Biology subjects

Chen, Y.-c.

Publications and source records attributed to Chen, Y.-c..

4 recordsLinked to original sources

bioRxiv2023

Uncovering the Roles of Mycobacterium tuberculosis melH in Redox and Bioenergetic Homeostasis: Implications for Antitubercular Therapy

Mycobacterium tuberculosis (Mtb), the pathogenic bacterium that causes tuberculosis, has evolved sophisticated defense mechanisms to counteract the cytotoxicity of reactive oxygen species (ROS) generated within host macrophages during infection. The melH gene in Mtb and Mycobacterium marinum (Mm) plays a crucial role in defense mechanisms against ROS generated during infection. We demonstrate that melH encodes an epoxide hydrolase and contributes to ROS detoxification. Deletion of melH in Mm resulted in a mutant with increased sensitivity to oxidative stress, increased accumulation of aldehyde species, and decreased production of mycothiol and ergothioneine. This heightened vulnerability is attributed to the increased expression of whiB3, a universal stress sensor. The absence of melH also resulted in reduced intracellular levels of NAD+, NADH, and ATP. Bacterial growth was impaired, even in the absence of external stressors, and the impairment was carbon-source-dependent. Initial MelH substrate specificity studies demonstrate a preference for epoxides with a single aromatic substituent. Taken together, these results highlight the role of melH in mycobacterial bioenergetic metabolism and provide new insights into the complex interplay between redox homeostasis and generation of reactive aldehyde species in mycobacteria. ImportanceThis study unveils the pivotal role played by the melH gene in Mycobacterium tuberculosis and Mycobacterium marinum in combatting the detrimental impact of oxidative conditions during infection. This investigation revealed notable alterations in the level of cytokinin-associated aldehyde, para-hydroxybenzaldehyde, as well as the redox buffer ergothioneine, upon deletion of melH. Moreover, changes in crucial cofactors responsible for electron transfer highlighted melHs crucial function in maintaining a delicate equilibrium of redox and bioenergetic processes. MelH prefers epoxide small substrates with a phenyl substituted substrate. These findings collectively emphasize the potential of melH as an attractive target for the development of novel antitubercular therapies that sensitize mycobacteria to host stress, offering new avenues for combating tuberculosis.

microbiology↗

bioRxiv2021

Postsynaptic plasticity of cholinergic synapses underlies the induction and expression of appetitive memories in Drosophila

In vertebrates, several forms of memory-relevant synaptic plasticity involve postsynaptic rearrangements of glutamate receptors. In contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic plasticity of cholinergic synapses. Here, we provide evidence for postsynaptic plasticity at cholinergic output synapses from the Drosophila mushroom bodies (MBs). We find that the nicotinic acetylcholine receptor (nAChR) subunit 5 is required within specific MB output neurons (MBONs) for appetitive memory induction, but is dispensable for aversive memories. In addition, nAChR 2 subunits mediate memory expression and likely functions downstream of 5 and the postsynaptic scaffold protein Dlg. We show that postsynaptic plasticity traces can be induced independently of the presynapse, and that in vivo dynamics of 2 nAChR subunits are changed both in the context of associative and non-associative memory formation, underlying different plasticity rules. Therefore, regardless of neurotransmitter identity, key principles of postsynaptic plasticity support memory storage across phyla.

neuroscience↗

bioRxiv2021

A quick and versatile protocol for the 3D visualization of transgene expression across the whole body of larval Drosophila

Larval Drosophila are used as a genetically accessible study case in many areas of biological research. Here we report a fast, robust and user-friendly procedure for the whole-body multifluorescence imaging of Drosophila larvae; the protocol has been optimized specifically for larvae by systematically tackling the pitfalls associated with clearing this small but cuticularized organism. Tests on various fluorescent proteins reveal that the recently introduced monomeric infrared fluorescent protein (mIFP) is particularly suitable for our approach. This approach comprises an effective, low-cost clearing protocol with minimal handling time and reduced toxicity in the reagents employed. It combines a success rate high enough to allow for small-scale screening approaches and a resolution sufficient for cellular-resolution analyses with light sheet and confocal microscopy. Given that publications and database documentations typically specify expression patterns of transgenic driver lines only within a given organ system of interest, the present procedure should be versatile enough to extend such documentation systematically to the whole body. As examples, the expression patterns of transgenic driver lines covering the majority of neurons, or subsets of chemosensory, central brain or motor neurons, are documented in the context of whole larval body volumes (using nsyb-Gal4, IR76b-Gal4, APL-Gal4 and mushroom body Kenyon cells, or OK371-Gal4, respectively). Notably, the presented protocol allows for triple-color fluorescence imaging with near-infrared, red and yellow fluorescent proteins.

neuroscience↗

bioRxiv2018

Population Pharmacokinetics Study of Morinidazole in Patients with Moderate Hepatic Impairment

ObjectiveMorinidazole is a novel third generation 5-nitroimidazole antimicrobial drug which has demonstrated substantial antibacterial activity against clinical isolates of anaerobe. The aim of this study was to build population pharmacokinetic (PPK) model of morinidazole among patients with hepatic impairment and to provide dosage adjustment strategy for morinidazole in patients with hepatic impairment and/or renal dysfunction.\n\nMethodsThe nonlinear mixed effects modeling tool NONMEM (version7.3, ICON Development Solutions) was used to develop the PPK model of morinidazole.\n\nResultsOne-compartment model was conducted to establish the morinidazole PPK model. Disease condition was the significant covariate for CL and weight was the significant covariate for V. The AUC0-{infty} was 120.44{+/-}37.05 (79.25-207.20) gxh/mL in hepatic impairment group and was 79.46{+/-}23.71 (42.94-116.75) gxh/mL in control group. The AUC0-{infty} was 164.9{+/-}44.8 gxh/mL and 77.2{+/-}23.1 gxh/mLin in the 3 subjects with both hepatic impairment and mild renal impairment and in the 3 matched healthy subjects, respectively.\n\nConclusionIt is not necessary to adjust morinidazole dosage for patients with moderate hepatic impairment without confirmed renal dysfunction. For patient with moderate hepatic and mild renal impairment, morinidazole regimen should be considered as 500mg every 24 hours. When used in patients with moderate/severe hepatic impairment combined with renal dysfunction, both dosage and interval adjustment of morinidazole should be considered.

pharmacology and toxicology↗