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  1. Species delimitation with gene flow: A methodological comparison and population genomics approach to elucidate cryptic species boundaries in Malaysian Torrent Frogs
    Chan KO, Alexander AM, Grismer LL, Su YC, Grismer JL, Quah ESH, et al.
    Mol Ecol, 2017 Oct;26(20):5435-5450.
    PMID: 28802073 DOI: 10.1111/mec.14296
    Accurately delimiting species boundaries is a nontrivial undertaking that can have significant effects on downstream inferences. We compared the efficacy of commonly used species delimitation methods (SDMs) and a population genomics approach based on genomewide single-nucleotide polymorphisms (SNPs) to assess lineage separation in the Malaysian Torrent Frog Complex currently recognized as a single species (Amolops larutensis). First, we used morphological, mitochondrial DNA and genomewide SNPs to identify putative species boundaries by implementing noncoalescent and coalescent-based SDMs (mPTP, iBPP, BFD*). We then tested the validity of putative boundaries by estimating spatiotemporal gene flow (fastsimcoal2, ABBA-BABA) to assess the extent of genetic isolation among putative species. Our results show that the A. larutensis complex runs the gamut of the speciation continuum from highly divergent, genetically isolated lineages (mean Fst  = 0.9) to differentiating populations involving recent gene flow (mean Fst  = 0.05; Nm  > 5). As expected, SDMs were effective at delimiting divergent lineages in the absence of gene flow but overestimated species in the presence of marked population structure and gene flow. However, using a population genomics approach and the concept of species as separately evolving metapopulation lineages as the only necessary property of a species, we were able to objectively elucidate cryptic species boundaries in the presence of past and present gene flow. This study does not discount the utility of SDMs but highlights the danger of violating model assumptions and the importance of carefully considering methods that appropriately fit the diversification history of a particular system.
    Matched MeSH terms: DNA, Mitochondrial
  2. Fulltext Data on partial polyhydroxyalkanoate synthase genes (phaC) mined from Aaptos aaptos marine sponge-associated bacteria metagenome
    Amelia TSM, Amirul AA, Bhubalan K
    Data Brief, 2018 Feb;16:75-80.
    PMID: 29188224 DOI: 10.1016/j.dib.2017.11.011
    We report data associated with the identification of three polyhydroxyalkanoate synthase genes (phaC) isolated from the marine bacteria metagenome of Aaptos aaptos marine sponge in the waters of Bidong Island, Terengganu, Malaysia. Our data describe the extraction of bacterial metagenome from sponge tissue, measurement of purity and concentration of extracted metagenome, polymerase chain reaction (PCR)-mediated amplification using degenerate primers targeting Class I and II phaC genes, sequencing at First BASE Laboratories Sdn Bhd, and phylogenetic analysis of identified and known phaC genes. The partial nucleotide sequences were aligned, refined, compared with the Basic Local Alignment Search Tool (BLAST) databases, and released online in GenBank. The data include the identified partial putative phaC and their GenBank accession numbers, which are Rhodocista sp. phaC (MF457754), Pseudomonas sp. phaC (MF437016), and an uncultured bacterium AR5-9d_16 phaC (MF457753).
    Matched MeSH terms: DNA Primers
  3. Fulltext Small, Enigmatic Plasmids of the Nosocomial Pathogen, Acinetobacter baumannii: Good, Bad, Who Knows?
    Lean SS, Yeo CC
    Front Microbiol, 2017;8:1547.
    PMID: 28861061 DOI: 10.3389/fmicb.2017.01547
    Acinetobacter baumannii is a Gram-negative nosocomial pathogen that has become a serious healthcare concern within a span of two decades due to its ability to rapidly acquire resistance to all classes of antimicrobial compounds. One of the key features of the A. baumannii genome is an open pan genome with a plethora of plasmids, transposons, integrons, and genomic islands, all of which play important roles in the evolution and success of this clinical pathogen, particularly in the acquisition of multidrug resistance determinants. An interesting genetic feature seen in majority of A. baumannii genomes analyzed is the presence of small plasmids that usually ranged from 2 to 10 kb in size, some of which harbor antibiotic resistance genes and homologs of plasmid mobilization genes. These plasmids are often overlooked when compared to their larger, conjugative counterparts that harbor multiple antibiotic resistance genes and transposable elements. In this mini-review, we will examine our current knowledge of these small A. baumannii plasmids and look into their genetic diversity and phylogenetic relationships. Some of these plasmids, such as the Rep-3 superfamily group and the pRAY-type, which has no recognizable replicase genes, are quite widespread among diverse A. baumannii clinical isolates worldwide, hinting at their usefulness to the lifestyle of this pathogen. Other small plasmids especially those from the Rep-1 superfamily are truly enigmatic, encoding only hypothetical proteins of unknown function, leading to the question of whether these small plasmids are "good" or "bad" to their host A. baumannii.
    Matched MeSH terms: DNA Transposable Elements
  4. Fulltext Identification and Preliminary Evaluation of a Novel Recombinant Protein for Serodiagnosis of Strongyloidiasis
    Arifin N, Yunus MH, Nolan TJ, Lok JB, Noordin R
    Am J Trop Med Hyg, 2018 04;98(4):1165-1170.
    PMID: 29436335 DOI: 10.4269/ajtmh.17-0697
    Strongyloides stercoralis is a human parasite that can cause a long-term infection. In immunosuppressed patients, strongyloidiasis may be fatal when there is overwhelming autoinfection resulting in the migration of large numbers of larvae through many organs. Definitive diagnosis is still a challenge, and a combination of symptoms, microscopic identification, and serology test results are often used to arrive at a clinical decision. However, intermittent larval excretion, low parasite burden, and occult infections are challenges with parasitological diagnosis of infection with S. stercoralis. Meanwhile, serologic tests using immunoglobulin G and parasite antigen extract have problems of cross-reactivity with other helminthic infections. Recombinant antigen-based serodiagnosis is a good alternative to overcome the laboratory diagnostic issues. Herein, we report on the isolation of cDNA clone encoding an antigen of potential diagnostic value identified from immunoscreening of a S. stercoralis cDNA library. The translated protein had highest similarity to Strongyloides ratti immunoglobulin-binding protein 1. The recombinant antigen produced, rSs1a, was assessed using western blot and enzyme-linked immunosorbent assay. The latter showed 96% diagnostic sensitivity and 93% specificity; thus, rSs1a has good potential for use in serodiagnosis of human strongyloidiasis.
    Matched MeSH terms: DNA, Complementary
  5. Fulltext Streptomyces colonosanans sp. nov., A Novel Actinobacterium Isolated from Malaysia Mangrove Soil Exhibiting Antioxidative Activity and Cytotoxic Potential against Human Colon Cancer Cell Lines
    Law JW, Ser HL, Duangjai A, Saokaew S, Bukhari SI, Khan TM, et al.
    Front Microbiol, 2017;8:877.
    PMID: 28559892 DOI: 10.3389/fmicb.2017.00877
    Streptomyces colonosanans MUSC 93JT, a novel strain isolated from mangrove forest soil located at Sarawak, Malaysia. The bacterium was noted to be Gram-positive and to form light yellow aerial and vivid yellow substrate mycelium on ISP 2 agar. The polyphasic approach was used to determine the taxonomy of strain MUSC 93JT and the strain showed a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. Phylogenetic and 16S rRNA gene sequence analysis indicated that closely related strains include Streptomyces malachitofuscus NBRC 13059T (99.2% sequence similarity), Streptomyces misionensis NBRC 13063T (99.1%), and Streptomyces phaeoluteichromatogenes NRRL 5799T (99.1%). The DNA-DNA relatedness values between MUSC 93JT and closely related type strains ranged from 14.4 ± 0.1 to 46.2 ± 0.4%. The comparison of BOX-PCR fingerprints indicated MUSC 93JT exhibits a unique DNA profile. The genome of MUSC 93JT consists of 7,015,076 bp. The DNA G + C content was determined to be 69.90 mol%. The extract of strain MUSC 93JT was demonstrated to exhibit potent antioxidant activity via ABTS, metal chelating, and SOD assays. This extract also exhibited anticancer activity against human colon cancer cell lines without significant cytotoxic effect against human normal colon cells. Furthermore, the chemical analysis of the extract further emphasizes the strain is producing chemo-preventive related metabolites. Based on this polyphasic study of MUSC 93JT, it is concluded that this strain represents a novel species, for which the name Streptomyces colonosanans sp. nov. is proposed. The type strain is MUSC 93JT (= DSM 102042T = MCCC 1K02298T).
    Matched MeSH terms: DNA
  6. Fulltext Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML
    Islam M, Mohamed Z, Assenov Y
    Int J Genomics, 2017;2017:2913648.
    PMID: 28713819 DOI: 10.1155/2017/2913648
    Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T (9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.
    Matched MeSH terms: DNA Methylation
  7. Fulltext In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3
    Hanafi MMM, Afzan A, Yaakob H, Aziz R, Sarmidi MR, Wolfender JL, et al.
    Front Pharmacol, 2017;8:895.
    PMID: 29326585 DOI: 10.3389/fphar.2017.00895
    This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 μg/mL, SRB staining of PC3 cells) were further fractionated. Active compound/s were dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3 and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D invasion were tested by exclusion assays and modified Boyden chamber, respectively. Their mechanisms of action on these tests were further studied by measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by nuclear DNA fragmentation. This was accompanied by an increase in MMP depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3 and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO, down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Both plant extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene expressions (P < 0.001). LC-MS dereplication using taxonomy filters and molecular networking databases identified isovitexin in FD1c; and oleanolic acid, moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis by activating of the intrinsic pathway, (2) inhibition of both migration and invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by modulating VEGF-A expression. Moreover, isovitexin is here reported for the first time as an antiproliferative principle (IC50 = 43 μg/mL, SRB staining of PC3 cells).
    Matched MeSH terms: DNA Fragmentation
  8. Genomic analyses of five Roseivirga species: Insights into marine adaptation
    Selvaratnam C, Thevarajoo S, Goh KM, Chan KG, Chong CS
    Mar Genomics, 2018 Apr;38:97-101.
    PMID: 29306571 DOI: 10.1016/j.margen.2017.12.008
    To date, the genus Roseivirga consists of six species with one subspecies and is one of the least-studied genera among the family Flammeovirgaceae. In order to further explore this genus, the genome sequences of five Roseivirga spp. were compared and described in this study. The Roseivirga genomes have similar sizes in the range of 4.08-4.47Mb with an average of 4.22Mb. Several key proteins related to osmotic stress adaptation were identified in Roseivirga spp. including betaine transporter, choline dehydrogenase, and glutamate synthases. Significant amount of proteins associated with amino acid transport and metabolism were also present in Roseivirga genome. All five Roseivirga spp. were able to grow in medium contained casamino acids (mixture of amino acids) as sole carbon or nitrogen sources. Taken together, these findings suggested the potential role of Roseivirga in decomposing organic nitrogen matter in marine environment.
    Matched MeSH terms: Sequence Analysis, DNA
  9. Occurrence of Blastocystis sp. in water catchments at Malay villages and Aboriginal settlement during wet and dry seasons in Peninsular Malaysia
    Noradilah SA, Lee IL, Anuar TS, Salleh FM, Abdul Manap SN, Mohd Mohtar NS, et al.
    PeerJ, 2016;4:e2541.
    PMID: 27761331
    In the tropics, there are too few studies on isolation of Blastocystis sp. subtypes from water sources; in addition, there is also an absence of reported studies on the occurrence of Blastocystis sp. subtypes in water during different seasons. Therefore, this study was aimed to determine the occurrence of Blastocystis sp. subtypes in river water and other water sources that drained aboriginal vicinity of highly endemic intestinal parasitic infections during wet and dry seasons. Water samples were collected from six sampling points of Sungai Krau (K1-K6) and a point at Sungai Lompat (K7) and other water sources around the aboriginal villages. The water samples were collected during both seasons, wet and dry seasons. Filtration of the water samples were carried out using a flatbed membrane filtration system. The extracted DNA from concentrated water sediment was subjected to single round polymerase chain reaction and positive PCR products were subjected to sequencing. All samples were also subjected to filtration and cultured on membrane lactose glucuronide agar for the detection of faecal coliforms. During wet season, Blastocystis sp. ST1, ST2 and ST3 were detected in river water samples. Blastocystis sp. ST3 occurrence was sustained in the river water samples during dry season. However Blastocystis sp. ST1 and ST2 were absent during dry season. Water samples collected from various water sources showed contaminations of Blastocystis sp. ST1, ST2, ST3 and ST4, during wet season and Blastocystis sp. ST1, ST3, ST8 and ST10 during dry season. Water collected from all river sampling points during both seasons showed growth of Escherichia coli and Enterobacter aerogenes, indicating faecal contamination. In this study, Blastocystis sp. ST3 is suggested as the most robust and resistant subtype able to survive in any adverse environmental condition. Restriction and control of human and animal faecal contaminations to the river and other water sources shall prevent the transmission of Blastocystis sp. to humans and animals in this aboriginal community.
    Matched MeSH terms: DNA
  10. The first riparian skink (Genus: Sphenomorphus Strauch, 1887) from Peninsular Malaysia and its relationship to other Indochinese and Sundaic species
    Sumarli A, Grismer LL, Wood PL, Ahmad AB, Rizal S, Ismail LH, et al.
    Zootaxa, 2016 Oct 02;4173(1):29-44.
    PMID: 27701201 DOI: 10.11646/zootaxa.4173.1.3
    Recently discovered populations of skinks of the genus Sphenomorphus from central Peninsular Malaysia represent a new species, S. sungaicolus sp. nov., and the first riparian skink known from Peninsular Malaysia. Morphological analyses of an earlier specimen reported as S. tersus from the Forest Research Institute of Malaysia (FRIM), Selangor indicate that it too is the new riparian species S. sungaicolus sp. nov. Additionally, two specimens from the Tembat Forest Reserve, Hulu Terengganu, Kelantan and another from Ulu Gombak, Selangor have been diagnosed as new the species. The latter specimen remained unidentified in the Bernice Pauahi Bishop Museum, Honolulu, Hawaii since its collection in June 1962. Morphological and molecular analyses demonstrate that S. sungaicolus sp. nov. forms a clade with the Indochinese species S. maculatus, S. indicus, and S. tersus and is the sister species of the latter. Sphenomorphus sungaicolus sp. nov. can be differentiated from all other members of this clade by having a smaller SVL (66.5-89.6 mm); 39-44 midbody scale rows; 72-81 paravertebral scales; 74-86 ventral scales; a primitive plantar scale arrangement; and 20-22 scale rows around the tail at the position of the 10th subcaudal.
    Matched MeSH terms: Sequence Analysis, DNA
  11. Speciation in Indo-Pacific swiftlets (Aves: Apodidae): integrating molecular and phenotypic data for a new provisional taxonomy of the Collocalia esculenta complex
    Rheindt FE, Christidis L, Norman JA, Eaton JA, Sadanandan KR, Schodde R
    Zootaxa, 2017 Apr 07;4250(5):401-433.
    PMID: 28609999 DOI: 10.11646/zootaxa.4250.5.1
    White-bellied swiftlets of the Collocalia esculenta complex constitute a radiation of colony-breeding swifts distributed throughout the tropical Indo-Pacific region. Resolution of their taxonomy is challenging due to their morphological uniformity. To analyze the evolutionary history of this complex, we combine new biometric measurements and results from plumage assessment of museum specimens with novel as well as previously published molecular data. Together, this body of information constitutes the largest systematic dataset for white-bellied swiftlets yet compiled, drawn from 809 individuals belonging to 32 taxa for which new molecular, biometric, and/or plumage data are presented. We propose changing the classification of white-bellied swiftlets, for which two species are currently recognized, to elevate eight regional forms to species level, and we also describe two new subspecies. The ten taxa we recommend recognizing at the species level are: Collocalia linchi (Java to Lombok, Sumatran hills), C. dodgei (montane Borneo), C. natalis (Christmas Island), C. affinis (Greater Sundas, including the Thai-Malay Peninsula and Andaman-Nicobar Islands), C. marginata (Philippines), C. isonota (Philippines), C. sumbawae (west Lesser Sundas), C. neglecta (east Lesser Sundas), C. esculenta (Sulawesi, Moluccas, New Guinea, Bismarck Archipelago, Solomon Islands), and C. uropygialis (Vanuatu, New Caledonia). Future molecular and morphological work is needed to resolve questions of speciation and population affinities in the Philippines, Christmas Island, Wallacea and central Melanesia, and to shed light on historic diversification and patterns of gene flow in the complex.
    Matched MeSH terms: DNA, Mitochondrial
  12. Fulltext Development and immunogenic potentials of chitosan-saponin encapsulated DNA vaccine against avian infectious bronchitis coronavirus
    Bande F, Arshad SS, Bejo MH, Omar AR, Moeini H, Khadkodaei S, et al.
    Microb Pathog, 2020 Dec;149:104560.
    PMID: 33068733 DOI: 10.1016/j.micpath.2020.104560
    Infectious Bronchitis (IB) is an economically important avian disease that considerably threatens the global poultry industry. This is partly, as a result of its negative consequences on egg production, weight gain as well as mortality rate.The disease is caused by a constantly evolving avian infectious bronchitis virus whose isolates are classified into several serotypes and genotypes that demonstrate little or no cross protection. In order to curb the menace of the disease therefore, broad based vaccines are urgently needed. The aim of this study was to develop a recombinant DNA vaccine candidate for improved protection of avian infectious bronchitis in poultry. Using bioinformatics and molecular cloning procedures, sets of monovalent and bivalent DNA vaccine constructs were developed based on the S1 glycoprotein from classical and variants IBV strains namely, M41 and CR88 respectively. The candidate vaccine was then encapsulated with a chitosan and saponin formulated nanoparticle for enhanced immunogenicity and protective capacity. RT-PCR assay and IFAT were used to confirm the transcriptional and translational expression of the encoded proteins respectively, while ELISA and Flow-cytometry were used to evaluate the immunogenicity of the candidate vaccine following immunization of various SPF chicken groups (A-F). Furthermore, histopathological changes and virus shedding were determined by quantitative realtime PCR assay and lesion scoring procedure respectively following challenge of various subgroups with respective wild-type IBV viruses. Results obtained from this study showed that, groups vaccinated with a bivalent DNA vaccine construct (pBudCR88-S1/M41-S1) had a significant increase in anti-IBV antibodies, CD3+ and CD8+ T-cells responses as compared to non-vaccinated groups. Likewise, the bivalent vaccine candidate significantly decreased the oropharyngeal and cloacal virus shedding (p < 0.05) compared to non-vaccinated control. Chickens immunized with the bivalent vaccine also exhibited milder clinical signs as well as low tracheal and kidney lesion scores following virus challenge when compared to control groups. Collectively, the present study demonstrated that bivalent DNA vaccine co-expressing dual S1 glycoprotein induced strong immune responses capable of protecting chickens against infection with both M41 and CR88 IBV strains. Moreso, it was evident that encapsulation of the vaccine with chitosan-saponin nanoparticle further enhanced immune responses and abrogates the need for multiple booster administration of vaccine. Therefore, the bivalent DNA vaccine could serve as efficient and effective alternative strategy for the control of IB in poultry.
    Matched MeSH terms: Vaccines, DNA/genetics; Vaccines, DNA/immunology*; Vaccines, DNA/chemistry
  13. Identification of Newcastle Disease Virus sub-genotype VII 1.1 isolated from chickens in Sabah, Malaysia
    Syamsiah Aini S, Leow BL, Faizul Fikri MY, Muhammad Redzwan S, Faizah Hanim MS
    Trop Biomed, 2022 Dec 01;39(4):579-586.
    PMID: 36602219 DOI: 10.47665/tb.39.4.015
    Newcastle disease (ND) is an extremely contagious and fatal viral disease causing huge economic losses to the poultry industry. Following recent ND outbreaks in Sabah in commercial poultry and backyard farms, it was speculated that this could be due to a new introduction of Newcastle Disease Virus (NDV) genotype/sub-genotype. Here we report the genetic characterization of NDVs isolated from Sabah during early 2021. All isolates were amplified and sequenced with primers specific to the viral fusion (F) gene using reverse transcription-polymerase chain reaction (RT-PCR). Nucleotide sequence analysis of the F gene showed that all isolates shared similar homology of 99.4% with NDV strain from Iran isolated in 2018. Amino acid sequences of the F protein cleavage site revealed the motif of 112RRQKRF117 indicating all isolates were of virulent strain. Phylogenetic analysis demonstrated that all isolates were clustered under sub-genotype VII 1.1 and clustered together with isolates from Iran (previously known as subgenotype VIIl). The present findings suggested that there is an emerging of a new sub-genotype into the poultry population in Sabah and this sub-genotype has never been reported before in Malaysia. Therefore, transboundary monitoring and continuous surveillance should be implemented for proper control and prevention of the disease. A further molecular epidemiological analysis of NDV is needed to well understand the circulatory patterns of virulent strains of NDV in the country to prevent future outbreaks.
    Matched MeSH terms: Sequence Analysis, DNA
  14. Fulltext Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
    Hakkaart C, Pearson JF, Marquart L, Dennis J, Wiggins GAR, Barnes DR, et al.
    Commun Biol, 2022 Oct 06;5(1):1061.
    PMID: 36203093 DOI: 10.1038/s42003-022-03978-6
    The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
    Matched MeSH terms: DNA Copy Number Variations
  15. Mytilus galloprovincialis (Lamarck, 1819) spermatozoa: hsp70 expression and protamine-like protein property studies
    Piscopo M, Notariale R, Rabbito D, Ausió J, Olanrewaju OS, Guerriero G
    Environ Sci Pollut Res Int, 2018 May;25(13):12957-12966.
    PMID: 29478169 DOI: 10.1007/s11356-018-1570-9
    In this work, we describe results of the reproductive health monitoring studies in Mytilus galloprovincialis following spermatozoa hsp70 expression and protamine-like protein properties. Mussels control (ctr) were released within cages for 30 days in three different marine sites near Naples (Campania, Italy): Bagnoli south (BAs) and Bagnoli north (BAn), both close to a disposal metallurgical factory and in Capo Miseno (CM). Studies of hsp70 gene expression carried out, by RT-qPCR, in mussel spermatozoa have shown varied expression levels, particularly 5, 13, and 15-fold more than ctr in CM, BAs, and BAn, respectively, indicating highest involvement of stress proteins in spermatozoa of mussels in Bagnoli. In order to evaluate the possible risk on Mytilus galloprovincialis sustainability loss, electrophoretic analyses were performed on protamine-like proteins (PL) of collected spermatozoa. The results showed that CM PL were apparently unaltered with respect to ctr PL, while BAs and BAn PL appeared in part in the form of peptides and in part as bands with low mobility. Further, CM and BAs PL showed, by electrophoretic mobility shift assay, a decrease in DNA binding ability and a change in their DNA binding mode. The results of this investigation show the usefulness of the study of alterations of spermatozoa hsp70 expression and protamine-like protein properties for eco-toxicological evaluation using Mytilus galloprovincialis as a bioindicator.
    Matched MeSH terms: DNA
  16. Changes in the Proteome Profile of A549 Cells Following Helichrysetin-Induced Apoptosis Suggest the Involvement of DNA Damage Response and Cell Cycle Arrest-Associated Proteins
    Ho YF, Yajit NLM, Shiau JY, Malek SNA, Shyur LF, Karsani SA
    Appl Biochem Biotechnol, 2023 Nov;195(11):6867-6880.
    PMID: 36947367 DOI: 10.1007/s12010-023-04384-2
    Our previous findings demonstrated that Helichrysetin possessed promising anti-cancer activity. It was able to induce apoptosis in the A549 cell line. However, its mechanism of action is unknown. The present study aimed to unravel possible underlying molecular mechanisms of helichrysetin-induced apoptosis in A549 (human lung carcinoma) cells using comparative quantitative proteomics (iTRAQ labeled), followed by an exhaustive bioinformatics analysis. Our results suggested that DNA damage response (DDR) and cell cycle arrest were responsible for lung cancer cell death with helichrysetin treatment. Among proteins that changed in abundance were Nrf2 and HMOX1. They are oxidative stress-related proteins and were increased in abundance. BRAT1 was also increased in abundance, suggesting an increase in DNA damage repair, indicating the occurrence of DNA damage due to oxidative stress. However, several essential DDR downstream proteins such as p-ATM, BRCA1, FANCD2, and Rb1 that would further increase DNA damage were found to be dramatically decreased in relative abundance. Cell cycle-related proteins, p53, p21, and cyclin D1, were increased while cyclin A, cyclin E, and cdk2 were decreased. This is predicted to facilitate S-phase arrest. Furthermore, excessive DNA damage and prolonged arrest would in turn result in the induction of mitochondrial-mediated apoptosis. Based on these observations, we postulate that the effects of helichrysetin were in part via the suppression of DNA damage response which led to DNA damage and prolonged cell cycle arrest. Subsequently, this event initiated mitochondrial-mediated apoptosis in A549 lung cancer cells.
    Matched MeSH terms: DNA Damage
  17. Fulltext Mycoplasma genitalium in Singapore is associated with Chlamydia trachomatis infection and displays high macrolide and Fluoroquinolone resistance rates
    Hart T, Tang WY, Mansoor SAB, Chio MTW, Barkham T
    BMC Infect Dis, 2020 Apr 28;20(1):314.
    PMID: 32345231 DOI: 10.1186/s12879-020-05019-1
    BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates.

    METHODS: Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium. Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance.

    RESULTS: We report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection.

    CONCLUSIONS: Our results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.

    Matched MeSH terms: DNA, Bacterial/genetics; DNA, Bacterial/metabolism; Sequence Analysis, DNA
  18. Fulltext Mitochondrial DNA alterations may influence the cisplatin responsiveness of oral squamous cell carcinoma
    Aminuddin A, Ng PY, Leong CO, Chua EW
    Sci Rep, 2020 May 12;10(1):7885.
    PMID: 32398775 DOI: 10.1038/s41598-020-64664-3
    Cisplatin is the first-line chemotherapeutic agent for the treatment of oral squamous cell carcinoma (OSCC). However, the intrinsic or acquired resistance against cisplatin remains a major obstacle to treatment efficacy in OSCC. Recently, mitochondrial DNA (mtDNA) alterations have been reported in a variety of cancers. However, the role of mtDNA alterations in OSCC has not been comprehensively studied. In this study, we evaluated the correlation between mtDNA alterations (mtDNA content, point mutations, large-scale deletions, and methylation status) and cisplatin sensitivity using two OSCC cell lines, namely SAS and H103, and stem cell-like tumour spheres derived from SAS. By microarray analysis, we found that the tumour spheres profited from aberrant lipid and glucose metabolism and became resistant to cisplatin. By qPCR analysis, we found that the cells with less mtDNA were less responsive to cisplatin (H103 and the tumour spheres). Based on the findings, we theorised that the metabolic changes in the tumour spheres probably resulted in mtDNA depletion, as the cells suppressed mitochondrial respiration and switched to an alternative mode of energy production, i.e. glycolysis. Then, to ascertain the origin of the variation in mtDNA content, we used MinION, a nanopore sequencer, to sequence the mitochondrial genomes of H103, SAS, and the tumour spheres. We found that the lower cisplatin sensitivity of H103 could have been caused by a constellation of genetic and epigenetic changes in its mitochondrial genome. Future work may look into how changes in mtDNA translate into an impact on cell function and therefore cisplatin response.
    Matched MeSH terms: DNA, Mitochondrial/drug effects*; DNA, Mitochondrial/genetics; DNA, Mitochondrial/metabolism
  19. Fulltext Inclusion of 2-Mercaptoethanol in Lysis Buffer Could Interfere with Isolation of High Molecular Weight DNA from Freshwater Microalgae
    Yee W, Kumar JN, Muthusamy PD
    Indian J Microbiol, 2018 Mar;58(1):109-113.
    PMID: 29434405 DOI: 10.1007/s12088-017-0698-5
    2-mercaptoethanol (2-ME), alongside polyvinylpyrrolidone is commonly used in plant DNA extractions to deal with polyphenols, which could interfere with extraction and downstream applications. 2-ME is also commonly used to denature proteins and nucleases, especially RNAses. On the contrary, we found that the presence of 2-ME in lysis buffer interfered with DNA extraction from 12 strains of freshwater microalgae, resulting in DNA with poor integrity. We also found that the TNES-urea buffer, commonly used for preservation and DNA extraction from fish, appears as effective as the SDS and CTAB buffer for some microalgae strains. Results from our study suggests that the inclusion of 2-ME in DNA extraction protocols may be detrimental for isolation of good quality DNA from freshwater microalgae, and therefore recommend eliminating it or testing varying concentrations of 2-ME when developing species-specific extraction protocols for microalgae.
    Matched MeSH terms: DNA, Plant
  20. Fulltext Petroselinum crispum has antioxidant properties, protects against DNA damage and inhibits proliferation and migration of cancer cells
    Tang EL, Rajarajeswaran J, Fung S, Kanthimathi MS
    J Sci Food Agric, 2015 Oct;95(13):2763-71.
    PMID: 25582089 DOI: 10.1002/jsfa.7078
    BACKGROUND: Petroselinum crispum (English parsley) is a common herb of the Apiaceae family that is cultivated throughout the world and is widely used as a seasoning condiment. Studies have shown its potential as a medicinal herb. In this study, P. crispum leaf and stem extracts were evaluated for their antioxidant properties, protection against DNA damage in normal 3T3-L1 cells, and the inhibition of proliferation and migration of the MCF-7 cells.

    RESULTS: The dichloromethane extract of P. crispum exhibited the highest phenolic content (42.31 ± 0.50 mg GAE g(-1) ) and ferric reducing ability (0.360 ± 0.009 mmol g(-1) ) of the various extractions performed. The extract showed DPPH radical scavenging activity with an IC50 value of 3310.0 ± 80.5 µg mL(-1) . Mouse fibroblasts (3T3-L1) pre-treated with 400 µg mL(-1) of the extract showed 50.9% protection against H2 O2 -induced DNA damage, suggesting its potential in cancer prevention. The extract (300 µg mL(-1) ) inhibited H2 O2 -induced MCF-7 cell migration by 41% ± 4%. As cell migration is necessary for metastasis of cancer cells, inhibition of migration is an indication of protection against metastasis.

    CONCLUSION: Petroselinum crispum has health-promoting properties with the potential to prevent oxidative stress-related diseases and can be developed into functional food.

    Matched MeSH terms: DNA/drug effects; DNA Damage*
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