Displaying publications 81 - 100 of 991 in total

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  1. Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
    Verusingam ND, Chen YC, Lin HF, Liu CY, Lee MC, Lu KH, et al.
    J Chin Med Assoc, 2021 03 01;84(3):248-254.
    PMID: 33009209 DOI: 10.1097/JCMA.0000000000000438
    BACKGROUND: Lung cancer contributes to high cancer mortality worldwide with 80% of total cases diagnosed as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain serves as a druggable target in NSCLC patients with exon 19 deletion and L858R mutation. However, patients eventually succumbed to resistance to first- and second-generation EGFR-TK inhibitors through activation of T790M mutation. Third-generation EGFR-TKI, Osimertinib exhibits high efficacy in patients with exon 19 deletion/L858R/T790M mutation but they experienced acquired resistance thereafter. Available treatment options in NSCLC patients remains a challenge due to unknown molecular heterogeneity responsible for acquired resistance to EGFR-TKI. In this study, we aim to generate Osimertinib-resistant (OR) cells from H1975 carrying L858R/T790M double mutation which can be used as a model to elucidate mechanism of resistance.

    METHODS: OR cells were established via stepwise-dose escalation and limiting single-cell dilution method. We then evaluated Osimertinib resistance potential via cell viability assay. Proteins expression related to EGFR-signalling, epithelial to mesenchymal transition (EMT), and autophagy were analyzed via western blot.

    RESULTS: OR cell lines exhibited increased drug resistance potential compared to H1975. Distinguishable mesenchymal-like features were observed in OR cells. Protein expression analysis revealed EGFR-independent signaling involved in the derived OR cells as well as EMT and autophagy activity.

    CONCLUSION: We generated OR cell lines in-vitro as evidenced by increased drug resistance potential, increased mesenchymal features, and enhanced autophagy activity. Development of Osimertinib resistance cells may serve as in-vitro model facilitating discovery of molecular aberration present during acquired mechanism of resistance.

    Matched MeSH terms: Mutation/drug effects*
  2. Molecular target therapeutics of EGF-TKI and downstream signaling pathways in non-small cell lung cancers
    Liu CY, Lin HF, Lai WY, Lin YY, Lin TW, Yang YP, et al.
    J Chin Med Assoc, 2022 Apr 01;85(4):409-413.
    PMID: 35383703 DOI: 10.1097/JCMA.0000000000000703
    Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.
    Matched MeSH terms: Mutation
  3. Fulltext Predominance of G to A codon 12 mutation K-ras gene in Dukes' B colorectal cancer
    Zulhabri O, Rahman J, Ismail S, Isa MR, Wan Zurinah WN
    Singapore Med J, 2012 Jan;53(1):26-31.
    PMID: 22252179
    K-ras gene mutations in codons 12 and 13 are one of the earliest events in colon carcinogenesis.
    Matched MeSH terms: Mutation*
  4. Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations
    Ballinger SW, Schurr TG, Torroni A, Gan YY, Hodge JA, Hassan K, et al.
    Genetics, 1992 Jan;130(1):139-52.
    PMID: 1346259
    Human mitochondrial DNAs (mtDNAs) from 153 independent samples encompassing seven Asian populations were surveyed for sequence variation using the polymerase chain reaction (PCR), restriction endonuclease analysis and oligonucleotide hybridization. All Asian populations were found to share two ancient AluI/DdeI polymorphisms at nps 10394 and 10397 and to be genetically similar indicating that they share a common ancestry. The greatest mtDNA diversity and the highest frequency of mtDNAs with HpaI/HincII morph 1 were observed in the Vietnamese suggesting a Southern Mongoloid origin of Asians. Remnants of the founding populations of Papua New Guinea (PNG) were found in Malaysia, and a marked frequency cline for the COII/tRNA(Lys) intergenic deletion was observed along coastal Asia. Phylogenetic analysis indicates that both insertion and deletion mutations in the COII/tRNA(Lys) region have occurred more than once.
    Matched MeSH terms: Mutation/genetics
  5. Fulltext The association between GJB2 mutation and GJB6 gene in non syndromic hearing loss school children
    Asma A, Ashwaq A, Norzana AG, Atmadini AM, Ruszymah BH, Saim L, et al.
    Med J Malaysia, 2011 Jun;66(2):124-8.
    PMID: 22106692 MyJurnal
    Recently, molecular testing for GJB2 mutations has become the standard of care for the diagnosis of patients with non syndromic hearing impairment of unknown cause. The aims of this study are to determine the association between GJB2 mutation and GJB6 and to report the variation of mutations in deaf students who have heterozygous GJB2. This retrospective study was conducted at Universiti Kebangsaan Malaysia Medical Center (UKMMC). Data was collected from previous files and records from Tissue Engineering and Human Genetic Research Group Laboratory. Approval from Ethical Committee was obtained prior to the study. A total of 138 students have been screened in previous studies in UKMMC for the presence of GJB2 mutations as a cause for hearing loss. Thirty four of the 138 subjects have GJB2 mutations; 2 showed homozygous mutations whereas another 32 were heterozygous for GJB2 gene mutation. Only 31 DNA samples of students presented with sensorineural hearing loss with heterozygous mutation in GJB2 gene were included in this study. The sequencing results obtained were analyzed. The degree of hearing loss of those students with association between GJB2 mutation and GJB6 mutation will be discussed. Five out of 31 subjects (16.2%) have mutations in their GJB6 gene, suggesting a digenic inheritance of GJB2/GJB6 mutation. In total, four novel mutations were identified; E137D (n=1), R32Q (n=1), E101K (n=1) and Y156H (n=1) and one mutation deletion; 366delT (n=1). All students with association GJB2 mutation and GJB6 showed severe to profound hearing loss in both ears. Interestingly this study not detected the large deletion of 342 kb in GJB6 gene suggesting that the mutation is very rare in this region compared to certain parts of the world.
    Matched MeSH terms: Mutation/genetics*
  6. H274Y's Effect on Oseltamivir Resistance: What Happens Before the Drug Enters the Binding Site
    Yusuf M, Mohamed N, Mohamad S, Janezic D, Damodaran KV, Wahab HA
    J Chem Inf Model, 2016 Jan 25;56(1):82-100.
    PMID: 26703840 DOI: 10.1021/acs.jcim.5b00331
    Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.
    Matched MeSH terms: Mutation*
  7. Human Papillomavirus Infection, p16INK4a Expression and Genetic Alterations in Vietnamese Cervical Neuroendocrine Cancer
    Van Ta T, Nguyen QN, Truong VL, Tran TT, Nguyen HP, Vuong LD
    Malays J Med Sci, 2019 Sep;26(5):151-157.
    PMID: 31728128 DOI: 10.21315/mjms2019.26.5.15
    Neuroendocrine cervical cancer is a rare subtype of cervical cancer with a highly aggressive malignancy. This study was conducted to analyse the human papillomavirus (HPV) infection and molecular abnormalities in Vietnamese neuroendocrine carcinomas of the uterine cervix. HPV genotyping and p53 mutations were examined using polymerase chain reaction (PCR)-based direct sequencing. Mutations of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF) were identified using commercial kits. Four high-risk HPV genotypes were identified in 26 (86.7%) out of a total of 30 tumours. The prevalence of HPV 16, 18, 31 and 45 was 20.0%, 50.0%, 20.0% and 36.7%, respectively. Overexpression of p16INK4a was observed in 93.3% of cases and was significantly correlated with high-risk HPV infections. Furthermore, p53 and NRAS mutations were detected in five (16.7%) and one (3.3%) cases, respectively, whereas no EGFR, KRAS or BRAF mutations were observed. These results demonstrate that high-risk HPV infection may be an important oncogenic factor for the development and progression of cervical neuroendocrine carcinoma.
    Matched MeSH terms: Mutation
  8. Fulltext Characterization of malaria infection at two border areas of Thailand adjoining with Myanmar and Malaysia
    Sermwittayawong N, Nishibuchi M, Sawangjaroen N, Vuddhakul V
    Southeast Asian J. Trop. Med. Public Health, 2015 Jul;46(4):551-7.
    PMID: 26867373
    During 2009 to 2010, a total of 408 blood samples collected from malaria patients in Ranong (149) and Yala (259) Provinces, Thailand were investigated for Plasmodium spp using microscopic examination. There are no statistical differences in the prevalence of P. falciparum and P. vivax in samples collected from Ranong and Yala (46% vs 52%, and 54% vs 45%, respectively). Single nucleotide polymorphism of codon 86 in pfmdr1 (encoding P. falciparum multidrug resistance protein 1) was investigated among 75 samples of P. falciparum and 2 samples of P. knowlesi. A pfmdr1 N86Y mutation was detected in 1 out of 29 samples and 45 out of 46 samples obtained from Ranong and Yala Provinces, respectively. It is interesting that pfmdr1 was detected in two P. knowlesi DNA samples obtained previously from Ranong Province which was 99% homologous to pfmdr1 obtained from falciparum parasites in the same area but the mutation was not observed. The difference in multidrug resistance protein in Plasmodium obtained from those two border areas of Thailand will be of use in monitoring drug resistance in these border regions of the country.
    Matched MeSH terms: Mutation
  9. Fulltext Monoclonal antibody-escape variant of dengue virus serotype 1: Genetic composition and envelope protein expression
    Chem YK, Chua KB, Malik Y, Voon K
    Trop Biomed, 2015 Jun;32(2):344-51.
    PMID: 26691263 MyJurnal
    Monoclonal antibody-escape variant of dengue virus type 1 (MabEV DEN-1) was discovered and isolated in an outbreak of dengue in Klang Valley, Malaysia from December 2004 to March 2005. This study was done to investigate whether DEN152 (an isolate of MabEV DEN-1) is a product of recombination event or not. In addition, the non-synonymous mutations that correlate with the monoclonal antibody-escape variant were determined in this study. The genomes of DEN152 and two new DEN-1 isolates, DENB04 and DENK154 were completely sequenced, aligned, and compared. Phylogenetic tree was plotted and the recombination event on DEN152 was investigated. DEN152 is sub-grouped under genotype I and is closely related genetically to a DEN-1 isolated in Japan in 2004. DEN152 is not a recombinant product of any parental strains. Four amino acid substitutions were unique only to DEN 152. These amino acid substitutions were (Ser)[326](Leu), (Ser)[340](Leu) at the deduced E protein, (Ile)[250](Thr) at NS1 protein, and (Thr)[41](Ser) at NS5 protein. Thus, DEN152 is an isolate of the emerging monoclonal antibody-escape variant DEN-1 that escaped diagnostic laboratory detection.
    Matched MeSH terms: Mutation, Missense*
  10. A novel complex mutation of the OTC (ornithine transcarbamylase) gene in a Malaysian pedigree
    Khoo AS, Balraj P, Rachedi A, Chin CN, Volpi L
    Hum Mutat, 1999 Nov;14(5):448.
    PMID: 10533073
    Matched MeSH terms: Frameshift Mutation
  11. An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome
    Balraj P, Concannon P, Jamal R, Beghini A, Hoe TS, Khoo AS, et al.
    Mutat Res, 2002 Oct 31;508(1-2):99-105.
    PMID: 12379465
    Rothmund-Thomson syndrome (OMIM #268400) is a severe autosomal recessive genodermatosis: characterised by growth retardation, hyperpigmentation and frequently accompanied by congenital bone defects, brittle hair and hypogonadism. Mutations in helicase RECQ4 gene are responsible for a subset of cases of RTS. Only six mutations have been reported, thus, far and each affecting the coding sequence or the splice junctions. We report the first homozygous mutation in RECQ4 helicase: 2746-2756-delTGGGCTGAGGC in IVS8 responsible for the severe phenotype associated with RTS in a Malaysian pedigree. We report also a 5321 G-->A transition in exon 17 and the updated list of the RECQ4 gene mutations.
    Matched MeSH terms: Mutation*
  12. Fulltext Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction
    den Hoed J, de Boer E, Voisin N, Dingemans AJM, Guex N, Wiel L, et al.
    Am J Hum Genet, 2021 02 04;108(2):346-356.
    PMID: 33513338 DOI: 10.1016/j.ajhg.2021.01.007
    Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.
    Matched MeSH terms: Mutation*; Mutation, Missense
  13. Fulltext The distribution and host range of the banana Fusarium wilt fungus, Fusarium oxysporum f. sp. cubense, in Asia
    Mostert D, Molina AB, Daniells J, Fourie G, Hermanto C, Chao CP, et al.
    PLoS One, 2017;12(7):e0181630.
    PMID: 28719631 DOI: 10.1371/journal.pone.0181630
    Fusarium oxysporum formae specialis cubense (Foc) is a soil-borne fungus that causes Fusarium wilt, which is considered to be the most destructive disease of bananas. The fungus is believed to have evolved with its host in the Indo-Malayan region, and from there it was spread to other banana-growing areas with infected planting material. The diversity and distribution of Foc in Asia was investigated. A total of 594 F. oxysporum isolates collected in ten Asian countries were identified by vegetative compatibility groups (VCGs) analysis. To simplify the identification process, the isolates were first divided into DNA lineages using PCR-RFLP analysis. Six lineages and 14 VCGs, representing three Foc races, were identified in this study. The VCG complex 0124/5 was most common in the Indian subcontinent, Vietnam and Cambodia; whereas the VCG complex 01213/16 dominated in the rest of Asia. Sixty-nine F. oxysporum isolates in this study did not match any of the known VCG tester strains. In this study, Foc VCG diversity in Bangladesh, Cambodia and Sri Lanka was determined for the first time and VCGs 01221 and 01222 were first reported from Cambodia and Vietnam. New associations of Foc VCGs and banana cultivars were recorded in all the countries where the fungus was collected. Information obtained in this study could help Asian countries to develop and implement regulatory measures to prevent the incursion of Foc into areas where it does not yet occur. It could also facilitate the deployment of disease resistant banana varieties in infested areas.
    Matched MeSH terms: Mutation
  14. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review
    Prinz JC, Choon SE, Griffiths CEM, Merola JF, Morita A, Ashcroft DM, et al.
    J Eur Acad Dermatol Venereol, 2023 Feb;37(2):256-273.
    PMID: 36331364 DOI: 10.1111/jdv.18720
    Generalized pustular psoriasis (GPP) is a rare auto-inflammatory skin disease characterised by acute episodes of sterile pustule formation. Diagnosis and treatment of the disease have historically been complicated by a lack of awareness, and no consistent global definition or clinical coding standards. Now acknowledged as a distinct clinical entity with a recognised genetic component, GPP can take a serious and life-threatening course due to systemic inflammatory complications and its association with various comorbidities. As with other rare diseases, there are significant challenges to understanding the epidemiology of GPP, notably a small patient population, non-standardised study methodologies and ethnic differences in its presentation. A clearer understanding of GPP is therefore required for clinicians to better manage patients with this rare condition. In this review article, we present an overview of the available data on GPP prevalence estimates in key demographics and report the frequency of genetic mutations associated with the disease. We detail the incidence of known comorbidities and summarise the data on mortality and assigned causes of death. Lastly, we discuss the various factors that impact the collection, interpretation and comparison of these data.
    Matched MeSH terms: Mutation
  15. Cuticle thickening associated with fenitrothion and imidacloprid resistance and influence of voltage-gated sodium channel mutations on pyrethroid resistance in the tropical bed bug, Cimex hemipterus
    Soh LS, Veera Singham G
    Pest Manag Sci, 2021 Nov;77(11):5202-5212.
    PMID: 34272799 DOI: 10.1002/ps.6561
    BACKGROUND: The common bed bug, Cimex lectularius L., and the tropical bed bug, Cimex hemipterus (F.), are now widely regarded as important public health pests following their rapid global resurgence, largely due to insecticide resistance and an increased rate of global travel. The insecticide resistance mechanisms are well documented in C. lectularius, however, only one mechanism is validated in C. hemipterus thus far. This demands further understanding on the resistance mechanisms involved in C. hemipterus.

    RESULTS: Here, we identified differences in resistance to fenitrothion (organophosphate) and imidacloprid (neonicotinoid) related cuticle thickness in C. hemipterus. There is evidence of a possible association between cuticle thickness and resistance, but the association can be tenuous, likely because resistance is multifactorial in C. hemipterus. We also discovered a novel T1011 residue in domain IIS6 of the voltage-gated sodium channel that likely enhanced susceptibility to deltamethrin (pyrethroid) despite the presence of a L1014F mutation known to confer pyrethroid resistance in C. hemipterus. Our findings also confirmed that the M918I mutation enhanced resistance to pyrethroid when present with the L1014F mutation, which was consistent with a super-kdr phenotype, as reported previously. Multiple resistance mechanisms can be found within a single C. hemipterus population, and the presence of both M918I + L1014F mutations likely masked the influence of cuticle thickness in conferring resistance against deltamethrin. The elevated metabolic enzyme activities in some strains were not necessarily associated with increased insecticide resistance.

    CONCLUSION: This study has enhanced our understanding on the penetration resistance mechanism and target site insensitivity of sodium channels in C. hemipterus.

    Matched MeSH terms: Mutation
  16. Fulltext DARS-associated leukoencephalopathy can mimic a steroid-responsive neuroinflammatory disorder
    Wolf NI, Toro C, Kister I, Latif KA, Leventer R, Pizzino A, et al.
    Neurology, 2015 Jan 20;84(3):226-30.
    PMID: 25527264 DOI: 10.1212/WNL.0000000000001157
    To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset.
    Matched MeSH terms: Mutation/genetics*
  17. Fulltext Quantum changes in Helicobacter pylori gene expression accompany host-adaptation
    Chua EG, Wise MJ, Khosravi Y, Seow SW, Amoyo AA, Pettersson S, et al.
    DNA Res, 2017 Feb 01;24(1):37-49.
    PMID: 27803027 DOI: 10.1093/dnares/dsw046
    Helicobacter pylori is a highly successful gastric pathogen. High genomic plasticity allows its adaptation to changing host environments. Complete genomes of H. pylori clinical isolate UM032 and its mice-adapted serial derivatives 298 and 299, generated using both PacBio RS and Illumina MiSeq sequencing technologies, were compared to identify novel elements responsible for host-adaptation. The acquisition of a jhp0562-like allele, which encodes for a galactosyltransferase, was identified in the mice-adapted strains. Our analysis implies a new β-1,4-galactosyltransferase role for this enzyme, essential for Ley antigen expression. Intragenomic recombination between babA and babB genes was also observed. Further, we expanded on the list of candidate genes whose expression patterns have been mediated by upstream homopolymer-length alterations to facilitate host adaption. Importantly, greater than four-fold reduction of mRNA levels was demonstrated in five genes. Among the down-regulated genes, three encode for outer membrane proteins, including BabA, BabB and HopD. As expected, a substantial reduction in BabA protein abundance was detected in mice-adapted strains 298 and 299 via Western analysis. Our results suggest that the expression of Ley antigen and reduced outer membrane protein expressions may facilitate H. pylori colonisation of mouse gastric epithelium.
    Matched MeSH terms: Mutation
  18. Fulltext Eukaryotic pathways targeted by the type III secretion system effector protein, BipC, involved in the intracellular lifecycle of Burkholderia pseudomallei
    Kang WT, Vellasamy KM, Vadivelu J
    Sci Rep, 2016 09 16;6:33528.
    PMID: 27634329 DOI: 10.1038/srep33528
    Burkholderia pseudomallei, the etiological agent for melioidosis, is known to secrete a type III secretion system (TTSS) protein into the host's internal milieu. One of the TTSS effector protein, BipC, has been shown to play an important role in the B. pseudomallei pathogenesis. To identify the host response profile that was directly or indirectly regulated by this protein, genome-wide transcriptome approach was used to examine the gene expression profiles of infected mice. The transcriptome analysis of the liver and spleen revealed that a total of approximately 1,000 genes were transcriptionally affected by BipC. Genes involved in bacterial invasion, regulation of actin cytoskeleton, and MAPK signalling pathway were over-expressed and may be specifically regulated by BipC in vivo. These results suggest that BipC mainly targets pathways related to the cellular processes which could modulate the cellular trafficking processes. The host transcriptional response exhibited remarkable differences with and without the presence of the BipC protein. Overall, the detailed picture of this study provides new insights that BipC may have evolved to efficiently manipulate host-cell pathways which is crucial in the intracellular lifecycle of B. pseudomallei.
    Matched MeSH terms: Mutation/genetics
  19. Characterization of Coconut cadang-cadang viroid variants from oil palm affected by orange spotting disease in Malaysia
    Wu YH, Cheong LC, Meon S, Lau WH, Kong LL, Joseph H, et al.
    Arch Virol, 2013 Jun;158(6):1407-10.
    PMID: 23397332 DOI: 10.1007/s00705-013-1624-8
    A 246-nt variant of Coconut cadang-cadang viroid (CCCVd) has been identified and described from oil palms with orange spotting symptoms in Malaysia. Compared with the 246-nt form of CCCVd from coconut, the oil palm variant substituted C(31)→U in the pathogenicity domain and G(70)→C in the central conserved domain. This is the first sequence reported for a 246-nt variant of CCCVd in oil palms expressing orange spotting symptoms.
    Matched MeSH terms: Point Mutation/genetics
  20. Fulltext PreS1 Mutations Alter the Large HBsAg Antigenicity of a Hepatitis B Virus Strain Isolated in Bangladesh
    Hossain MG, Mahmud MM, Nazir KHMNH, Ueda K
    Int J Mol Sci, 2020 Jan 15;21(2).
    PMID: 31952213 DOI: 10.3390/ijms21020546
    Mutations in the hepatitis B virus (HBV) genome can potentially lead to vaccination failure, diagnostic escape, and disease progression. However, there are no reports on viral gene expression and large hepatitis B surface antigen (HBsAg) antigenicity alterations due to mutations in HBV isolated from a Bangladeshi population. Here, we sequenced the full genome of the HBV isolated from a clinically infected patient in Bangladesh. The open reading frames (ORFs) (P, S, C, and X) of the isolated HBV strain were successfully amplified and cloned into a mammalian expression vector. The HBV isolate was identified as genotype C (sub-genotype C2), serotype adr, and evolutionarily related to strains isolated in Indonesia, Malaysia, and China. Clinically significant mutations, such as preS1 C2964A, reverse transcriptase domain I91L, and small HBsAg N3S, were identified. The viral P, S, C, and X genes were expressed in HEK-293T and HepG2 cells by transient transfection with a native subcellular distribution pattern analyzed by immunofluorescence assay. Western blotting of large HBsAg using preS1 antibody showed no staining, and preS1 ELISA showed a significant reduction in reactivity due to amino acid mutations. This mutated preS1 sequence has been identified in several Asian countries. To our knowledge, this is the first report investigating changes in large HBsAg antigenicity due to preS1 mutations.
    Matched MeSH terms: Mutation*
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