Biology subjects

Thorpe, R.

Publications and source records attributed to Thorpe, R..

3 recordsLinked to original sources

bioRxiv2024

Dysfunctional oscillatory bursting patterns underlie working memory deficits in adolescents with ADHD

Identifying neural markers of clinical symptom fluctuations is prerequisite to developing more precise brain-targeted treatments in psychiatry. We have recently shown that working memory (WM) in healthy adults is dependent on the rise and fall interplay between alpha/beta and gamma bursts within frontoparietal regions, and that deviations in these patterns lead to WM performance errors. However, it is not known whether such bursting deviations underlie clinically relevant WM-related symptoms or clinical status in individuals with WM deficits. In adolescents (n=27) with attention deficit hyperactivity disorder (ADHD), we investigated WM-related dynamics between alpha/beta and gamma bursts in relation to clinical status fluctuations. Participants repeatedly completed a visual Sternberg spatial working memory task during EEG recording as part of their participation in two research studies (n=224 person-sessions). Source localizing EEG data to each participants structural MRI, the rate and volume of alpha, beta, and gamma bursts were examined within the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC). Alpha/beta and gamma bursts at the DLPFC and PPC displayed complimentary roles in WM processes. Alpha/beta bursting decreased during stimuli encoding and increased during the delay, while gamma bursting was elevated during encoding and decreased during the delay. Deviations in bursting patterns were associated with WM errors and clinical symptoms. We conclude that dysfunctional alpha/beta and gamma burst dynamics within the frontoparietal region underlie both intra-individual WM performance and WM symptom fluctuations in adolescents with ADHD. Such burst dynamics reflect a novel target and biomarker for WM-related treatment development.

neuroscience↗

bioRxiv2024

The association between oscillatory burst features and deviations during human working memory

Oscillatory power across multiple frequency bands has been associated with distinct working memory (WM) processes. Recent research has shown that previous observations based on averaged power are driven by the presence of transient, oscillatory burst-like events, particularly within the alpha, beta, and gamma bands. However, the interplay between different burst events in human WM is not well understood. The current EEG study aimed to investigate the dynamics between alpha (8-12 Hz)/beta (15-29 Hz) and high frequency activity (HFA; 55-80 Hz) bursts in human WM, particularly burst features and error-related deviations during the encoding and maintenance of WM in healthy adults. Oscillatory burst features within the alpha, beta and HFA bands were examined at frontal and parietal electrodes in healthy young adults during a Sternberg working memory task. Averaged power dynamics were driven by oscillatory burst features, most consistently the burst rate and burst power. Alpha/beta and HFA bursts displayed complementary roles in WM processes, in that alpha and beta bursting decreased during encoding and increased during delay, while HFA bursting had the opposite pattern, i.e., increased during encoding and decreased during the delay. Critically, weaker variation in burst dynamics across stages was associated with incorrect responses and impaired overall task performance. Together, these results indicate that successful human WM is dependent on the rise and fall interplay between alpha/beta and HFA bursts, with such burst dynamics reflecting a novel target for the development of treatment in clinical populations with WM deficits.

neuroscience↗

bioRxiv2022

Dual function of the O-antigen WaaL ligase of Aggregatibacter actinomycetemcomitans

Protein glycosylation is critical to the quaternary structure and collagen binding activity of the extracellular matrix protein adhesin A (EmaA) associated with Aggregatibacter actinomycetemcomitans. The glycosylation of this large, trimeric autotransporter adhesin is postulated to be mediated by WaaL, an enzyme with the canonical function to ligate the O-polysaccharide (O-PS) antigen with a terminal sugar of the lipid A-core oligosaccharide of lipopolysaccharide (LPS). In this study, we have determined that the Escherichia coli waaL ortholog (rflA) does not restore collagen binding of a waaL mutant strain of A. actinomycetemcomitans but does restore O-PS ligase activity following transformation of a plasmid expressing waaL. Therefore, a heterologous E. coli expression system was developed constituted of two independently replicating plasmids expressing either waaL or emaA of A. actinomycetemcomitans to directly demonstrate the necessity of ligase activity for EmaA collagen binding. Proper expression of the protein encoded by each plasmid was characterized, and the individually transformed strains did not promote collagen binding. However, co-expression of the two plasmids resulted in a strain with a significant increase in collagen binding activity and a change in the biochemical properties of the protein. These results provide additional data supporting the novel hypothesis that the WaaL ligase of A. actinomycetemcomitans shares a dual role as a ligase in LPS biosynthesis and is required for collagen binding activity of EmaA. ImportanceThe human oral pathogen A. actinomycetemcomitans is a causative agent of periodontal and several systemic diseases. The organism expresses an adhesin, EmaA, important for the colonization of this pathobiont via collagen binding and biofilm formation. EmaA is suggested to be modified with sugars and the modification is mediated using the same enzymes involved in lipopolysaccharide (LPS) biosynthesis. In this study, evidence is presented which suggests that the WaaL ligase, the enzyme that ligates the O-polysaccharide (O-PS) antigen with a terminal sugar of the lipid A-core oligosaccharide of LPS, is required for the collagen binding activity of EmaA. This finding represents a new paradigm for the posttranslational modification of this type of autotransporter protein.

microbiology↗