Biology subjects

Rodrigues, F. S.

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

3 recordsLinked to original sources

bioRxiv2025

Cancer-driven neutrophil priming couples systemic epithelial regenerative programs with pre-metastatic niche formation

Cancer progression involves systemic changes that extend beyond the primary tumour. Through cancer-induced systemic conditioning, breast tumours generate subclinical alterations in distant organs that facilitate metastatic seeding and pre-metastatic niche formation. Neutrophils, mobilized through cancer-driven emergency granulopoiesis, actively contribute to this process. In this study we extend the concept of neutrophil-dependent conditioning beyond pre-metastatic sites, uncovering a broader systemic regenerative activation that links inflammation, tissue regeneration, and metastasis. This activation manifests as enhanced epithelial progenitor activity, measured by increased organoid formation, across multiple organs, including those with low risk of breast cancer metastasis. This neutrophil-dependent perturbation in lung alveolar progenitors and intestinal epithelial lineage commitment, is an indication of an altered organ physiology, enhancing tissue resilience to injury. Moreover, we identify UPP1 expression, which exclusively characterizes neutrophils generated through emergency granulopoiesis, as a key factor sustaining high translational activity in neutrophil progenitors and enabling the full acquisition of cancer-primed properties. Consequently, neutrophil loss of UPP1 reduces both their lung pro-metastatic function and their capacity to activate alveolar progenitors. Mechanistically, this involves interactions between cancer-primed neutrophils and platelets, which localize within lung interstitial spaces near alveolar cells to stimulate epithelial progenitor activity. Together, these findings uncover a previously unrecognized tumour-induced systemic conditioning in which neutrophils coordinate epithelial regenerative activation as part of a pro-metastatic epithelial niche, with UPP1 as a key determinant of their cancer-primed state.

cancer biology↗

bioRxiv2023

Dorsolateral striatum encodes a temporal basis for the organization of behavior

To behave adaptively, the brain must register temporal structure in the environment and use it to organize behavior. The dorsolateral striatum (DLS) integrates sensorimotor input, and is necessary for accurate timing and structuring behavior in general. However, if DLS provides the basis for mapping temporal features in the environment to behavior, its activity should predict variation in that mapping. A reanalysis of DLS population activity in rats comparing the duration of two sequentially presented vibratory stimuli revealed a striking correspondence between neural activity and behavior. Varying vibration intensity of the second stimulus induced systematic biases in temporal judgments, and corresponding biases in multiple features of DLS activity during stimulus presentation, including population coding of time. In contrast, the same intensity manipulations applied to the first stimulus affected neither behavior nor neural activity. Furthermore, neuronal response profiles were best described as a continuum, arguing against hypotheses where categories of responses, e.g., ramping activity, selectively underpin temporal processing. These data represent important additional evidence that striatal population dynamics support the organization of behavior by mapping temporal information to action.

neuroscience↗

bioRxiv2020

Manipulation of striatal population dynamics using temperature warps judgment of time

The basal ganglia (BG) are thought to contribute to decision-making and motor control by influencing action selection based on consequences. These functions are critically dependent on timing information that can be extracted from the evolving state of neural populations in the striatum, the major input area of the BG. However, it is debated whether striatal activity underlies latent, dynamic decision processes or kinematics of overt movement. Here, we measured the impact of temperature on striatal population activity and the behavior of rats and compared the observed effects to neural activity and behavior collected in multiple versions of a temporal categorization task. Cooler temperatures caused dilation, and warmer temperatures contraction, of both neural activity and patterns of judgment in time, mimicking endogenous decision-related variability in striatal activity. However, temperature did not similarly affect movement kinematics. These data provide compelling evidence that the time course of evolving striatal population activity dictates the speed of a latent process that is used to guide choices, but not moment by moment kinematics. More broadly, they establish temporal scaling of population activity as a likely cause and not simply a correlate of timing behavior in the brain.

neuroscience↗