Biology subjects

Rodrigues, F. R.

Publications and source records attributed to Rodrigues, F. R..

4 recordsLinked to original sources

bioRxiv2023

A multi-tissue single-cell tumor microenvironment atlas reveals myeloid-derived cell states with significant impact on clinical outcome

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment response due to their remarkable plasticity and tumorigenic behaviors. We integrated single-cell RNA-Sequencing datasets from seven different cancers, resulting in a comprehensive collection of 29 MDC subpopulations in the tumor microenvironment (TME). Distinguishing resident-tissue from monocyte-derived macrophages, we discovered a resident-tissue-like subpopulation within monocyte-derived macrophages. Additionally, hypoxia-driven macrophages emerged as a prominent TME component. Deconvolution of these profiles revealed five subpopulations as independent prognostic markers across various cancer types. Validation in large cohorts confirmed the FOLR2-expressing macrophage association with poor clinical outcomes in ovarian and triple-negative breast cancer. Moreover, the marker TREM2, commonly used to define immunosuppressive tumor-associated macrophages, cannot solely predict cancer prognosis, as different polarization states of macrophages express this marker in a context-dependent manner. This comprehensive MDC atlas offers valuable insights and a foundation for novel analyses, advancing strategies for treating solid cancers.

cancer biology↗

bioRxiv2021

Altered low frequency brain rhythms precede changes in gamma power during tauopathy

Alzheimers disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with diverse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.

neuroscience↗

bioRxiv2020

Plasticity in visual cortex is disrupted in a mouse model of tauopathy and neurodegeneration

Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease. HighlightsO_LIVisual plasticity is disrupted at early stages of neurodegeneration in rTg4510 mice C_LIO_LIVisual plasticity is reduced in older animals, particularly during neurodegeneration C_LIO_LIInstinctive visual behaviours are reduced in neurodegeneration C_LIO_LIShort-term visual plasticity is reduced in neurodegeneration C_LI

neuroscience↗

bioRxiv2020

BonVision - an open-source software to create and control visual environments

Real-time rendering of closed-loop visual environments is necessary for next-generation understanding of brain function and behaviour, but is prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks and communication with behavioural and physiological measurement and manipulation devices.

neuroscience↗