Biology subjects

Proctor, E.

Publications and source records attributed to Proctor, E..

4 recordsLinked to original sources

bioRxiv2026

Frontal stimulation reshapes SCAN connectivity and improves motor function in Parkinson's disease

Parkinson's disease is a neurodegenerative disorder with characteristic motor deficits of bradykinesia and impaired coordination, and non-motor deficits affecting cognitive abilities such as attention and executive functions. Recent evidence suggests that some canonical motor deficits in Parkinson's disease (e.g., freezing of gait) are associated with abnormalities in frontal cortical processing typically thought to underlie executive functions such as cognitive control. The evidence from human research linking frontal cognitive disruption and motor deficits in people with Parkinson's disease is correlational. Individuals with cognitive impairments often also display gait and balance deficits, but causal evidence remains lacking. We combined non-invasive brain stimulation with functional MRI (fMRI) to ascertain whether dorsolateral prefrontal cortex (DLPFC) exerts a causal influence modulating motor function and to test the hypothesis that an excitatory stimulation protocol applied to a cognitive control network can improve motor performance in Parkinson disease. Participants with Parkinson's disease performed a precision force-tracking task shown to track with gait impairment while undergoing functional neuroimaging scans. On half of trials, participants were required to simultaneously perform a cognitively demanding 2-back working memory task to tax attentional systems. Following the initial baseline scan, participants returned for three separate counterbalanced sessions that combined transcranial magnetic stimulation (TMS) in the form of theta burst stimulation (TBS) with fMRI. Just prior to task performance, participants received either excitatory (intermittent TBS) or inhibitory (continuous TBS) stimulation protocols over right DLPFC. In the third session, participants received stimulation to a control site outside the cognitive and motor areas implicated in our task. Our within-subjects experimental design allowed us to examine the effects of stimulation on motor behavior, the influence of cognitive load on motor behavior, and the neural systems supporting cognitive control and motor execution. Consistent with our hypothesis, excitatory stimulation of DLPFC improved motor performance in a precision force-tracking task as indexed by reduced tracking error and smoother movement execution. These effects emerged preferentially under dual-task conditions when cognitive demands were high. Our results show that this improved motor performance coincides with reductions in functional connectivity not only between the stimulation site and primary motor cortex, but also within the recently described somato-cognitive action network (SCAN) thought to support action planning and whole-body movement coordination. We conclude that frontal cognitive control systems play a causal role in modulating movement in Parkinson's disease and suggest that targeting these systems with non-invasive interventions may enhance motor function.

neuroscience↗

bioRxiv2026

COB: a comprehensive database of chloroplast outer envelope beta-barrel proteins

Despite their central role in metabolite exchange, lipid trafficking, and protein import, chloroplast outer envelope beta-barrel proteins lack a dedicated comprehensive sequence database spanning many plant proteomes. Here we present the database COB (chloroplast outer-envelope beta-barrel), consisting of 16,586 beta-barrel sequences organized across ten protein categories and an uncharacterized group. COB was constructed using a machine learning classifier that identifies chloroplast beta-barrels based on features derived from evolutionary protein contact maps. Analysis of COB reveals that Streptophyta have more barrels overall and use a greater variety of solute transporters than Chlorophyta. Furthermore, we find considerable structural diversity across OEP categories, including variation in beta-strand count and a high prevalence of open barrel conformations not observed in bacterial outer membrane proteins. Structure predictions for Arabidopsis thaliana outer envelope proteins identified candidate hybrid barrel assemblies, with TOC159 family members emerging as universal interaction partners. We also report single-chain multi-barrel domain architectures in the chloroplast outer envelope, a topology previously described only in Gram-negative bacteria. Finally, we find chloroplast membrane barrels have more open topologies and shorter strands than bacterial membrane barrels. COB provides a comprehensive sequence resource for chloroplast outer envelope beta-barrels and establishes a foundation for investigating the evolution, structure, and function of this essential protein in chloroplast.

plant biology↗

bioRxiv2025

Two sites in the C-terminal β-chain tail mediate interactions of the chaperone clusterin with amyloid beta and other misfolded client proteins

Clusterin (CLU) is a constitutively secreted mammalian chaperone that binds in extracellular body fluids to misfolded client proteins to neutralise their toxicity and mediate their safe disposal by cell uptake and intracellular degradation. However, the regions of CLU critical for its interactions with misfolded proteins remain still largely unknown. To identify binding sites, we expressed a panel of CLU deletion and alanine-stretch mutants in a recently developed mammalian expression system. Mutant CLU molecules lacking detectable structural aberrations were subjected to functional analyses to compare their abilities with that of wild type CLU to bind to misfolded proteins and to inhibit protein aggregation. These analyses implicated two regions in the flexible {beta}-chain C-terminal tail of CLU as being important in the interactions of the chaperone with misfolded proteins, including aggregating the Alzheimers amyloid {beta}-peptide (A{beta}). We then designed in silico sequence-specific single-domain camelid nanobodies to confirm the function of the two putative client protein binding sites. Based on our experimental results and in silico binding site predictions, we suggest that the potent ability of CLU to promiscuously interact with many different misfolded proteins, regardless of their size or structure, arises from the location of multiple client protein binding sites in its flexible tail region.

biochemistry↗

bioRxiv2018

Multivariate Computational Analysis of Gamma Delta T cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging

Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age ([≤]35 or [≥]50 years old). For data analysis, multiple multivariate computational algorithms (cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)) were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta ({gamma}{delta}) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from {gamma}{delta} T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ {gamma}{delta} T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of {gamma}{delta} T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate {gamma}{delta} T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct inflamm-aging processes with and without ART-suppressed HIV infection.

immunology↗