. On day one, the pilot maps a forest area of up to [~]200 ha with the wide-angle camera to generate a high-resolution digital surface model (DSM) and orthomosaic using structure-from-motion (SfM) photogrammetry. On subsequent days, the pilot acquires close-up photos with the telephoto camera from up to 300 selected canopy trees per day. These close-up photos are acquired from 6 m above the canopy and contain a high level of visual detail that allows botanists to reliably identify many tree and liana species. The photos are geolocated with survey-grade accuracy using RTK GNSS, thus facilitating spatial co-registration with other data sources, including the photogrammetry products. The primary operational challenge of our workflow is the need to maintain RTK corrections with the drone to ensure that close-up photos are acquired exactly at the predefined locations. The maximum operational range we achieved was 3 km, which would allow the pilot to reach any tree within a [~]2800 ha area from the take-off point. Although our workflow was developed to support taxonomic identification of tropical trees and lianas, it could be extended to any other forest or vegetation type to support botanical, phenological, and ecological studies. We provide harpia, an open-source Python library to program these automatic close-up photo missions with the M3E drone (https://github.com/traitlab/harpia). Data/code for peer review statementWe provide harpia, an open-source Python library to program these automatic close-up photo missions (https://github.com/traitlab/harpia). Drone imagery and labelled close-up photo data are not yet publicly available because they were acquired with the goal of publishing benchmark machine learning datasets and models for tree and liana species classification and prior publication of the data would jeopardize this future publication.

ecology↗

bioRxiv2025

Enhanced PIEZO1 Function Contributes to the Pathogenesis of Sickle Cell Disease

Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the {beta}-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, causing anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions to restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a non-selective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte homeostasis, its role in SCD remains unknown. Here, we demonstrate that the function of the PIEZO1 channel is upregulated in sickle erythrocytes of humans and mice, and this enhancement can be restored through a dietary intervention. We found that PIEZO1 function in sickle erythrocytes resembles that of the GOF mutation causing hemolytic anemia. A diet enriched in the{omega} -3 fatty acid eicosapentaenoic (EPA) acid decreases PIEZO1 function in sickle erythrocytes and hemolysis in a mouse model of SCD. Furthermore, EPA decreases hemolysis and reduces inflammatory markers. We propose that PIEZO1 contributes to the increase in nonselective cationic conductance (i.e., Psickle), which leads to dehydration downstream of hemoglobin polymerization. Our results suggest that reducing PIEZO1 function is a promising therapeutic approach to reestablishing normal cation permeability in SCD.

physiology↗

bioRxiv2024

Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases

TAR DNA-binding protein 43 (TDP-43) proteinopathy plays a critical role in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We recently reported that TDP-43 plays an essential role in DNA double-strand break (DSB) repair via the non-homologous end-joining (NHEJ) pathway. Here, we provide evidence that the brain of patients with ALS exhibit persistent DNA damage in the transcribed regions of the genome. While investigating the mechanistic basis, we found that the activity of polynucleotide kinase 3-phosphatase (PNKP) was severely impaired in the nuclear extracts of patient brains and TDP-43-depleted cells. PNKP is a key player in DSB repair within the transcribed genome, where its 3-phosphate termini processing activity is crucial for preventing persistent DNA strand breaks and neuronal death. The inactivation of PNKP was due to the reduced level of its interacting partner, phosphofructo-2-kinase fructose 2,6 bisphosphatase (PFKFB3), and its biosynthetic product, fructose-2,6-bisphosphate (F2,6BP), an allosteric modulator of glycolysis. Recently, we have demonstrated that F2,6BP acts as a positive modulator of PNKP activity in vivo. Furthermore, F2,6BP supplementation in cultured ALS patient-derived neural progenitor stem cells (NPSCs) reduced the toxic aggregation of polyubiquitinated TDP-43 and cytosolic pTDP-43 (S409/410). Notably, F2,6BP supplementation restored the PNKP activity in the nuclear extracts from autopsied ALS/FTD brain tissues and patient iPSC-derived NPSCs harboring TDP-43 mutations. Importantly, F2,6BP administration significantly restored the genome integrity and motor phenotypes in a Drosophila model of ALS-TDP-43. Collectively, these findings underscore the therapeutic potential of F2,6BP in TDP-43 pathology-associated motor neuron diseases.

neuroscience↗

bioRxiv2024

RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability

TDP43 is an RNA/DNA binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to the formation of detrimental cytosolic aggregates and a reduction in nuclear functionality within neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expressions. Here, we show that TDP43 depletion or overexpression directly affects the expression of key MMR genes. Alterations include MLH1, MSH2, MSH3, MSH6, and PMS2 levels across various primary cell lines, independent of their proliferative status. Our results specifically establish that TDP43 selectively influences the expression of MLH1 and MSH6 by influencing their alternative transcript splicing patterns and stability. We furthermore find aberrant MMR gene expression is linked to TDP43 proteinopathy in two distinct ALS mouse models and post-mortem brain and spinal cord tissues of ALS patients. Notably, MMR depletion resulted in the partial rescue of TDP43 proteinopathy-induced DNA damage and signaling. Moreover, bioinformatics analysis of the TCGA cancer database reveals significant associations between TDP43 expression, MMR gene expression, and mutational burden across multiple cancers. Collectively, our findings implicate TDP43 as a critical regulator of the MMR pathway and unveil its broad impact on the etiology of both neurodegenerative and neoplastic pathologies.

biochemistry↗

bioRxiv2023

Mutation in F-actin Polymerization Factor Suppresses Distal Arthrogryposis Type 5 (DA5) PIEZO2 Pathogenic Variant in Caenorhabditis elegans

The mechanosensitive PIEZO channel family has been linked to over 26 disorders and diseases. Although progress has been made in understanding these channels at the structural and functional levels, the underlying mechanisms of PIEZO-associated diseases remain elusive. In this study, we engineered four PIEZO-based disease models using CRISPR/Cas9 gene editing. We performed an unbiased chemical mutagen-based genetic suppressor screen to identify putative suppressors of a conserved gain-of-function variant pezo-1[R2405P] that in human PIEZO2 causes distal arthrogryposis type 5 (DA5; p. R2718P). Electrophysiological analyses indicate that pezo-1(R2405P) is a gain-of-function allele. Using genomic mapping and whole genome sequencing approaches, we identified a candidate suppressor allele in the C. elegans gene gex-3. This gene is an ortholog of human NCKAP1(NCK-associated protein 1), a subunit of the Wiskott-Aldrich syndrome protein (WASP)-verprolin homologous protein (WAVE/SCAR) complex, which regulates F-actin polymerization. Depletion of gex-3 by RNAi, or with the suppressor allele gex-3(av259[L353F]), significantly restored the small brood size and low ovulation rate, as well as alleviated the crushed oocyte phenotype of the pezo-1(R2405P) mutant. Auxin-inducible degradation of GEX-3 revealed that only somatic-specific degradation of GEX-3 restored the reduced brood size in the pezo-1(R2405P) mutants. Additionally, actin organization and orientation were disrupted and distorted in the pezo-1 mutants. Mutation of gex-3(L353F) partially alleviated these defects. The identification of gex-3 as a suppressor of the pathogenic variant pezo-1(R2405P) suggests that the cytoskeleton plays an important role in regulating PIEZO channel activity and provides insight into the molecular mechanisms of DA5 and other PIEZO-associated diseases.

genetics↗

bioRxiv2022

Excessive Mechanotransduction in Sensory Neurons Causes Joint Contractures in a Mouse Model of Arthrogryposis

Distal arthrogryposis (DA) is a collection of rare disorders characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Remarkably, Botox and a dietary fatty acid that modulates PIEZO2 activity markedly reduce DA5-like deficits. This reveals an unexpected role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development.

neuroscience↗

bioRxiv2021

C. elegans PEZO-1 is a Mechanosensitive Channel Involved in Food Sensation

PIEZO channels are force sensors essential for physiological processes, including baroreception and proprioception. The Caenorhabditis elegans genome encodes an ortholog gene of the Piezo family, pezo-1, which is expressed in several tissues, including the pharynx. This myogenic pump is an essential component of the C. elegans alimentary canal, whose contraction and relaxation are modulated by mechanical stimulation elicited by food content. Whether pezo-1 encodes a mechanosensitive ion channel and contributes to pharyngeal function remain unknown. Here, we leverage genome editing, genetics, microfluidics, and electropharyngeogram recording to establish that pezo-1 is expressed in the pharynx, including in a proprioceptive-like neuron, and regulates pharyngeal function. Knockout (KO) and gain-of-function (GOF) mutants reveal that pezo-1 is involved in fine-tuning pharyngeal pumping frequency, sensing osmolarity, and food mechanical properties. Using pressure-clamp experiments in primary C. elegans embryo cultures, we determine that pezo-1 KO cells do not display mechanosensitive currents, whereas cells expressing wild-type or GOF PEZO-1 exhibit mechanosensitivity. Moreover, infecting the Spodoptera frugiperda cell line with a baculovirus containing the G-isoform of pezo-1 (among the longest isoforms) demonstrates that pezo-1 encodes a mechanosensitive channel. Our findings reveal that pezo-1 is a mechanosensitive ion channel that regulates food sensation in worms.

physiology↗