Morgado, M. | Search bioRxiv

bioRxiv2025

The novel phenomenon of inter-retinal coupling predicts cortical neurovascular responses in health and disease

It has recently been discovered that physiological crosstalk exists between human retinas. Accordingly, visual stimulation of one retina elicited a neurovascular coupling (NVC) response of the contralateral retina in about 30% of individuals. The functional significance of this feature in health and disease remains unknown. Here, we asked the question whether inter-retina crosstalk predicts the nature of neurovascular coupling in the brain. To test this hypothesis, we assessed BOLD fMRI (blood-oxygen-level-dependent functional magnetic resonance imaging signal) in healthy individuals and a disease model of neurovascular coupling, type 1 diabetes. We used three visual paradigms: a Threshold speed and Sub-maximum speed discrimination tasks, and flicker stimulation. The presence or absence of inter-retinal coupling was predictive of the time course of the cortical hemodynamic response, either during the initial or late phases. The presence of interocular coupling predicted larger BOLD responses. Diabetic patients with interocular coupling showed a very similar profile to the healthy group. In sum, we identified a direct relationship between interocular physiological coupling and cortical hemodynamic responses, suggesting that this NVC response may serve as a disease biomarker in diabetes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/684136v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@74ae56org.highwire.dtl.DTLVardef@61a2ccorg.highwire.dtl.DTLVardef@7349dorg.highwire.dtl.DTLVardef@10f61b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

Discovery of novel tumor suppressors from CRISPR screens reveals lipid-sensitive subtype of AML

CRISPR knockout screens in hundreds of cancer cell lines have revealed a substantial number of context-specific essential genes that, when associated with a biomarker such as lineage or oncogenic mutation, offer candidate tumor-specific vulnerabilities for targeted therapies or novel drug development. Data-driven analysis of knockout fitness screens also yields many other functionally coherent modules that show emergent essentiality or, in rarer cases, the opposite phenotype of faster proliferation. We develop a systematic approach to classify these suppressors of proliferation, which are highly enriched for tumor suppressor genes, and define a network of 145 genes in 22 discrete modules. One surprising module contains several elements of the glycerolipid biosynthesis pathway and operates exclusively in a subset of AML lines, which we call Fatty Acid Synthesis/Tumor Suppressor (FASTS) cells. The proliferation suppressor activity of genes involved in the synthesis of saturated fatty acids, coupled with a more severe fitness phenotype for the desaturation pathway, suggests that these cells operate at the limit of their carrying capacity for saturated fatty acids, which we confirmed biochemically. Overexpression of genes in this module is associated with a survival advantage in an age-matched cohort of AML patients, suggesting the gene cluster driving an in vitro phenotype may be associated with a novel, clinically relevant subtype.

genetics↗