Biology subjects

Chan, R. W.

Publications and source records attributed to Chan, R. W..

4 recordsLinked to original sources

bioRxiv2021

Global and network functional connectivity of nucleus basalis of Meynert is strengthened in blind individuals

Plasticity in the brain is differentially affected by age of blindness onset. One possible, but not yet identified mechanism is that the cholinergic signals originating from the nucleus basalis of Meynert may underlie differential extent of plasticity in early and late blind individuals. This prospect is based on the fact that the nucleus basalis of Meynert modulates cortical processes such as plasticity and sensory encoding and that the degree of cross-modal plasticity varies depending on the age of blindness onset. However, this question yet remains largely unclear. Here, we tested whether the early and late blind individuals develop dissociable plasticity in the nucleus basalis of Meynert using multi-parametric magnetic resonance imaging. We found the relatively preserved volumetric size and cerebrovascular reactivity, but significant disruption in the white matter integrity of the nucleus basalis of Meynert in both early and late blind individuals. Critically, despite its reduction in the white matter integrity, the nucleus basalis of Meynert of early blind individuals presented greater global and network functional connectivity including visual, language, and default-mode networks. Such changes in the functional connectivity were not observed in the late-blind individuals. Further, less duration of the visual experience was associated with greater global and network functional connectivity. These results indicate that the nucleus basalis of Meynert is differentially involved in the plasticity of early and late blind individuals - a similar amount of reduction in microstructural integrity in early and late blind individuals, but stronger and more widespread functional connectivity of the NBM in the early blind individuals. Our findings suggest that the nucleus basalis of Meynert may develop greater cholinergic influence on the cortex of early blind individuals. Such change may explain why early blind individuals present stronger and more widespread cross-modal plasticity during non-visual tasks compared to late blind individuals.

neuroscience↗

bioRxiv2021

Deuterium Magnetic Resonance Spectroscopy of Early Treatment-Induced Changes in Tumour Lactate in vitro

Elevated production of lactate is a key characteristic of aberrant tumour cell metabolism and can be non-invasively measured as an early marker of tumour response using deuterium (2H) magnetic resonance spectroscopy (MRS). Following treatment, changes in the 2H-labeled lactate signal could identify tumour cell death or impaired metabolic function, which precede morphological changes conventionally used to assess tumour response. In this work, the association between apoptotic cell death, extracellular lactate concentration, and early treatment-induced changes in the 2H-labeled lactate signal was established in an in vitro tumour model. Experiments were conducted at 7 T on acute myeloid leukemia cells which had been treated with 10 {micro}g/mL of the chemotherapeutic agent cisplatin. At 24 and 48 hours after cisplatin treatment, the cells were injected with 20 mM of [6,6-2H2]glucose and scanned over two hours using a two-dimensional 2H MR spectroscopic imaging sequence. The resulting signals from 2H-labeled glucose, lactate, and water were quantified using a spectral fitting algorithm implemented on the OXford Spectroscopy Analysis (OXSA) MATLAB toolbox. After scanning, the cells were processed for histological stains (TUNEL [terminal deoxynucleotidyl transferase UTP nick end labeling] and H&E [hematoxylin and eosin]) to assess apoptotic area fraction and cell morphology respectively, while a colorimetric assay was used to measure extracellular lactate concentrations in the supernatant. Significantly lower levels of 2H-labeled lactate were observed in the 48-hour treated cells compared to the untreated and 24-hour treated cells, and these changes were significantly correlated with an increase in apoptotic fraction and a decrease in extracellular lactate. By establishing the biological processes associated with treatment-induced changes in the 2H-labeled lactate signal, these findings suggest that 2H MRS of lactate may be valuable in evaluating early tumour response.

biophysics↗

bioRxiv2020

Temporal patterns in the evolutionary genetic distance of SARS-CoV-2 during the COVID-19 pandemic

BackgroundDuring the pandemic of coronavirus disease 2019 (COVID-19), the genetic mutations occurred in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cumulatively or sporadically. In this study, we employed a computational approach to identify and trace the emerging patterns of the SARS-CoV-2 mutations, and quantify accumulative genetic distance across different periods and proteins. MethodsFull-length human SARS-CoV-2 strains in United Kingdom were collected. We investigated the temporal variation in the evolutionary genetic distance defined by the Hamming distance since the start of COVID-19 pandemic. FindingsOur results showed that the SARS-CoV-2 was in the process of continuous evolution, mainly involved in spike protein (S protein), the RNA-dependent RNA polymerase (RdRp) region of open reading frame 1 (ORF1) and nucleocapsid protein (N protein). By contrast, mutations in other proteins were sporadic and genetic distance to the initial sequenced strain did not show an increasing trend.

bioinformatics↗

bioRxiv2020

Characterization of the evolutionary dynamics of influenza A H3N2 hemagglutinin

Virus evolution drives the annual influenza epidemics in human population worldwide. However, it has been challenging to evaluate the mutation effect of the influenza virus on evading the population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics by the effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by the effective mutation periods (EMPs). Extensive analysis is performed on the genome and epidemiology data of 13-year worldwide H3N2 epidemics involving nine regions in four continents. We showed that the identified EM processed similar profile in geographically adjacent regions, while only 40% are common to Europe, North America, Asia and Oceania, indicating that the regional specific mutations also contributed significantly to the global H3N2 epidemics. The mutation dynamics calibrated that around 90% of the common EMs underlying global epidemics were originated from South East Asia, led by Thailand and India, and the rest were originated from North America. New Zealand was found to be the dominate sink region of H3N2 circulation, followed by UK. All regions might act as the intersection in the H3N2 transmission network. The proposed methodology provided a way to characterize key amino acids from the genetic epidemiology point of view. This approach is not restricted by the genomic region or type of the virus, and will find broad applications in identifying therapeutic targets for combating infectious diseases.

evolutionary biology↗