Biology subjects

Castillo, P.

Publications and source records attributed to Castillo, P..

6 recordsLinked to original sources

bioRxiv2025

Skuas mortalities linked to positives HPAIV A/H5 beyond Polar Antarctic Circle

The ongoing extinction crisis, driven by human activity, poses a significant threat to seabirds and its especially relevant in highly valuable environments such as Antarctica. Among these threats, seabirds face the risk of local extinctions due to emerging infectious diseases like the Highly Pathogenic Avian Influenza Virus (HPAIV).Progressive spread of HPAIV A/H5N1 outbreaks across South America and the sub-Antarctic islands have been detected, reaching the northern regions of the West Antarctic Peninsula (WAP) during the 2023-2024 season. Here we conducted a comprehensive epidemiological survey conducted on sixteen seabird nesting localities along the WAP from November 2024 to January 2025 to assess the health status of the Antarctic seabirds and detect the presence of HPAIV. We observed unusual mortalities among nesting populations of skuas, with a total of 35 deaths skuas recorded along the WAP and beyond the Antarctic Polar Circle, including Important bird breeding areas around Margarita Bay. HPAIV A/H5 was confirmed in all dead skuas sampled (n=11), from six different locations. This finding represents the southernmost record of seabird mortality in Antarctica related to HPAIV to date. The expansion of HPAIV observed here raises concerns about further spread of avian flu out the Antarctic Peninsula, potentially leading to increased mortality rates in the Antarctic bird populations. These findings are relevant for the assessment of the general health status of Antarctic seabird populations and provide a baseline for the continuous monitoring of the HPAIV spread in avian species during the next breeding seasons.

ecology↗

bioRxiv2025

Quantitative evaluation of the role of the microenvironment in the phenotype, metabolism, and drug resistance of PDAC tumor organoids

Tumor organoids are powerful tools to study cancer. However, the clinical translation of organoid-based studies depends on how closely the organoid scaffolding material recapitulates the tumor extracellular matrix (ECM). We present a quantitative analysis of the effect of scaffold composition on the phenotype, tissue remodeling, metabolism, and drug resistance of pancreatic ductal adenocarcinoma (PDAC) organoids. We grew PDAC organoids within hydrogels made of Matrigel, collagen-I, or a mixture of collagen-I and Matrigel. Our results show that 1) PDAC organoids grown in Matrigel-only are phenotypically and metabolically similar to low-physiological two-dimensional PDAC cultures; 2) collagen-containing hydrogels, and especially so those grown in hydrogels of mixed collagen-Matrigel composition, accurately reproduce invasive tumors that underwent epithelial-to-mesenchymal transition (EMT) regarding phenotype, tissue remodeling, metabolic activity, and drug resistance. In summary, our work illustrates the importance of three-dimensional (3D) matrix composition for PDAC growth and postulates that organoids grown in collagen-Matrigel hydrogels are the most adequate for studying the biology of invasive PDAC tumors.

bioengineering↗

bioRxiv2023

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

cancer biology↗

bioRxiv2023

Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell Interactions

Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an "immune escape" response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.

bioengineering↗

bioRxiv2020

Distinct genetic pathways define pre-leukemic and compensatory clonal hematopoiesis in Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome with predisposition to developing leukemia. We found that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. EIF6 mutations cause functional compensation for the germline deficiency by alleviating the SDS ribosome joining defect, improving translation, and reducing p53 activation. TP53 mutations decrease checkpoint activation without affecting ribosome assembly. We link development of leukemia with acquisition of biallelic TP53 alterations. Our results define distinct pathways of clonal selection driven by germline fitness constraint and provide a mechanistic framework for clinical surveillance.

cancer biology↗

bioRxiv2017

Angiogenesis inhibiting capacity of Basella rubra and Syszygium cumini fruit extracts using chorioallantoic membrane assay

Angiogenesis is a physiological process of new blood vessel development from pre-existing capillaries. This process is also the main qualification for tumor growth and plays a vital role in tumor invasion and metastasis. Nevertheless, angiogenesis inhibitors can be used to impede abnormal blood vessel growth. The study was conducted to assess angiogenesis inhibiting potential of B. rubra (Alugbati) and S. cumini (Lumboy) fruit extracts as cell mass growth retardants using Chorioallantoic Membrane (CAM) Assay in Anas platyrhyncho (common Duck) embryo. The treatments were individually compared to Retinol palmitate as positive control and 0.9% sterilized normal saline solution as negative control. Data were gathered and analyzed using Analysis of Variance (ANOVA) and Least Significant Difference (LSD) to test for the significant anti-angiogenic activity and pair-wise comparison among the treatments respectively using a p-value of less than 0.01. Analysis showed that there is no significant difference between the fruit extracts and positive control while a significant difference between the fruit extracts and negative control was observed. Both treatments showed very good anti-angiogenic effect with average scores of 1.33 and 1.67 respectively compared to the positive control with a scoring averaging of 1.78. Furthermore, toxicity test is recommended for both treatments.

developmental biology↗