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Choe, E.

Publications and source records attributed to Choe, E..

3 recordsLinked to original sources

Seeing at Will: Shared Neural Representations of Motion Perception and Intention

Volitional intention can bias perception in cases where two or more interpretations of a stimulus are available to us. The neural mechanisms whereby such an intention influences perception are poorly understood. Here we investigated whether intending to see horizontal versus vertical motion in a subsequently presented instantaneous position shift of a quartet apparent motion stimulus establishes decodable sensory representations prior to both the position shift and the perception of motion. Twelve participants underwent fMRI scanning under three conditions: (1) while passively viewing either continuously or (2) discretely moving quartet stimuli, or (3) while actively intending to see a subsequent single-shot apparent motion as either a vertical or horizontal motion. Multivariate decoding analyses revealed that activity patterns during the intention period of (3) generalized to patterns evoked by both (1) physical and (2) ambiguous motion perception. Cross-decoding was strongest within dorsal/lateral visual regions, including hMT+, V3AB, and the intraparietal sulcus (IPS), but was largely absent from ventral visual cortex. Widespread overlap was also observed between intention-related and perceptual motion representations throughout the dorsal/lateral visual cortex. Our findings suggest that volitional intention establishes prospective sensory representations before perceptual experience emerges and that these representations closely resemble those associated with illusory motion perception. The predominance of intention-related representations within dorsal/lateral visual regions is consistent with top-down influences from attentional control systems. More broadly, the results demonstrate that internally generated cognitive states can shape sensory representations, constraining subsequent perceptual experience.

neuroscience↗

Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress

Activated Notch signaling is highly prevalent in T-cell acute lymphoblastic leukemia (T-ALL) but pan-Notch inhibitors were toxic in clinical trials. To find alternative ways to target Notch signals, we investigated Cell division cycle 73 (Cdc73), which is a Notch cofactor and component of transcriptional machinery, a potential target in T-ALL. While we confirmed previous work that CDC73 interacts with NOTCH1, we also found that the interaction in T-ALL was context-dependent and facilitated by the lymphoid transcription factor ETS1. Using mouse models, we showed that Cdc73 is important for Notch-induced T-cell development and T-ALL maintenance. Mechanistically, Cdc73, Ets1, and Notch intersect chromatin at promoters and enhancers to activate oncogenes and genes that are important for DNA repair and oxidative phosphorylation. Consistently, Cdc73 deletion in T-ALL cells induced DNA damage and impaired mitochondrial function. Our data suggests that Cdc73 might promote a gene expression program that was eventually intersected by Notch to mitigate the genotoxic and metabolic stresses of elevated Notch signaling. We also provide mechanistic support for testing inhibitors of DNA repair, oxidative phosphorylation, and transcriptional machinery. Inhibiting pathways like Cdc73 that intersect with Notch at chromatin might constitute a strategy to weaken Notch signals without directly targeting the Notch complex.

cancer biology↗

Novel Cluster AZ Arthrobacter phages Powerpuff, Lego, and YesChef exhibit close functional relationships with Microbacterium phages

Bacteriophages exhibit a vast spectrum of relatedness and there is increasing evidence of close genomic relationships independent of host genus. The variability in phage similarity at the nucleotide, amino acid, and gene content levels confounds attempts at quantifying phage relatedness, especially as more novel phages are isolated. This study describes three highly similar novel Arthrobacter globiformis phages-Powerpuff, Lego, and YesChef-which were assigned to Cluster AZ using a nucleotide-based clustering parameter. Phages in Cluster AZ and Microbacterium Cluster EH, as well as the former Microbacterium singleton Zeta1847, exhibited low nucleotide similarity but gene content similarity in excess of the recently adopted Microbacterium clustering parameter, which resulted in the reassignment of Zeta1847 to Cluster EH. Additionally, Clusters AZ and EH phages encode a shared integrase indicative of a lysogenic life cycle; in the first experimental verification of a Cluster AZ phages life cycle, we show that phage Powerpuff is a true temperate phage and forms stable lysogens that exhibit immunity to superinfection by related phages, despite lacking identifiable repressors typically required for lysogenic maintenance and superinfection immunity. The ability of phage Powerpuff to undergo and maintain lysogeny suggests that other closely related phages encoding an integrase but lacking an identified repressor may be temperate as well. Our findings further highlight the importance of using multiple metrics to capture phage relatedness, provide additional evidence of significant shared phage genomic content spanning multiple actinobacterial host genera, and demonstrate the continued need for verification and characterization of life cycles in newly isolated phages.

microbiology↗