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  1. Fulltext Comparative genomic analysis of six bacteria belonging to the genus Novosphingobium: insights into marine adaptation, cell-cell signaling and bioremediation
    Gan HM, Hudson AO, Rahman AY, Chan KG, Savka MA
    BMC Genomics, 2013;14:431.
    PMID: 23809012 DOI: 10.1186/1471-2164-14-431
    Bacteria belonging to the genus Novosphingobium are known to be metabolically versatile and occupy different ecological niches. In the absence of genomic data and/or analysis, knowledge of the bacteria that belong to this genus is currently limited to biochemical characteristics. In this study, we analyzed the whole genome sequencing data of six bacteria in the Novosphingobium genus and provide evidence to show the presence of genes that are associated with salt tolerance, cell-cell signaling and aromatic compound biodegradation phenotypes. Additionally, we show the taxonomic relationship between the sequenced bacteria based on phylogenomic analysis, average amino acid identity (AAI) and genomic signatures.
    Matched MeSH terms: Adaptation, Physiological/genetics*; Bacterial Proteins/genetics; Genes, Bacterial/genetics; Signal Transduction/genetics*; Alphaproteobacteria/genetics; Gene Transfer, Horizontal/genetics; Dioxygenases/genetics; Quorum Sensing/genetics
  2. Molecular alterations of Ras-Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase-Akt signaling pathways in colorectal cancers from a tertiary hospital at Kuala Lumpur, Malaysia
    Yip WK, Choo CW, Leong VC, Leong PP, Jabar MF, Seow HF
    APMIS, 2013 Oct;121(10):954-66.
    PMID: 23992303 DOI: 10.1111/apm.12152
    Molecular alterations in KRAS, BRAF, PIK3CA, and PTEN have been implicated in designing targeted therapy for colorectal cancer (CRC). The present study aimed to determine the status of these molecular alterations in Malaysian CRCs as such data are not available in the literature. We investigated the mutations of KRAS, BRAF, and PTEN, the gene amplification of PIK3CA, and the protein expression of PTEN and phosphatidylinositol 3-kinase (PI3K) catalytic subunit (p110α) by direct DNA sequencing, quantitative real-time PCR, and immunohistochemistry, respectively, in 49 CRC samples. The frequency of KRAS (codons 12, 13, and 61), BRAF (V600E), and PTEN mutations, and PIK3CA amplification was 25.0% (11/44), 2.3% (1/43), 0.0% (0/43), and 76.7% (33/43), respectively. Immunohistochemical staining demonstrated loss of PTEN protein in 54.5% (24/44) of CRCs and no significant difference in PI3K p110α expression between CRCs and the adjacent normal colonic mucosa (p = 0.380). PIK3CA amplification was not associated with PI3K p110α expression level, but associated with male cases (100% of male cases vs 56% of female cases harbored amplified PIK3CA, p = 0.002). PI3K p110α expression was significantly higher (p = 0.041) in poorly/moderately differentiated carcinoma compared with well-differentiated carcinoma. KRAS mutation, PIK3CA amplification, PTEN loss, and PI3K p110α expression did not correlate with Akt phosphorylation or Ki-67 expression. KRAS mutation, PIK3CA amplification, and PTEN loss were not mutually exclusive. This is the first report on CRC in Malaysia showing comparable frequency of KRAS mutation and PTEN loss, lower BRAF mutation rate, higher PIK3CA amplification frequency, and rare PTEN mutation, as compared with published reports.
    Matched MeSH terms: Carcinoma/genetics*; Proto-Oncogene Proteins/genetics*; Colorectal Neoplasms/genetics*; ras Proteins/genetics*; Phosphatidylinositol 3-Kinases/genetics*; Proto-Oncogene Proteins B-raf/genetics*; Proto-Oncogene Proteins c-akt/genetics; PTEN Phosphohydrolase/genetics*
  3. Purification and functional analysis of recombinant Acholeplasma laidlawii histone-like HU protein
    Levitskiy SA, Sycheva AM, Kharlampieva DD, Oberto J, Kamashev DE, Serebryakova MV, et al.
    Biochimie, 2011 Jul;93(7):1102-9.
    PMID: 21443922 DOI: 10.1016/j.biochi.2011.03.005
    HU is a most abundant DNA-binding protein in bacteria. This protein is conserved either in its heterodimeric form or in one of its homodimeric forms in all bacteria, in plant chloroplasts, and in some viruses. HU protein non-specifically binds and bends DNA as a hetero- or homodimer and can participate in DNA supercoiling and DNA condensation. It also takes part in some DNA functions such as replication, recombination, and repair. HU does not recognize any specific sequences but shows some specificity to cruciform DNA and to repair intermediates, e.g., nick, gap, bulge, 3'-overhang, etc. To understand the features of HU binding to DNA and repair intermediates, a fast and easy HU proteins purification procedure is required. Here we report overproduction and purification of the HU homodimers. The method of HU purification allows obtaining a pure recombinant non-tagged protein cloned in Escherichia coli. We applied this method for purification of Acholeplasma laidlawii HU and demonstrated that this protein possesses a DNA-binding activity and is free of contaminating nuclease activity. Besides that we have shown that expression of A. laidlawii ihf_hu gene in a slow-growing hupAB E. coli strain restores the wild-type growth indicating that aclHU can perform the basic functions of E. coli HU in vivo.
    Matched MeSH terms: Acholeplasma laidlawii/genetics; Bacterial Proteins/genetics; DNA/genetics; DNA-Binding Proteins/genetics; DNA, Circular/genetics; DNA, Superhelical/genetics; Escherichia coli/genetics; Plasmids/genetics
  4. Genome-wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11
    Vincent-Chong VK, Ismail SM, Rahman ZA, Sharifah NA, Anwar A, Pradeep PJ, et al.
    Oral Dis, 2012 Jul;18(5):469-76.
    PMID: 22251088 DOI: 10.1111/j.1601-0825.2011.01894.x
    Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression.
    Matched MeSH terms: Carcinoma, Squamous Cell/genetics*; Intermediate Filament Proteins/genetics*; Mouth Neoplasms/genetics*; Nerve Tissue Proteins/genetics*; Ubiquitins/genetics*; Signal Transduction/genetics; Cytokines/genetics*; Wnt Proteins/genetics*
  5. Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients
    Jada SR, Lim R, Wong CI, Shu X, Lee SC, Zhou Q, et al.
    Cancer Sci, 2007 Sep;98(9):1461-7.
    PMID: 17627617
    The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m(2) once every 3 weeks (n = 45). Genotypic-phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC < or = 500/microL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study.
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/genetics; Lung Neoplasms/genetics; Neoplasm Proteins/genetics*; Neutropenia/genetics*; Glucuronosyltransferase/genetics*; Urogenital Neoplasms/genetics; Colorectal Neoplasms/genetics; ATP-Binding Cassette Transporters/genetics*
  6. The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin
    Hossain MM, Mukheem A, Kamarul T
    Life Sci, 2015 Aug 15;135:55-67.
    PMID: 25818192 DOI: 10.1016/j.lfs.2015.03.010
    Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications.
    Matched MeSH terms: Diabetes Mellitus, Type 2/genetics; Metabolic Syndrome X/genetics; Hyperuricemia/genetics; PPAR gamma/genetics; Dyslipidemias/genetics; Atherosclerosis/genetics; Adiponectin/genetics; Obesity, Abdominal/genetics
  7. Association of p53 tumor suppressor gene with paraclinical and clinical modalities of gliomas patients in Malaysia
    Yusoff AA, Abdullah J, Abdullah MR, Mohd Ariff AR, Isa MN
    Acta Neurochir (Wien), 2004 Jun;146(6):595-601.
    PMID: 15168228
    Alteration of the tumor suppressor gene p53 is considered to be a critical step in the development of human cancer. Changes in this gene have been detected in a wide range of human tumours, including gliomas. In glioma, the presence of p53 gene alterations has been associated with worse prognosis.
    Matched MeSH terms: Astrocytoma/genetics*; Brain Neoplasms/genetics*; Glioblastoma/genetics*; Tumor Suppressor Protein p53/genetics*; Frameshift Mutation/genetics; Point Mutation/genetics; Base Pairing/genetics; Asian Continental Ancestry Group/genetics*
  8. Fulltext Ser-653-Asn substitution in the acetohydroxyacid synthase gene confers resistance in weedy rice to imidazolinone herbicides in Malaysia
    Ruzmi R, Ahmad-Hamdani MS, Mazlan N
    PLoS One, 2020;15(9):e0227397.
    PMID: 32925921 DOI: 10.1371/journal.pone.0227397
    The continuous and sole dependence on imidazolinone (IMI) herbicides for weedy rice control has led to the evolution of herbicide resistance in weedy rice populations across various countries growing IMI herbicide-resistant rice (IMI-rice), including Malaysia. A comprehensive study was conducted to elucidate occurrence, level, and mechanisms endowing resistance to IMI herbicides in putative resistant (R) weedy rice populations collected from three local Malaysian IMI-rice fields. Seed bioassay and whole-plant dose-response experiments were conducted using commercial IMI herbicides. Based on the resistance index (RI) quantification in both experiments, the cross-resistance pattern of R and susceptible (S) weedy rice populations and control rice varieties (IMI-rice variety MR220CL2 and non-IMI-rice variety MR219) to imazapic and imazapyr was determined. A molecular investigation was carried out by comparing the acetohydroxyacid synthase (AHAS) gene sequences of the R and S populations and the MR220CL2 and MR219 varieties. The AHAS gene sequences of R weedy rice were identical to those of MR220CL2, exhibiting a Ser-653-Asn substitution, which was absent in MR219 and S plants. In vitro assays were conducted using analytical grade IMI herbicides of imazapic (99.3%) and imazapyr (99.6%) at seven different concentrations. The results demonstrated that the AHAS enzyme extracted from the R populations and MR220CL2 was less sensitive to IMI herbicides than that from S and MR219, further supporting that IMI herbicide resistance was conferred by target-site mutation. In conclusion, IMI resistance in the selected populations of Malaysian weedy rice could be attributed to a Ser-653-Asn mutation that reduced the sensitivity of the target site to IMI herbicides. To our knowledge, this study is the first to show the resistance mechanism in weedy rice from Malaysian rice fields.
    Matched MeSH terms: Acetolactate Synthase/genetics*; Asparagine/genetics; Plant Proteins/genetics*; Oryza/genetics; Serine/genetics; DNA, Plant/genetics; Herbicide Resistance/genetics*; Plant Weeds/genetics
  9. Cytogenetic profile of patients with clinical spectrum of ambiguous genitalia, amenorrhea, and Turner phenotype: A 21-year single-center experience
    Elkarhat Z, Belkady B, Charoute H, Zarouf L, Razoki L, Aboulfaraj J, et al.
    Am J Med Genet A, 2019 08;179(8):1516-1524.
    PMID: 31207162 DOI: 10.1002/ajmg.a.61257
    The aim of the present study was to determine the frequency and nature of chromosomal abnormalities involved in patients with the clinical spectrum of ambiguous genitalia (AG), amenorrhea, and Turner phenotype, in order to compare them with those reported elsewhere. The study was conducted in the Cytogenetic Department of Pasteur Institute of Morocco, and it reports on the patients who were recruited between 1996 and 2016. Cytogenetic analysis was performed according to the standard method. Among 1,415 patients, chromosomal abnormalities were identified in 7.13% (48/673) of patients with AG, 17.39% (28/161) of patients with primary amenorrhea (PA), 4% (1/25) of patients with secondary amenorrhea, and 23.20% (129/556) of patients with Turner phenotype. However, Turner syndrome was diagnosed in 0.89% (6/673) of patients with AG, 10.56% (17/161) of patients with PA, and 19.78% (110/556) of patients with Turner phenotype. In addition, Klinefelter syndrome and mixed gonadal dysgenesis were confirmed in 2.97% and 1.93% of patients, respectively, with AG, while, chimerism, trisomy 8, and trisomy 13 were confirmed only in 0.15% each. Trisomy 21 was confirmed in patients with AG and Turner phenotype (0.15% and 0.36%, respectively). Moreover, 5.60% (9/161) of patients with PA have been diagnosed as having sex reversal. Thus, the frequency of chromosomal abnormalities observed in Moroccan patients with PA is comparable to that reported in Tunisia, Turkey, Iran, and Hong Kong. However, the frequency is significantly less than that identified in India, Malaysia, Italy, and Romania.
    Matched MeSH terms: Amenorrhea/genetics*; Chromosomes, Human, Pair 8/genetics; Down Syndrome/genetics; Gonadal Dysgenesis, Mixed/genetics; Klinefelter Syndrome/genetics; Disorders of Sex Development/genetics*; Trisomy/genetics; Turner Syndrome/genetics*
  10. Fulltext Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma
    Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, et al.
    Blood, 2018 06 07;131(23):2552-2567.
    PMID: 29685921 DOI: 10.1182/blood-2017-07-794529
    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
    Matched MeSH terms: Herpesvirus 4, Human/genetics*; Inflammation/genetics; Lymphoma/genetics; RNA, Viral/genetics*; Epstein-Barr Virus Infections/genetics; MicroRNAs/genetics; Exosomes/genetics; Carcinogenesis/genetics
  11. From the High Arctic to the Equator: Do Soil Metagenomes Differ According to Our Expectations?
    Kerfahi D, Tripathi BM, Dong K, Kim M, Kim H, Ferry Slik JW, et al.
    Microb Ecol, 2019 Jan;77(1):168-185.
    PMID: 29882154 DOI: 10.1007/s00248-018-1215-z
    Comparing the functional gene composition of soils at opposite extremes of environmental gradients may allow testing of hypotheses about community and ecosystem function. Here, we were interested in comparing how tropical microbial ecosystems differ from those of polar climates. We sampled several sites in the equatorial rainforest of Malaysia and Brunei, and the high Arctic of Svalbard, Canada, and Greenland, comparing the composition and the functional attributes of soil biota between the two extremes of latitude, using shotgun metagenomic Illumina HiSeq2000 sequencing. Based upon "classical" views of how tropical and higher latitude ecosystems differ, we made a series of predictions as to how various gene function categories would differ in relative abundance between tropical and polar environments. Results showed that in some respects our predictions were correct: the polar samples had higher relative abundance of dormancy related genes, and lower relative abundance of genes associated with respiration, and with metabolism of aromatic compounds. The network complexity of the Arctic was also lower than the tropics. However, in various other respects, the pattern was not as predicted; there were no differences in relative abundance of stress response genes or in genes associated with secondary metabolism. Conversely, CRISPR genes, phage-related genes, and virulence disease and defense genes, were unexpectedly more abundant in the Arctic, suggesting more intense biotic interaction. Also, eukaryote diversity and bacterial diversity were higher in the Arctic of Svalbard compared to tropical Brunei, which is consistent with what may expected from amplicon studies in terms of the higher pH of the Svalbard soil. Our results in some respects confirm expectations of how tropical versus polar nature may differ, and in other respects challenge them.
    Matched MeSH terms: Bacteria/genetics; Metabolic Networks and Pathways/genetics; Metagenome/genetics*; Eukaryota/genetics; Biota/genetics*; Clustered Regularly Interspaced Short Palindromic Repeats/genetics; Secondary Metabolism/genetics; Microbiota/genetics
  12. Fulltext Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients
    Zhang XC, Wang J, Shao GG, Wang Q, Qu X, Wang B, et al.
    Nat Commun, 2019 04 16;10(1):1772.
    PMID: 30992440 DOI: 10.1038/s41467-019-09762-1
    Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/genetics*; Carcinoma, Squamous Cell/genetics*; Lung Neoplasms/genetics*; Proto-Oncogene Proteins p21(ras)/genetics; Antigen Presentation/genetics; Asian Continental Ancestry Group/genetics*; Wnt Signaling Pathway/genetics; ErbB Receptors/genetics
  13. Fulltext Single-Cell Gene Profiling Reveals Social Status-Dependent Modulation of Nuclear Hormone Receptors in GnRH Neurons in a Male Cichlid Fish
    Ogawa S, Parhar IS
    Int J Mol Sci, 2020 Apr 15;21(8).
    PMID: 32326396 DOI: 10.3390/ijms21082724
    Gonadotropin-releasing hormone (GnRH) is essential for the initiation and maintenance of reproductive functions in vertebrates. To date, three distinct paralogue lineages, GnRH1, GnRH2, and GnRH3, have been identified with different functions and regulatory mechanisms. Among them, hypothalamic GnRH1 neurons are classically known as the hypophysiotropic form that is regulated by estrogen feedback. However, the mechanism of action underlying the estrogen-dependent regulation of GnRH1 has been debated, mainly due to the coexpression of low levels of estrogen receptor (ER) genes. In addition, the role of sex steroids in the modulation of GnRH2 and GnRH3 neurons has not been fully elucidated. Using single-cell real-time PCR, we revealed the expression of genes for estrogen, androgen, glucocorticoid, thyroid, and xenobiotic receptors in GnRH1, GnRH2, and GnRH3 neurons in the male Nile tilapia Oreochromis niloticus. We further quantified expression levels of estrogen receptor genes (ERα, ERβ, and ERγ) in three GnRH neuron types in male tilapia of two different social statuses (dominant and subordinate) at the single cell level. In dominant males, GnRH1 mRNA levels were positively proportional to ERγ mRNA levels, while in subordinate males, GnRH2 mRNA levels were positively proportional to ERβ mRNA levels. These results indicate that variations in the expression of nuclear receptors (and possibly steroid sensitivities) among individual GnRH cells may facilitate different physiological processes, such as the promotion of reproductive activities through GnRH1 neurons, and the inhibition of feeding and sexual behaviors through GnRH2 neurons.
    Matched MeSH terms: Androgens/genetics; Estrogens/genetics; Glucocorticoids/genetics; Gonadotropin-Releasing Hormone/genetics; Receptors, Estrogen/genetics; Stress, Psychological/genetics; Thyroid Hormones/genetics; Cichlids/genetics
  14. Fulltext Expression of the Streptococcus pneumoniae yoeB chromosomal toxin gene causes cell death in the model plant Arabidopsis thaliana
    Bakar FA, Yeo CC, Harikrishna JA
    BMC Biotechnol, 2015;15:26.
    PMID: 25887501 DOI: 10.1186/s12896-015-0138-8
    Bacterial toxin-antitoxin systems usually comprise of a pair of genes encoding a stable toxin and its cognate labile antitoxin and are located in the chromosome or in plasmids of several bacterial species. Chromosomally-encoded toxin-antitoxin systems are involved in bacterial stress responses and activation of the toxins usually leads to cell death or dormancy. Overexpression of the chromosomally-encoded YoeB toxin from the yefM-yoeB toxin-antitoxin locus of the Gram-positive bacterium Streptococcus pneumoniae has been shown to cause cell death in S. pneumoniae as well as E. coli.
    Matched MeSH terms: Bacterial Proteins/genetics; Bacterial Toxins/genetics; Estradiol/genetics; Recombinant Fusion Proteins/genetics; Streptococcus pneumoniae/genetics*; Arabidopsis/genetics; Plants, Genetically Modified/genetics; Green Fluorescent Proteins/genetics
  15. Fulltext Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma
    Li HB, You QS, Xu LX, Sun LX, Abdul Majid AS, Xia XB, et al.
    Cell Physiol Biochem, 2017;43(5):2117-2132.
    PMID: 29065394 DOI: 10.1159/000484231
    BACKGROUND/AIMS: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma.

    METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis.

    RESULTS: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups.

    CONCLUSION: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

    Matched MeSH terms: Glaucoma/genetics; Intraocular Pressure/genetics; Apoptosis/genetics; Antigens, Thy-1/genetics; Phosphatidylinositol 3-Kinases/genetics; Transcription Factor Brn-3A/genetics; Proto-Oncogene Proteins c-akt/genetics; RNA, Long Noncoding/genetics
  16. Evaluation of PCR-RFLP analysis targeting hsp65 and rpoB genes for the typing of mycobacterial isolates in Malaysia
    Ong CS, Ngeow YF, Yap SF, Tay ST
    J Med Microbiol, 2010 Nov;59(Pt 11):1311-1316.
    PMID: 20688949 DOI: 10.1099/jmm.0.021139-0
    In this study, PCR-RFLP analysis (PRA) targeting hsp65 and rpoB gene regions was evaluated for the identification of mycobacterial species isolated from Malaysian patients. Overall, the hsp65 PRA identified 92.2 % of 90 isolates compared to 85.6 % by the rpoB PRA. With 47 rapidly growing species, the hsp65 PRA identified fewer (89.4 %) species than the rpoB PRA (95.7 %), but with 23 slow-growing species the reverse was true (91.3 % identification by the hsp65 PRA but only 52.5 % by the rpoB PRA). There were 16 isolates with discordant PRA results, which were resolved by 16S rRNA and hsp65 gene sequence analysis. The findings in this study suggest that the hsp65 PRA is more useful than the rpoB PRA for the identification of Mycobacterium species, particularly with the slow-growing members of the genus. In addition, this study reports 5 and 12 novel restriction patterns for inclusion in the hsp65 and rpoB PRA algorithms, respectively.
    Matched MeSH terms: Bacterial Proteins/genetics*; DNA, Bacterial/genetics; DNA, Ribosomal/genetics; Mycobacterium/genetics; DNA-Directed RNA Polymerases/genetics*; RNA, Bacterial/genetics; RNA, Ribosomal, 16S/genetics; Chaperonin 60/genetics*
  17. Molecular characterization of carbapenemase and cephalosporinase genes among clinical isolates of Acinetobacter baumannii in a tertiary medical centre in Malaysia
    Biglari S, Alfizah H, Ramliza R, Rahman MM
    J Med Microbiol, 2015 Jan;64(Pt 1):53-8.
    PMID: 25381148 DOI: 10.1099/jmm.0.082263-0
    Antimicrobial resistance in Acinetobacter baumannii is a growing public health concern and an important pathogen in nosocomial infections. We investigated the genes involved in resistance to carbapenems and cephalosporins in clinical A. baumannii isolates from a tertiary medical centre in Malaysia. A. baumannii was isolated from 167 clinical specimens and identified by sequencing of the 16S rRNA and rpoB genes. The MIC for imipenem, meropenem, ceftazidime and cefepime were determined by the E-test method. The presence of carbapenemase and cephalosporinase genes was investigated by PCR. The isolates were predominantly nonsusceptible to carbapenems and cephalosporins (>70 %) with high MIC values. ISAba1 was detected in all carbapenem-nonsusceptible A. baumannii harbouring the blaOXA-23-like gene. The presence of blaOXA-51-like and ISAba1 upstream of blaOXA-51 was not associated with nonsusceptibility to carbapenems. A. baumannii isolates harbouring ISAba1-blaADC (85.8 %) were significantly associated with nonsusceptibility to cephalosporins (P<0.0001). However, ISAba1-blaADC was not detected in a minority (<10 %) of the isolates which were nonsusceptible to cephalosporins. The acquired OXA-23 enzymes were responsible for nonsusceptibility to carbapenems in our clinical A. baumannii isolates and warrant continuous surveillance to prevent further dissemination of this antibiotic resistance gene. The presence of ISAba1 upstream of the blaADC was a determinant for cephalosporin resistance. However, the absence of this ISAba1-blaADC in some of the isolates may suggest other resistance mechanisms and need further investigation.
    Matched MeSH terms: Bacterial Proteins/genetics*; beta-Lactamases/genetics*; Cephalosporinase/genetics*; DNA, Bacterial/genetics; DNA, Ribosomal/genetics; DNA-Directed RNA Polymerases/genetics; RNA, Ribosomal, 16S/genetics; Acinetobacter baumannii/genetics
  18. Fulltext Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy
    Miyake N, Fukai R, Ohba C, Chihara T, Miura M, Shimizu H, et al.
    Am J Hum Genet, 2016 Oct 06;99(4):950-961.
    PMID: 27666374 DOI: 10.1016/j.ajhg.2016.08.005
    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy.
    Matched MeSH terms: Brain Diseases/genetics*; Drosophila melanogaster/genetics; Microtubule-Associated Proteins/genetics*; Mutation/genetics*; Frameshift Mutation/genetics; Molecular Chaperones/genetics; Neurodegenerative Diseases/genetics*; RNA Splice Sites/genetics
  19. Fulltext High throughput silencing identifies novel genes in endometrioid endometrial cancer
    Md Fuzi AA, Omar SZ, Mohamed Z, Mat Adenan NA, Mokhtar NM
    Taiwan J Obstet Gynecol, 2018 Apr;57(2):217-226.
    PMID: 29673664 DOI: 10.1016/j.tjog.2018.02.009
    OBJECTIVE: To validate the gene expression profile obtained from the previous microarray analysis and to further study the biological functions of these genes in endometrial cancer. From our previous study, we identified 621 differentially expressed genes in laser-captured microdissected endometrioid endometrial cancer as compared to normal endometrial cells. Among these genes, 146 were significantly up-regulated in endometrial cancer.

    MATERIALS AND METHODS: A total of 20 genes were selected from the list of up-regulated genes for the validation assay. The qPCR confirmed that 19 out of the 20 genes were up-regulated in endometrial cancer compared with normal endometrium. RNA interference (RNAi) was used to knockdown the expression of the upregulated genes in ECC-1 and HEC-1A endometrial cancer cell lines and its effect on proliferation, migration and invasion were examined.

    RESULTS: Knockdown of MIF, SOD2, HIF1A and SLC7A5 by RNAi significantly decreased the proliferation of ECC-1 cells (p < 0.05). Our results also showed that the knockdown of MIF, SOD2 and SLC7A5 by RNAi significantly decreased the proliferation and migration abilities of HEC-1A cells (p < 0.05). Moreover, the knockdown of SLC38A1 and HIF1A by RNAi resulted in a significant decrease in the proliferation of HEC1A cells (p < 0.05).

    CONCLUSION: We have identified the biological roles of SLC38A1, MIF, SOD2, HIF1A and SLC7A5 in endometrial cancer, which opens up the possibility of using the RNAi silencing approach to design therapeutic strategies for treatment of endometrial cancer.

    Matched MeSH terms: Macrophage Migration-Inhibitory Factors/genetics; Superoxide Dismutase/genetics; Endometrial Neoplasms/genetics*; Intramolecular Oxidoreductases/genetics; Amino Acid Transport System A/genetics; Large Neutral Amino Acid-Transporter 1/genetics; Cell Proliferation/genetics; Hypoxia-Inducible Factor 1, alpha Subunit/genetics
  20. Differential attenuation of Marek's disease virus-induced tumours and late-Marek's disease virus-induced immunosuppression
    Faiz NM, Cortes AL, Guy JS, Reddy SM, Gimeno IM
    J Gen Virol, 2018 07;99(7):927-936.
    PMID: 29767614 DOI: 10.1099/jgv.0.001076
    Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs induce a form of immunosuppression (late-MDV-IS) that might involve both neoplastic and non-neoplastic mechanisms. The objective of this study was to evaluate whether the attenuation of MDV-induced tumours and late-MDV-IS occurs simultaneously or can be dissociated. The immunosuppressive ability of three viruses derived from vv+ MDV strain 686 (wild-type 686, the somewhat attenuated molecular clone 686-BAC, and the nononcogenic molecular clone lacking the two copies of the oncogene meq 686-BACΔMEQ) was evaluated. Late-MDV-IS was evaluated indirectly by assessing the negative effect of MDV strains on the protection conferred by infectious laryngotracheitis (ILT) vaccines. Our results showed that the ability to induce late-MDV-IS was attenuated before the ability to induce tumours. Strain 686 induced both tumours and late-MDV-IS, 686-BAC induced tumours but did not induce late-MDV-IS and 686-BACΔMEQ did not induce either tumours or late-MDV-IS. Further comparison of strains 686 and 686-BAC revealed that strain 686 reduced the humoral immune responses to ILTV (1132 vs 2167) more severely, showed higher levels of meq transcripts (2.1E+09 vs 4.98E+8) and higher expression of MDV microRNAs (mdv1-miR-M4-5p and mdv1-miR-M2-3p) in the spleen, and further reduced the percentage of CD45+-MHC-I+splenocytes (13 vs32 %) compared to molecular clone 686-BAC. This study suggests that the immunosuppressive ability of MDV might follow a continuous spectrum and only the most virulent MDVs can overcome a certain threshold level and induce clinical MDV-IS in the ILT model.
    Matched MeSH terms: Herpesvirus 1, Gallid/genetics; Immunologic Deficiency Syndromes/genetics; Lymphoma/genetics; Marek Disease/genetics; Herpesvirus 2, Gallid/genetics; RNA, Viral/genetics; MicroRNAs/genetics; Carcinogenesis/genetics
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