Biology subjects

Kwon, Y. H.

Publications and source records attributed to Kwon, Y. H..

9 recordsLinked to original sources

bioRxiv2026

Topological reprogramming transforms an integral membrane oligosaccharyltransferase into a water-soluble glycosylation catalyst

Glycosyltransferases (GTs) catalyze the formation of new glycosidic bonds and thus are vital for synthesizing natures vast repertoire of glycans and glycoconjugates and for engineering glycan-related medicines and materials. However, obtaining detailed structural and functional insights for the >750,000 known GTs is limited by difficulties associated with their efficient recombinant expression. Members of the GT-C fold, in particular, pose the most significant expression challenges due to the integration and folding requirements of their multiple membrane-spanning regions. Here, we address this challenge by engineering water-soluble variants of an archetypal GT-C fold enzyme, namely the oligosaccharyltransferase PglB from Campylobacter jejuni (CjPglB), which possesses 13 hydrophobic transmembrane helices. To render CjPglB water-soluble, we leveraged two advanced protein engineering methods: one that is universal called SIMPLEx (solubilization of IMPs with high levels of expression) and the other that is custom tailored called WRAPs (water-soluble RFdiffused amphipathic proteins). Each approach was able to transform CjPglB into a water-soluble enzyme that could be readily expressed in the cytoplasm of Escherichia coli cells at yields in the 3-6 mg/L range. Importantly, solubilization was achieved without the need for detergents and with retention of catalytic function. Collectively, our findings demonstrate that both SIMPLEx and WRAPs are promising platforms for advancing the molecular characterization of even the most structurally complex GTs, while also enabling broader GT-mediated glycosylation capabilities within synthetic glycobiology applications.

synthetic biology↗

bioRxiv2026

A putative GtrB-like glycosyltransferase modulates cation-dependent BCP8-2 phage infection and cell surface structure in Bacillus cereus

Bacillus cereus is a foodborne pathogen of growing concern due to its persistence and antimicrobial resistance. To identify host determinants influencing susceptibility to phage BCP8-2, a mini-Tn10 transposon mutant library of B. cereus ATCC 14579 was constructed and screened for altered phage susceptibility. A mutant (BC2012) showing partial resistance carried an insertion in BC_RS27090 (previously BC_5432), encoding a putative GtrB-like bactoprenol glycosyltransferase. Complementation restored phage sensitivity, confirming its functional involvement. Adsorption and efficiency-of-plating assays revealed significantly reduced phage binding and infectivity in the mutant, particularly under cation-rich conditions. Microscopy showed altered surface morphology with thinner, smoother cell walls. These data indicate that gtrB affects surface properties essential for cation-dependent phage adsorption and infection and provide a foundation for future studies on the role of surface glycosylation and ionic interactions in Gram-positive phage biology. ImportancePathogenic Bacillus cereus is resilient across diverse environments and produces diverse toxins linked to foodborne outbreaks. Bacteriophages provide an effective strategy to control B. cereus; however, molecular targets of phage-host interaction are poorly understood, limiting the effective phage-based control. Current study addresses this gap by identifying a putative bactoprenol glycosyltransferase (GtrB), a vital factor in phage BCP8-2 susceptibility. Data obtained highlights partial reduction of phage infection in the gtrB mutant, demonstrating that precise glycosylation is essential for effective phage binding and entry. Our findings provide significant insights for advancing phage therapy, antibiotic resistance, and B. cereus biocontrol in food and clinical settings.

microbiology↗

bioRxiv2023

Situating the parietal memory network in the context of multiple parallel distributed networks using high-resolution functional connectivity

A principle of brain organization is that networks serving higher cognitive functions are widely distributed across the brain. One exception has been the parietal memory network (PMN), which plays a role in recognition memory but is often defined as being restricted to posteromedial association cortex. We hypothesized that high-resolution estimates of the PMN would reveal small regions that had been missed by prior approaches. High-field 7T functional magnetic resonance imaging (fMRI) data from extensively sampled participants was used to define the PMN within individuals. The PMN consistently extended beyond the core posteromedial set to include regions in the inferior parietal lobule; rostral, dorsal, medial, and ventromedial prefrontal cortex; the anterior insula; and ramus marginalis of the cingulate sulcus. The results suggest that, when fine-scale anatomy is considered, the PMN matches the expected distributed architecture of other association networks, reinforcing that parallel distributed networks are an organizing principle of association cortex.

neuroscience↗

bioRxiv2023

High performers demonstrate greater neural synchrony than low performers across behavioral domains

Heterogeneity in brain activity gives rise to heterogeneity in behavior, which in turn comprises our distinctive characteristics as individuals. Studying the path from brain to behavior, however, often requires making assumptions about how similarity in behavior scales with similarity in brain activity. Here, we expand upon recent work which proposes a theoretical framework for testing the validity of such assumptions. Using intersubject representational similarity analysis in two independent movie-watching fMRI datasets, we probe how brain-behavior relationships vary as a function of behavioral domain and participant sample. We find evidence that, in some cases, the neural similarity of two individuals is not correlated with behavioral similarity. Rather, individuals with higher behavioral scores are more similar to other high scorers whereas individuals with lower behavioral scores are dissimilar from everyone else. Ultimately, our findings motivate a more extensive investigation of both the structure of brain-behavior relationships and the tacit assumption that people who behave similarly will demonstrate shared patterns of brain activity.

neuroscience↗

bioRxiv2021

A brain-based universal measure of attention: predicting task-general and task-specific attention performance and their underlying neural mechanisms from task and resting state fMRI

Attention is central for many aspects of cognitive performance, but there is no singular measure of a persons overall attentional functioning across tasks. To develop a universal measure that integrates multiple components of attention, we collected data from more than 90 participants performing three different attention-demanding tasks during fMRI. We constructed a suite of whole-brain models that can predict a profile of multiple attentional components - sustained attention, divided attention and tracking, and working memory capacity - from a single fMRI scan type within novel individuals. Multiple brain regions across the frontoparietal, salience, and subcortical networks drive accurate predictions, supporting a universal (general) attention factor across tasks, which can be distinguished from task-specific attention factors and their neural mechanisms. Furthermore, connectome-to-connectome transformation modeling enhanced predictions of an individuals attention-task connectomes and behavioral performance from their rest connectomes. These models were integrated to produce a new universal attention measure that generalizes best across multiple, independent datasets, and which should have broad utility for both research and clinical applications.

neuroscience↗

bioRxiv2020

A cognitive state transformation model for task-general and task-specific subsystems of the brain connectome

The human brain flexibly controls different cognitive behaviors, such as memory and attention, to satisfy contextual demands. Much progress has been made to reveal task-induced modulations in the whole-brain functional connectome, but we still lack a way to model changes in the brains functional organization. Here, we present a novel connectome-to-connectome (C2C) state transformation framework that enables us to model the brains functional reorganization in response to specific task goals. Using functional magnetic resonance imaging data from the Human Connectome Project, we demonstrate that the C2C model accurately generates an individuals task-specific connectomes from their task-free connectome with a high degree of specificity across seven different cognitive states. Moreover, the C2C model amplifies behaviorally relevant individual differences in the task-free connectome, thereby improving behavioral predictions. Finally, the C2C model reveals how the connectome reorganizes between cognitive states. Previous studies have reported that task-induced modulation of the brain connectome is domain-specific as well as domain-general, but did not specify how brain systems reconfigure to specific cognitive states. Our observations support the existence of reliable state-specific systems in the brain and indicate that we can quantitatively describe patterns of brain reorganization, common across individuals, in a computational model.

neuroscience↗

bioRxiv2020

E prostanoid receptor 4 expressing macrophages promote the regeneration of the intestinal epithelial barrier upon inflammation

Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of resolution of inflammation but the mechanisms underlying their mucosal healing capacity remains elusive. Here, we describe a subset of E prostanoid receptor 4 (EP4) expressing intestinal macrophages with mucosal healing properties both in human and mice. Notably, Csf1r-iCre EP4-fl/fl mice showed defective mucosal healing and intestinal epithelial barrier regeneration in a dextran sodium sulfate-induced colitis model. Mechanistically, an increased mucosal level of prostaglandin E2 (PGE2) triggers the secretion of chemokine (C-X-C motif) ligand 1 (CXCL1) in monocyte-derived EP4+ macrophages via MAPKs. Subsequently, CXCL1 drives epithelial cell differentiation and proliferation from regenerating crypts during the resolution phase of colitis. Thus, EP4+ intestinal macrophages are essential for the support of the intestinal stem cell niche and for the regeneration of the injured epithelium. One Sentence SummaryProstaglandin E2 licenses E-type prostanoid receptor 4 intestinal macrophage regenerative capacity promoting mucosal healing via the secretion of CXCL1

immunology↗

bioRxiv2019

Repetita iuvant: repetition facilitates online planning of sequential movements

Beyond being essential for long-term motor-skill development, movement repetition has immediate benefits on performance, increasing speed and accuracy of a second execution. While repetition effects have been reported for single reaching movements, it has yet to be determined whether they also occur for movement sequences, and what aspects of sequence production are improved. We addressed these questions in two behavioral experiments using a discrete sequence production (DSP) task in which human volunteers had to perform short sequences of finger movements. In Experiment 1, we presented participants with randomly varying sequences and manipulated 1) whether the same sequence was repeated on successive trials, and 2) whether participants had to execute the sequence (Go), or not (No-Go). We establish that sequence repetition led to immediate improvements in speed without associated accuracy costs. The largest benefit was observed in the middle part of a sequence, suggesting that sequence repetition facilitated online planning. This claim was further supported by Experiment 2, in which we kept a set of sequences fixed throughout the experiment, thus allowing participants to develop sequence-specific learning: once the need for online planning decreased, the benefit of repetition disappeared. Finally, we found that repetition-related improvements only occurred for the trials that had been preceded by sequence production, suggesting that action selection and sequence pre-planning may not be sufficient to reap the benefits of repetition. Together, these results show that repetition can enhance representations at the level of movement sequences (rather than of individual movements) and facilitate online planning. New & NoteworthyEven for overlearned motor skills such as reaching, movement repetition improves performance. How brain processes associated with motor planning or execution benefit from repetition, however, remains unclear. Here we report the novel finding of repetition effects for sequential movements. Our results show that repetition benefits are tied to improved online planning of upcoming sequence elements. We also highlight how actual movement experience appears to be more beneficial than mental rehearsal for observing short-term repetition effects.

neuroscience↗

bioRxiv2019

Functional connectivity predicts changes in attention over minutes, days, and months

The ability to sustain attention differs across people and changes within a single person over time. Although recent work has demonstrated that patterns of functional brain connectivity predict individual differences in sustained attention, whether these same patterns capture fluctuations in attention in single individuals remains unclear. Here, across five independent studies, we demonstrate that the sustained attention connectome-based predictive model (CPM), a validated model of sustained attention function, generalizes to predict attention changes across minutes, days, weeks, and months. Furthermore, the sustained attention CPM is sensitive to within-subject state changes induced by propofol as well as sevoflurane, such that individuals show functional connectivity signatures of stronger attentional states when awake than when under deep sedation and light anesthesia. Together these results demonstrate that fluctuations in attentional state reflect variability in the same functional connectivity patterns that predict individual differences in sustained attention.

neuroscience↗