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Fulltext Implication of single year seasonal sampling to genetic diversity fluctuation that coordinates with oceanographic dynamics in torpedo scads near Taiwan

Su YC, Su SH, Li HY, Wang HY, Lee SC

Sci Rep, 2020 10 08;10(1):16829.
PMID: 33033371 DOI: 10.1038/s41598-020-74025-9

Many fisheries management and conservation plans are based on the genetic structure of organisms in pelagic ecosystems; however, these structures tend to vary over time, particularly in cyclic ocean currents. We performed genetic analyses on the populations of the pelagic fish, Megalaspis cordyla (Osteichthyes: Carangidae) in the area surrounding Taiwan during 2000-2001. Genotyping was performed on M. cordyla collected seasonally around Taiwan as well as specimens collected from Singapore (Malacca strait) and Indonesia (Banda Sea). Gonadosomatic indices (GSI) revealed that M. cordyla does not spawn near Taiwan. Data related to the mitochondrial control region revealed that the samples from Singapore and Indonesia represented two distinct genetic cohorts. Genotyping revealed that during the summer (June-August 2000), the Indonesian variant was dominant in eastern Taiwan (presumably following the Kuroshio Current) and in the Penghu region (following the Kuroshio Branch Current). During the same period, the Singapore genotype was dominant along the western coast of Taiwan (presumably following the South China Sea Current); however, the number dropped during the winter (December-February 2001) under the effects of the China Coast Current. Divergence time estimates indicate that the two genetic cohorts split during the last glacial maximum. Despite the fact that these results are based on sampling from a single year, they demonstrate the importance of seasonal sampling in unravelling the genetic diversity in pelagic ecosystems.
Fulltext An online time-to-event dashboard comparing the effective control of COVID-19 among continents using the inflection point on an ogive curve: Observational study

Lee KW, Chien TW, Yeh YT, Chou W, Wang HY

Medicine (Baltimore), 2021 Mar 12;100(10):e24749.
PMID: 33725830 DOI: 10.1097/MD.0000000000024749

BACKGROUND: During the COVID-19 pandemic, one of the frequently asked questions is which countries (or continents) are severely hit. Aside from using the number of confirmed cases and the fatality to measure the impact caused by COVID-19, few adopted the inflection point (IP) to represent the control capability of COVID-19. How to determine the IP days related to the capability is still unclear. This study aims to (i) build a predictive model based on item response theory (IRT) to determine the IP for countries, and (ii) compare which countries (or continents) are hit most.
METHODS: We downloaded COVID-19 outbreak data of the number of confirmed cases in all countries as of October 19, 2020. The IRT-based predictive model was built to determine the pandemic IP for each country. A model building scheme was demonstrated to fit the number of cumulative infected cases. Model parameters were estimated using the Solver add-in tool in Microsoft Excel. The absolute advantage coefficient (AAC) was computed to track the IP at the minimum of incremental points on a given ogive curve. The time-to-event analysis (a.k.a. survival analysis) was performed to compare the difference in IPs among continents using the area under the curve (AUC) and the respective 95% confidence intervals (CIs). An online comparative dashboard was created on Google Maps to present the epidemic prediction for each country.
RESULTS: The top 3 countries that were hit severely by COVID-19 were France, Malaysia, and Nepal, with IP days at 263, 262, and 262, respectively. The top 3 continents that were hit most based on IP days were Europe, South America, and North America, with their AUCs and 95% CIs at 0.73 (0.61-0.86), 0.58 (0.31-0.84), and 0.54 (0.44-0.64), respectively. An online time-event result was demonstrated and shown on Google Maps, comparing the IP probabilities across continents.
CONCLUSION: An IRT modeling scheme fitting the epidemic data was used to predict the length of IP days. Europe, particularly France, was hit seriously by COVID-19 based on the IP days. The IRT model incorporated with AAC is recommended to determine the pandemic IP.
Human neutrophil peptide 1 promotes immune sterilization in vivo by reducing the virulence of multidrug-resistant Klebsiella pneumoniae and increasing the ability of macrophages

Wang HY, Chen XC, Yan ZH, Tu F, He T, Gopinath SCB, et al.

Biotechnol Appl Biochem, 2021 Oct 19.
PMID: 34664729 DOI: 10.1002/bab.2270

By studying the expression in patients and cell modeling in vitro, antimicrobial peptides for Klebsiella were screened. Killing curve and membrane permeability experiments are used to study the antibacterial effect of antimicrobial peptides in vitro. Cytotoxicity-related indicators including lipopolysaccharide (LPS), capsule polysaccharide (CPS), and outer membrane protein expression were measured. Intranasal inoculation of pneumoconiosis was used to construct a mouse infection model, and the survival rate and cytokine expression level were tested. Human neutrophil peptide 1 (HNP-1) showed a significant antibacterial effect, which improved the permeability of the outer membrane of K. pneumoniae. Moreover, HNP-1 decreased LPS, CPS content, and outer membrane proteins. K. pneumoniae infection decreased antimicrobial peptide, oxidative stress, and autophagy-related genes, while HNP-1 increased these genes. After coculture with macrophages, the endocytosis of macrophages is enhanced and the bacterial load is greater in the K. pneumoniae + peptide group. Besides, higher levels of pp38 and pp65 in the K. pneumoniae + peptide group. HNP-1 rescued the cytotoxicity induced by K. pneumoniae. The survival rate is significantly improved after K. pneumoniae is treated by HNP-1. All cytokines in the peptide group were significantly higher. HNP-1 promotes immune sterilization by reducing the virulence of multidrug-resistant K. pneumoniae and increasing the ability of macrophages.
Fulltext Genotype v Japanese encephalitis virus is emerging

Li MH, Fu SH, Chen WX, Wang HY, Guo YH, Liu QY, et al.

PLoS Negl Trop Dis, 2011 Jul;5(7):e1231.
PMID: 21750744 DOI: 10.1371/journal.pntd.0001231

Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia. JE has become the most important cause of viral encephalitis in the world. Japanese encephalitis viruses (JEV) are divided into five genotypes, based on the nucleotide sequence of the envelope (E) gene. The Muar strain, isolated from patient in Malaya in 1952, is the sole example of genotype V JEV. Here, the XZ0934 strain of JEV was isolated from Culex tritaeniorhynchus, collected in China. The complete nucleotide and amino acid sequence of XZ0934 strain have been determined. The nucleotide divergence ranged from 20.3% to 21.4% and amino acid divergence ranged from 8.4% to 10.0% when compared with the 62 known JEV isolates that belong to genotype I-IV. It reveals low similarity between XZ0934 and genotype I-IV JEVs. Phylogenetic analysis using both complete genome and structural gene nucleotide sequences demonstrates that XZ0934 belongs to genotype V. This, in turn, suggests that genotype V JEV is emerging in JEV endemic areas. Thus, increased surveillance and diagnosis of viral encephalitis caused by genotype V JEV is an issue of great concern to nations in which JEV is endemic.
Fulltext Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3

Wang HY, Yang H, Holm M, Tom H, Oltion K, Al-Khdhairawi AAQ, et al.

Nat Chem, 2022 Dec;14(12):1443-1450.
PMID: 36123449 DOI: 10.1038/s41557-022-01039-3

Ternatin-family cyclic peptides inhibit protein synthesis by targeting the eukaryotic elongation factor-1α. A potentially related cytotoxic natural product ('A3') was isolated from Aspergillus, but only 4 of its 11 stereocentres could be assigned. Here, we synthesized SR-A3 and SS-A3-two out of 128 possible A3 epimers-and discovered that synthetic SR-A3 is indistinguishable from naturally derived A3. Relative to SS-A3, SR-A3 exhibits an enhanced residence time and rebinding kinetics, as revealed by single-molecule fluorescence imaging of elongation reactions catalysed by eukaryotic elongation factor-1α in vitro. An increased residence time-stereospecifically conferred by the unique β-hydroxyl in SR-A3-was also observed in cells. Consistent with its prolonged duration of action, thrice-weekly dosing with SR-A3 led to a reduced tumour burden and increased survival in an aggressive Myc-driven mouse lymphoma model. Our results demonstrate the potential of SR-A3 as a cancer therapeutic and exemplify an evolutionary mechanism for enhancing cyclic peptide binding kinetics via stereospecific side-chain hydroxylation.
Fulltext Identification of a Newly Isolated Getah Virus in the China-Laos Border, China

Li YY, Fu SH, Guo XF, Lei WW, Li XL, Song JD, et al.

Biomed Environ Sci, 2017 Mar;30(3):210-214.
PMID: 28427491 DOI: 10.3967/bes2017.028

In this study, we isolated a virus strain (YN12031) from specimens of Armigeres subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031 exhibited an evident cytopathic effect (CPE) 32 h post-infection. The virus particles were spherical, 70 nm in diameter, and enveloped; they also featured surface fibers. Molecular genetic analysis revealed that YN12031 was closely related to alpha viruses such as Chikungunya virus and Sindbis virus, and located in the same clade as MM2021, the prototype of Getahvirus (GETV) isolated in Malaysia in 1955. Phylogenetic analysis of the E2 and capsid genes further revealed that YN12031 was located in the same clade as the Russian isolate LEIV/16275/Mag. Analysis of the homology of nucleotides and amino acids in the coding area and E2 gene demonstrated that the YN12031 isolated from the China-Laos border (tropical region) was related closest to the LEIV/16275/Mag isolate obtained in Russia (North frigid zone area) among other isolates studied. These results suggest that GETV can adapt to different geographical environments to propagate and evolve. Thus, strengthening the detection and monitoring of GETV and its related diseases is very crucial.
From discovery to spread: The evolution and phylogeny of Getah virus

Li YY, Liu H, Fu SH, Li XL, Guo XF, Li MH, et al.

Infect Genet Evol, 2017 11;55:48-55.
PMID: 28827175 DOI: 10.1016/j.meegid.2017.08.016

Getah virus (GETV) was first isolated in Malaysia in 1955. Since then, epidemics in horses and pigs caused by GETV have resulted in huge economic losses. At present, GETV has spread across Eurasia and Southeast Asia, including mainland China, Korea, Japan, Mongolia, and Russia. Data show that the Most Recent Common Ancestor (MRCA) of GETV existed about 145years ago (95% HPD: 75-244) and gradually evolved into four distinct evolutionary populations: Groups I-IV. The MRCA of GETVs in Group III, which includes all GETVs isolated from mosquitoes, pigs, horses, and other animals since the 1960s (from latitude 19°N to 60°N), existed about 51years ago (95% HPD: 51-72). Group III is responsible for most viral epidemics among domestic animals. An analysis of the GETV E2 protein sequence and structure revealed seven common amino acid mutation sites. These sites are responsible for the structural and electrostatic differences detected between widespread Group III isolates and the prototype strain MM2021. These differences may account for the recent geographical radiation of the virus. Considering the economic significance of GETV infection in pigs and horses, we recommend the implementation of strict viral screening and monitoring programs.