848 results on '"Kok Gan Chan"'
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2. Application of a VP4/VP2-inferred transmission clusters in estimating the impact of interventions on rhinovirus transmission
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Kim Tien Ng, Liang Jie Ng, Xiang Yong Oong, Jack Bee Chook, Kok Gan Chan, Yutaka Takebe, Adeeba Kamarulzaman, and Kok Keng Tee
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Acute respiratory tract infection ,Rhinovirus ,VP4/VP2 gene ,Transmission clusters ,Interventions ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Despite the clinical burden attributable to rhinovirus (RV) infections, the RV transmission dynamics and the impact of interventions on viral transmission remain elusive. Methods A total of 3,935 nasopharyngeal specimens were examined, from which the VP4/VP2 gene was sequenced and genotyped. RV transmission clusters were reconstructed using the genetic threshold of 0.005 substitutions/site, estimated from the global VP4/VP2 sequences. A transmission cluster is characterized by the presence of at least two individuals (represent by nodes), whose viral sequences are genetically linked (represent by undirected edges) at the estimated genetic distance threshold supported by bootstrap value of ≥ 90%. To assess the impact of facemask, pleconaril and social distancing on RV transmission clusters, trials were simulated for interventions with varying efficacy and were evaluated based on the reduction in the number of infected patients (nodes) and the reduction in the number of nodes-connecting edges. The putative impact of intervention strategies on RV transmission clusters was evaluated through 10,000 simulations. Results A substantial clustering of 168 RV transmission clusters of varying sizes were observed. This suggests that RV disease burden observed in the population was largely due to multiple sub-epidemics, predominantly driven by RV-A, followed by RV-C and -B. No misclassification of RV species and types were observed, suggesting the specificity and sensitivity of the analysis. Through 10,000 simulations, it was shown that social distancing may be effective in decelerating RV transmission, by removing more than 95% of nodes and edges within the RV transmission clusters. However, facemask removed less than 8% and 66% of nodes and edges, respectively, conferring moderate advantage in limiting RV transmission. Conclusion Here, we presented a network-based approach of which the degree of RV spread that fuel disease transmission in the region was mapped for the first time. The utilization of RV transmission clusters in assessing the putative impact of interventions on disease transmission at the population level was demonstrated.
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- 2022
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3. Probiotics: Comprehensive Exploration of the Growth Promotion Mechanisms in Shrimps
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Joanna Xuan Hui Goh, Loh Teng-Hern Tan, Jodi Woan-Fei Law, Kooi-Yeong Khaw, Gokhan Zengin, Kok Gan Chan, Vengadesh Letchumanan, Learn-Han Lee, and Bey-Hing Goh
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Biology (General) ,QH301-705.5 ,Microbiology ,QR1-502 - Abstract
As feed accounts for a significant proportion of a farm’s expenditure, animal nutrition is one of the key profit determinants. Attributed to the size-dependent market value, enhancing shrimps' growth is essential to maximize profit. Despite not being the best option, antibiotics are often used as growth-promoting agents in farming. Although this trend is less explicit in aquaculture, increasing production yield is paramount, especially when intensive aquafarming compromises animal growth and increases disease prevalence. However, the environmental and clinical pitfalls of indiscriminate antibiotic usage are surfacing. Fortunately, increasing evidence demonstrated probiotics as a safer, more sustainable, and environmental-friendly substitute for antibiotics. Nonetheless, most studies are observational, and the growth-promotion mechanisms of these agents are yet to be elucidated. In this light, this review aims to decipher the growth promotion mechanisms of probiotics in shrimps based on the primary works conducted. Evidently, probiotic treatment modulates the gut microbiome composition. The growth promotion effect of probiotics is partly mediated through the production of bioactive compounds such as short-chain fatty acids, vitamins, and polyamines. Besides, elevated digestive enzyme activities following the introduction of probiotics may help enhance digestibility and utilization. Histological changes at the hepatopancreas and intestine were evident. Furthermore, probiotics may reinforce the protective mechanisms in the gut and strengthen immune function. Treated shrimps demonstrate better appetite and exhibit superior metabolic and growth-related genes profile. Contrasting these recognized mechanisms with antibiotics helps construct the initial framework for designing high-quality probiotics for growth enhancement in farmed animals.
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- 2023
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4. Genetic diversity of Coxsackievirus A21 associated with sporadic cases of acute respiratory infections in Malaysia
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Nur Izzati Supian, Kim Tien Ng, Jack Bee Chook, Yutaka Takebe, Kok Gan Chan, and Kok Keng Tee
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Enterovirus ,Coxsackievirus ,Acute respiratory tract infections ,Outbreak ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Coxsackievirus A21 (CVA21), a member of Enterovirus C from the Picornaviridae family, has been associated with respiratory illnesses in humans. Methods A molecular epidemiological investigation of CVA21 was conducted among patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014 in Kuala Lumpur, Malaysia. Results Epidemiological surveillance of acute respiratory infections (n = 3935) showed low-level detection of CVA21 (0.08%, 1.4 cases/year) in Kuala Lumpur, with no clear seasonal distribution. Phylogenetic analysis of the new complete genomes showed close relationship with CVA21 strains from China and the United States. Spatio-temporal mapping of the VP1 gene determined 2 major clusters circulating worldwide, with inter-country lineage migration and strain replacement occurring over time. Conclusions The study highlights the emerging role of CVA21 in causing sporadic acute respiratory outbreaks.
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- 2021
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5. Whole-Genome Sequence of Chelatococcus daeguensis Strain M38T9, Isolated from Ulu Slim Hot Spring in Malaysia
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Yi Xian Goh, Kok Gan Chan, and Kar Wai Hong
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Biology (General) ,QH301-705.5 ,Microbiology ,QR1-502 - Abstract
Chelatococcus daeguensis strain M38T9 is a thermotolerant bacterium isolated from a hot-spring in Malaysia. The draft genome of C. daeguensis strain M38T9 consists of 4,218,658 bp assembled into 50 scaffolds. The GC content of the genome is 67.91 %, and the sequencing coverage of 184×. There are 4,046 predicted genes, 3,962 protein-coding genes, and 53 RNA-coding genes (tRNA: 45, rRNA: 4). The draft genome has been deposited at DDBJ/ENA/GenBank under the BioProject accession number PRJNA668056. The raw reads were deposited in the Sequence Read Archive (SRA) under accession number SRR13805582. Here we report the draft genome of this strain to expand our understanding of the genomic information available on the genus Chelatococcus.
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- 2022
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6. Lateral Flow Immunoassays for SARS-CoV-2
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Geik Yong Ang, Kok Gan Chan, Chan Yean Yean, and Choo Yee Yu
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dipstick ,immunochromatography ,antigen ,antibody ,diagnostic ,serology ,Medicine (General) ,R5-920 - Abstract
The continued circulation of SARS-CoV-2 virus in different parts of the world opens up the possibility for more virulent variants to evolve even as the coronavirus disease 2019 transitions from pandemic to endemic. Highly transmissible and virulent variants may seed new disruptive epidemic waves that can easily put the healthcare system under tremendous pressure. Despite various nucleic acid-based diagnostic tests that are now commercially available, the wide applications of these tests are largely hampered by specialized equipment requirements that may not be readily available, accessible and affordable in less developed countries or in low resource settings. Hence, the availability of lateral flow immunoassays (LFIs), which can serve as a diagnostic tool by detecting SARS-CoV-2 antigen or as a serological tool by measuring host immune response, is highly appealing. LFI is rapid, low cost, equipment-free, scalable for mass production and ideal for point-of-care settings. In this review, we first summarize the principle and assay format of these LFIs with emphasis on those that were granted emergency use authorization by the US Food and Drug Administration followed by discussion on the specimen type, marker selection and assay performance. We conclude with an overview of challenges and future perspective of LFI applications.
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- 2022
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7. Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin.
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Francesco Saverio Tarantini, Mara Brunati, Anna Taravella, Lucia Carrano, Francesco Parenti, Kar Wai Hong, Paul Williams, Kok Gan Chan, Stephan Heeb, and Weng C Chan
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Medicine ,Science - Abstract
As part of a screening programme for antibiotic-producing bacteria, a novel Actinomadura species was discovered from a soil sample collected in Santorini, Greece. Preliminary 16S rRNA gene sequence comparisons highlighted Actinomadura macra as the most similar characterised species. However, whole-genome sequencing revealed an average nucleotide identity (ANI) value of 89% with A. macra, the highest among related species. Further phenotypic and chemotaxonomic analyses confirmed that the isolate represents a previously uncharacterised species in the genus Actinomadura, for which the name Actinomadura graeca sp. nov. is proposed (type strain 32-07T). The G+C content of A. graeca 32-07 is 72.36%. The cell wall contains DL-diaminopimelic acid, intracellular sugars are glucose, ribose and galactose, the predominant menaquinone is MK-9(H6), the major cellular lipid is phosphatidylinositol and fatty acids consist mainly of hexadecanoic acid. No mycolic acid was detected. Furthermore, A. graeca 32-07 has been confirmed as a novel producer of the non-ribosomal peptide antibiotic zelkovamycin and we report herein a provisional description of the unique biosynthetic gene cluster.
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- 2021
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8. Angelicin—A Furocoumarin Compound With Vast Biological Potential
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Camille Keisha Mahendra, Loh Teng Hern Tan, Wai Leng Lee, Wei Hsum Yap, Priyia Pusparajah, Liang Ee Low, Siah Ying Tang, Kok Gan Chan, Learn Han Lee, and Bey Hing Goh
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angelicin ,psolaren ,furocoumarin ,biological activities ,biological potential ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-β/BMP, Wnt/β-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.
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- 2020
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9. The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults
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Xiang Yong Oong, Jack Bee Chook, Kim Tien Ng, Wei Zhen Chow, Kok Gan Chan, Nik Sherina Hanafi, Yong Kek Pang, Yoke Fun Chan, Adeeba Kamarulzaman, and Kok Keng Tee
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Human metapneumovirus (HMPV) ,Genetic diversity ,Viral load ,Symptom severity ,Acute respiratory tract infection ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. Methods Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. Results Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log10 RNA copies/μl) (p = 0.003). Conclusions Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission.
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- 2018
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10. Harnessing CRISPR-Cas to Combat COVID-19: From Diagnostics to Therapeutics
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Kok Gan Chan, Geik Yong Ang, Choo Yee Yu, and Chan Yean Yean
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coronavirus ,COVID-19 ,isothermal amplification ,antiviral ,CRISPR-Dx ,Science - Abstract
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global threat with an ever-increasing death toll even after a year on. Hence, the rapid identification of infected individuals with diagnostic tests continues to be crucial in the on-going effort to combat the spread of COVID-19. Viral nucleic acid detection via real-time reverse transcription polymerase chain reaction (rRT-PCR) or sequencing is regarded as the gold standard for COVID-19 diagnosis, but these technically intricate molecular tests are limited to centralized laboratories due to the highly specialized instrument and skilled personnel requirements. Based on the current development in the field of diagnostics, the programmable clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system appears to be a promising technology that can be further explored to create rapid, cost-effective, sensitive, and specific diagnostic tools for both laboratory and point-of-care (POC) testing. Other than diagnostics, the potential application of the CRISPR–Cas system as an antiviral agent has also been gaining attention. In this review, we highlight the recent advances in CRISPR–Cas-based nucleic acid detection strategies and the application of CRISPR–Cas as a potential antiviral agent in the context of COVID-19.
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- 2021
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11. Complete genome of Arthrobacter alpinus strain R3.8, bioremediation potential unraveled with genomic analysis
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Wah-Seng See-Too, Robson Ee, Yan-Lue Lim, Peter Convey, David A. Pearce, Taznim Begam Mohd Mohidin, Wai-Fong Yin, and Kok Gan Chan
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Cold active enzymes ,Anti-freeze protein ,Chitinase ,Pyschrotolerant bacteria ,Plant growth promoting bacteria ,Genetics ,QH426-470 - Abstract
Abstract Arthrobacter alpinus R3.8 is a psychrotolerant bacterial strain isolated from a soil sample obtained at Rothera Point, Adelaide Island, close to the Antarctic Peninsula. Strain R3.8 was sequenced in order to help discover potential cold active enzymes with biotechnological applications. Genome analysis identified various cold adaptation genes including some coding for anti-freeze proteins and cold-shock proteins, genes involved in bioremediation of xenobiotic compounds including naphthalene, and genes with chitinolytic and N-acetylglucosamine utilization properties and also plant-growth-influencing properties. In this genome report, we present a complete genome sequence of A. alpinus strain R3.8 and its annotation data, which will facilitate exploitation of potential novel cold-active enzymes.
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- 2017
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12. Mutations in the tail domain of MYH3 contributes to atrial septal defect.
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Sathiya Maran, Robson Ee, Siti Aisyah Faten, Choi Sy Bing, Kooi Yeong Khaw, Swee-Hua Erin Lim, Kok-Song Lai, Wan Pauzi Wan Ibrahim, Mohd Rizal Mohd Zain, Kok Gan Chan, Siew Hua Gan, and Huay Lin Tan
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Medicine ,Science - Abstract
Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.
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- 2020
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13. Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review
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Yew Rong Kong, Yong Xin Jong, Manisha Balakrishnan, Zhui Ken Bok, Janice Kwan Kah Weng, Kai Ching Tay, Bey Hing Goh, Yong Sze Ong, Kok Gan Chan, Learn Han Lee, and Kooi Yeong Khaw
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oxidative stress ,antioxidant ,Carica papaya ,inflammation ,diabetes ,cancer ,Biology (General) ,QH301-705.5 - Abstract
Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.
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- 2021
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14. Identification and evolutionary dynamics of two novel human coronavirus OC43 genotypes associated with acute respiratory infections: phylogenetic, spatiotemporal and transmission network analyses
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Xiang Yong Oong, Kim Tien Ng, Yutaka Takebe, Liang Jie Ng, Kok Gan Chan, Jack Bee Chook, Adeeba Kamarulzaman, and Kok Keng Tee
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comparative genomic analyses ,evolutionary dynamics ,human coronavirus OC43 ,recombination ,transmission network ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.Emerging Microbes & Infections (2017) 6, e3; doi:10.1038/emi.2016.132; published online 4 January 2017
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- 2017
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15. Nucleic Acid-Based Diagnostic Tests for the Detection SARS-CoV-2: An Update
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Choo Yee Yu, Kok Gan Chan, Chan Yean Yean, and Geik Yong Ang
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COVID-19 ,rapid test ,RT-PCR ,isothermal ,lateral flow ,LAMP ,Medicine (General) ,R5-920 - Abstract
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began as a cluster of pneumonia cases in Wuhan, China before spreading to over 200 countries and territories on six continents in less than six months. Despite rigorous global containment and quarantine efforts to limit the transmission of the virus, COVID-19 cases and deaths have continued to increase, leaving devastating impacts on the lives of many with far-reaching effects on the global society, economy and healthcare system. With over 43 million cases and 1.1 million deaths recorded worldwide, accurate and rapid diagnosis continues to be a cornerstone of pandemic control. In this review, we aim to present an objective overview of the latest nucleic acid-based diagnostic tests for the detection of SARS-CoV-2 that have been authorized by the Food and Drug Administration (FDA) under emergency use authorization (EUA) as of 31 October 2020. We systematically summarize and compare the principles, technologies, protocols and performance characteristics of amplification- and sequencing-based tests that have become alternatives to the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel. We highlight the notable features of the tests including authorized settings, along with the advantages and disadvantages of the tests. We conclude with a brief discussion on the current challenges and future perspectives of COVID-19 diagnostics.
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- 2021
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16. Convergence between the microcosms of Southeast Asian and North American pitcher plants
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Leonora S Bittleston, Charles J Wolock, Bakhtiar E Yahya, Xin Yue Chan, Kok Gan Chan, Naomi E Pierce, and Anne Pringle
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microbial ecology ,Nepenthes ,Sarracenia ,communities ,species interactions ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The ‘pitchers’ of carnivorous pitcher plants are exquisite examples of convergent evolution. An open question is whether the living communities housed in pitchers also converge in structure or function. Using samples from more than 330 field-collected pitchers of eight species of Southeast Asian Nepenthes and six species of North American Sarracenia, we demonstrate that the pitcher microcosms, or miniature ecosystems with complex communities, are strikingly similar. Compared to communities from surrounding habitats, pitcher communities house fewer species. While communities associated with the two genera contain different microbial organisms and arthropods, the species are predominantly from the same phylogenetic clades. Microbiomes from both genera are enriched in degradation pathways and have high abundances of key degradation enzymes. Moreover, in a manipulative field experiment, Nepenthes pitchers placed in a North American bog assembled Sarracenia-like communities. An understanding of the convergent interactions in pitcher microcosms facilitates identification of selective pressures shaping the communities.
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- 2018
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17. Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset
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Lily Boo, Wan Yong Ho, Norlaily Mohd Ali, Swee Keong Yeap, Huynh Ky, Kok Gan Chan, Wai Fong Yin, Dilan Amila Satharasinghe, Woan Charn Liew, Sheau Wei Tan, Soon Keng Cheong, and Han Kiat Ong
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Breast cancer ,Cancer stem cells ,MDA-MB-231 ,Next generation sequencing ,Triple-negative breast cancer cells ,MicroRNA ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.
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- 2017
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18. Purification and biochemical characterization of recombinant Persicaria minor β-sesquiphellandrene synthase
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De-Sheng Ker, Sze Lei Pang, Noor Farhan Othman, Sekar Kumaran, Ee Fun Tan, Thiba Krishnan, Kok Gan Chan, Roohaida Othman, Maizom Hassan, and Chyan Leong Ng
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Farnesyl diphosphate ,β-sesquiphellandrene ,Persicaria minor ,Sesquiterpene synthase ,Homology modelling ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Sesquiterpenes are 15-carbon terpenes synthesized by sesquiterpene synthases using farnesyl diphosphate (FPP) as a substrate. Recently, a sesquiterpene synthase gene that encodes a 65 kDa protein was isolated from the aromatic plant Persicaria minor. Here, we report the expression, purification and characterization of recombinant P. minor sesquiterpene synthase protein (PmSTS). Insights into the catalytic active site were further provided by structural analysis guided by multiple sequence alignment. Methods The enzyme was purified in two steps using affinity and size exclusion chromatography. Enzyme assays were performed using the malachite green assay and enzymatic product was identified using gas chromatography-mass spectrometry (GC-MS) analysis. Sequence analysis of PmSTS was performed using multiple sequence alignment (MSA) against plant sesquiterpene synthase sequences. The homology model of PmSTS was generated using I-TASSER server. Results Our findings suggest that the recombinant PmSTS is mainly expressed as inclusion bodies and soluble aggregate in the E. coli protein expression system. However, the addition of 15% (v/v) glycerol to the protein purification buffer and the removal of N-terminal 24 amino acids of PmSTS helped to produce homogenous recombinant protein. Enzyme assay showed that recombinant PmSTS is active and specific to the C15 substrate FPP. The optimal temperature and pH for the recombinant PmSTS are 30 °C and pH 8.0, respectively. The GC-MS analysis further showed that PmSTS produces β-sesquiphellandrene as a major product and β-farnesene as a minor product. MSA analysis revealed that PmSTS adopts a modified conserved metal binding motif (NSE/DTE motif). Structural analysis suggests that PmSTS may binds to its substrate similarly to other plant sesquiterpene synthases. Discussion The study has revealed that homogenous PmSTS protein can be obtained with the addition of glycerol in the protein buffer. The N-terminal truncation dramatically improved the homogeneity of PmSTS during protein purification, suggesting that the disordered N-terminal region may have caused the formation of soluble aggregate. We further show that the removal of the N-terminus disordered region of PmSTS does not affect the product specificity. The optimal temperature, optimal pH, Km and kcat values of PmSTS suggests that PmSTS shares similar enzyme characteristics with other plant sesquiterpene synthases. The discovery of an altered conserved metal binding motif in PmSTS through MSA analysis shows that the NSE/DTE motif commonly found in terpene synthases is able to accommodate certain level of plasticity to accept variant amino acids. Finally, the homology structure of PmSTS that allows good fitting of substrate analog into the catalytic active site suggests that PmSTS may adopt a sesquiterpene biosynthesis mechanism similar to other plant sesquiterpene synthases.
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- 2017
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19. Whole-Genome Phylogenetic Analysis of Influenza B/Phuket/3073/2013-Like Viruses and Unique Reassortants Detected in Malaysia between 2012 and 2014.
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Xiang Yong Oong, Kim Tien Ng, Joon Ling Tan, Kok Gan Chan, Adeeba Kamarulzaman, Yoke Fun Chan, I-Ching Sam, and Kok Keng Tee
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Medicine ,Science - Abstract
Reassortment of genetic segments between and within influenza B lineages (Victoria and Yamagata) has been shown to generate novel reassortants with unique genetic characteristics. Based on hemagglutinin (HA) and neuraminidase (NA) genes, recent surveillance study has identified reassortment properties in B/Phuket/3073/2013-like virus, which is currently used in the WHO-recommended influenza vaccine. To understand the potential reassortment patterns for all gene segments, four B/Phuket/3073/2013-like viruses and two unique reassortants (one each from Yamagata and Victoria) detected in Malaysia from 2012-2014 were subjected to whole-genome sequencing. Each gene was phylogenetically classified into lineages, clades and sub-clades. Three B/Phuket/3073/2013-like viruses from Yamagata lineage were found to be intra-clade reassortants, possessing PA and NA genes derived from Stockholm/12-like sub-clade, while the remaining genes from Wisconsin/01-like sub-clade (both sub-clades were within Yamagata Clade 3/Yam-3). However, the other B/Phuket/3073/2013-like virus had NS gene that derived from Stockholm/12-like sub-clade instead of Wisconsin/01-like sub-clade. One inter-clade reassortant had Yamagata Clade 2/Yam-2-derived HA and NP, and its remaining genes were Yam-3-derived. Within Victoria Clade 1/Vic-1 in Victoria lineage, one virus had intra-clade reassortment properties: HA and PB2 from Vic-1B sub-clade, MP and NS from a unique sub-clade "Vic-1C", and the remaining genes from Vic-1A sub-clade. Although random reassortment event may generate unique reassortants, detailed phylogenetic classification of gene segments showed possible genetic linkage between PA and NA genes in B/Phuket/3073/2013-like viruses, which requires further investigation. Understanding on reassortment patterns in influenza B evolution may contribute to future vaccine design.
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- 2017
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20. Golden needle mushroom: A culinary medicine with evidenced-based biological activities and health promoting properties
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Calyn Tang, Ching-Xin Hoo, Tan Loh Teng Hern, Priyia Pusparajah, Tahir Mehmood Khan, Learn-Han Lee, Bey Hing Goh, and Kok Gan Chan
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mushroom ,Nutritional value ,Biological activity ,Flammulina velutipes ,Enoki ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Flammulina velutipes (enoki, velvet shank, golden needle mushroom or winter mushroom), one of the main edible mushrooms on the market, has long been recognised for its nutritional value and delicious taste. In recent decades, research has expanded beyond detailing its nutritional composition and delved into the biological activities and potential health benefits of its constituents. Many bioactive constituents from a range of families have been isolated from different parts of the mushroom, including carbohydrates, protein, lipids, glycoproteins, phenols and sesquiterpenes. These compounds have been demonstrated to exhibit various biological activities, such as antitumour and anticancer activities, anti-atherosclerotic and thrombosis inhibition activity, antihypertensive and cholesterol lowering effects, anti-aging and antioxidant properties, ability to aid with restoring memory and overcoming learning deficits, anti-inflammatory, immunomodulatory, anti-bacterial, ribosome inactivation and melanosis inhibition. This review aims to consolidate the information concerning the phytochemistry and biological activities of various compounds isolated from Flammulina velutipes to demonstrate that this mushroom is not only a great source of nutrients but also possesses tremendous potential in pharmaceutical drug development.
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- 2016
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21. Rhizoma coptidis: A potential cardiovascular protective agent
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Hui-Li Tan, Kok Gan Chan, Priyia Pusparajah, Acharaporn Duangjai, Surasak Saokaew, Learn-Han Lee, and Bey Hing Goh
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Cardiovascular Diseases ,Ethnopharmacology ,Coptis chinensis Franch ,Huang Lian ,Coptis root ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, protection from myocardial ischemia-reperfusion injury, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks of CVDs.
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- 2016
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22. Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid
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Seow Hoon Saw, Joon Liang Tan, Xin Yue Chan, Kok Gan Chan, and Yun Fong Ngeow
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Meningitis ,Comparative genomics ,Mycobacterium tuberculosis ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background Meningitis is a major cause of mortality in tuberculosis (TB). It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb) might have genetic traits associated with neurotropism. Methods In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF) of patients presenting with tuberculous meningitis (TBM) in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. Results Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions) and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate)/PPE (proline-proline-glutamate), transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. Discussion The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB meningeal infection is more likely to be related to the expression of multiple virulence factors on interaction with host defences than to CNS tropism associated with specific genetic traits.
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- 2016
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23. Genome Analysis of a New Rhodothermaceae Strain Isolated from a Hot Spring
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Kian Mau Goh, Kok Gan Chan, Soon Wee Lim, Kok Jun Liew, Chia Sing Chan, Mohd Shahir Shamsir, Robson Ee, and Tan-Guan-Sheng Adrian
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Rhodothermus ,salinibacter ,Rhodothermaceae ,Salisaeta ,Rubricoccus ,Rubrivirga ,Microbiology ,QR1-502 - Abstract
A bacterial strain, designated RA, was isolated from water sample of a hot spring on Langkawi Island of Malaysia using marine agar. Strain RA is an aerophilic and thermophilic microorganism that grows optimally at 50–60°C and is capable of growing in marine broth containing 1–10% (w/v) NaCl. 16S rRNA gene sequence analysis demonstrated that this strain is most closely related (< 90% sequence identity) to Rhodothermaceae, which currently comprises of six genera: Rhodothermus (two species), Salinibacter (three species), Salisaeta (one species), Rubricoccus (one species), Rubrivirga (one species), and Longimonas (one species). Notably, analysis of average nucleotide identity values indicated that strain RA may represent the first member of a novel genus of Rhodothermaceae. The draft genome of strain RA is 4,616,094 bp with 3,630 protein-coding gene sequences. Its GC content is 68.3%, which is higher than that of most other genomes of Rhodothermaceae. Strain RA has genes for sulfate permease and arylsulfatase to withstand the high sulfur and sulfate contents of the hot spring. Putative genes encoding proteins involved in adaptation to osmotic stress were identified which encode proteins namely Na+/H+ antiporters, a sodium/solute symporter, a sodium/glutamate symporter, trehalose synthase, malto-oligosyltrehalose synthase, choline-sulfatase, potassium uptake proteins (TrkA and TrkH), osmotically inducible protein C, and the K+ channel histidine kinase KdpD. Furthermore, genome description of strain RA and comparative genome studies in relation to other related genera provide an overview of the uniqueness of this bacterium.
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- 2016
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24. Insights into bacteriophage application in controlling Vibrio species
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Vengadesh Letchumanan, Kok Gan Chan, Priyia Pusparajah, Surasak Saokaew, Acharaporn Duangjai, Bey Hing Goh, Nurul-Syakima Ab Mutalib, and Learn-Han Lee
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Bacteriophages ,antibiotics ,bacterial ,Vibrio sp. ,Multidrug resistant strains ,Microbiology ,QR1-502 - Abstract
Bacterial infections from various organisms including Vibrio sp. pose a serious hazard to humans in many forms from clinical infection to affecting the yield of agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the main foodborne pathogens causing human infection and is also a common cause of losses in the aquaculture industry. Prophylactic and therapeutic usage of antibiotics has become the mainstay of managing this problem, however this in turn led to the emergence of multidrug resistant strains of bacteria in the environment; which has raised awareness of the critical need for alternative non antibiotic based methods of preventing and treating bacterial infections. Bacteriophages - viruses that infect and result in the death of bacteria – are currently of great interest as a highly viable alternative to antibiotics. This article provides an insight into bacteriophage application in controlling Vibrio species as well underlining the advantages and drawbacks of phage therapy.
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- 2016
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25. The Effects of Chinese Herbal Medicines on the Quorum Sensing-Regulated Virulence in Pseudomonas aeruginosa PAO1
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Yee Meng Chong, Kah Yan How, Wai Fong Yin, and Kok Gan Chan
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quorum sensing ,natural products ,Pseudomonas aeruginosa PAO1 ,Poria cum Radix pini ,Angelica dahurica ,Rhizoma cibotii ,Schizonepeta tenuifolia ,Organic chemistry ,QD241-441 - Abstract
The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation or transmission to combat QS pathogens. In this study, we report the anti-QS activities of four different Chinese herbal plant extracts: Poria cum Radix pini, Angelica dahurica, Rhizoma cibotii and Schizonepeta tenuifolia, on Pseudomonas aeruginosa PAO1. All the plants extracted using hexane, chloroform and methanol were tested and found to impair swarming motility and pyocyanin production in P. aeruginosa PAO1, particularly by Poria cum Radix pini. In addition, all the plant extracts also inhibited violacein production in C. violaceum CV026 up to 50% while bioluminescence activities were reduced in lux-based E. coli biosensors, pSB401 and pSB1075, up to about 57%. These anti-QS properties of the four medicinal plants are the first documentation that demonstrates a potential approach to attenuate pathogens’ virulence determinants.
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- 2018
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26. Identification of new genomospecies in the Mycobacterium terrae complex.
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Yun Fong Ngeow, Yan Ling Wong, Joon Liang Tan, Kar Wai Hong, Hien Fuh Ng, Bee Lee Ong, and Kok Gan Chan
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Medicine ,Science - Abstract
Members of the Mycobacterium terrae complex are slow-growing, non-chromogenic acid-fast bacilli found in the natural environment and occasionally in clinical material. These genetically closely-related members are difficult to differentiate by conventional phenotypic and molecular tests. In this paper we describe the use of whole genome data for the identification of four strains genetically similar to Mycobacterium sp. JDM601, a newly identified member of the M. terrae complex. Phylogenetic information from the alignment of genome-wide orthologous genes and single nucleotide polymorphisms show consistent clustering of the four strains together with M. sp. JDM601 into a distinct clade separate from other rapid and slow growing mycobacterial species. More detailed inter-strain comparisons using average nucleotide identity, tetra-nucleotide frequencies and analysis of synteny indicate that our strains are closely related to but not of the same species as M. sp. JDM601. Besides the 16S rRNA signature described previously for the M. terrae complex, five more hypothetical proteins were found that are potentially useful for the rapid identification of mycobacterial species belonging to the M. terrae complex. This paper illustrates the versatile utilization of whole genome data for the delineation of new bacterial species and introduces four new genomospecies to add to current members in the M. terrae complex.
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- 2015
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27. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.
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Hui Ting Cheong, Wei Zhen Chow, Yutaka Takebe, Jack Bee Chook, Kok Gan Chan, Haider Abdulrazzaq Abed Al-Darraji, Clayton Koh, Adeeba Kamarulzaman, and Kok Keng Tee
- Subjects
Medicine ,Science - Abstract
In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.
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- 2015
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28. Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014.
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Xiang Yong Oong, Kim Tien Ng, Tommy Tsan-Yuk Lam, Yong Kek Pang, Kok Gan Chan, Nik Sherina Hanafi, Adeeba Kamarulzaman, and Kok Keng Tee
- Subjects
Medicine ,Science - Abstract
Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors-total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.
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- 2015
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29. The complete genome sequence of Escherichia coli EC958: a high quality reference sequence for the globally disseminated multidrug resistant E. coli O25b:H4-ST131 clone.
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Brian M Forde, Nouri L Ben Zakour, Mitchell Stanton-Cook, Minh-Duy Phan, Makrina Totsika, Kate M Peters, Kok Gan Chan, Mark A Schembri, Mathew Upton, and Scott A Beatson
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Medicine ,Science - Abstract
Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage.
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- 2014
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30. Cross-border sexual transmission of the newly emerging HIV-1 clade CRF51_01B.
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Hui Ting Cheong, Kim Tien Ng, Lai Yee Ong, Jack Bee Chook, Kok Gan Chan, Yutaka Takebe, Adeeba Kamarulzaman, and Kok Keng Tee
- Subjects
Medicine ,Science - Abstract
A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross-border transmission of HIV-1 involving sexual networks is crucial for effective intervention strategies in the region.
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- 2014
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31. A newly emerging HIV-1 recombinant lineage (CRF58_01B) disseminating among people who inject drugs in Malaysia.
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Wei Zhen Chow, Yutaka Takebe, Nur Ezreen Syafina, Malarvelli Soorya Prakasa, Kok Gan Chan, Haider Abdulrazzaq Abed Al-Darraji, Clayton Koh, Adeeba Kamarulzaman, and Kok Keng Tee
- Subjects
Medicine ,Science - Abstract
The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention.
- Published
- 2014
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32. Unusual long-chain N-acyl homoserine lactone production by and presence of quorum quenching activity in bacterial isolates from diseased tilapia fish.
- Author
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Chien-Yi Chang, Chong-Lek Koh, Choon-Kook Sam, Xin-Yue Chan, Wai Fong Yin, and Kok Gan Chan
- Subjects
Medicine ,Science - Abstract
Growth-dependent cell-cell communication termed quorum sensing is a key regulatory system in bacteria for controlling gene expression including virulence factors. In this study five potential bacterial pathogens including Bacillus sp. W2.2, Klebsiella sp. W4.2, Pseudomonas sp. W3 and W3.1 and Serratia sp. W2.3 were isolated from diseased Tilapia fish in Malaysia, supplied by the leading global fish supplier. Proteolytic activity assays confirmed that with the exception of Klebsiella sp. W4.2, all isolates showed distinct proteolytic activity. Furthermore Bacillus sp. W2.2 and Pseudomonas sp. strains W3 and W3.1 also displayed haemolytic activity. By using high resolution liquid chromatography mass spectrometry, we revealed the presence of unusually long-chain N-(3-oxohexadecanoyl)-homoserine lactone (3-oxo-C16-HSL) from Pseudomonas sp. W3.1 and N-dodecanoyl-homoserine lactone (C12-HSL) from Serratia sp. W2.3, respectively. Interestingly, Pseudomonas sp. W3.1 also produced a wide range of Pseudomonas quinolone signalling (PQS) molecules. Pseudomonas sp. W3 did not show any quorum sensing properties but possessed quorum quenching activity that inactivated AHLs. This study is the first documentation that shows unusual long-chain AHLs production in Serratia sp. and Pseudomonas sp. isolated from diseased fish and the latter also produce a wide range of PQS molecules.
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- 2012
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33. Identification of key bacterial players during successful full-scale soil field bioremediation in Antarctica
- Author
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Martinez Alvarez, Lucas, Bolhuis, Henk, Mau, Goh Kian, Kok-Gan, Chan, Sing, Chan Chia, Mac Cormack, Walter, and Ruberto, Lucas
- Published
- 2022
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34. A roadmap for the generation of benchmarking resources for antimicrobial resistance detection using next generation sequencing [version 2; peer review: 1 approved, 2 approved with reservations]
- Author
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Mauro Petrillo, Marco Fabbri, Dafni Maria Kagkli, Maddalena Querci, Guy Van den Eede, Erik Alm, Derya Aytan-Aktug, Salvador Capella-Gutierrez, Catherine Carrillo, Alessandro Cestaro, Kok-Gan Chan, Teresa Coque, Christoph Endrullat, Ivo Gut, Paul Hammer, Gemma L. Kay, Jean-Yves Madec, Alison E. Mather, Alice Carolyn McHardy, Thierry Naas, Valentina Paracchini, Silke Peter, Arthur Pightling, Barbara Raffael, John Rossen, Etienne Ruppé, Robert Schlaberg, Kevin Vanneste, Lukas M. Weber, Henrik Westh, and Alexandre Angers-Loustau
- Subjects
Opinion Article ,Articles ,Antimicrobial resistance ,bioinformatics ,next-generation sequencing ,benchmarking - Abstract
Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data, partly because of the reliance on bioinformatics pipelines, which can produce different results and therefore lead to different interpretations. With the constant evolution of the field, it is difficult to identify, harmonise and recommend specific methods for large-scale implementations over time. In this article, we propose to address this challenge through establishing a transparent, performance-based, evaluation approach to provide flexibility in the bioinformatics tools of choice, while demonstrating proficiency in meeting common performance standards. The approach is two-fold: first, a community-driven effort to establish and maintain “live” (dynamic) benchmarking platforms to provide relevant performance metrics, based on different use-cases, that would evolve together with the AMR field; second, agreed and defined datasets to allow the pipelines’ implementation, validation, and quality-control over time. Following previous discussions on the main challenges linked to this approach, we provide concrete recommendations and future steps, related to different aspects of the design of benchmarks, such as the selection and the characteristics of the datasets (quality, choice of pathogens and resistances, etc.), the evaluation criteria of the pipelines, and the way these resources should be deployed in the community.
- Published
- 2022
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35. The Current Landscape of CRISPR-Cas9-based Technologies for Imaging of Genomic Loci in Fixed and Live Cells.
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Choo Yee Yu, Chan Yean Yean, Kok Gan Chan, and Geik Yong Ang
- Subjects
CRISPRS ,FLUORESCENCE in situ hybridization ,GENOME editing ,IMAGING systems ,CELL imaging - Abstract
Visualization of the spatiotemporal organization and dynamics of the genome in the nucleus is essential to elucidate how chromatin structure and nuclear function are intertwined. In the past, such studies were limited by the lack of appropriate tools. However, various imaging techniques now allow direct visualization of genomic loci in living cells. One of the main drivers behind this progress is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) technology. Initially used as an efficient and specific genome editing tool, the versatility of the CRISPR/Cas system has rapidly expanded its application range to include diagnostics, therapeutics, and, more recently, live cell imaging. In contrast to traditional fluorescent in situ hybridization, CRISPR/Cas-based imaging systems enable real-time dynamic tracking of genomic sequences down to the level of single cells and even a single locus. Recognizing the vital role played by CRISPR/Cas-based imaging systems in advancing our understanding of genome function in relation to its spatiotemporal organization, this review aimed to depict the current landscape of CRISPR/Cas-based technologies in genomic imaging. It discusses the principles, notable features, advantages, and limitations of these CRISPR/Cas-based imaging systems and concludes with a brief outlook into the future. [ABSTRACT FROM AUTHOR]
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- 2024
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36. A roadmap for the generation of benchmarking resources for antimicrobial resistance detection using next generation sequencing [version 1; peer review: 2 approved with reservations]
- Author
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Mauro Petrillo, Marco Fabbri, Dafni Maria Kagkli, Maddalena Querci, Guy Van den Eede, Erik Alm, Derya Aytan-Aktug, Salvador Capella-Gutierrez, Catherine Carrillo, Alessandro Cestaro, Kok-Gan Chan, Teresa Coque, Christoph Endrullat, Ivo Gut, Paul Hammer, Gemma L. Kay, Jean-Yves Madec, Alison E. Mather, Alice Carolyn McHardy, Thierry Naas, Valentina Paracchini, Silke Peter, Arthur Pightling, Barbara Raffael, John Rossen, Etienne Ruppé, Robert Schlaberg, Kevin Vanneste, Lukas M. Weber, Henrik Westh, and Alexandre Angers-Loustau
- Subjects
Opinion Article ,Articles ,Antimicrobial resistance ,bioinformatics ,next-generation sequencing ,benchmarking - Abstract
Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data, partly because of the reliance on bioinformatics pipelines, which can produce different results and therefore lead to different interpretations. With the constant evolution of the field, it is difficult to identify, harmonise and recommend specific methods for large-scale implementations over time. In this article, we propose to address this challenge through establishing a transparent, performance-based, evaluation approach to provide flexibility in the bioinformatics tools of choice, while demonstrating proficiency in meeting common performance standards. The approach is two-fold: first, a community-driven effort to establish and maintain “live” (dynamic) benchmarking platforms to provide relevant performance metrics, based on different use-cases, that would evolve together with the AMR field; second, agreed and defined datasets to allow the pipelines’ implementation, validation, and quality-control over time. Following previous discussions on the main challenges linked to this approach, we provide concrete recommendations and future steps, related to different aspects of the design of benchmarks, such as the selection and the characteristics of the datasets (quality, choice of pathogens and resistances, etc.), the evaluation criteria of the pipelines, and the way these resources should be deployed in the community.
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- 2021
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37. Migratory behaviour is positively associated with genetic diversity in butterflies
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Aurora García‐Berro, Venkat Talla, Roger Vila, Hong Kar Wai, Daria Shipilina, Kok Gan Chan, Naomi E. Pierce, Niclas Backström, Gerard Talavera, National Geographic Society, Ministerio de Ciencia e Innovación (España), Museum of Comparative Zoology (US), Generalitat de Catalunya, University of Malaya, Swedish Collegium for Advanced Study, and Swedish Research Council
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demography ,Evolutionary Biology ,insect migration ,Outbreaks ,migratory connectivity ,genetic diversity ,population bottlenecks ,Genetic diversity ,Evolutionsbiologi ,Migratory connectivity ,Effective population size ,outbreaks ,Population bottlenecks ,PSMC ,Vanessa cardui ,Genetics ,effective population size ,Insect migration ,Ecology, Evolution, Behavior and Systematics ,Demography - Abstract
Migration is typically associated with risk and uncertainty at the population level, but little is known about its cost¿benefit trade-offs at the species level. Migratory insects in particular often exhibit strong demographic fluctuations due to local bottlenecks and outbreaks. Here, we use genomic data to investigate levels of heterozygosity and long-term population size dynamics in migratory insects, as an alternative to classical local and short-term approaches such as regional field monitoring. We analyse whole-genome sequences from 97 Lepidoptera species and show that individuals of migratory species have significantly higher levels of genome-wide heterozygosity, a proxy for effective population size, than do nonmigratory species. Also, we contribute whole-genome data for one of the most emblematic insect migratory species, the painted lady butterfly (Vanessa cardui), sampled across its worldwide distributional range. This species exhibits one of the highest levels of genomic heterozygosity described in Lepidoptera (2.95 ± 0.15%). Coalescent modelling (PSMC) shows historical demographic stability in V. cardui, and high effective population size estimates of 2 -20 million individuals 10,000 years ago. The study reveals that the high risks associated with migration and local environmental fluctuations do not seem to decrease overall genetic diversity and demographic stability in migratory Lepidoptera. We propose a "compensatory" demographic model for migratory r-strategist organisms in which local bottlenecks are counterbalanced by reproductive success elsewhere within their typically large distributional ranges. Our findings highlight that the boundaries of populations are substantially different for sedentary and migratory insects, and that, in the latter, local and even regional field monitoring results may not reflect whole population dynamics. Genomic diversity patterns may elucidate key aspects of an insect's migratory nature and population dynamics at large spatiotemporal scales., This work was funded by the National Geographic Society (grant WW1-300R-18) and by the grant PID2020-117739GA-I00 from MCIN/AEI/10.13039/501100011033 to G.T., by fellowship FPU19/01593 to A.G.-B., by project LINKA20399 from the CSIC i-LINK-2021 programme to G.T., N.E.P., R.V. and N.B., by grants from the Putnam Expeditionary Fund of the Museum of Comparative Zoology to G.T. and N.E.P., by projects PID2019-107078GB-I00/MCIN/AEI/10.13039/501100011033 and 2017-SGR-991 (Generalitat de Catalunya) to R.V. and G.T., by the University of Malaya (grant H50001-A-000027) to K.G.C., by the Swedish Collegium for Advanced Science (SCAS; Natural Sciences Programme, Knut and Alice Wallenberg Foundation, Postdoc funding) to D.S., by NSF grant DEB-1541560 to N.E.P., and by the Swedish Research Council FORMAS (grant 2019-00670) to N.B., G.T. and R.V., 1 INTRODUCTION2 MATERIALS AND METHODS2.1 Heterozygosity estimates2.2 Behavioural scoring2.3 Comparative analyses2.4 Vanessa cardui sampling and sequencing2.5 Vanessa cardui reference-based assemblies2.6 Vanessa cardui demographic inference3 RESULTS3.1 Heterozygosity rates in Lepidoptera3.2 Vanessa cardui demographic history4 DISCUSSION4.1 Genomic heterozygosity, effective population size and migration4.2 Short-term migratory cost but long-term demographic stability4.3 Delimiting populations in migratory insect speciesAUTHOR CONTRIBUTIONSACKNOWLEDGEMENTSCONFLICT OF INTEREST
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- 2022
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38. Complete chloroplast genome of Boesenbergia rotunda and a comparative analysis with members of the family Zingiberaceae
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Yvonne Jing Mei Liew, Kah-Ooi Chua, Hoi-Sen Yong, Sze-Looi Song, and Kok-Gan Chan
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Plant Science - Published
- 2022
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39. The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies [version 2; referees: 2 approved]
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Alexandre Angers-Loustau, Mauro Petrillo, Johan Bengtsson-Palme, Thomas Berendonk, Burton Blais, Kok-Gan Chan, Teresa M. Coque, Paul Hammer, Stefanie Heß, Dafni M. Kagkli, Carsten Krumbiegel, Val F. Lanza, Jean-Yves Madec, Thierry Naas, Justin O'Grady, Valentina Paracchini, John W.A. Rossen, Etienne Ruppé, Jessica Vamathevan, Vittorio Venturi, and Guy Van den Eede
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Opinion Article ,Articles ,Antimicrobial resistance ,bioinformatics ,next-generation sequencing ,benchmarking - Abstract
Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms. In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed. NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced. Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process. This concept was explored as part of a workshop on 'Next-generation sequencing technologies and antimicrobial resistance' held October 4-5 2017. Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a “One Health” approach.
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- 2018
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40. The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies [version 1; referees: 2 approved]
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Alexandre Angers-Loustau, Mauro Petrillo, Johan Bengtsson-Palme, Thomas Berendonk, Burton Blais, Kok-Gan Chan, Teresa M. Coque, Paul Hammer, Stefanie Heß, Dafni M. Kagkli, Carsten Krumbiegel, Val F. Lanza, Jean-Yves Madec, Thierry Naas, Justin O'Grady, Valentina Paracchini, John W.A. Rossen, Etienne Ruppé, Jessica Vamathevan, Vittorio Venturi, and Guy Van den Eede
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Opinion Article ,Articles ,Antimicrobial resistance ,bioinformatics ,next-generation sequencing ,benchmarking - Abstract
Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms. In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed. NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced. Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process. This concept was explored as part of a workshop on 'Next-generation sequencing technologies and antimicrobial resistance' held October 4-5 2017. Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a “One Health” approach.
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- 2018
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41. Streptomyces sp. MUM 195J: A Promising Probiotic for Controlling Vibrio parahaemolyticus Infection in Aquaculture.
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Xuan Hui Goh, Joanna, Loh Teng-Hern Tan, Woan-Fei Law, Jodi, Kuppusamy, Giva, M., Janaranjani, Kooi-Yeong Khaw, Wei Hsum Yap, Kok-Gan Chan, Letchumanan, Vengadesh, Learn-Han Lee, and Bey-Hing Goh
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STREPTOMYCES ,PROBIOTICS ,VIBRIO parahaemolyticus ,BACTERIAL diseases ,AQUACULTURE - Abstract
Aquaculture is gaining prominence in meeting the increasing global food demand. However, persistent episodes of pathogenic infections have greatly affected production and incurred substantial financial losses to the industry. Regrettably, there is a lack of effective contemporary therapeutic measures to control infectious diseases in aquaculture. The repercussions of antimicrobial resistance have underscored the drawbacks of the contemporary practice of relying solely on antibiotics in disease control. The aquaculture industry needs a safer, environmentally viable, and economically efficient means for disease management. In this regard, this study aims to investigate the effectiveness of mangrove-derived Streptomyces sp. probiotics in controlling Vibrio parahaemolyticus infections. In vitro screenings were undertaken to evaluate the inhibitory activity of five Streptomyces sp. isolates. Subsequently, a series of in vivo trials was conducted, with the Malaysian giant freshwater prawn, Macrobrachium rosenbergii larvae as the animal model. Following that, molecular analyses were employed to examine the changes in gene expression. In essence, Streptomyces sp. MUM 195J emerges as a promising probiotic strain that demonstrates a strong inhibitory effect against V. parahaemolyticus. Its application as a feed additive elevates the survival rate of M. rosenbergii threefold, thus demonstrating efficacy at par with florfenicol antibiotic when challenged with the V. parahaemolyticus pathogen. Besides, Streptomyces sp. MUM 195J elevated the growth rate of M. rosenbergii by 17%. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis revealed that probiotic supplementation elevated the immune function of the animal. Additionally, Streptomyces sp. MUM 195J demonstrates the potential to ameliorate the quality of the rearing water. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Genomic and Resistome Analyses of Elizabethkingia anophelis Strain B2D isolated from Dental Plaque of Patient.
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Share Yuan Goh, Kah-Ooi Chua, Saad Ahmed Khan, Noor Hayaty Abu Kasim, Yvonne Jing Mei Liew, Yin Yin Lau, Kar-Wai Hong, Wai-Fong Yin, Hoi-Sen Yong, Chien-Yi Chang, and Kok-Gan Chan
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ELIZABETHKINGIA ,DENTAL plaque ,DRUG resistance in bacteria ,BETA lactamases ,IMMUNOCOMPROMISED patients - Abstract
In this study, strain B2D isolated from a dental plaque sample of a human patient was studied for its general characteristics, taxonomic identification, genome features, and resistome profile. The bacterium exhibited antibiotic resistance to all beta-lactam antibiotics, nitrofuran, and sulfonamides, with high minimum inhibitory concentrations. It was only sensitive to the fluoroquinolone ciprofloxacin and intermediately susceptible to aminoglycoside tobramycin. A preliminary identification through 16S rRNA gene sequences revealed that it shared the highest sequence identity with Elizabethkingia anophelis subsp. endophytica JM-87
T (100%) and Elizabethkingia anophelis subsp. anophelis R26T (99.31%). The draft genome of strain B2D was approximately 3.9 Mbp with 50 contigs and 35.5% GC content. A 16S rRNA gene and core genes-based phylogenetic analyses revealed a close phylogenetic relationship between strain B2D and the other Elizabethkingia type strains. An above species level threshold average nucleotide identity value confirmed its taxonomic identity as Elizabethkingia anophelis. Furthermore, we conducted a resistome analysis of strain B2D and Elizabethkingia type strains, revealing the presence of widespread antibiotic resistance genes, including beta-lactamases and genes associated with cationic antiseptic resistance and glycopeptide resistance. Overall, the multidrug resistant profile of strain B2D as elucidated and confirmed through whole genome analysis indicated its potential as a reservoir of beta-lactamase genes. Moreover, its presence within dental plaque in the human oral cavity prompts speculation regarding its role as an opportunistic pathogen capable of causing infections, particularly in immunocompromised individuals. [ABSTRACT FROM AUTHOR]- Published
- 2024
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43. Complete Whole-Genome Sequence of Streptomyces sp. MUM 178J, a Potential Anti-Vibrio Agent.
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Ke-Yan Loo, Loh Teng-Hern Tan, Kah-Ooi Chua, Pusparajah, Priyia, Kok-Gan Chan, Learn-Han Lee, Woan-Fei Law, Jodi, and Letchumanan, Vengadesh
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WHOLE genome sequencing ,STREPTOMYCES ,ANTIBACTERIAL agents ,BIOACTIVE compounds ,MELANINS - Abstract
Streptomyces sp. is a group of filamentous, Gram-positive bacteria well known for their capabilities in producing bioactive compounds that have been used as novel drugs and lead in drug development. The Streptomyces sp. MUM 178J was isolated from a mangrove forest in Malaysia. This isolate was found to harbor anti-Vibrio properties as its crude extract inhibited the growth of multidrug-resistant Vibrio parahaemolyticus. Therefore, the strain was subjected to whole genome sequencing to unearth its genomic potential. The genome of Streptomyces sp. MUM 178J consists of 6,699,249 bp with a G+C content of 71.3%. 66 tRNA genes and 18 rRNA genes were also predicted to be present within the genome. Further analysis with the bioinformatics tool, antiSMASH (antibiotics & Secondary Metabolite Analysis Shell), detected nine biosynthetic gene clusters displaying more than 70% similarity to known gene clusters, including one associated with melanin production. Melanin has demonstrated antagonistic activity against the growth of members of the Vibrio family, including V. parahaemolyticus. This indicates the potential correlation between the production of melanin and the anti-Vibrio properties of MUM 178J. The availability of the whole genome sequence of Streptomyces sp. MUM 178J allows for future in-depth investigation and potential exploitation of MUM 178J to harvest useful bioactive compounds. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Surveillance, isolation and genomic characterization of Pteropine orthoreovirus of probable bat origin among patients with acute respiratory infection in Malaysia
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Kok Keng Tee, Po Qhuan Chan, Alson Mun‐Khin Loh, Sarbhan Singh, Chee How Teo, Thevambiga Iyadorai, Jack Bee Chook, Kim Tien Ng, Yutaka Takebe, Kok Gan Chan, I‐Ching Sam, and Kenny Voon
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Infectious Diseases ,Virology - Published
- 2023
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45. Through the Looking-Glass: A curious outbreak of extended-spectrum beta-lactamase-producing Escherichia coli in Aotearoa New Zealand
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White, Rhys Thomas, Ashcroft, Melinda M., Kok-Gan Chan, Teik-Min Chong, Forde, Brian M, Peters, Kate M., Minh-Duy Phan, Xiaoyun Ren, Schembri, Mark A, Yin, Wai-Fong, Williamson, Deborah A., Dyet, Kristin H., Beatson, Scott A., and De Ligt, Joep
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- 2023
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46. Treatment Costs for Patients with Streptococcus suis infection in Northern Thailand: A Hospital-based Observational Study of 14-year data
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Ajaree Rayanakorn, Wasan Katip, Zanfina Ademi, and Kok-Gan Chan
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Public Health, Environmental and Occupational Health - Abstract
Background Streptococcus suis (S.suis) is a neglected zoonotic disease that imposes a significant economic burden on healthcare and society. To our knowledge, studies estimating the cost of illness associated with S.suis treatment are limited, and no study focuses on treatment costs and potential key drivers in Thailand. This study aimed to estimate the direct medical costs associated with S.suis treatment in Thailand and identify key drivers affecting high treatment costs from the provider’s perspective. Methods A retrospective analysis of the 14-year data from 2005–2018 of confirmed S.suis patients admitted at Chiang Mai University Hospital (CMUH) was conducted. Descriptive statistics were used to summarize the data of patients’ characteristics, healthcare utilization and costs. The multiple imputation with predictive mean matching strategy was employed to deal with missing Glasgow Coma Scale (GCS) data. Generalized linear models (GLMs) were used to forecast costs model and identify determinants of costs associated with S.suis treatment. The modified Park test was adopted to determine the appropriate family. All costs were inflated applying the consumer price index for medical care and presented to the year 2019. Results Among 130 S.suis patients, the average total direct medical cost was 12,4675 Thai baht (THB) (US$ 4,016), of which the majority of expenses were from the “others” category (room charges, staff services and medical devices). Infective endocarditis (IE), GCS, length of stay, and bicarbonate level were significant predictors associated with high total treatment costs. Overall, marginal increases in IE and length of stay were significantly associated with increases in the total costs (standard error) by 132,443 THB (39,638 THB) and 5,490 THB (1,715 THB), respectively. In contrast, increases in GCS and bicarbonate levels were associated with decreases in the total costs (standard error) by 13,118 THB (5,026 THB) and 7,497 THB (3,430 THB), respectively. Conclusions IE, GCS, length of stay, and bicarbonate level were significant cost drivers associated with direct medical costs. Patients’ clinical status during admission significantly impacts the outcomes and total treatment costs. Early diagnosis and timely treatment were paramount to alleviate long-term complications and high healthcare expenditures.
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- 2022
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47. Patterns of Genomic Variations in the Plant Pathogen Dickeya solani
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Slimane Khayi, Denis Faure, Kok Gan Chan, Institut national de la recherche agronomique [Maroc] (INRA Maroc), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), JiangSu University, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), the CNRS, grant number I2BC-2022, and University of Malaya, grant number RMF1252-2021
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Microbiology (medical) ,population genomics ,Virology ,[SDV]Life Sciences [q-bio] ,soft rot ,horizontal gene transfer ,phylogenomics ,Microbiology - Abstract
International audience; The plant pathogen Dickeya solani causes soft rot and blackleg diseases in several crops including Solanum tuberosum. Unveiling the patterns of its diversity contributes to understanding the emergence and virulence of this pathogen in potato agro-systems. In this study, we analyzed the genome of several D. solani strains exhibiting an atypically high number of genetic variations. Variant calling and phylogenomics support the evidence that the strains RNS10-105-1A, A623S-20A-17 and RNS05.1.2A belong to a divergent sub-group of D. solani for which we proposed RNS05.1.2A as a reference strain. In addition, we showed that the variations (1253 to 1278 snp/indels) in strains RNS13-30-1A, RNS13-31-1A and RNS13-48-1A were caused by a horizontal gene transfer event from a donor belonging to the D. solani RNS05.1.2A subgroup. The overall results highlight the patterns driving the diversification in D. solani species. This work contributes to understanding patterns and causes of diversity in the emerging pathogen D. solani.
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- 2022
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48. Core members and differential abundance of chrysomelid microbiota in the life stages of Podontia affinis (Galerucinae) and adult Silana farinosa (Cassidinae, Coleoptera)
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Sze-Looi Song, Hoi-Sen Yong, Kah-Ooi Chua, Praphathip Eamsobhana, Phaik-Eem Lim, and Kok-Gan Chan
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Insecta ,Bacterial OTUs ,Arthropoda ,Ecology ,Chrysomelidae ,Chrysomeloidea ,Biota ,Cassidini ,Coleoptera ,Galerucinae ,Silana ,phytophagous ,Animalia ,Silana farinosa ,16S rRNA gene amplicon sequencing ,Cassidinae ,Ecology, Evolution, Behavior and Systematics - Abstract
The chrysomelid beetles Podontia affinis and Silana farinosa are members of the subfamilies Galerucinae and Cassidinae, respectively. This study, based on 16S rRNA gene-targeted metagenomics sequencing, reports the core members and differential abundance of bacterial communities in the larvae and adult beetles of P. affinis and the adult S. farinosa. Cyanobacteria/Melainabacteria group was the predominant phylum in the larvae of P. affinis, while Proteobacteria was the predominant phylum in adult P. affinis and S. farinosa. The number of Order, Family, Genus and Species OTUs in the adult stage of P. affinis was higher than that in the larval stage. The bacterial species richness of adult P. affinis was significantly higher than that of adult S. farinosa. Betaproteobacteria was the predominant class in adult P. affinis, Cyanobacteria in the larvae of P. affinis and Gammaproteobacteria in S. farinosa. The larvae and adult beetles of P. affinis and adult S. farinosa had a low number of unique and shared bacterial OTUs (> 5% relative abundance). The differences in the microbiota indicate possible differences in nutrient assimilation, host taxonomy and other stochastic processes. These findings provide new information to our understanding of the bacteria associated with specialist phytophagous chrysomelid beetles and beetles in general.
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- 2022
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49. Complete mitochondrial genome of Dacus vijaysegarani and phylogenetic relationships with congeners and other tephritid fruit flies (Insecta: Diptera)
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Hoi-Sen Yong, Yvonne Jing Mei Liew, Kah-Ooi Chua, Sze-Looi Song, Kok-Gan Chan, and Praphathip Eamsobhana
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Subfamily Dacinae ,Mitochondrial DNA ,Tephritoidea ,Insecta ,Lineage (evolution) ,Biology ,DNA, Mitochondrial ,Monophyly ,Phylogenetics ,Systematics ,Genetics ,Animals ,Bactrocera ,Molecular Biology ,Phylogeny ,Base Composition ,Base Sequence ,Phylogenetic tree ,Diptera ,Tephritidae ,High-Throughput Nucleotide Sequencing ,Subclade ,Tribe Dacini ,Sequence Analysis, DNA ,General Medicine ,biology.organism_classification ,Mitogenome ,Dacus ,Evolutionary biology ,Genome, Mitochondrial ,Original Article - Abstract
Background Tephritid fruit flies of the genus Dacus are members of the tribe Dacini, subfamily Dacinae. There are some 274 species worldwide, distributed in Africa and the Asia-Pacific. To date, only five complete mitochondrial genomes (mitogenomes) of Dacus fruit flies have been published and are available in the GenBank. Methods and results In view of the lack of study on their mitogenome, we sequenced (by next generation sequencing) and annotated the complete mitogenome of D. vijaysegarani from Malaysia to determine its features and phylogenetic relationship. The whole mitogenome of D. vijaysegarani has identical gene order with the published mitogenomes of the genus Dacus, with 13 protein-coding genes, two rRNA genes, 22 tRNAs, a non-coding A + T rich control region, and intergenic spacer and overlap sequences. Phylogenetic analysis based on 15 mitochondrial genes (13 PCGs and two rRNA genes), reveals Dacus, Zeugodacus and Bactrocera forming a distinct clade. The genus Dacus forms a monophyletic group in the subclade containing also the Zeugodacus group; this Dacus-Zeugodacus subclade is distinct from the Bactrocera subclade. D. (Mellesis) vijaysegarani forms a lineage with D. (Mellesis) trimacula in the subcluster containing also the lineage of D. (Mellesis) conopsoides and D. (Callantra) longicornis. D. (Dacus) bivittatus and D. (Didacus) ciliatus form a distinct subcluster. Based on cox1 sequences, the Malaysia and Vietnam taxa of D. vijaysegarani may not be conspecific. Conclusions Overall, the mitochondrial genome of D. vijaysegarani provided essential molecular data that could be useful for further studies for species diagnosis, evolution and phylogeny research of other tephritid fruit flies in the future. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-021-06608-2.
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- 2021
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50. Pseudomonas cremoricolorata Strain ND07 Produces N-acyl Homoserine Lactones as Quorum Sensing Molecules.
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Nina Yusrina Muhamad Yunos, Wen-Si Tan, Chong-Lek Koh, Choon-Kook Sam, Nur Izzati Mohamad, Pui-Wan Tan, Tan-Guan-Sheng Adrian, Wai-Fong Yin, and Kok-Gan Chan
- Published
- 2014
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