Biology subjects

Teixeira, B.

Publications and source records attributed to Teixeira, B..

4 recordsLinked to original sources

bioRxiv2025

Oncogenic RAS activity is linked to immune priming and adenosine-driven immune evasion in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is a leading cause of cancer death worldwide, with RAS signalling as a key oncogenic driver. Although KRAS mutations have been linked to immune evasion in preclinical models, the relationship between RAS activity and tumour immunity or response to immunotherapy in patients remains unclear. Here, we applied our previously validated RAS84 transcriptional signature to stratify LUAD patient cohorts and dissect the immune landscape associated with RAS signalling. We report that tumours with elevated RAS activity exhibited features of immune priming, including increased immune infiltration, interferon response, and immune checkpoint gene expression, and showed improved progression-free survival in an independent cohort of patients treated with anti-PD-1. Yet, in both LUAD tumours and cell lines, RAS activity also correlated with elevated immunosuppressive interstitial adenosine mediated by transcriptional regulation of several components of the adenosinergic pathway. In orthotopic pre-clinical models of high-RAS activity lung tumours, blocking adenosine signalling delayed tumour growth and improved response to anti-PD-1 and KRAS inhibition, with a significant effect on innate immunity. This study reveals a dual role for RAS signalling in tumour progression, fostering a pro-immunogenic environment whilst simultaneously dampening anti-tumoural immunity via mechanisms including extracellular adenosine accumulation. Stratifying patients based on RAS transcriptional activity, rather than genetic alterations alone, could inform immunotherapy strategies and improve clinical outcomes.

cancer biology↗

bioRxiv2025

Flow cytometry-based evaluation of hepatic infection by non-fluorescent Plasmodium parasites

The complex life cycle of Plasmodium parasites, involving both liver and blood stages of infection in the mammalian host, presents significant challenges for malaria research. Although advances have been made in malaria vaccination and treatment strategies, important gaps in our understanding of the asymptomatic liver stage of Plasmodium infection remain. While reporter gene-expressing parasites are commonly used for drug screening and parasite biology studies during this phase of the Plasmodium life cycle, tools for assessing and quantifying hepatic infection in the absence of parasite-encoded reporter genes are limited. Here, we present a novel flow cytometry-based method that enables the quantitative assessment of infection of hepatic cells by non-fluorescent Plasmodium parasites. This method uses two parasite proteins, heat shock protein 70 (HSP70), found in the parasite cytoplasm, and upregulated in infectious sporozoites 4 (UIS4), located on the parasitophorous vacuole membrane, as markers for parasite detection and quantification. We demonstrate that the use of these markers facilitates the rapid and cost-effective quantification of hepatic infection and intracellular development of Plasmodium parasites devoid of fluorescent reporter genes. This method addresses critical regulatory and technical challenges to the evaluation of reporter-free whole-sporozoite vaccine candidates and could serve as a versatile tool for broader malaria research. Author SummaryPlasmodium parasites, the causative agents of malaria, initially infect their mammalian hosts liver, where they replicate silently before entering the bloodstream and triggering disease. The hepatic stage of infection is a critical target for vaccine and drug development, but remains technically challenging to study, particularly when using parasite lines that do not express fluorescent or luminescent reporter genes. Reporter-free parasite lines are often required for regulatory reasons, particularly in the context of whole-sporozoite vaccine research. To address this limitation, we developed a flow cytometry-based method that enables the detection and quantification of hepatic infection by reporter-free Plasmodium parasites. The approach relies on the detection of two parasite proteins, HSP70 and UIS4, enabling the quantification of infected cells and the assessment of intracellular parasite development. This method is rapid, scalable, and cost-effective, and can be applied to Plasmodium lines relevant for vaccine studies. By facilitating the analysis of hepatic infection in the absence of reporter genes, our approach expands the experimental toolkit available for malaria research and supports ongoing efforts to develop interventions that target this clinically silent but biologically essential stage of the parasites life cycle.

microbiology↗

bioRxiv2025

Amyloid pathology reduces dynamic range and disrupts neural coding in a mouse model of Alzheimer's Disease

Alzheimers disease (AD) disrupts neural circuits vital for memory and cognition. Using two-photon calcium imaging in behaving 5xFAD mice, we examined how amyloid pathology alters hippocampal CA1 activity and spatial coding. We found elevated baseline activity but reduced locomotion-driven firing, leading to a diminished neuronal dynamic range. To our knowledge, this is the first direct experimental evidence for reduced dynamic range in an AD model. These abnormalities were strongest near amyloid plaques and became more widespread with age. We also observed altered network synchrony, degraded spatial coding and increased neuronal response variability. Furthermore, place fields emerged more slowly in both familiar and novel environments, indicating impaired recall and learning. By showing a link between local plaque pathology and impaired flexible modulation of CA1 activity and progressive deficits in spatial memory coding, our study offers new insights into the circuit basis of cognitive decline in AD.

neuroscience↗

bioRxiv2025

High throughput isolation of male gametophyte cells of Solanum lycopersicum var. Micro-Tom by fluorescence-activated cell sorting.

Efficient isolation of male gametes has enabled unprecedented advances in omics research, crucial for elucidating the molecular mechanisms governing male gametogenesis and fertilization. In this study, we developed a method for isolating generative and sperm cells from the economically important crop Solanum lycopersicum. A double fluorescent marker line was generated in the tomato variety Micro-Tom, employing mTurquoise and mScarlet-I fluorescent proteins under the control of promoters exhibiting preferential activity in generative and sperm cells, respectively. Then we developed a protocol that combines male gamete release from pollen of this line and SYTOX Red live/dead cell stain to obtain viable cells by Fluorescence-activated cell sorting. This allows the isolation of generative cells from mature pollen grains, and of sperm cells from pollen tubes after semi-in vivo growth, both in high quantity and purity. Additionally, an unexpected mScarlet-I signal in the vegetative nucleus, that persists until the sperm cells are formed, allows the sorting of vegetative nuclei. We anticipate that our novel double-marker line will accelerate research into tomato male gametogenesis, thereby enhancing efforts to improve the resilience of fertilization processes to climate change.

plant biology↗