Biology subjects

Garcia, C. A.

Publications and source records attributed to Garcia, C. A..

6 recordsLinked to original sources

bioRxiv2026

BSG.S regulates ionocyte radial intercalation and function in the developing Xenopus mucociliary epithelium.

Mucociliary epithelia (MCE) line multiple vertebrate organs, including the mammalian airways, and rely on coordinated interactions among specialized cell types to clear pathogens and maintain epithelial homeostasis. Proper MCE function requires the appropriate specification and spatial organization of ionocytes, multiciliated cells, secretory cells, and basal cells. Ionocytes regulate ion transport and pH homeostasis, yet the mechanisms governing their integration and function within the developing epithelium remain incompletely understood. Basigin (BSG), also known as CD147 or EMMPRIN, is a conserved transmembrane glycoprotein implicated in cell migration, adhesion, and signaling. However, its role in mucociliary epithelial development remains unclear. Here, we show that the short isoform of BSG (BSG.S) is expressed in ionocytes of the Xenopus laevis MCE. Our findings demonstrate that BSG.S depletion impairs ionocyte radial intercalation, alters intracellular pH, and disrupts epithelial organization. Furthermore, BSG.S loss alters epithelial cell-type composition, decreasing the number of basal cells and increasing the number of multiciliated cells. These findings suggest BSG.S as a regulator of ionocyte integration, epithelial organization, and cell-type composition during mucociliary epithelial development.

developmental biology↗

bioRxiv2023

Clinically relevant concurrent BRAF and MEK inhibition alters differentiation states and sensitizes BRAF V600E-mutated high-grade gliomas to immune checkpoint blockade

Resistance to BRAF plus MEK inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poorly understood. This study addresses the urgent need to develop treatments for BRAFi+MEKi-resistant glioma in novel mouse models and patient-derived materials. BRAFi+MEKi reveals glioma plasticity by heightening cell state transitions along glial differentiation trajectories, giving rise to astrocyte- and immunomodulatory oligodendrocyte (OL)-like states. PD-L1 upregulation in OL-like cells links cell state transitions to tumor evasion, possibly orchestrated by Galectin-3. BRAFi+MEKi induces interferon response signatures, tumor infiltration, and suppression of T cells. Combining BRAFi+MEKi with immune checkpoint inhibition enhances survival in a T cell-dependent manner, reinvigorates T cells, and outperforms individual or sequential therapies in mice. Elevated PD-L1 expression in BRAF-mutant versus BRAF-wildtype glioblastoma supports the rationale for PD-1 inhibition in patients. These findings underscore the potential of targeting glioma plasticity and highlight combination strategies to overcome therapy resistance in BRAFV600E-mutant HGG. In briefXing et al. show that combined BRAF and MEK inhibitor (BRAFi+MEKi) treatment induces cell state transitions in BRAFV600E-mutant high-grade glioma cells linked with programmed death-ligand (PD-L1) upregulation and T cell suppression, potentially orchestrated through the secretion of galectin-3. These tumor-intrinsic adaptations may be overcome by concurrent immune checkpoint inhibition (ICI), as demonstrated in murine studies, offering novel therapeutic opportunities. HighlightsO_LIBRAFV600E-mutant HGG exhibits cell plasticity induced by BRAFi+MEKi, which links cell state transitions towards glial differentiation with immune evasion C_LIO_LIBRAFi+MEKi enhances anti-tumor immunity and simultaneously suppresses T cells via PD-L1 upregulation C_LIO_LIBRAF-mutant glioblastoma has elevated PD-L1 expression compared to BRAF-wildtype counterparts, providing a criterion for PD-1 inhibition therapy C_LIO_LIConcurrent BRAFi+MEKi and immune checkpoint inhibition enhance T cell-mediated anti-tumor activity and boost survival more effectively than sequential treatment in mice, guiding clinical translation C_LI

cancer biology↗

bioRxiv2021

Transcriptional landscape of human microglia reveals robust gene expression signatures that implicates age, sex and APOE-related immunometabolic pathway perturbations

Microglia have fundamental roles in health and disease, however effects of age, sex and genetic factors on human microglia have not been fully explored. We applied bulk and single cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex and APOE-{varepsilon}4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2 and BIN1. Meta-analyses with published bulk and single cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource; and highlight age, sex and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.

genetics↗

bioRxiv2020

High spatial resolution global ocean metagenomes from Bio-GO-SHIP repeat hydrography transects

Detailed descriptions of microbial communities have lagged far behind physical and chemical measurements in the marine environment. Here, we present 720 globally distributed surface ocean metagenomes collected at high spatio-temporal resolution. Our low-cost metagenomic sequencing protocol produced 2.75 terabases of data, where the median number of base pairs per sample was 3.48 billion. The median distance between sampling stations was 26 km. The metagenomic libraries described here were collected as a part of a biological initiative for the Global Ocean Ship-based Hydrographic Investigations Program, or "Bio-GO-SHIP." One of the primary aims of GO-SHIP is to produce high spatial and vertical resolution measurements of key state variables to directly quantify climate change impacts on ocean environments. By similarly collecting marine metagenomes at high spatiotemporal resolution, we expect that this dataset will help answer questions about the link between microbial communities and biogeochemical fluxes in a changing ocean.

genomics↗

bioRxiv2020

Independent Tryptophan pathway in Trichoderma asperellum and T koningiopsis: New insights with bioinformatic and molecular analysis

The synthesis of Indole Acetic Acid from tryptophan has been described in plants, fungi and bacteria; it is thus known as tryptophan-dependent indole acetic acid. Four possible pathways of IAA formation have been described, including the indole acetonitrile acid (IAN), indole acetamide (IAM), indole-pyruvic (IAP) and tryptamine (TRM) pathways. Of these, the indole acetonitrile pathway is particularly important because when this compound is transformed into IAA, a nitrogenated molecule is released. The microorganisms that have this pathway are thus called nitrogen fixers. There is another little-studied pathway called TRP-Independent, so-called because the IAA that is formed in it can have an exogenous origin, chorismic acid (CHA), and it enters the pathway through anthranilic acid (ANA). The TRP-Independent pathway is made up of three stages. The first from CHA to ANA, the second from AA to IAA and the third from TRP to ANA through Kynurenine (KYN). This work describes the different stages of the pathway, as well as the enzymes and the genes that control the production of IAA, using a bioinformatic analysis of the genes involved, which were identified by PCR. An expression analysis showed that only T asperellum has the necessary genes to incorporate ANA into the TRP-I pathway and synthesize IAA through it. The analysis also detected the gene that regulates anthranilate phosphoribosyl transferase (AFT), an enzyme necessary for the synthesis of AIA from ANA; the presence of this gene was confirmed in the two species analyzed.

microbiology↗

bioRxiv2019

Novel Variants in COL4A3 and COL4A4 are Causes of Alport Syndrome in Rio Grande do Norte, Brazil

BackgroundAlport syndrome is a progressive and hereditary nephropathy, characterized by hematuria and proteinuria, and extrarenal manifestations as hearing loss and eye abnormalities. The disease can be expressed as autosomal recessive or dominant, caused by variants in COL4A3 and COL4A4 loci, respectively, or X-linked caused by variants in COL4A5 locus. MethodsTwo unrelated families with Alport Syndrome from northeast of Brazil were studied and whole exome sequencing were performed. DNA sequences were mapped against the human genome (GRCh38/hg38 build) to identify associated mutations. ResultsVariant analysis showed deleterious variants in COL4A3 and COL4A4 loci in chromosome 2. Two variants were detected with alternative alleles in a homozygous state in the probands. One novel premature stop codon at position 481 of COL4A3 protein is present in one family and one frameshift mutation leading to a premature stop codon at position 786 of COL4A4 protein in the other family. Both Alport cases presented their variants surrounded by a broad runs of homozygosity (ROH). ConclusionsThe autosome recessive inheritance coupled with the runs of homozygosity in both families suggest inbreeding.

genomics↗