Biology subjects

Chiang, C.-H.

Publications and source records attributed to Chiang, C.-H..

6 recordsLinked to original sources

bioRxiv2026

Semirandom DNA adducts regulate a filamentous defence-associated reverse transcriptase

Retrons and several defence-associated reverse transcriptases (DRTs) synthesize non-genomic DNA for bacteriophage immunity. In some instances, this non-genomic DNA is of undefined, semirandom sequence. How undefined DNA sequences impart antiphage defence is not known. Here we report the cryo-EM structure and functional characterization of the DRT1 antiphage defence system. We show that DRT1 performs template-free, protein-primed DNA synthesis to generate semirandom DNA adducts. DNA synthesis activates the nitrilase domain of DRT1 while DNA adducts drive assembly of quiescent DRT1 filaments. Filamentous DRT1 is comprised of domain-swapped C-termini that are entwined, forming pseudoknots between tetrameric stacks. This configuration occludes the apo-nitrilase active site, resulting in a dormant state. Bacteriophage escape mutants identify a T4 single-stranded DNA helicase required for DRT1 activity. Functionally, DRT1 resembles a minimal retron where a single gene produces an RT, effector, and non-genomic antitoxin DNA.

microbiology↗

bioRxiv2024

Neural mechanisms of the transition from planning to execution in speech production

Speaking is the primary way that humans communicate. This communication is enabled by a production system that can plan and execute unique combinations of speech sounds. Although a distributed network of brain regions has been implicated in speaking, it is unclear how planning and execution of speech are coordinated to produce meaningful sounds. Leveraging the high spatio-temporal resolution of intracranial recordings at different spatial scales, we show distinct neural mechanisms that facilitate speech planning and execution. During planning, different levels of speech units are coded discretely at distinct prefrontal sites. These planned units are then dynamically integrated at various cortical levels to guide subsequent execution. During speech execution, speech motor regions generate continuous sequences that reflect both discrete speech sound units and their transitional properties between units. This rapid neural transition from discrete speech units to motor sequences links speech planning with execution and enables our effortless ability to speak.

neuroscience↗

bioRxiv2023

Cerebellar Activity in Hemi-Parkinsonian Rats during Volitional Gait and Freezing

Parkinsons disease is a neurodegenerative disease characterized by gait dysfunction in the advanced stages of the disease. The unilateral 6-OHDA toxin-induced model is the most studied animal model of Parkinsons disease, which reproduces gait dysfunction after greater than 68% dopamine (DA) loss in the substantia nigra pars compacta (SNc). The extent to which the neural activity in hemi-parkinsonian rats correlates to gait dysfunction and DAergic cell loss is not clear. In this paper we report the effects of unilateral DA depletion on cerebellar vermis activity using micro-electrocorticography (ECoG) during walking and freezing on a runway. Gait and neural activity were measured in 6-OHDA lesioned and sham lesioned rats at 14d, 21d, and 28d after infusion of 6-OHDA or control vehicle into the medial forebrain bundle (MFB) (n=20). Gait deficits in 6-OHDA rats were different from sham rats at 14d (p<0.05). Gait deficits in 6-OHDA rats improved at 21d and 28d except for run speed, which decreased at 28d (p=0.018). No differences in gait deficits were observed in sham lesioned rats at any time points. Hemiparkinsonian rats showed hyperactivity in the cerebellar vermis at 21d (p<0.05), but not at 14d and 28d, and the activity was reduced during freezing epochs in lobules VIa, VIb, and VIc (p<0.05). These results suggest that DAergic cell loss causes pathological cerebellar activity at 21d postlesion and suggests that compensatory mechanisms from the intact hemisphere contribute to normalized cerebellar activity at 28d. The decrease in cerebellar oscillatory activity during freezing may be indicative of neurological changes during freezing of gait in Parkinsons disease patients making this region a potential location for biomarker detection. Although the unilateral 6-OHDA model presents gait deficits that parallel clinical presentations of Parkinsons disease, further studies in animal models of bilateral DA loss are needed to understand the role of the cerebellar vermis in Parkinsons disease.

neuroscience↗

bioRxiv2023

Cerebellar Activity in PINK1 Knockout Rats during Volitional Gait

Preclinical models of Parkinsons disease are imperative to gain insight into the neural circuits that contribute to gait dysfunction in advanced stages of the disease. The PTEN-induced putative kinase 1 (P1) knockout (KO) early onset model of Parkinsons disease may be a useful rodent model to study the effects of neurotransmitter degeneration caused by loss of P1 function on brain activity during volitional gait. The goal of this study was to measure changes in neural activity at the cerebellar vermis (CBLv) at 8 months of age. Gait deficits, except run speed, were not significantly different from age-matched wild-type (WT) controls as previously reported. P1KO (n=4) and WT (n=4) rats were implanted with a micro-electrocorticographic array placed over CBLv lobules VI (a, b, and c) and VII. Local field potential recordings were obtained during volitional gait across a runway. Power spectral analysis and coherence analysis were used to quantify network oscillatory activity in frequency bands of interest. CBLv power was hypoactive in the beta (VIb, VIc, and VII) and alpha (VII) bands at CBLv lobules VIb, VIc, and VII in P1KO rats compared to WT controls during gait (p<0.05). These results suggest that gait improvement in P1KO rats at 8 months may be a compensatory mechanism attributed to movement corrections caused by decreased inhibition of the alpha band of CBLv lobule VII and beta band of lobules VIb, VIc, and VII. The P1KO model may be a valuable tool for understanding the circuit mechanisms underlying gait dysfunction in early-onset Parkinsons disease patients with functional loss of P1. Future studies investigating the CBLv as a potential biomarker and therapeutic target for the treatment of gait dysfunction in Parkinsons disease are warranted.

neuroscience↗

bioRxiv2022

Accurate speech decoding requires high-resolution neural interfaces

Patients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One promising solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals. To resolve this limitation, we performed novel, high-resolution, micro-electrocorticographic (ECoG) neural recordings during intra-operative speech production. We obtained neural signals with 57x higher spatial resolution and 48% higher signal-to-noise ratio compared to standard invasive recordings. This increased signal quality improved phoneme decoding by 35% compared to standard intracranial signals. Accurate decoding was dependent on the high-spatial resolution of the neural interface. Non-linear decoding models designed to utilize enhanced spatio-temporal neural information produced better results than linear techniques. We show for the first time that ECoG can enable high-quality speech decoding, demonstrating its ability to improve neural interfaces for neural speech prostheses.

neuroscience↗

bioRxiv2020

Two-photon microscopy at >500 volumes/second

We demonstrate a multi-focal multi-photon volumetric microscopy via combination of 32-beam parallel lateral-scanning, a 70-kHz axial-scanning acoustic lens, and a 32-channel photodetector, enabling unprecedented data rate (2-10 GHz) and >500-volumes/second imaging speed over ~200x200x200-m3.

biophysics↗