Biology subjects

Castillo, K.

Publications and source records attributed to Castillo, K..

11 recordsLinked to original sources

bioRxiv2026

Metagenomic analysis of the effects of European bison Bison bonasus (Linnaeus, 1758) presence on soil community structure and function in West Blean and Thornden Woods, Kent

The reintroduction of extinct or endangered species to restore ecosystem function is an essential aspect of rewilding. The Wilder Blean Project at West Blean and Thornden Woods in Canterbury, UK, is committed to rewilding natural processes and enhancing biodiversity in one of England's oldest and largest areas of ancient woodland. The introduction of European bison (Bison bonasus) is an important part of the project. However, how the reintroduction of large herbivores influences local biodiversity and ecosystem functions during the early stages of rewilding remains poorly understood. Soil samples were collected from the same sampling sites before and two years after bison were reintroduced and profiled by metagenomic sequencing using Oxford Nanopore Technologies sequencing platforms. The results showed that the alpha diversity of soil organisms did not change significantly before and after the introduction of European bison, while beta diversity showed modest shifts in community composition. The relative abundance of some nitrogen-fixing and photosynthetic microbial genera showed declines in the 2024 Bison Area, while the mycorrhizal fungus genus Rhizophagus was significantly less abundant than in the 2024 Control Area. Despite relatively stable taxonomic diversity, functional composition differed significantly between the 2022 and 2024 Bison areas and among the 2024 rewilding treatments, revealing a decoupling between taxonomic diversity and functional composition. Amino acid synthesis pathways and carbon metabolism pathways were significantly enriched. These findings highlight the potential of long-read Oxford Nanopore metagenomics to reveal functional shifts that may not be apparent from taxonomic diversity alone. Although these early-stage responses cannot yet predict long-term rewilding trajectories, continued longitudinal monitoring integrating microbial, soil physicochemical, and ecosystem-level measurements will be essential to determine the persistence and ecological significance of these functional shifts.

ecology↗

bioRxiv2026

Testicular but not ovarian hormones shape patch-leaving adaptation and impulsive choice in rats

Hormonal regulation of patch-leaving decision-making remains poorly understood. Here, young adult male and female Long-Evans rats were tested in a patch-leaving task before and after orchiectomy (ORCH), ovariectomy (OVX), or sham surgery, and were subsequently assessed in an impulsive-choice task. Patch leaving was measured under long- and short-travel conditions. Before surgery, males showed longer overstay than females during long-travel sessions, whereas no clear sex difference was detected during short-travel sessions. After surgery, orchiectomy did not produce a uniform shift in patch leaving but selectively disrupted the progressive reduction in overstay that normally emerged across repeated long-travel sessions. By contrast, ovariectomy produced weaker effects and did not reveal a comparably robust change in female patch leaving. Spatial and idle occupancy analyses showed that gonadectomy also altered within-patch behavior, with orchiectomy most strongly increasing idling-related measures in males, whereas ovariectomy more strongly redistributed female patch occupancy. Estrous stage did not significantly organize pre-surgical female overstay. Greater impulsive choice was associated with smaller post-surgical reductions in long-travel overstay in the unadjusted analysis. Together, these findings indicate that testicular hormones selectively support patch-leaving adaptation under high travel cost.

animal behavior and cognition↗

bioRxiv2026

Modeling cell-cell interactions to advance drug discovery in Idiopathic Pulmonary Fibrosis

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is characterized by scarring and remodeling of lung tissue, leading to progressive pulmonary dysfunction. Currently, very little is known about the steps involved in disease initiation and progression because models of IPF poorly replicate these processes. However, understanding the pathogenesis of IPF is essential for developing effective therapies. To address this, we have developed a scaffold-based co-culture IPF organoid that uses healthy and diseased human primary and iPSC-derived alveolar epithelial cells and fibroblasts to recapitulate the cellular communication and cell fate during progressive fibrosis. MethodsWe generated microbead scaffolds that mimic alveolar air-sacs and coated them in a rotating bioreactor with primary lung fibroblasts and induced pluripotent stem cell-derived type 2 alveolar cells (iAT2s). iAT2s with the surfactant protein C (SFTPC) I73T variant and the syngeneic corrected control iAT2s were cultured with primary healthy and IPF fibroblasts in different combinations. The epithelial-mesenchymal interactions during fibrosis initiation and progression were evaluated by single-cell RNA sequencing. ResultsWe found that the interaction between epithelial cells and fibroblasts plays a key role in inducing fibrotic responses in this model, with the secretion of chemokines, cytokines, TGF{beta}, and matrix metalloproteinases that mirror those observed in the serum of patients with pulmonary fibrosis. Single-cell RNA sequencing revealed the emergence of many cell subtypes observed in progressive lung fibrosis, along with key cellular interactions that correlated with the initial upregulation of fibrosis pathways, extracellular matrix (ECM) remodeling, inflammation, and changes in lipid metabolism. The anti-fibrotic compounds, Nintedanib and the TGF{beta} inhibitor, SB431542, demonstrated dose-dependent efficacy in the model, with IC50 values comparable to those observed in the clinic, and significantly reduced secretion of fibrosis-related factors. ConclusionOverall, this study shows that the three-dimensional, reductionist, cell co-culture organoid effectively models several components of progressive lung fibrosis, facilitating the investigation of epithelial-mesenchymal interactions and serving as a patient-relevant model to better predict the efficacy of therapeutics in the clinic.

cell biology↗

bioRxiv2024

Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis

The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease. Our findings reveal a downregulation of cell junctional components, upregulation of epithelial-mesenchymal transition signatures and dysregulated basement membrane matrix in IPF distal bronchioles, facilitating epithelial desquamation. Further, functional assays identified regulation between Collagen IV in the matrix, and the junctional genes JUP and PLEC, that is crucial for maintaining distal bronchiolar homeostasis. In IPF, this balanced regulation between matrix and cell-junctions is disrupted, leading to loss of epithelial adhesion, peribronchiolar fibrosis and epithelial desquamation. Overall, our study suggests that in IPF the interplay between the loss of cell junctions and a dysregulated matrix results in desquamation of distal bronchiolar epithelium and lung remodeling, exacerbating the disease. One Sentence SummaryTwo-way regulation of cell junctional proteins and matrix proteins drives cellular desquamation and fibrosis in the distal bronchioles of patients with Idiopathic Pulmonary Fibrosis.

pathology↗

bioRxiv2024

High Throughput Screening with a Primary Human Mucociliary Airway Model Identifies a Small Molecule with Anti-SARS-CoV-2 Activity

Respiratory viruses (e.g. influenza, RSV, SARS etc.) attack the proximal airway and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. Here we present a microscale, primary human stem cell-based proximal airway model of SARS-CoV-2 infection, which is amenable to moderate-to-high throughput drug screening. The model recapitulates the heterogeneity of infection seen among different patients and with different SARS-CoV-2 variants. We applied this model to screen 2100 compounds from targeted drug libraries using an image-based quantification method. While there were heterogeneous responses across variants for host factor targeting compounds, the direct acting antivirals showed a consistent response and we characterized a new antiviral drug that is effective against both the parental strain and the Omicron variant.

cell biology↗

bioRxiv2023

Discrete Multiwalled Carbon Nanotubes for Versatile Intracellular Transport of Functional Biomolecular Complexes

In recent years, carbon nanotubes have emerged as a potentially revolutionary material with numerous uses in biomedical applications. Compared to other nanoparticles, discrete multi-walled carbon nanotubes (dMWCNTs) have been shown to exhibit advantageous characteristics such as high surface area to volume ratio, biocompatibility, and unique chemical and physical properties. dMWCNTs can be modified to load various molecules such as proteins and nucleic acids and are capable of crossing the cell membrane, making them attractive delivery vehicles for biomolecules. To investigate this, we measured the impact of dMWCNTs on cell proliferation. Furthermore, we used electron microscopy to demonstrate that dMWCNTs enter the cytoplasm of mammalian cells via an endocytosis-like process. And lastly, we employed various in vitro reporter and gene assays to demonstrate dMWCNT-mediated delivery of peptides, mRNA, siRNA, and dsRNA. Our work here has helped further characterize dMWCNTs as a versatile delivery platform for biomolecular cargo.

bioengineering↗

bioRxiv2020

Sex differences in central inflammatory pain sensitization are associated with differential expression of glycine receptors and GLP-1 at the spinal cord

BackgroundFemales have higher inflammatory pain representation. However, sex differences in central pain sensitization and the regulation of nociceptive response to peripheral inflammation remain unclear. The central pain sensitization is mediated by inhibitory neurotransmission and glial cell activity dysregulation where spinal glycine and GLP-1 receptors have described play a critical role. ObjectivesThe aim of this study was to compare the mechanical withdrawal nociceptive threshold with spinal glycine receptor subunits and GLP-1 expression in adult male and female rats after inflammatory hypersensitivity. MethodsSex differences in inflammatory nociception were evaluated before and after intraplantar hindpaw Zymosan A injection in Sprague-Dawley rats. Mechanical paw withdrawal thresholds were tested using von Frey filaments. Western blot was used to measure GlyRs subunits protein levels in the spinal cord. GLP-1 was determined using the Magnetic Luminex Assay. ResultsA reduced nociceptive threshold was observed in males and females rats after 4 hours of inflammatory Zymosan A injection. However, this reduction was significantly major in females. Western blot analysis demonstrated significantly increased 1, 2, 3 and {beta} GlyR subunit levels in male rats. Female rats only increased 3 and {beta} GlyR subunits after Zymosan A injection. GLP-1 was reduced in female spinal tissues after an inflammatory injury. ConclusionsOur study indicates that sex differences in nociceptive threshold after inflammatory Zymosan A rat pain sensitization is related to the sex differences in glycine receptor subunits and GLP-1 expression at the spinal cord.

physiology↗

bioRxiv2019

Calcium-driven regulation of voltage-sensing domains in BK channels

Allosteric interplays between voltage-sensing domains (VSD), Ca2+-binding sites, and the pore domain govern the Ca2+- and voltage-activated K+ (BK) channel opening. However, the functional relevance of the Ca2+- and voltage-sensing mechanisms crosstalk on BK channel gating is still debated. We examined the energetic interaction between Ca2+ binding and VSD activation measuring and analyzing the effects of internal Ca2+ on BK channels gating currents. Our results indicate that the Ca2+ sensors occupancy has a strong impact on the VSD activation through a coordinated interaction mechanism in which Ca2+ binding to a single -subunit affects all VSDs equally. Moreover, the two distinct high-affinity Ca2+-binding sites contained in the C-terminus domains, RCK1 and RCK2, appear to contribute equally to decrease the free energy necessary to activate the VSD. We conclude that voltage-dependent gating and pore opening in BK channels is modulated to a great extent by the interaction between Ca2+ sensors and VSDs.

biophysics↗

bioRxiv2018

Corals sustain growth but not skeletal density across the Florida Keys Reef Tract despite ongoing warming

Through the continuous growth of their carbonate skeletons, corals record invaluable information about past environmental conditions and their effect on colony fitness. Here, we characterize century-scale growth records of inner and outer reef corals across ~200 km of the Florida Keys Reef Tract (FKRT) using skeletal cores extracted from two ubiquitous reef-building species, Siderastrea siderea and Pseudodiploria strigosa. We find that corals across the FKRT have sustained extension and calcification rates over the past century but have experienced a long-term reduction in skeletal density, regardless of reef zone. Notably, P. strigosa colonies exhibit temporary reef zone-dependent reductions in extension rate corresponding to two known extreme temperature events in 1969-70 and 1997-98. We propose that the subtropical climate of the FKRT may buffer corals from chronic growth declines associated with climate warming, though the significant reduction in skeletal density may indicate underlying vulnerability to present and future trends in ocean acidification.

ecology↗

bioRxiv2018

Nearshore corals on the Mesoamerican Barrier Reef System on pace to cease growing as soon as year 2110

Anthropogenic global change and local anthropogenic stressors are decreasing coral growth and survival globally, thus altering the structure and function of coral reef ecosystems. We show that skeletal extension rates of nearshore colonies of Siderastrea siderea and Pseudodiploria strigosa across the Belize Mesoamerican Barrier Reef System (MBRS) have declined at average rates of 0.01 and 0.08 mm/yr, respectively, over approximately the past century, while offshore conspecifics exhibited no significant trend in extension with time. This caused extension rates of nearshore colonies to converge with their historically slower-growing offshore conspecifics. Bleaching events negatively impacted extension rates in S. siderea but not in P. strigosa. The more negative trend in linear extension for nearshore versus offshore colonies may arise from ocean warming combined with stronger land-based anthropogenic stressors within nearshore environments. Extrapolating these trends in linear extension into the future suggests that nearshore P. strigosa and S. siderea will cease growing by years 2110 and 2370, respectively.

ecology↗

bioRxiv2017

The social and spatial ecology of dengue presence and burden during an outbreak in Guayaquil, Ecuador, 2012

Dengue fever, a mosquito-borne viral disease, is an ongoing public health problem in Ecuador and throughout the tropics, yet we have a limited understanding of the disease transmission dynamics in these regions. The objective of this study was to characterize the spatial dynamics and social-ecological risk factors associated with a recent dengue outbreak in Guayaquil, Ecuador. We examined georeferenced dengue cases (n = 4,248) and block-level census data variables to identify potential social-ecological variables associated with the presence and burden of dengue fever in Guayaquil in 2012. We applied LISA and Morans I tests to analyze hotspots of dengue cases and used multimodel selection in R computing language to identify covariates associated with dengue incidence at the census zone level. Significant hotspots of dengue transmission were found near the North Central and Southern portions of Guayaquil. Significant risk factors for presence of dengue included poor housing conditions (e.g., poor condition of ceiling, floors, and walls), access to paved roads, and receipt of remittances. Counterintuitive positive correlations with dengue presence were observed with several municipal services such as garbage collection and access to piped water. Risk factors for the increased burden of dengue included poor housing conditions, garbage collection, receipt of remittances, and sharing a property with more than one household. Social factors such as education and household demographics were negatively correlated with increased dengue burden. Our findings elucidate underlying differences with dengue presence and burden and indicate the potential to develop dengue vulnerability and risk maps to inform disease prevention and control - information that is also relevant for emerging epidemics of chikungunya and zika.\n\nHighlightsO_LIIn 2012, Guayaquil, Ecuador had a large outbreak of dengue cases\nC_LIO_LIDengue case presence and burden exhibited spatial heterogeneity at the census block level\nC_LIO_LISocial-ecological drivers of case presence and burden differed in this outbreak, highlighting the need to model both types of epidemiological data\nC_LIO_LIAccess to municipal resources such as garbage collection and piped water had counterintuitive relationships with dengue presence, but poor housing, garbage collection and remittances correlated to dengue burden.\nC_LIO_LIOur findings inform risk mapping and vector control and surveillance allocation, relevant to this and other concurrent emergent epidemics such as chikungunya and zika\nC_LI

epidemiology↗