Biology subjects

Hougland, J.

Publications and source records attributed to Hougland, J..

4 recordsLinked to original sources

bioRxiv2026

Aperiodic neural activity predicts cortical excitability in TMS-EEG

Background: Fluctuating cortical excitability states are inherent to and critical for brain function. They can be probed non-invasively using transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) by measuring early local TMS-evoked potentials (EL-TEPs). Pre-stimulus periodic neural activity can predict fluctuating excitability states. To what extent aperiodic neural activity represents a marker of cortical excitability has not been explored. Objectives: We investigated the relationship between pre-stimulus aperiodic and periodic neural activity and EL-TEP amplitude in both the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC). Methods: Single-pulse TMS was delivered to the left M1 or left DLPFC in 29 and 11 healthy adults, respectively, while EEG was recorded simultaneously. Pre-stimulus EEG was parameterized into aperiodic and periodic components to extract the aperiodic exponent (slope of 1/f-like activity), alpha power (8-13 Hz), and beta power (13-30 Hz). EL-TEP peak-to-peak amplitudes were extracted from approximately 20-65 ms after the TMS pulse. Results: Aperiodic exponent showed a strong negative relationship with EL-TEP amplitude in both M1 and DLPFC, with steeper 1/f-like slopes associated with smaller EL-TEP amplitudes. Inconsistent relationships were found between alpha and beta power with EL-TEP amplitude across the two regions. Conclusions: These findings indicate that pre-stimulus aperiodic neural activity influences cortical excitability in both motor and prefrontal areas. Notably, the aperiodic exponent exhibited stronger associations with cortical excitability compared to periodic alpha or beta power. Brain-state-dependent protocols may benefit from real-time extraction of aperiodic exponent as a target feature to improve the precision and efficacy of TMS.

neuroscience↗

bioRxiv2025

Development of Dendritic Cell Membrane-Coated Nanoparticles for Antigen-Specific T Cell Engagement

Dendritic cell (DC) membrane-coated nanoparticles (DCmPs) hold significant potential for antigen-specific therapies. DCmPs carry key DC membrane proteins that facilitate DC-T cell interaction, such as major histocompatibility complex (MHC), costimulatory CD80/86, and adhesive molecules ICAM-1. However, our current understanding of the impact of the coating processes and the composition of the final products is very limited, significantly hindering the development of DCmP-based therapy. Here, using DC2.4 cell membrane proteins and poly (lactic-co-glycolic acid) (PLGA) nanoparticles, we comprehensively characterized and compared the compositions and functions of DCmPs produced using sonication, extrusion, and a newly developed combined coating approach (sonication coating following by extrusion process). The combined coating approach achieved relatively high level of protein coating and exerted superior control over the diameter and uniformity of DCmPs relative to sonication and extrusion. We also developed a characterization strategy by leveraging the homotypic interactions between DCmPs and DC2.4 cells and determined that about 80% of PLGA particles are coated with membrane proteins and both unbound proteins and uncoated particles similarly present in the final products after the three coating processes. Because DC2.4 cells exclusively express MHC class I molecules, DCmPs showed preferentially bind to cognate B3Z CD8+ T cells over DOBW CD4+ T cells, confirming that DCmPs bind to T cells in an antigen-specific fashion. Furthermore, we demonstrated that DCmPs can activate B3Z CD8+ T cells in vitro, similar to DC2.4 cells. These findings demonstrate a new coating approach that potentially improves size control over membrane-coated particles and a characterization strategy for detailed analysis of coated particle composition, having important and broad implications for the therapeutic development of DCmPs and other membrane-coated particle technology.

bioengineering↗

bioRxiv2021

Ghrelin O-acyltransferase interacts with extracellular peptides and exhibits unexpected cellular localization for a secretory pathway enzyme

Ghrelin O-acyltransferase (GOAT) plays a central role in the maturation and activation of the peptide hormone ghrelin, which performs a wide range of endocrinological signaling roles. Using a tight-binding fluorescent ghrelin-derived peptide designed for high selectivity for GOAT over the ghrelin receptor GHS-R1a, we demonstrate that GOAT interacts with extracellular ghrelin and facilitates ligand cell internalization in both transfected cells and prostate cancer cells endogenously expressing GOAT. Coupled with enzyme mutagenesis, ligand uptake studies provide the first direct evidence supporting interaction of the putative histidine general base within GOAT with the ghrelin peptide acylation site. Our work provides a new understanding of GOATs catalytic mechanism, establishes a key step required for autocrine/paracrine ghrelin signaling involving local reacylation by GOAT, and raises the possibility that other peptide hormones may exhibit similar complexity in their intercellular and organismal-level signaling pathways.

biochemistry↗

bioRxiv2020

Pursuing the Mechanisms Underlying Alcohol-Induced Changes in the Ghrelin System: New Insights from Preclinical and Clinical Investigations

Ghrelin is a gastric-derived peptide hormone with demonstrated impact on alcohol intake and craving, but the reverse side of this bidirectional link, i.e., the effects of alcohol on the ghrelin system, remains to be fully established. To characterize the downstream effects of alcohol on the ghrelin system, we examined the following: (1) plasma ghrelin levels across four human laboratory alcohol administration experiments with non-treatment seeking, heavy-drinking participants, (2) expression of ghrelin, ghrelin receptor, and ghrelin-O-acyltransferase (GOAT) genes (GHRL, GHSR, and MBOAT4, respectively) in human post-mortem brain tissue from individuals with alcohol use disorder (AUD) vs. controls, (3) plasma ghrelin levels in Ghsr knockout and wild-type rats following intraperitoneal (i.p.) ethanol administration, (4) effect of ethanol on ghrelin secretion from gastric mucosa cells ex vivo and GOAT enzymatic activity in vitro, and (5) plasma ghrelin levels in rats following i.p. ethanol administration vs. an iso-caloric sucrose solution. Peripheral acyl- and total ghrelin levels significantly decreased following acute ethanol administration in humans. No difference in GHRL, GHSR, and MBOAT4 mRNA expression in the brain was observed between AUD vs. control post-mortem samples. In rats, acyl-ghrelin levels significantly decreased following i.p. ethanol administration in both genotype groups (Ghsr knockout and wild-type), while des-acyl-ghrelin was not affected by ethanol. No effect of ethanol was observed ex vivo on ghrelin secretion from gastric mucosa cells or in vitro on GOAT acylation activity. Lastly, we observed different effects of i.p. ethanol and sucrose solution on acyl- and des-acyl-ghrelin in rats despite administering amounts with equivalent caloric value. Ethanol acutely decreases peripheral ghrelin concentrations in humans and rats, and our findings suggest that this effect does not occur through interaction with ghrelin-secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme. Moreover, this effect does not appear to be proportional to caloric load. Our findings, therefore, suggest that ethanol does not suppress circulating ghrelin through direct interaction with the ghrelin system, or in proportion to the caloric value of alcohol, and may differentially affect ghrelin acylation and ghrelin peptide secretion.

physiology↗