Biology subjects

Castro, I.

Publications and source records attributed to Castro, I..

7 recordsLinked to original sources

bioRxiv2026

Investigating the role of the hippocampus in the implicit and explicit expression of statistical learning in patients with temporal lobe epilepsy

Statistical learning (SL) has been proposed to depend on the hippocampus, but traditional neuropsychological theories of long-term memory posit that the hippocampus is only necessary for explicit memory processes, not implicit memory processes. To reconcile these two accounts, we exposed 27 temporal lobe epilepsy (TLE) patients to a continuous speech stream containing embedded trisyllabic words, then tested their statistical knowledge using both implicit and explicit behavioural measures. TLE patients showed impairments on two explicit measures of SL alongside intact performance on an implicit measure of SL. These results suggest that the hippocampus may only be necessary for the explicit expression, but not the initial acquisition or implicit expression, of statistical knowledge.

neuroscience↗

bioRxiv2024

DDO-adjuvanted influenza A virus nucleoprotein mRNA vaccine induces robust humoral and cellular type 1 immune responses and protects mice from challenge

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8+ T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA vaccines offer an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8+ T-cells remains a challenge. Here we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice. DDO268 safely induced local type I interferon (IFN) production, stimulated dendritic cells type 1 (DC1) activation and migration to the draining lymph nodes, and improved the generation of IgG2c antibodies and antigen-specific effector Th1 CD4+ and CD8+ T-cells (IFN{gamma}+TNF+IL2+) when co-packaged with NP mRNA. The DDO268 adjuvanted vaccine provided enhanced protection against lethal IAV challenge and reduced the antigen dose required to achieve this protection. These results highlight the potential of DDO268 as an effective mRNA vaccine adjuvant and show that an IAV NP mRNA/DDO268 vaccine is a promising approach for generating protective immunity against conserved IAV epitopes. IMPORTANCEVaccines that generate neutralizing antibodies and cytotoxic CD8+ T-cells targeting conserved epitopes are ideal for effective protection against viruses. mRNA vaccines combined with the right adjuvant offer a promising solution to this challenge. We show that the virus-derived oligonucleotide DDO268 enhances antibody and T cell responses to an influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in mice. DDO268 safely induces local type I interferon production and stimulates dendritic cell activation providing enhanced protection against IAV challenge. In addition, the adjuvant activity of DDO268 allows for the use of lower antigen doses during vaccination.

immunology↗

bioRxiv2023

Loss of IRF5 increases ribosome biogenesis leading to alterations in mammary gland architecture and metastasis

Despite the progress made in identifying cellular factors and mechanisms that predict progression and metastasis, breast cancer remains the second leading cause of death for women in the US. Using The Cancer Genome Atlas and mouse models of spontaneous and invasive mammary tumorigenesis, we identified that loss of function of interferon regulatory factor 5 (IRF5) is a predictor of metastasis and survival. Histologic analysis of Irf5-/- mammary glands revealed expansion of luminal and myoepithelial cells, loss of organized glandular structure, and altered terminal end budding and migration. RNA-seq and ChIP-seq analyses of primary mammary epithelial cells from Irf5+/+ and Irf5-/-littermate mice revealed IRF5-mediated transcriptional regulation of proteins involved in ribosomal biogenesis. Using an invasive model of breast cancer lacking Irf5, we demonstrate that IRF5 re-expression inhibits tumor growth and metastasis via increased trafficking of tumor infiltrating lymphocytes and altered tumor cell protein synthesis. These findings uncover a new function for IRF5 in the regulation of mammary tumorigenesis and metastasis. HighlightsLoss of IRF5 is a predictor of metastasis and survival in breast cancer. IRF5 contributes to the regulation of ribosome biogenesis in mammary epithelial cells. Loss of IRF5 function in mammary epithelial cells leads to increased protein translation.

cancer biology↗

bioRxiv2022

Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment.

immunology↗

bioRxiv2021

Evidence of post-domestication hybridization and adaptive introgression in Western European grapevine varieties

Grapevine (Vitis vinifera L.) is one of the most significant crops in the world. Todays richness in grapevine diversity results from a complex domestication history over multiple historical periods. Here, we employed whole genome resequencing to elucidate different aspects of the recent evolutionary history of this crop. Our results support a model in which a central domestication event in grapevine was followed by post-domestication hybridization with local wild genotypes, leading to the presence of an introgression signature in modern wine varieties across Western Europe. The strongest signal was associated with a subset of Iberian grapevine varieties, which show large introgression tracts. We targeted this study group for further analysis, demonstrating how regions under selection in wild populations from the Iberian Peninsula were preferentially passed on to the cultivated varieties by geneflow. Examination of underlying genes suggests that environmental adaptation played a fundamental role in both the evolution of wild genotypes and the outcome of hybridization with cultivated varieties, supporting a case of adaptive introgression in grapevine.

plant biology↗

bioRxiv2021

The UCR Minicore: a valuable resource for cowpea research and breeding

Incorporation of new sources of genetic diversity into plant breeding programs is crucial for continuing to improve yield and quality, as well as tolerance to abiotic and biotic stresses. A minicore (the "UCR Minicore") composed of 368 worldwide accessions of cultivated cowpea has been assembled, having been derived from the University of California, Riverside cowpea collection. High-density genotyping with 51,128 SNPs followed by principal component and genetic assignment analyses identified six subpopulations in the UCR Minicore, mainly differentiated by cultivar group and geographic origin. All six subpopulations were present to some extent in West African material, suggesting that West Africa is a center of diversity for cultivated cowpea. Additionally, population structure analyses supported two routes of introduction of cowpea into the U.S.: (1) from Spain to the southwest U.S. through Northern Mexico, and (2) from Africa to the southeast U.S. via the Caribbean. Genome-wide association studies (GWAS) of important agronomic traits including flowering time, resulted in the identification of significant SNPs for all traits and environments. The mapping resolution achieved by high-density genotyping of this diverse minicore collection allowed the identification of strong candidate genes, including orthologs of the Arabidopsis FLOWERING LOCUS T. In summary, this diverse, yet compact cowpea collection constitutes a suitable resource to identify loci controlling complex traits, consequently providing markers to assist with breeding to improve this crop of high relevance to global food and nutritional security.

genetics↗

bioRxiv2020

Precision as a metric for acoustic survey design using occupancy or spatial capture-recapture

Passive acoustic surveys provide a convenient and cost-effective way to monitor animal populations. Methods for conducting and analysing such surveys, especially for performing automated call recognition from sound recordings, are undergoing rapid development. However, no standard metric exists to evaluate the proposed changes. Furthermore, most metrics that are currently used are specific to a single stage of the survey workflow, and therefore may not reflect the overall effects of a design choice. Here, we attempt to define and evaluate the effectiveness of surveys conducted in two common frameworks of population inference - occupancy modelling and spatially explicit capture-recapture (SCR). Specifically, we investigate precision (standard error of the final estimate) as a possible metric of survey performance, but we show that it does not lead to generally optimal designs in occupancy modelling. In contrast, precision of the SCR density estimate can be optimised with fewer experiment-specific parameters. We illustrate these issues using simulations. We further demonstrate how SCR precision can be used to evaluate design choices on a field survey of little spotted kiwi (Apteryx owenii). We show that precision correctly measures tradeoffs involving sampling effort. As a case study, we compare automated call recognition software with human annotations. The proposed metric captured the tradeoff between missed calls (8% loss of precision when using the software) and faster data through-put (60% gain), while common metrics based on per-second agreement failed to identify optimal improvements and could be inflated by deleting data. Due to the flexibility of SCR framework, the approach presented here can be applied to a wide range of different survey designs. As the precision is directly related to the power of detecting temporal trends or other effects in the subsequent inference, this metric evaluates design choices at the application level, and can capture tradeoffs that are missed by stage-specific metrics, thus enabling reliable comparison between different experimental designs and analysis methods.

ecology↗