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Biology subjects

Brown, Z.

Publications and source records attributed to Brown, Z..

3 recordsLinked to original sources

The School Cafeteria Problem: Disrupted Visuospatial Attention During Multisensory Speech-in-Noise Perception in Children with ADHD

BackgroundMany children with attention deficit hyperactivity disorder (ADHD) have difficulty distinguishing speech in crowded scenarios with competing conversations and noise. This can impact learning and community participation. Prior work has implicated audiovisual integration of lip movements with speech sounds as a potential underlying mechanism, but difficulty in accurately deploying spatial attention is an important, often overlooked, factor that may impact the accuracy of speech perception in noisy environments. ObjectiveEvaluate patterns of audiovisual integration and allocation of visuospatial attention during speech processing in a multiple-talker scenario among school-age children with ADHD and typically developing children (TD). MethodsWe recruited 7-12-year-old children with ADHD to participate in an integrated virtual reality and electrophysiologic (EEG) speech-in-noise perception paradigm. In virtual reality, children were asked to press a button whenever a centrally-located target character spoke a target monosyllabic word, while ignoring any words spoken by two flanking distractor characters. We manipulated 1) audiovisual (AV) content by intermixing trials containing either audio, visual, or multisensory AV representations of the three characters and 2) spatial attention demands by including trials with and without interference from the distracting speakers. We measured AV gain in target detection accuracy. Simultaneously, steady-state visual evoked potentials (SSVEP) were continuously recorded via a 128-channel electrode array as an index of visuospatial attention allocation to each speaker. To elicit SSVEP, the target and distractor speakers were tagged with different visual frequency oscillations (23hz and 15hz, respectively). EEG signal-to-noise ratio (SNR) in the corresponding first and second harmonics for those frequency bands was measured over the occipital scalp. ResultsChildren with ADHD showed reduced AV gain relative to TD controls. TD controls also demonstrated more robust SSVEP at 23Hz and 46Hz (target speaker) than at 15Hz (distractor speakers). Compared to TD children, children with ADHD had reduced selective activation in response to the target. As a result, children with ADHD showed more equivalent allocation of visuospatial attention between 23Hz target and 15Hz distractor frequencies. ConclusionsChildren with ADHD demonstrate a reduction in the typical perceptual benefit afforded by exposure to multisensory compared to unisensory speech stimuli, accompanied by substantial differences in the allocation of visuospatial attention to the relevant speaker. Thus, dysregulation of selective visuospatial attention may impair their ability to effectively perceive language in noisy settings.

neuroscience↗

The mechanism of ribosomal recruitment during translation initiation on Type 2 IRESs

The encephalomyocarditis virus (EMCV) IRES and other Type 2 IRESs comprise domains H-L and specifically interact with eIF4G/eIF4A through their essential JK domain. However, the JK domain is not sufficient for IRES function, which also requires the preceding domain I of unknown function. To identify interactions that drive ribosomal recruitment of eIF4G/eIF4A-bound Type 2 IRESs, we determined the cryo-EM structure of 48S initiation complexes formed on the EMCV IRES. It revealed that the apical domain I cloverleaf contacts ribosomal proteins uS13 and uS19 via its Id subdomain and that the essential GNRA tetraloop in subdomain Ic interacts directly with the T{psi}C domain of initiator tRNA. Functional assays supported the exceptional role of these interactions for initiation on this IRES. The strong conservation of primary and secondary structures of the apex of domain I among Type 2 IRESs suggests that the reported interactions are a common essential feature of them all.

molecular biology↗

Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAA, Valine, Leucine, and Isoleucine) are essential for anabolic processes like protein synthesis, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2 (PGE2) and psychological stress. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2 administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.

cell biology↗