Displaying publications 4441 - 4460 of 8213 in total

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  1. Sensitive Leptospira DNA detection using tapered optical fiber sensor
    Zainuddin NH, Chee HY, Ahmad MZ, Mahdi MA, Abu Bakar MH, Yaacob MH
    J Biophotonics, 2018 08;11(8):e201700363.
    PMID: 29570957 DOI: 10.1002/jbio.201700363
    This paper presents the development of tapered optical fiber sensor to detect a specific Leptospira bacteria DNA. The bacteria causes Leptospirosis, a deadly disease but with common early flu-like symptoms. Optical single mode fiber (SMF) of 125 μm diameter is tapered to produce 12 μm waist diameter and 15 cm length. The novel DNA-based optical fiber sensor is functionalized by incubating the tapered region with sodium hydroxide (NaOH), (3-Aminopropyl) triethoxysilane and glutaraldehyde. Probe DNA is immobilized onto the tapered region and subsequently hybridized by its complementary DNA (cDNA). The transmission spectra of the DNA-based optical fiber sensor are measured in the 1500 to 1600 nm wavelength range. It is discovered that the shift of the wavelength in the SMF sensor is linearly proportional with the increase in the cDNA concentrations from 0.1 to 1.0 nM. The sensitivity of the sensor toward DNA is measured to be 1.2862 nm/nM and able to detect as low as 0.1 fM. The sensor indicates high specificity when only minimal shift is detected for non-cDNA testing. The developed sensor is able to distinguish between actual DNA of Leptospira serovars (Canicola and Copenhageni) against Clostridium difficile (control sample) at very low (femtomolar) target concentrations.
    Matched MeSH terms: Leptospira/genetics*; Genome, Bacterial/genetics
  2. Fulltext Single-cell RNA sequencing analysis of shrimp immune cells identifies macrophage-like phagocytes
    Yang P, Chen Y, Huang Z, Xia H, Cheng L, Wu H, et al.
    Elife, 2022 Oct 06;11.
    PMID: 36200862 DOI: 10.7554/eLife.80127
    Despite the importance of innate immunity in invertebrates, the diversity and function of innate immune cells in invertebrates are largely unknown. Using single-cell RNA-seq, we identified prohemocytes, monocytic hemocytes, and granulocytes as the three major cell-types in the white shrimp hemolymph. Our results identified a novel macrophage-like subset called monocytic hemocytes 2 (MH2) defined by the expression of certain marker genes, including Nlrp3 and Casp1. This subtype of shrimp hemocytes is phagocytic and expresses markers that indicate some conservation with mammalian macrophages. Combined, our work resolves the heterogenicity of hemocytes in a very economically important aquatic species and identifies a novel innate immune cell subset that is likely a critical player in the immune responses of shrimp to threatening infectious diseases affecting this industry.
    Matched MeSH terms: Immunity, Innate/genetics; Mammals/genetics
  3. Fulltext Anti-pancreatic lipase and anti-adipogenic effects of 5, 7, 3',4',5' -pentamethoxy and 6, 2',4'-trimethoxy flavone - An In vitro study
    Ahmad B, Friar EP, Taylor E, Vohra MS, Serpell CJ, Garrett MD, et al.
    Eur J Pharmacol, 2023 Jan 05;938:175445.
    PMID: 36473593 DOI: 10.1016/j.ejphar.2022.175445
    In this study, the anti-obesity effects of 5,7,3',4',5-pentamethoxyflavone (PMF) and 6,2',4'-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.
    Matched MeSH terms: CCAAT-Enhancer-Binding Protein-alpha/genetics; PPAR gamma/genetics
  4. Fulltext Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations
    Ahn MJ, Mendoza MJL, Pavlakis N, Kato T, Soo RA, Kim DW, et al.
    Clin Lung Cancer, 2022 Dec;23(8):670-685.
    PMID: 36151006 DOI: 10.1016/j.cllc.2022.07.012
    Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with many oncogenic driver mutations, including de novo mutations in the Mesenchymal Epithelial Transition (MET) gene (specifically in Exon 14 [ex14]), that lead to tumourigenesis. Acquired alterations in the MET gene, specifically MET amplification is also associated with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutant NSCLC. Although MET has become an actionable biomarker with the availability of MET-specific inhibitors in selected countries, there is differential accessibility to diagnostic platforms and targeted therapies across countries in Asia-Pacific (APAC). The Asian Thoracic Oncology Research Group (ATORG), an interdisciplinary group of experts from Australia, Hong Kong, Japan, Korea, Mainland China, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, discussed testing for MET alterations and considerations for using MET-specific inhibitors at a consensus meeting in January 2022, and in subsequent offline consultation. Consensus recommendations are provided by the ATORG group to address the unmet need for standardised approaches to diagnosing MET alterations in NSCLC and for using these therapies. MET inhibitors may be considered for first-line or second or subsequent lines of treatment for patients with advanced and metastatic NSCLC harbouring MET ex14 skipping mutations; MET ex14 testing is preferred within multi-gene panels for detecting targetable driver mutations in NSCLC. For patients with EGFR-mutant NSCLC and MET amplification leading to EGFR TKI resistance, enrolment in combination trials of EGFR TKIs and MET inhibitors is encouraged.
    Matched MeSH terms: Drug Resistance, Neoplasm/genetics; ErbB Receptors/genetics
  5. Telomerase: is it the future diagnostic and prognostic tool in human cancer?
    Mabruk MJ, O'Flatharta C
    Expert Rev Mol Diagn, 2005 Nov;5(6):907-16.
    PMID: 16255632
    A number of methods exist to detect levels of telomerase activity and the presence of telomerase subunits in a variety of tissues. As telomerase activation seems to be an important step in tumorigenesis, accurate detection of the presence and activity of the enzyme and its subunits is vital. The original method of detecting telomerase activity was developed by Kim and coworkers in 1994, and was termed the telomeric repeat amplification protocol. This assay led to a staggering increase in the number of telomerase-associated publications in scientific journals (85 publications from 1974-1994, 5063 publications from 1994-2004). A number of methods have been described to detect telomeres and to measure their length, with the standard measurement of telomere length performed using a modification of the Southern blot protocol. RNA in situ hybridization can be performed to detect levels of the RNA component of telomerase, and standard in situ hybridization and immunohistochemistry can be applied to examine expression levels and localization of the catalytic subunit of the enzyme. Reverse transcriptase PCR has also been applied to assess expression levels of the telomerase components in various tissues. This review provides a synopsis of telomeres, telomerase, telomerase and cancer, and finally, methods for the detection of telomerase in cancer.
    Matched MeSH terms: Neoplasms/genetics; Telomerase/genetics
  6. Fulltext In Silico Study and Effects of BDMC33 on TNBS-Induced BMP Gene Expressions in Zebrafish Gut Inflammation-Associated Arthritis
    Mostofa F, Yasid NA, Shamsi S, Ahmad SA, Mohd-Yusoff NF, Abas F, et al.
    Molecules, 2022 Nov 28;27(23).
    PMID: 36500396 DOI: 10.3390/molecules27238304
    The bone morphogenic protein (BMP) family is a member of the TGF-beta superfamily and plays a crucial role during the onset of gut inflammation and arthritis diseases. Recent studies have reported a connection with the gut-joint axis; however, the genetic players are still less explored. Meanwhile, BDMC33 is a newly synthesized anti-inflammatory drug candidate. Therefore, in our present study, we analysed the genome-wide features of the BMP family as well as the role of BMP members in gut-associated arthritis in an inflammatory state and the ability of BDMC33 to attenuate this inflammation. Firstly, genome-wide analyses were performed on the BMP family in the zebrafish genome, employing several in silico techniques. Afterwards, the effects of curcumin analogues on BMP gene expression in zebrafish larvae induced with TNBS (0.78 mg/mL) were determined using real time-qPCR. A total of 38 identified BMP proteins were revealed to be clustered in five major clades and contain TGF beta and TGF beta pro peptide domains. Furthermore, BDMC33 suppressed the expression of four selected BMP genes in the TNBS-induced larvae, where the highest gene suppression was in the BMP2a gene (an eight-fold decrement), followed by BMP7b (four-fold decrement), BMP4 (four-fold decrement), and BMP6 (three-fold decrement). Therefore, this study reveals the role of BMPs in gut-associated arthritis and proves the ability of BDMC33 to act as a potential anti-inflammatory drug for suppressing TNBS-induced BMP genes in zebrafish larvae.
    Matched MeSH terms: Transforming Growth Factor beta/genetics; Bone Morphogenetic Proteins/genetics
  7. Fulltext Development of qPCR platform with probes for quantifying prevalent and biomedically relevant human gut microbial taxa
    Kurina I, Popenko A, Klimenko N, Koshechkin S, Chuprikova L, Filipenko M, et al.
    Mol Cell Probes, 2020 Aug;52:101570.
    PMID: 32304824 DOI: 10.1016/j.mcp.2020.101570
    Nowadays the advent of innovative high-throughput sequencing allows obtaining high-quality microbiome profiling. However, PCR-based tests are still considered the "golden standard" for many clinical applications. Here, we designed a qPCR-based platform with fluorescent-labeled oligonucleotide probes for assessing human gut microbiome composition. The system allows conducting qualitative and semiquantitative analysis for 12 prokaryotic taxa that are prevalent in the human gut and associated with diseases, diet, age and other factors. The platform was validated by comparing microbiome profile data obtained with two different methods - the platform and high-throughput 16S rRNA sequencing - across 42 stool samples. The test can form the basis for precise and cost-efficient microbiome assay for large-scale surveys including clinical trials with interventions related to diet and disease risks.
    Matched MeSH terms: Gastrointestinal Microbiome/genetics*; RNA, Ribosomal, 16S/genetics
  8. Fulltext Characterization of bacterial communities associated with blood-fed and starved tropical bed bugs, Cimex hemipterus (F.) (Hemiptera): a high throughput metabarcoding analysis
    Lim L, Ab Majid AH
    Sci Rep, 2021 Apr 19;11(1):8465.
    PMID: 33875727 DOI: 10.1038/s41598-021-87946-w
    With the development of new metagenomic techniques, the microbial community structure of common bed bugs, Cimex lectularius, is well-studied, while information regarding the constituents of the bacterial communities associated with tropical bed bugs, Cimex hemipterus, is lacking. In this study, the bacteria communities in the blood-fed and starved tropical bed bugs were analysed and characterized by amplifying the v3-v4 hypervariable region of the 16S rRNA gene region, followed by MiSeq Illumina sequencing. Across all samples, Proteobacteria made up more than 99% of the microbial community. An alpha-proteobacterium Wolbachia and gamma-proteobacterium, including Dickeya chrysanthemi and Pseudomonas, were the dominant OTUs at the genus level. Although the dominant OTUs of bacterial communities of blood-fed and starved bed bugs were the same, bacterial genera present in lower numbers were varied. The bacteria load in starved bed bugs was also higher than blood-fed bed bugs.
    Matched MeSH terms: Bacteria/genetics; DNA/genetics*
  9. Fulltext Differential accumulation of tau pathology between reciprocal F1 hybrids of rTg4510 mice
    Yanagisawa D, Hamezah HS, Pahrudin Arrozi A, Tooyama I
    Sci Rep, 2021 May 05;11(1):9623.
    PMID: 33953293 DOI: 10.1038/s41598-021-89142-2
    Tau, a family of microtubule-associated proteins, forms abnormal intracellular inclusions, so-called tau pathology, in a range of neurodegenerative diseases collectively known as tauopathies. The rTg4510 mouse model is a well-characterized bitransgenic F1 hybrid mouse model of tauopathy, which was obtained by crossing a Camk2α-tTA mouse line (on a C57BL/6 J background) with a tetO-MAPT*P301L mouse line (on a FVB/NJ background). The aim of this study was to investigate the effects of the genetic background and sex on the accumulation of tau pathology in reciprocal F1 hybrids of rTg4510 mice, i.e., rTg4510 on the (C57BL/6 J × FVB/NJ)F1 background (rTg4510_CxF) and on the (FVB/NJ × C57BL/6 J)F1 background (rTg4510_FxC). As compared with rTg4510_CxF mice, the rTg4510_FxC mice showed marked levels of tau pathology in the forebrain. Biochemical analyses indicated that the accumulation of abnormal tau species was accelerated in rTg4510_FxC mice. There were strong effects of the genetic background on the differential accumulation of tau pathology in rTg4510 mice, while sex had no apparent effect. Interestingly, midline-1 (Mid1) was identified as a candidate gene associated with this difference and exhibited significant up/downregulation according to the genetic background. Mid1 silencing with siRNA induced pathological phosphorylation of tau in HEK293T cells that stably expressed human tau with the P301L mutation, suggesting the role of Mid1 in pathological alterations of tau. Elucidation of the underlying mechanisms will provide novel insights into the accumulation of tau pathology and is expected to be especially informative to researchers for the continued development of therapeutic interventions for tauopathies.
    Matched MeSH terms: tau Proteins/genetics; Tauopathies/genetics
  10. Fulltext Cross-Neutralizing CRF01_AE-Infected Plasma from Malaysia Targets CD4-Binding Site of Human Immunodeficiency Virus Type-1 Envelope Glycoprotein
    Ng QR, Tee KK, Binley JM, Tong T
    AIDS Res Hum Retroviruses, 2022 Feb;38(2):162-172.
    PMID: 34006141 DOI: 10.1089/AID.2020.0299
    Human immunodeficiency virus type-1 (HIV-1) antigenic variation poses a great challenge for vaccine immunogen design to elicit broadly neutralizing antibodies (bNAbs). Over the last 10-15 years, great progress has been made to understand the conserved sites of sensitivity on HIV envelope glycoprotein spikes targeted by bNAbs. Plasma neutralization mapping and monoclonal antibody isolation efforts have revealed five major conserved epitope clusters. Most of this work has focused on subtype B and C-infected Caucasian or African donors. It is not clear if the same epitopes and epitope rank order preferences are also true in donors infected with different HIV-1 subtypes and with different racial backgrounds. To investigate this point, in this study we report the first attempt to profile the bNAb specificities of CRF01_AE-infected Malaysian plasmas. We first measured neutralization titers of 21 plasmas against a subtype A, B, and AE pseudovirus panel. This revealed that 14% (3 of 21) plasmas had cross-clade breadth. Focusing on the cross-neutralizing plasma P9, we used AE and JR-FL mutant pseudoviruses, gp120 monomer interference, and native polyacrylamide gel electrophoresis to better understand the neutralization specificity. P9 demonstrates CD4-binding-site specificity with trimer dependence and D368 independence.
    Matched MeSH terms: HIV Envelope Protein gp120/genetics; env Gene Products, Human Immunodeficiency Virus/genetics
  11. Multiplexed genotyping of beta globin mutations with MALDI-TOF mass spectrometry
    Looi ML, Sivalingam M, Husin ND, Radin FZ, Isa RM, Zakaria SZ, et al.
    Clin Chim Acta, 2011 May 12;412(11-12):999-1002.
    PMID: 21315703 DOI: 10.1016/j.cca.2011.02.006
    BACKGROUND: Beta thalassemia represents a great heterogeneity as over 300 mutations have been identified and each population at-risk has its own spectrum of mutations. Molecular characterization with high accuracy, sensitivity and economics is required for population screening and genetic counseling.
    METHODS: We used the MALDI-TOF mass spectrometry (MS) platform to develop novel multiplex assays for comprehensive detection of 27 mutations in beta-thalassemia patients. Six multiplex assays were designed to detect 13 common known ß-mutations, namely CD41/42, CD71/72, IVS1-5, IVS1-1, CD26, IVS2-654, CAP+1, CD19, -28, -29, IVS1-2, InCD (T-G) and CD17; and 14 rare ß-mutations, i.e. InCD (A-C), CD8/9, CD43, -86, CD15, Poly A, Poly T/C, IVS2-1, CD1, CD35/36, CD27/28, CD16, CD37, and 619bpDEL in 165 samples. We compared the efficiencies of genotyping by MS and Amplification Refractory Mutation System (ARMS). Discrepant results were confirmed by sequencing analysis.
    RESULTS: A total of 88.7% (260/293 allele) of MS and ARMS results was in agreement. More than fifty percent of the discrepant result was due to the false interpretation of ARMS results. Failed CD19 assay by MS method might be due to the assay design. The MS method detected 5 rare ß-mutations (CD15, CD35/36, CD8/9, Poly A and Poly T/C) presented in 13 alleles, which were not included in the ARMS screening panel.
    CONCLUSION: We revealed that the MS method is a sensitive, high-throughput, highly automated, flexible, and cost-effective alternative to conventional ß-thalassemia genotyping methods.
    Matched MeSH terms: beta-Thalassemia/genetics; beta-Globins/genetics*
  12. Circulating miR-3197 and miR-2116-5p as novel biomarkers for diabetic retinopathy
    Ji H, Yi Q, Chen L, Wong L, Liu Y, Xu G, et al.
    Clin Chim Acta, 2020 Feb;501:147-153.
    PMID: 31678272 DOI: 10.1016/j.cca.2019.10.036
    Diabetic retinopathy (DR) is the leading cause of vision loss among older adults. The goal of this case-control study was to identify circulating miRNAs for the diagnosis of DR. The miRNeasy Serum/Plasma Kit was used to extract serum miRNAs. The μParaflo™ MicroRNA microarray was used to detect the expression levels of the miRNAs. The miRWalk algorithm was applied to predict the target genes of the miRNAs, which were further confirmed by the dual luciferase reporter gene system in HEK293T cells. A microarray was performed between 5 DR cases and 5 age-, sex-, body mass index-, and duration of diabetes-matched type 2 diabetic (T2DM) controls. The quantitative reverse transcription polymerase chain reaction technique was used to validate the differentially expressed circulating miRNAs in 45 DR cases and 45 well-matched controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the circulating miRNAs as diagnostic biomarkers for DR. Our microarray analysis screened out miR-2116-5p and miR-3197 as significantly up-regulated in DR cases compared with the controls. Furthermore, two miRNAs were validated in the 45 DR cases and 45 controls. The ROC analysis suggested that both miR-3197 and miR-2116-5p distinguished DR cases from controls. An additional dual-luciferase reporter gene assay confirmed that notch homolog 2 (NOTCH2) was the target gene of miR-2116-5p. Both miR-3197 and miR-2116-5p were identified as promising diagnostic biomarkers for DR. Future research is still needed to explore the molecular mechanisms of miR-3197 and miR-2116-5p in the pathogenesis of DR.
    Matched MeSH terms: Diabetic Retinopathy/genetics*; MicroRNAs/genetics
  13. Standard CYP2D6 genotyping procedures fail for the CYP2D6*5 and duplication alleles when hair roots are used as a source of DNA
    Gan SH, Ismail R, Wan Adnan WA, Wan Z
    Clin Chim Acta, 2003 Mar;329(1-2):61-8.
    PMID: 12589966 DOI: 10.1016/s0009-8981(03)00019-6
    BACKGROUND: Hair roots provide a useful alternative to blood as a source of DNA for genotyping. Besides simple and non-invasive collections, the DNA extraction step is also easy to perform and is fast. The aim of our study is to determine if hair roots can be used to genotype all of the common CYP2D6 alleles for routine screening purposes.

    METHOD: The study complies with the Declaration of Helsinki. After obtaining informed consents, both blood and hair samples were collected from 92 patients for genotyping of the CYP2D6 gene. PCR was used to detect the following mutations: CYP2D6*1, *3, *4, *5, *9, *10, *17 and duplication gene. The results were compared where hair roots and blood were used as templates for DNA respectively.

    RESULTS: When blood was used as a source of DNA for genotyping, all of the investigated CYP2D6 alleles were successfully amplified. However, with hair roots, the genes with the larger fragment sizes: CYP2D6*5 and the duplication gene could not be amplified and the bands of other alleles investigated were faint when visualized under UV light.

    CONCLUSIONS: DNA extraction from hair roots and leucocytes yielded similar results but the DNA extracted from hair roots did not allow successful amplification of the longer genes such as the CYP2D6*5 and the duplication gene.
    Matched MeSH terms: Isoenzymes/genetics; Cytochrome P-450 CYP2D6/genetics*
  14. Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder
    Badamasi IM, Lye MS, Ibrahim N, Abdul Razaq NA, Ling KH, Stanslas J
    Pharmacogenomics J, 2021 Aug;21(4):498-509.
    PMID: 33731884 DOI: 10.1038/s41397-021-00228-6
    The polymorphisms of the 5HTR1A and 5HTR2A receptor genes (rs6295C/G and rs6311G/A) have been evaluated for association with SSRI treatment outcome in various populations with different results. The present study was carried out to determine the association between genotypes of HTR1A-rs6295 and HTR2A-rs6311 with SSRI treatment outcome among the ethnic Malay patients diagnosed with first-episode major depressive disorder (MDD). The patients were recruited from four tertiary hospitals in the Klang Valley region of Malaysia. Predefined efficacy phenotypes based on 25% (partial early response) and 50% (clinical efficacy response) reduction in Montgomery Asberg Depression Rating Scale-self Rated score (MADRS-S) were adopted for assessment of treatment efficacy in this study. Self-reporting for adverse effects (AE) was documented using the Patient Rated Inventory of Side Effect (PRISE) after treatment with SSRI for up to 6 weeks. Adjusted binary logistic regression between genotypes of the polymorphism obtained using sequencing technique with the treatment outcome phenotypes was performed. The 142 patients recruited were made up of 96 females (67.6%) and 46 males (32.4%). Clinical efficacy and Partial early response phenotypes were not significantly associated with genotypes of HTR1A and HTR2A polymorphism. The GG genotype of HTR2A polymorphism has decreased odds for dizziness (CNS) and increased odds for poor concentration. The GA genotype increases the odd for excessive sweating, diarrhoea, constipation and blurred vision. The CC genotype of HTR1A-rs6295 decreases the odd for nausea/vomiting and increases the odd for anxiety. Thus, some genotypes of HTR1A and HTR2A polymorphism were associated with SSRI treatment outcomes in ethnic Malay MDD patients.
    Matched MeSH terms: Depressive Disorder, Major/genetics*; Polymorphism, Single Nucleotide/genetics*
  15. Fulltext DNA-based taxonomy of a mangrove-associated community of fishes in Southeast Asia
    Zainal Abidin DH, Mohd Nor SA, Lavoué S, A Rahim M, Jamaludin NA, Mohammed Akib NA
    Sci Rep, 2021 Sep 07;11(1):17800.
    PMID: 34493747 DOI: 10.1038/s41598-021-97324-1
    The Merbok Estuary comprises one of the largest remaining mangrove forests in Peninsular Malaysia. Its value is significant as it provides important services to local and global communities. It also offers a unique opportunity to study the structure and functioning of mangrove ecosystems. However, its biodiversity is still partially inventoried, limiting its research value. A recent checklist based on morphological examination, reported 138 fish species residing, frequenting or subject to entering the Merbok Estuary. In this work, we reassessed the fish diversity of the Merbok Estuary by DNA barcoding 350 specimens assignable to 134 species initially identified based on morphology. Our results consistently revealed the presence of 139 Molecular Operational Taxonomic Units (MOTUs). 123 of them are congruent with morphology-based species delimitation (one species = one MOTU). In two cases, two morphological species share the same MOTU (two species = one MOTU), while we unveiled cryptic diversity (i.e. COI-based genetic variability > 2%) within seven other species (one species = two MOTUs), calling for further taxonomic investigations. This study provides a comprehensive core-list of fish taxa in Merbok Estuary, demonstrating the advantages of combining morphological and molecular evidence to describe diverse but still poorly studied tropical fish communities. It also delivers a large DNA reference collection for brackish fishes occurring in this region which will facilitate further biodiversity-oriented research studies and management activities.
    Matched MeSH terms: DNA/genetics; Fishes/genetics
  16. A RUNX1/ETO-SKP2-CDKN1B axis regulates expression of telomerase in t (8;21) acute myeloid leukemia
    Moses EJ, Azlan A, Khor KZ, Mot YY, Mohamed S, Seeni A, et al.
    Cell Mol Life Sci, 2023 Feb 23;80(3):70.
    PMID: 36820913 DOI: 10.1007/s00018-023-04713-y
    The fusion oncoprotein RUNX1/ETO which results from the chromosomal translocation t (8;21) in acute myeloid leukemia (AML) is an essential driver of leukemic maintenance. We have previously shown that RUNX1/ETO knockdown impairs expression of the protein component of telomerase, TERT. However, the underlying molecular mechanism of how RUNX1/ETO controls TERT expression has not been fully elucidated. Here we show that RUNX1/ETO binds to an intergenic region 18 kb upstream of the TERT transcriptional start site and to a site located in intron 6 of TERT. Loss of RUNX1/ETO binding precedes inhibition of TERT expression. Repression of TERT expression is also dependent on the destabilization of the E3 ubiquitin ligase SKP2 and the resultant accumulation of the cell cycle inhibitor CDKN1B, that are both associated with RUNX1/ETO knockdown. Increased CDKN1B protein levels ultimately diminished TERT transcription with E2F1/Rb involvement. Collectively, our results show that RUNX1/ETO controls TERT expression directly by binding to its locus and indirectly via a SKP2-CDKN1B-E2F1/Rb axis.
    Matched MeSH terms: Oncogene Proteins, Fusion/genetics; Core Binding Factor Alpha 2 Subunit/genetics
  17. Metabolic engineering of Lactococcus lactis influence of the overproduction of lipase enzyme
    Raftari M, Ghafourian S, Bakar FA
    J Dairy Res, 2013 Nov;80(4):490-5.
    PMID: 24063299 DOI: 10.1017/S0022029913000435
    The dairy industry uses lipase extensively for hydrolysis of milk fat. Lipase is used in the modification of the fatty acid chain length, to enhance the flavours of various chesses. Therefore finding the unlimited source of lipase is a concern of dairy industry. Due to the importance of lipase, this study was an attempt to express the lipase from Burkholderia cepacia in Lactococcus lactis. To achieve this, a gene associated with lipase transport was amplified and subcloned in inducible pNZ8148 vector, and subsequently transformed into Lc. lactis NZ9000. The enzyme assay as well as SDS-PAGE and western blotting were carried out to analysis the recombinant lipase expression. Nucleotide sequencing of the DNA insert from the clone revealed that the lipase activity corresponded to an open reading frame consisting of 1092 bp coding for a 37·5-kDa size protein. Blue colour colonies on nile blue sulphate agar and sharp band on 37·5-kD size on SDS-PAGE and western blotting results confirm the successful expression of lipase by Lc. lactis. The protein assay also showed high expression, approximately 152·2 μg/ml.h, of lipase by recombinant Lc. lactis. The results indicate that Lc. lactis has high potential to overproduce the recombinant lipase which can be used commercially for industrially purposes.
    Matched MeSH terms: Lipase/genetics; Lactococcus lactis/genetics
  18. Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals
    Saida K, Maroofian R, Sengoku T, Mitani T, Pagnamenta AT, Marafi D, et al.
    Genet Med, 2023 Jan;25(1):90-102.
    PMID: 36318270 DOI: 10.1016/j.gim.2022.09.010
    PURPOSE: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants.

    METHODS: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies.

    RESULTS: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities.

    CONCLUSION: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders.

    Matched MeSH terms: Caenorhabditis elegans/genetics; Vesicular Monoamine Transport Proteins/genetics
  19. Fulltext The role of autophagy-related proteins in the pathogenesis of neuromyelitis optica spectrum disorders
    Guo HL, Shen XR, Liang XT, Li LZ
    Bioengineered, 2022 Jun;13(6):14329-14338.
    PMID: 36694421 DOI: 10.1080/21655979.2022.2084273
    This study aimed to investigate the expression of autophagy-related proteins in a mouse model of neuromyelitis optica (NMO). Mice were assigned to one of four groups: an animal experimental model group (NMO-EAE group, given with exogenous IL-17A), Interleukin-17 monoclonal antibody intervention group (NMO-EAE_0IL17inb), No exogenous interleukin-17 enhanced immune intervention group (NMO-EAE_0IL17), and a control group. Behavioral scores were assessed in each group, and the protein expressions of sequestosome 1 (P62), Beclin-1, the mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K-I), and LC3II/LC3I were detected using Western blotting. In the NMO-EAE_0IL17 group, the expression of Beclin-1 decreased, the LC3II/LC3I ratio was lower, and the expressions of P62, mTOR, and PI3K-I increased; after administration of IL-17A inhibitor into the brain tissue, however, the expression of Beclin-1 increased significantly, along with the LC3II/LC3I ratio, while the expressions of P62, mTOR and PI3K-I protein decreased significantly. In terms of behavioral scores, the scores of optic neuritis and myelitis were more serious, onset occurred earlier and the progress was faster, after the administration of IL-17A. In the mechanism of NMO animal model, IL-17A may regulate autophagy and affect the disease process through the activation of the PI3K-mTOR signaling pathway.
    Matched MeSH terms: TOR Serine-Threonine Kinases/genetics; Beclin-1/genetics
  20. Fulltext Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
    Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, et al.
    Nat Genet, 2021 Jan;53(1):65-75.
    PMID: 33398198 DOI: 10.1038/s41588-020-00748-0
    Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
    Matched MeSH terms: Prostatic Neoplasms/genetics*; Continental Population Groups/genetics*
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