Biology subjects

Kim, D.-Y.

Publications and source records attributed to Kim, D.-Y..

6 recordsLinked to original sources

bioRxiv2024

PIEZO acts in an intestinal valve to regulate swallowing in C. elegans

Sensations of the internal state of the body play crucial roles in regulating the physiological processes and maintaining homeostasis of an organism. However, our understanding of how internal signals are sensed, processed, and integrated to generate appropriate biological responses remains limited. Here, we show that the C. elegans PIEZO channel, encoded by pezo-1, regulates food movement in the intestine by detecting food accumulation in the anterior part of the intestinal lumen, thereby triggering rhythmical movement of the pharynx, referred to as the pharyngeal plunge. pezo-1 deletion mutants exhibit defects in the pharyngeal plunge, which is rescued by PEZO-1 or mouse PIEZO1 expression, but not by PIEZO2, in a single isolated non-neuronal tissue of the digestive tract, the pharyngeal-intestinal valve. Genetic ablation or optogenetic activation of this valve inhibits or induces the pharyngeal plunge, respectively. Moreover, pressure built in the anterior lumen of the intestine results in a pezo-1-dependent pharyngeal plunge, which is driven by head muscle contraction. These findings illustrate how interoceptive processes in a digestive organ regulate swallowing through the PIEZO channel, providing insights into how interoception coordinates ingestive processes in higher animals, including humans.

neuroscience↗

bioRxiv2020

Determinants of Real-Time fMRI Neurofeedback Performance and Improvement: a Machine Learning Mega-Analysis

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in Open Science and data sharing.

neuroscience↗

bioRxiv2020

CREB mediates the C. elegans dauer polyphenism through direct and cell-autonomous regulation of TGF-β expression

Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larva and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-{omega}C3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-{beta} locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.

developmental biology↗

bioRxiv2020

Can we predict real-time fMRI neurofeedback learning success from pre-training brain activity?

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large interindividual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pre-training functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pre-training activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.

neuroscience↗

bioRxiv2019

Unveiling the crucial role of type IV secretion system and motility of Helicobacter pylori in IL-1β production via NLRP3 inflammasome activation in neutrophils

Helicobacter pylori is a gram-negative, microaerophilic, and spiral-shaped bacterium and causes gastrointestinal diseases in human. IL-1{beta} is a representative cytokine produced in innate immune cells and is considered to be a key factor in the development of gastrointestinal malignancies. However, the mechanism of IL-1{beta} production by neutrophils during H. pylori infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of H. pylori-induced IL-1{beta} production in neutrophils. We found that H. pylori-induced IL-1{beta} production is abolished in NLRP3-, ASC-, and caspase-1/11-deficient neutrophils, suggesting essential role for NLRP3 inflammasome in IL-1{beta} response against H. pylori. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1{beta} as well as secretion of IL-1{beta}. H. pylori lacking cagL, a key component of the type IV secretion system (T4SS), induced less IL-1{beta} production in neutrophils than did its isogenic WT strain, whereas vacA and ureA were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1{beta} maturation in H. pylori-infected neutrophils. We also found that FlaA is essential for H. pylori-mediated IL-1{beta} production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for H. pylori-induced IL-1{beta} production in neutrophils. Instead, bacterial motility is essential for the production of IL-1{beta} in response to H. pylori. In conclusion, our study shows that host TLR2 and NLRP3 inflammasome and bacterial T4SS and motility are essential factors for IL-1{beta} production by neutrophils in response to H. pylori.\n\nIMPORTANCEIL-1{beta} is a representative pro-inflammatory cytokine and is considered to be a central host factor for the development of gastric cancers. Although neutrophils have been considered to be involved in H. pylori-induced gastric inflammation, the underlying mechanism by which H. pylori triggers IL-1{beta} production in neutrophils remains to be defined. In this study, our data suggested a critical role for the host TLR2 and NLRP3 inflammasome in IL-1{beta} production by neutrophil during H. pylori infection. Moreover, we found the bacterial factors, T4SS and FlaA, to be essential for IL-1{beta} production and NLRP3 activation during the course of H. pylori infection. Our current findings provide detailed molecular genetic mechanisms associated with IL-1{beta} production in neutrophils in response to H. pylori infection, which can serve as innovative anti-inflammatory targets to reduce H. pylori-induced gastric malignancies.

immunology↗

bioRxiv2018

Molecular measurable residual disease testing of blood during AML cytotoxic therapy for early prediction of clinical response

AbstractO_ST_ABSPURPOSEC_ST_ABSMeasurable residual disease (MRD) testing after initial chemotherapy treatment can predict relapse and survival in AML. However, it has not been established if repeat molecular or genetic testing during chemotherapy can offer information regarding the chemotherapy sensitivity of the leukemic clone.\n\nPATIENTS AND METHODSBlood from 45 adult AML patients at day 1 and 4 of induction (n = 35) or salvage (n = 10) cytotoxic chemotherapy was collected for both quantitative real-time PCR (qPCR) assessment (WT1) and next generation sequencing (NGS, >500x depth) of 49 gene regions recurrently mutated in MDS/AML.\n\nRESULTSThe median age was 62 (23-78); 42% achieved a complete response. WT1 was overexpressed in most patients tested but was uninformative for very early MRD assessment. A median of 4 non-synonymous variants (range 0-7) were detected by DNA sequencing of blood on day 1 of therapy (median VAF: 29%). Only two patients had no variants detectable. All mutations remained detectable in blood on day 4 of intensive chemotherapy and remarkably the ratio of mutated to wild-type sequence was often maintained. This phenomenon was not limited to variants in DNMT3A, TET2 and ASXL1. The kinetics of NPM1 and TP53 variant burden early during chemotherapy appeared to be exceptions and exhibited consistent trends in this cohort.\n\nCONCLUSIONSMolecular testing of blood on day 4 of chemotherapy is not predictive of clinical response in AML. The observed stability in variant allele frequency suggests that cytotoxic therapy may have a limited therapeutic index for clones circulating in blood containing these mutations. Further validation is required to confirm the utility of monitoring NPM1 and TP53 kinetics in blood during cytotoxic therapy.

cancer biology↗