Stereotypes bias face perception via orbitofrontal-fusiform cortical interaction.

Previous research has shown that social-conceptual associations, such as stereotypes, can influence the visual representation of faces and neural pattern responses in ventral temporal cortex (VTC) regions, such as the fusiform gyrus (FG). Current models suggest that this social-conceptual impact requires medial orbitofrontal cortex (mOFC) feedback signals during perception. Backward masking can disrupt such signals, as it is a technique known to reduce functional connectivity between VTC regions and regions outside VTC. During functional magnetic resonance imaging (fMRI), subjects passively viewed masked and unmasked faces, and following the scan, perceptual biases and stereotypical associations were assessed. Multi-voxel representations of faces across the VTC, and in the FG and mOFC, reflected stereotypically biased perceptions when faces were unmasked, but this effect was abolished when faces were masked. However, the VTC still retained the ability to process masked faces and was sensitive to their categorical distinctions. Functional connectivity analyses confirmed that masking disrupted mOFC-FG connectivity, which predicted a reduced impact of stereotypical associations in the FG. Taken together, our findings suggest that the biasing of face representations in line with stereotypical associations does not arise from intrinsic processing within the VTC and FG alone, but instead it depends in part on top-down feedback from the mOFC during perception.

Transmembrane helix 6b links proton and metal release pathways and drives conformational change in an Nramp-family transition metal transporter.

The natural resistance-associated macrophage protein (Nramp) family encompasses transition metal and proton cotransporters that are present in many organisms from bacteria to humans. Recent structures of Deinococcus radiodurans Nramp (DraNramp) in multiple conformations revealed the intramolecular rearrangements required for alternating access of the metal-binding site to the external or cytosolic environment. Here, using recombinant proteins and metal transport and cysteine accessibility assays, we demonstrate that two parallel cytoplasm-accessible networks of conserved hydrophilic residues in DraNramp, one lining the wide intracellular vestibule for metal release and the other forming a narrow proton transport pathway, are essential for metal transport. We further show that mutagenic or posttranslational modifications of transmembrane helix (TM) 6b, which structurally links these two pathways, impede normal conformational cycling and metal transport. TM6b contains two highly conserved histidines, His232 and His237 We found that different mutagenic perturbations of His232, just below the metal-binding site along the proton exit route, differentially affect DraNramp's conformational state, suggesting that His232 serves as a pivot point for conformational changes. In contrast, any replacement of His237, lining the metal exit route, locked the transporter in a transport-inactive outward-closed state. We conclude that these two histidines, and TM6b more broadly, help trigger the bulk rearrangement of DraNramp to the inward-open state upon metal binding and facilitate return of the empty transporter to an outward-open state upon metal release.