Biology subjects

Chang, H.-H.

Publications and source records attributed to Chang, H.-H..

8 recordsLinked to original sources

bioRxiv2023

Mechanical transmission of Dengue Virus by Aedes aegypti may influence disease transmission dynamics during outbreaks

The escalating number of dengue virus (DENV) outbreaks and their worldwide spread pose a major threat to global public health. DENV transmission dynamics significantly influence outbreak duration and magnitude. Conventional DENV transmission requires an incubation period between mosquitoes biting infected humans and the mosquitoes becoming infectious. However, the possibility of immediate, mechanical transmission of DENV without viral replication in the mosquito has received little attention despite its potential importance. Here, we show that Aedes aegypti mosquitoes can mechanically transmit DENV to susceptible mice immediately after biting infected mice without the need for an incubation period. By incorporating parameters from our experiments into a newly developed mathematical model, we found a significant impact on DENV outbreak characteristics. Mechanical transmission may amplify existing disease transmission routes and influence outbreak dynamics. Our findings have implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes.

microbiology↗

bioRxiv2022

The evolution and structure of snake venom phosphodiesterase (svPDE) highlight its importance in venom actions

For decades, studies of snake venoms focused on the venom-ome-specific toxins (VSTs). VSTs are dominant soluble proteins believed to contribute to the main venomous effects and emerged into gene clusters for fast adaptation and diversification of snake venoms. However, the conserved minor venom components, such as snake venom phosphodiesterase (svPDE), remain largely unexplored. Here, we focus on svPDE by genomic and transcriptomic analysis across snake clades and demonstrate that soluble svPDE is co-opted from the ancestral membrane-attached ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3) gene by replacing the original 5 exon with the exon encoding a signal peptide. Notably, the exons, promoters and transcription/translation starts have been replaced multiple times during snake evolution, suggesting the evolutionary necessity of svPDE. The structural and biochemical analyses also show that svPDE shares the similar functions with ENPP family, suggesting its perturbation to the purinergic signaling and insulin transduction in venomous effects. Significance StatementWe provided a case of the evolutionary co-option strategy in which the secretory svPDE, one of the minor venom components, is generated from the ancestral membrane-anchored ENPP3 gene by using an alternative 5 exon. The first exon of the svPDE transcript encodes a signal peptide instead of the transmembrane domain of the ENPP3. Multiple replacement events of genomic elements during snake evolution maintain the expression of the svPDE transcripts, suggesting the crucial function of svPDE. Also, the structures and biochemical analyses indicate that svPDE reuse the original functions of ENPP3 in the bitten tissues and may interfere with normal cell signaling. Together, our study reveals the evolution of svPDE and suggests the importance of minor venom components.

evolutionary biology↗

bioRxiv2021

Distinguishing gene flow between malaria parasite populations

Measuring gene flow between malaria parasite populations in different geographic locations can provide strategic information for malaria control interventions. Multiple important questions pertaining to the design of such studies remain unanswered, limiting efforts to operationalize genomic surveillance tools for routine public health use. This report evaluates numerically the ability to distinguish different levels of gene flow between malaria populations, using different amounts of real and simulated data, where data are simulated using parameters that approximate different epidemiological conditions. Specifically, using Plasmodium falciparum whole genome sequence data and sequence data simulated for a metapopulation with different migration rates and effective population sizes, we compare two estimators of gene flow, explore the number of genetic markers and number of individuals required to reliably rank highly connected locations, and describe how these thresholds change given different effective population sizes and migration rates. Our results have implications for the design and implementation of malaria genomic surveillance efforts.

genomics↗

bioRxiv2019

Evaluating the performance of malaria genomics for inferring changes in transmission intensity using transmission modelling

Advances in genetic sequencing and accompanying methodological approaches have resulted in pathogen genetics being used in the control of infectious diseases. To utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment. Here we develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The best performing model successfully predicted malaria prevalence with mean absolute error of 0.055, suggesting genetic tools could be used for monitoring the impact of malaria interventions.

genetics↗

bioRxiv2019

Plant A20/AN1 proteins coordinate different immune responses including RNAi pathway for antiviral immunity

Salicylic acid (SA)-mediated immunity plays important roles in combating virus in plants. Two plant stress associated protein (SAPs) containing dual A20/AN1 zinc-finger domain were found to play important roles in SA-mediated immunity; however, detailed mechanisms remain elusive. In this study, another orchid homolog gene of Pha13, Pha21, was analyzed. Pha21 confers antiviral immunity in both transgenic orchid and Arabidopsis overexpressing Pha21. Expression of Pha21 is early-induced by SA treatment, and is involved in the expression of the orchid homolog of the master regulator NPR1. Pha21 but not Pha13 is involved in the expression of key RNAi-related genes, Dicer-like nuclease 4 (DCL4) and Argonaut 1 (AGO1) in orchids. The involvement of SAPs in expression of orchid DCL4 and AGO1 is not limited to orchid, as AtSAP5 also plays essential role in the expression of Arabidopsis DCL4 and AGO1. However, unlike Pha13 and AtSAP5, Pha21 does not play positive role in the expression of orchid homolog gene of RNA-dependent RNA polymerase 1 (RdR1), an important gene in RNAi pathway. Pha21 can be found localized in the nucleus, and confers self-E3 ligase and ubiquitin binding activities. Functional domain analysis revealed that both A20 and AN1 domains of Pha21 are required for decreasing virus accumulation, and the AN1 domain plays a more important role in the expression of orchid DCL4. Collectively, our data suggests SA regulated SAPs play important roles in antiviral immunity and is involved in delicate regulation of key genes in RNAi-mediated pathway.\n\nIMPORTANCESalicylic acid (SA)-mediated antiviral immunity plays an important role to protect plants from virus infection; however, the detailed mechanisms remain elusive. We previously demonstrated that two plant A20/AN1 proteins, orchid Pha13 and Arabidopsis AtSAP5, function similarly and serve as an important hub to regulate SA-mediated antiviral immunity. In this study, we identified another orchid A20/AN1 protein, Pha21, which is involved in SA-mediated antiviral immunity. In contrast to Pha13 and AtSAP5, Pha21 plays minor negative roles in the expression of PhaRdR1 (orchid homolog of RNA-dependent RNA polymerase 1). However, Pha21 and AtSAP5, but not Pha13, are involved in the expression of important players in RNAi pathway, Dicer-like nuclease 4 (DCL4) and Argonaut 1 (AGO1), in orchid and Arabidopsis. Our data demonstrates that plant A20/AN1 proteins are conserved players in SA-mediated antiviral resistance among plants, and provide links between the A20/AN1 proteins and the RNAi pathway.

plant biology↗

bioRxiv2019

Utilizing a PTPN22 gene signature to predict response to targeted therapies in rheumatoid arthritis

Despite the development of several targeted therapies for rheumatoid arthritis (RA), there is still no reliable drug-specific predictor to assist rheumatologists in selecting the most effective targeted therapy for each patient. Recently, a gene signature caused by impaired induction of PTPN22 in anti-CD3 stimulated peripheral blood mononuclear cells (PBMC) was observed in healthy at-risk individuals. However, the downstream target genes of PTPN22 and the molecular mechanisms regulating its expression are still poorly understood. Here we report that the PTPN22 gene signature is also present in PBMC from patients with active RA and can be reversed after effective treatment. The expression of PTPN22 correlates with that of more than 1000 genes in Th cells of anti-CD3 stimulated PBMC of healthy donors and is inhibited by TNF or CD28 signals, but not IL-6, through distinct mechanisms. In addition, the impaired induction of PTPN22 in PBMC of patients with active RA can be normalized in vitro by several targeted therapies. More importantly, the in vitro normalization of PTPN22 expression correlates with clinical response to the targeted therapies in a longitudinal RA cohort. Thus, in vitro normalization of PTPN22 expression by targeted therapies can potentially be used to predict clinical response in a drug-specific manner.

immunology↗

bioRxiv2018

The geography of malaria elimination in Bangladesh: combining data layers to estimate the spatial spread of parasites

Malaria control programs face difficult resource allocation decisions. Of particular concern for countries aiming for malaria elimination, the regular movement of individuals to and from endemic areas undermines local interventions by reintroducing infections and sustaining local transmission. Quantifying this movement of malaria parasites around a country has become a priority for national control programs, but remains methodologically challenging, particularly in areas with highly mobile populations. Here, we combined multiple data sources to measure the geographical spread of malaria parasites, including epidemiological surveillance data, travel surveys, parasite genetic data, and anonymized mobile phone data. We collected parasite genetic barcodes and travel surveys from 2,090 patients residing in 176 unions in southeast Bangladesh. We developed a genetic mixing index to quantify the likelihood of samples being local or imported. We then inferred the direction and intensity of parasite flow between locations using an epidemiological model, and estimated the proportion of imported cases assuming mobility patterns parameterized using the travel survey and mobile phone calling data. Our results show that each data source provided related but different information about the patterns of geographic spread of parasites. We identify a consistent north/south separation of the Chittagong Hill Tracts region in Bangladesh, and found that in addition to imported infections from forested regions, frequent mixing also occurs in low transmission but highly populated areas in the southwest. Thus, unlike risk maps generated from incidence alone, our maps provide evidence that elimination programs must address ongoing movement of parasites around the lower transmission areas in the southwest.

epidemiology↗

bioRxiv2018

Mapping malaria by combining parasite genomic and epidemiologic data

Recent global progress in scaling up malaria control interventions has revived the goal of complete elimination in many countries. Decreasing transmission intensity generally leads to increasingly patchy spatial patterns of malaria transmission, however, and control programs must accurately identify remaining foci in order to target interventions efficiently. In particular, mosquito control interventions like bed nets and insecticide spraying are best targeted to transmission hotspots, and the role of connectivity between different pockets of local transmission becomes increasingly important since humans are able to move parasites beyond the limits of mosquito dispersal and re-introduce parasites to previously malaria-free regions. Quantifying the connectivity between regions due to human travel, measuring malaria transmission intensity in different areas, and monitoring parasite spatial spread are therefore key issues for policy-makers because they underpin the feasibility of elimination and inform the path to its attainment. To this end, recent efforts have been made to develop new approaches to incorporating human mobility into spatial epidemiological models, for example using mobile phone data, and there has been a surge of interest in collecting spatially informative parasite samples to measure the genomic signatures of parasite connectivity. Due to their complicated life-cycles, Plasmodium parasites pose unique challenges to researchers in this respect and new methods that move beyond traditional phylogenetic and population genetic tools must be developed to harness genetic information effectively. Here, we discuss the spatial epidemiology of malaria in the context of transmission-reduction interventions, and the challenges and promising directions for the development of integrated mapping, modeling, and genomic approaches that leverage disparate data sets to measure both connectivity and transmission.

epidemiology↗