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  1. Fulltext Comparative analysis of nucleus-encoded plastid-targeting proteins in Rafflesia cantleyi against photosynthetic and non-photosynthetic representatives reveals orthologous systems with potentially divergent functions
    Ng SM, Lee XW, Mat-Isa MN, Aizat-Juhari MA, Adam JH, Mohamed R, et al.
    Sci Rep, 2018 Nov 22;8(1):17258.
    PMID: 30467394 DOI: 10.1038/s41598-018-35173-1
    Parasitic plants are known to discard photosynthesis thus leading to the deletion or loss of the plastid genes. Despite plastid genome reduction in non-photosynthetic plants, some nucleus-encoded proteins are transported back to the plastid to carry out specific functions. In this work, we study such proteins in Rafflesia cantleyi, a member of the holoparasitic genus well-known for producing the largest single flower in the world. Our analyses of three transcriptome datasets, two holoparasites (R. cantleyi and Phelipanche aegyptiaca) and one photosynthetic plant (Arabidopsis thaliana), suggest that holoparasites, such as R. cantleyi, retain some common plastid associated processes such as biosynthesis of amino acids and lipids, but are missing photosynthesis components that can be extensions of these pathways. The reconstruction of two selected biosynthetic pathways involving plastids correlates the trend of plastid retention to pathway complexity - transcriptome evidence for R. cantleyi suggests alternate mechanisms in regulating the plastidial heme and terpenoid backbone biosynthesis pathways. The evolution to holoparasitism from autotrophy trends towards devolving the plastid genes to the nuclear genome despite the functional sites remaining in the plastid, or maintaining non-photosynthetic processes in the plastid, before the eventual loss of the plastid and any site dependent functions.
    Matched MeSH terms: Cell Nucleus/genetics; Arabidopsis/genetics; Angiosperms/genetics; Chloroplast Proteins/genetics
  2. Fulltext Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance
    Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, et al.
    Cancer Res, 2013 Oct 15;73(20):6359-74.
    PMID: 24097820 DOI: 10.1158/0008-5472.CAN-13-1558-T
    Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack of IL-6 completely ablates cancer progression even in presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with oncogenic Kras to activate the reactive oxygen species detoxification program downstream of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory microenvironment of pancreatic cancer throughout its progression, providing several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a key player at all stages of pancreatic carcinogenesis and a potential therapeutic target.
    Matched MeSH terms: Pancreatic Neoplasms/genetics; Interleukin-6/genetics; Oxidative Stress/genetics; Mitogen-Activated Protein Kinases/genetics
  3. Establishment of a Nipah virus rescue system
    Yoneda M, Guillaume V, Ikeda F, Sakuma Y, Sato H, Wild TF, et al.
    Proc Natl Acad Sci U S A, 2006 Oct 31;103(44):16508-13.
    PMID: 17053073
    Nipah virus (NiV), a paramyxovirus, was first discovered in Malaysia in 1998 in an outbreak of infection in pigs and humans and incurred a high fatality rate in humans. Fruit bats, living in vast areas extending from India to the western Pacific, were identified as the natural reservoir of the virus. However, the mechanisms that resulted in severe pathogenicity in humans (up to 70% mortality) and that enabled crossing the species barrier were not known. In this study, we established a system that enabled the rescue of replicating NiVs from a cloned DNA by cotransfection of a constructed full-length cDNA clone and supporting plasmids coding virus nucleoprotein, phosphoprotein, and polymerase with the infection of the recombinant vaccinia virus, MVAGKT7, expressing T7 RNA polymerase. The rescued NiV (rNiV), by using the newly developed reverse genetics system, showed properties in vitro that were similar to the parent virus and retained the severe pathogenicity in a previously established animal model by experimental infection. A recombinant NiV was also developed, expressing enhanced green fluorescent protein (rNiV-EGFP). Using the virus, permissibility of NiV was compared with the presence of a known cellular receptor, ephrin B2, in a number of cell lines of different origins. Interestingly, two cell lines expressing ephrin B2 were not susceptible for rNiV-EGFP, indicating that additional factors are clearly required for full NiV replication. The reverse genetics for NiV will provide a powerful tool for the analysis of the molecular mechanisms of pathogenicity and cross-species infection.
    Matched MeSH terms: Plasmids/genetics; Recombinant Proteins/genetics; Ephrin-B2/genetics; Henipavirus Infections/genetics
  4. Fulltext Mitochondrial hepatopathies: advances in genetics, therapeutic approaches, and outcomes
    Lee WS, Sokol RJ
    J Pediatr, 2013 Oct;163(4):942-8.
    PMID: 23810725 DOI: 10.1016/j.jpeds.2013.05.036
    Matched MeSH terms: Acidosis, Lactic/genetics; DNA, Mitochondrial/genetics; Liver Failure, Acute/genetics*; Mitochondrial Diseases/genetics*
  5. Amelogenesis imperfecta: enamel ultra structure and molecular studies
    Gopinath VK, Al-Salihi KA, Yean CY, Ann MC, Ravichandran M
    J Clin Pediatr Dent, 2004;28(4):319-22.
    PMID: 15366620
    Amelogenesis imperfecta (AI) is a hereditary disorder resulting in generalized defects in the enamel. The case reported here is of a seven-year-old male child with yellow color of all his teeth. Two of his primary molars were extracted due to dental abscess with advanced root resorption. Histologically hypoplastic enamel layer, positively birefringent, generalized pitting, roughness with irregular general cracked borders were observed. Scanning electron microscope, revealed extensive irregular, disorganized rough superficial enamel layer. The enamel was irregularly decussate with filamentous prisms accompanied by small rounded formations. The morphological and histological examination of the tooth revealed that this patient has the features of AI. For genetic study blood sample were collected from the patient and PCR analysis revealed that there is no mutation in exons 1-7 of AMELX gene on the X chromosome of the patient. Hence, it is probable that the AI of this patient is not X-linked. It is more likely to be an autosomal mutation.
    Matched MeSH terms: Amelogenesis Imperfecta/genetics; Exons/genetics; Mutation/genetics; Chromosomes, Human, X/genetics
  6. A novel organic solvent tolerant lipase from Bacillus sphaericus 205y: extracellular expression of a novel OST-lipase gene
    Sulong MR, Abdul Rahman RN, Salleh AB, Basri M
    Protein Expr Purif, 2006 Oct;49(2):190-5.
    PMID: 16769222
    An organic solvent tolerant (OST) lipase gene from Bacillus sphaericus 205y was successfully expressed extracellularly. The expressed lipase was purified using two steps purification; ultrafiltration and hydrophobic interaction chromatography (HIC) to 8-fold purity and 32% recovery. The purified 205y lipase revealed homogeneity on denaturing gel electrophoresis and the molecular mass was at approximately 30 kDa. The optimum pH for the purified 205y lipase was 7.0-8.0 and its stability showed a broad range of pH value between pH 5.0 to 13.0 at 37 degrees C. The purified 205y lipase exhibited an optimum temperature of 55 degrees C. The activity of the purified lipase was stimulated in the presence of Ca2+ and Mg2+. Ethylenediaminetetraacetic acid (EDTA) has no effect on its activity; however inhibition was observed with phenylmethane sulfonoyl fluoride (PMSF) a serine hydrolase inhibitor. Organic solvents such as dimethylsulfoxide (DMSO), methanol, p-xylene and n-decane enhanced the activity. Studies on the effect of oil showed that the lipase was most active in the presence of tricaprin (C10). The lipase exhibited 1,3 positional specificity.
    Matched MeSH terms: Bacillus/genetics; Bacterial Proteins/genetics; Lipase/genetics; Recombinant Proteins/genetics
  7. Fulltext Genome sequence of the alkane-degrading bacterium Alcanivorax hongdengensis type strain A-11-3
    Lai Q, Shao Z
    J Bacteriol, 2012 Dec;194(24):6972.
    PMID: 23209226 DOI: 10.1128/JB.01849-12
    Alcanivorax hongdengensis A-11-3(T) was isolated from an oil-enriched consortium enriched from the surface seawater of Hong-Deng dock in the Straits of Malacca and Singapore. Strain A-11-3(T) can degrade n-alkane and produce a lipopeptide biosurfactant. Here we report the genome of A-11-3(T) and the genes associated with alkane degradation.
    Matched MeSH terms: Cytochrome P-450 Enzyme System/genetics; DNA, Bacterial/genetics; RNA, Ribosomal, 16S/genetics; Alcanivoraceae/genetics*
  8. Analysis of the genome of Mycobacterium abscessus strain M94 reveals an uncommon cluster of tRNAs
    Choo SW, Wong YL, Leong ML, Heydari H, Ong CS, Ng KP, et al.
    J Bacteriol, 2012 Oct;194(20):5724.
    PMID: 23012295
    Mycobacterium abscessus is a species of rapidly growing nontuberculous mycobacteria that is frequently associated with opportunistic infections in humans. Here, we report the annotated genome sequence of M. abscessus strain M94, which showed an unusual cluster of tRNAs.
    Matched MeSH terms: DNA, Bacterial/genetics*; Mycobacterium/genetics*; RNA, Bacterial/genetics; RNA, Transfer/genetics*
  9. Fulltext Genome analysis of Mycobacterium massiliense strain M172, which contains a putative mycobacteriophage
    Choo SW, Yusoff AM, Wong YL, Wee WY, Ong CS, Ng KP, et al.
    J Bacteriol, 2012 Sep;194(18):5128.
    PMID: 22933758 DOI: 10.1128/JB.01096-12
    The genome of Mycobacterium massiliense M172, isolated from a human sputum sample, was sequenced using Illumina GA IIX technology and found to contain 5,204,460 bp, including putative genes for virulence and antibiotic resistance as well as a 92-kb genomic region most likely to correspond to a mycobacteriophage.
    Matched MeSH terms: DNA, Bacterial/genetics*; Mycobacteriophages/genetics; Mycobacterium/genetics*; Virulence Factors/genetics
  10. Fulltext 2245G/A polymorphism of the receptor for advanced glycation end-products (RAGE) gene is associated with diabetic retinopathy in the Malaysian population
    Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Koay AC, Chua KH
    Br J Ophthalmol, 2012 Feb;96(2):289-92.
    PMID: 22116960 DOI: 10.1136/bjophthalmol-2011-300658
    The receptor for advanced glycation end-products (RAGE) has been implicated in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the association between 2245G/A gene polymorphism of the RAGE gene and retinopathy in Malaysian type 2 diabetic patients.
    Matched MeSH terms: Diabetes Mellitus, Type 2/genetics; Diabetic Retinopathy/genetics*; Receptors, Immunologic/genetics*; Asian Continental Ancestry Group/genetics
  11. Physio-chemical, microbiological properties of tempoyak and molecular characterisation of lactic acid bacteria isolated from tempoyak
    Chuah LO, Shamila-Syuhada AK, Liong MT, Rosma A, Thong KL, Rusul G
    Food Microbiol, 2016 Sep;58:95-104.
    PMID: 27217364 DOI: 10.1016/j.fm.2016.04.002
    This study aims to determine physio-chemical properties of tempoyak, characterise the various indigenous species of lactic acid bacteria (LAB) present at different stages of fermentation and also to determine the survival of selected foodborne pathogens in tempoyak. The predominant microorganisms present in tempoyak were LAB (8.88-10.42 log CFU/g). Fructobacillus durionis and Lactobacillus plantarum were the dominant members of LAB. Other LAB species detected for the first time in tempoyak were a fructophilic strain of Lactobacillus fructivorans, Leuconostoc dextranicum, Lactobacillus collinoides and Lactobacillus paracasei. Heterofermentative Leuconostoc mesenteroides and F. durionis were predominant in the initial stage of fermentation, and as fermentation proceeded, F. durionis remained predominant, but towards the end of fermentation, homofermentative Lb. plantarum became the predominant species. Lactic, acetic and propionic acids were present in concentrations ranging from 0.30 to 9.65, 0.51 to 7.14 and 3.90 to 7.31 mg/g, respectively. Genotyping showed a high degree of diversity among F. durionis and Lb. plantarum isolates, suggesting different sources of LAB. All tested Lb. plantarum and F. durionis (except for one isolate) isolates were multidrug resistant. Salmonella spp., Listeria monocytogenes and Staphylococcus aureus were not detected. However, survival study showed that these pathogens could survive up to 8-12 days. The results aiming at improving the quality and safety of tempoyak.
    Matched MeSH terms: Lactobacillaceae/genetics; Lactobacillus/genetics; Leuconostoc/genetics; Lactobacillus plantarum/genetics
  12. Genetic polymorphism of circumsporozoite protein (CSP) in Plasmodium malariae isolates from Malaysia
    Phang WK, Bukhari FDM, Zen LPY, Jaimin JJ, Dony JJF, Lau YL
    Parasitol Int, 2022 Apr;87:102519.
    PMID: 34800724 DOI: 10.1016/j.parint.2021.102519
    Information about Plasmodium malariae is scanty worldwide due to its "benign" nature and low infection rates. Consequently, studies on the genetic polymorphisms of P. malariae are lacking. Here, we report genetic polymorphisms of 28 P. malariae circumsporozoite protein (Pmcsp) isolates from Malaysia which were compared with those in other regions in Asia as well as those from Africa. Phylogenetic analysis revealed that most Malaysian P. malariae isolates clustered together but independently from other Asian isolates. Low nucleotide diversity was observed in Pmcsp non-repeat regions in contrast to high nucleotide diversity observed in non-repeat regions of Plasmodium knowlesi CSP gene, the current major cause of malaria in Malaysia. This study contributes to the characterisation of naturally occurring polymorphisms in the P. malariae CSP gene.
    Matched MeSH terms: Amino Acid Sequence/genetics; Plasmodium malariae/genetics*; Protozoan Proteins/genetics*; Plasmodium knowlesi/genetics
  13. Fulltext Thermotolerance and molecular chaperone function of an SGT1-like protein from the psychrophilic yeast, Glaciozyma antarctica
    Yusof NA, Hashim NH, Beddoe T, Mahadi NM, Illias RM, Bakar FD, et al.
    Cell Stress Chaperones, 2016 Jul;21(4):707-15.
    PMID: 27154490 DOI: 10.1007/s12192-016-0696-2
    The ability of eukaryotes to adapt to an extreme range of temperatures is critically important for survival. Although adaptation to extreme high temperatures is well understood, reflecting the action of molecular chaperones, it is unclear whether these molecules play a role in survival at extremely low temperatures. The recent genome sequencing of the yeast Glaciozyma antarctica, isolated from Antarctic sea ice near Casey Station, provides an opportunity to investigate the role of molecular chaperones in adaptation to cold temperatures. We isolated a G. antarctica homologue of small heat shock protein 20 (HSP20), GaSGT1, and observed that the GaSGT1 mRNA expression in G. antarctica was markedly increased following culture exposure at low temperatures. Additionally, we demonstrated that GaSGT1 overexpression in Escherichia coli protected these bacteria from exposure to both high and low temperatures, which are lethal for growth. The recombinant GaSGT1 retained up to 60 % of its native luciferase activity after exposure to luciferase-denaturing temperatures. These results suggest that GaSGT1 promotes cell thermotolerance and employs molecular chaperone-like activity toward temperature assaults.
    Matched MeSH terms: Basidiomycota/genetics; Fungal Proteins/genetics; RNA, Messenger/genetics; Molecular Chaperones/genetics
  14. Fulltext Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus
    Heskes AM, Sundram TCM, Boughton BA, Jensen NB, Hansen NL, Crocoll C, et al.
    Plant J, 2018 03;93(5):943-958.
    PMID: 29315936 DOI: 10.1111/tpj.13822
    Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus-castus show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus-castus. With the assistance of matrix-assisted laser desorption ionisation-mass spectrometry imaging (MALDI-MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome-specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus-castus. The identified CYP, VacCYP76BK1, was found to catalyse 16-hydroxylation of the diol-diterpene, peregrinol, to labd-13Z-ene-9,15,16-triol when expressed in Saccharomyces cerevisiae. Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan- and lactone-containing diterpenoids that are present in this species.
    Matched MeSH terms: Cytochrome P-450 Enzyme System/genetics; Plant Proteins/genetics; Plant Leaves/genetics; Vitex/genetics
  15. Fulltext The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity
    Colombo M, Lòpez-Perolio I, Meeks HD, Caleca L, Parsons MT, Li H, et al.
    Hum Mutat, 2018 May;39(5):729-741.
    PMID: 29460995 DOI: 10.1002/humu.23411
    Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10-115 . There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.
    Matched MeSH terms: Exons/genetics; RNA Splicing/genetics*; RNA, Messenger/genetics; BRCA2 Protein/genetics*
  16. Fulltext Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014
    Oong XY, Ng KT, Lam TT, Pang YK, Chan KG, Hanafi NS, et al.
    PLoS One, 2015;10(8):e0136254.
    PMID: 26313754 DOI: 10.1371/journal.pone.0136254
    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.
    Matched MeSH terms: Influenza, Human/genetics*; Neuraminidase/genetics*; Influenza B virus/genetics*; Hemagglutinin Glycoproteins, Influenza Virus/genetics*
  17. Fulltext Genome-Wide Detection of Genes Under Positive Selection in Worldwide Populations of the Barley Scald Pathogen
    Mohd-Assaad N, McDonald BA, Croll D
    Genome Biol Evol, 2018 Apr 01;10(5):1315-1332.
    PMID: 29722810 DOI: 10.1093/gbe/evy087
    Coevolution between hosts and pathogens generates strong selection pressures to maintain resistance and infectivity, respectively. Genomes of plant pathogens often encode major effect loci for the ability to successfully infect specific host genotypes. Hence, spatial heterogeneity in host genotypes coupled with abiotic factors could lead to locally adapted pathogen populations. However, the genetic basis of local adaptation is poorly understood. Rhynchosporium commune, the pathogen causing barley scald disease, interacts at least partially in a gene-for-gene manner with its host. We analyzed global field populations of 125 R. commune isolates to identify candidate genes for local adaptation. Whole genome sequencing data showed that the pathogen is subdivided into three genetic clusters associated with distinct geographic and climatic regions. Using haplotype-based selection scans applied independently to each genetic cluster, we found strong evidence for selective sweeps throughout the genome. Comparisons of loci under selection among clusters revealed little overlap, suggesting that ecological differences associated with each cluster led to variable selection regimes. The strongest signals of selection were found predominantly in the two clusters composed of isolates from Central Europe and Ethiopia. The strongest selective sweep regions encoded protein functions related to biotic and abiotic stress responses. Selective sweep regions were enriched in genes encoding functions in cellular localization, protein transport activity, and DNA damage responses. In contrast to the prevailing view that a small number of gene-for-gene interactions govern plant pathogen evolution, our analyses suggest that the evolutionary trajectory is largely determined by spatially heterogeneous biotic and abiotic selection pressures.
    Matched MeSH terms: Adaptation, Physiological/genetics; Ascomycota/genetics*; Genes, Fungal/genetics*; Selection, Genetic/genetics*
  18. Fulltext Characterization of the highly active polyhydroxyalkanoate synthase of Chromobacterium sp. strain USM2
    Bhubalan K, Chuah JA, Shozui F, Brigham CJ, Taguchi S, Sinskey AJ, et al.
    Appl Environ Microbiol, 2011 May;77(9):2926-33.
    PMID: 21398494 DOI: 10.1128/AEM.01997-10
    The synthesis of bacterial polyhydroxyalkanoates (PHA) is very much dependent on the expression and activity of a key enzyme, PHA synthase (PhaC). Many efforts are being pursued to enhance the activity and broaden the substrate specificity of PhaC. Here, we report the identification of a highly active wild-type PhaC belonging to the recently isolated Chromobacterium sp. USM2 (PhaC(Cs)). PhaC(Cs) showed the ability to utilize 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), and 3-hydroxyhexanoate (3HHx) monomers in PHA biosynthesis. An in vitro assay of recombinant PhaC(Cs) expressed in Escherichia coli showed that its polymerization of 3-hydroxybutyryl-coenzyme A activity was nearly 8-fold higher (2,462 ± 80 U/g) than that of the synthase from the model strain C. necator (307 ± 24 U/g). Specific activity using a Strep2-tagged, purified PhaC(Cs) was 238 ± 98 U/mg, almost 5-fold higher than findings of previous studies using purified PhaC from C. necator. Efficient poly(3-hydroxybutyrate) [P(3HB)] accumulation in Escherichia coli expressing PhaC(Cs) of up to 76 ± 2 weight percent was observed within 24 h of cultivation. To date, this is the highest activity reported for a purified PHA synthase. PhaC(Cs) is a naturally occurring, highly active PHA synthase with superior polymerizing ability.
    Matched MeSH terms: Acyltransferases/genetics*; Chromobacterium/genetics; Escherichia coli/genetics; Recombinant Proteins/genetics
  19. Fulltext Proteomic analysis of whole human saliva detects enhanced expression of interleukin-1 receptor antagonist, thioredoxin and lipocalin-1 in cigarette smokers compared to non-smokers
    Jessie K, Pang WW, Haji Z, Rahim A, Hashim OH
    Int J Mol Sci, 2010 Nov 09;11(11):4488-505.
    PMID: 21151451 DOI: 10.3390/ijms11114488
    A gel-based proteomics approach was used to screen for proteins of differential abundance between the saliva of smokers and those who had never smoked. Subjecting precipitated proteins from whole human saliva of healthy non-smokers to two-dimensional electrophoresis (2-DE) generated typical profiles comprising more than 50 proteins. While 35 of the proteins were previously established by other researchers, an additional 22 proteins were detected in the 2-DE saliva protein profiles generated in the present study. When the 2-DE profiles were compared to those obtained from subjects considered to be heavy cigarette smokers, three saliva proteins, including interleukin-1 receptor antagonist, thioredoxin and lipocalin-1, showed significant enhanced expression. The distribution patterns of lipocalin-1 isoforms were also different between cigarette smokers and non-smokers. The three saliva proteins have good potential to be used as biomarkers for the adverse effects of smoking and the risk for inflammatory and chronic diseases that are associated with it.
    Matched MeSH terms: Thioredoxins/genetics; Proteome/genetics; Interleukin 1 Receptor Antagonist Protein/genetics; Lipocalins/genetics
  20. Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis
    Bates T, Kennedy M, Diajil A, Goodson M, Thomson P, Doran E, et al.
    Cancer Epidemiol Biomarkers Prev, 2016 Jun;25(6):927-35.
    PMID: 27197272 DOI: 10.1158/1055-9965.EPI-15-0949
    BACKGROUND: Oral squamous cell carcinoma (OSCC) is a global healthcare problem associated with poor clinical outcomes. Early detection is key to improving patient survival. OSCC may be preceded by clinically recognizable lesions, termed oral potentially malignant disorders (OPMD). As histologic assessment of OPMD does not accurately predict their clinical behavior, biomarkers are required to detect cases at risk of malignant transformation. Epidermal growth factor receptor gene copy number (EGFR GCN) is a validated biomarker in lung non-small cell carcinoma. We examined EGFR GCN in OPMD and OSCC to determine its potential as a biomarker in oral carcinogenesis.

    METHODS: EGFR GCN was examined by in situ hybridization (ISH) in biopsies from 78 patients with OPMD and 92 patients with early-stage (stages I and II) OSCC. EGFR ISH signals were scored by two pathologists and a category assigned by consensus. The data were correlated with patient demographics and clinical outcomes.

    RESULTS: OPMD with abnormal EGFR GCN were more likely to undergo malignant transformation than diploid cases. EGFR genomic gain was detected in a quarter of early-stage OSCC, but did not correlate with clinical outcomes.

    CONCLUSION: These data suggest that abnormal EGFR GCN has clinical utility as a biomarker for the detection of OPMD destined to undergo malignant transformation. Prospective studies are required to verify this finding. It remains to be determined if EGFR GCN could be used to select patients for EGFR-targeted therapies.

    IMPACT: Abnormal EGFR GCN is a potential biomarker for identifying OPMD that are at risk of malignant transformation. Cancer Epidemiol Biomarkers Prev; 25(6); 927-35. ©2016 AACR.

    Matched MeSH terms: Carcinoma, Squamous Cell/genetics; Mouth Neoplasms/genetics; Carcinogenesis/genetics*; ErbB Receptors/genetics*
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