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Simple and rapid detection of Salmonella strains by direct PCR amplification of the hilA gene

Pathmanathan SG, Cardona-Castro N, Sánchez-Jiménez MM, Correa-Ochoa MM, Puthucheary SD, Thong KL

J Med Microbiol, 2003 Sep;52(Pt 9):773-6.
PMID: 12909653

The suitability of a PCR procedure using a pair of primers targeting the hilA gene was evaluated as a means of detecting Salmonella species. A total of 33 Salmonella strains from 27 serovars and 15 non-Salmonella strains from eight different genera were included. PCR with all the Salmonella strains produced a 784 bp DNA fragment that was absent from all the non-Salmonella strains tested. The detection limit of the PCR was 100 pg with genomic DNA and 3 x 10(4) c.f.u. ml(-1) with serial dilutions of bacterial culture. An enrichment-PCR method was further developed to test the sensitivity of the hilA primers for the detection of Salmonella in faecal samples spiked with different concentrations of Salmonella choleraesuis subsp. choleraesuis serovar Typhimurium. The method described allowed the detection of Salmonella Typhimurium in faecal samples at a concentration of 3 x 10(2) c.f.u. ml(-1). In conclusion, the hilA primers are specific for Salmonella species and the PCR method presented may be suitable for the detection of Salmonella in faeces.

Matched MeSH terms: Bacterial Proteins/genetics
Fulltext Identification of IncA/C Plasmid Replication and Maintenance Genes and Development of a Plasmid Multilocus Sequence Typing Scheme

Hancock SJ, Phan MD, Peters KM, Forde BM, Chong TM, Yin WF, et al.

Antimicrob Agents Chemother, 2017 02;61(2).
PMID: 27872077 DOI: 10.1128/AAC.01740-16

Plasmids of incompatibility group A/C (IncA/C) are becoming increasingly prevalent within pathogenic Enterobacteriaceae They are associated with the dissemination of multiple clinically relevant resistance genes, including blaCMY and blaNDM Current typing methods for IncA/C plasmids offer limited resolution. In this study, we present the complete sequence of a blaNDM-1-positive IncA/C plasmid, pMS6198A, isolated from a multidrug-resistant uropathogenic Escherichia coli strain. Hypersaturated transposon mutagenesis, coupled with transposon-directed insertion site sequencing (TraDIS), was employed to identify conserved genetic elements required for replication and maintenance of pMS6198A. Our analysis of TraDIS data identified roles for the replicon, including repA, a toxin-antitoxin system; two putative partitioning genes, parAB; and a putative gene, 053 Construction of mini-IncA/C plasmids and examination of their stability within E. coli confirmed that the region encompassing 053 contributes to the stable maintenance of IncA/C plasmids. Subsequently, the four major maintenance genes (repA, parAB, and 053) were used to construct a new plasmid multilocus sequence typing (PMLST) scheme for IncA/C plasmids. Application of this scheme to a database of 82 IncA/C plasmids identified 11 unique sequence types (STs), with two dominant STs. The majority of blaNDM-positive plasmids examined (15/17; 88%) fall into ST1, suggesting acquisition and subsequent expansion of this blaNDM-containing plasmid lineage. The IncA/C PMLST scheme represents a standardized tool to identify, track, and analyze the dissemination of important IncA/C plasmid lineages, particularly in the context of epidemiological studies.

Matched MeSH terms: Escherichia coli Proteins/genetics
Fulltext Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand

Alam MT, Vinayak S, Congpuong K, Wongsrichanalai C, Satimai W, Slutsker L, et al.

Antimicrob Agents Chemother, 2011 Jan;55(1):155-64.
PMID: 20956597 DOI: 10.1128/AAC.00691-10

The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxine-resistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.

Matched MeSH terms: Protozoan Proteins/genetics*
Fulltext A real-time loop-mediated isothermal amplification assay for rapid detection of Shigella species

Liew PS, Teh CS, Lau YL, Thong KL

Trop Biomed, 2014 Dec;31(4):709-20.
PMID: 25776596 MyJurnal

Shigellosis is a foodborne illness caused by the genus Shigella and is an important global health issue. The development of effective techniques for rapid detection of this pathogen is essential for breaking the chain of transmission. Therefore, we have developed a novel loop-mediated isothermal amplification (LAMP) assay targeting the invasion plasmid antigen H (ipaH) gene to rapidly detect Shigella species. This assay could be performed in 90 min at an optimal temperature of 64ºC, with endpoint results visualized directly. Notably, the method was found to be more sensitive than conventional PCR. Indeed, the detection limit for the LAMP assay on pure bacterial cultures was 5.9 x 10(5) CFU/ml, while PCR displayed a limit of 5.9 x 10(7) CFU/ml. In spiked lettuce samples, the sensitivity of the LAMP assay was 3.6 x 10(4) CFU/g, whereas PCR was 3.6 x 10(5) CFU/g. Overall, the assay accurately identified 32 Shigella spp. with one enteroinvasive Escherichia coli displaying positive reaction while the remaining 32 non-Shigella strains tested were negative.

Matched MeSH terms: Bacterial Proteins/genetics
Fulltext Low efficacy of delthamethrin-treated net against Singapore Aedes aegypti is associated with kdr-type resistance

Pang SC, Chiang LP, Tan CH, Vythilingam I, Lam-Phua SG, Ng LC

Trop Biomed, 2015 Mar;32(1):140-50.
PMID: 25801264 MyJurnal

There has been a worldwide surge in the number and severity of dengue in the past decades. In Singapore, relentless vector control efforts have been put in to control the disease since the 1960's. Space spraying, fogging, chemical treatment and source reduction are some commonly used methodologies for controlling its vectors, particularly Aedes aegypti. Here, as we explored the use of a commercially available delthamethrin-treated net as an alternative strategy and the efficacy of the treated net was found to be limited. Through bioassays and molecular studies, the failure of the treated net to render high mortality rate was found to be associated with the knockdown resistance (kdr) mutation. This is the first report of kdr- mutations in Singapore's Ae. aegypti. At least one point mutation, either homozygous or heterozygous, at amino acid residue V1016G of DIIS6 or F1269C of DIIIS6 was detected in 93% of field strains of Ae. aegypti. Various permutations of wild type and mutant amino acids of the four alleles were found to result in varying degree of survival rate among local field Ae. aegypti when exposed to the deltamethrin treated net. Together with the association of higher survival rate with the presence of both V1016G and F1269C, the data suggest the role of these mutations in the resistance to the deltamethrin. The high prevalence of these mutations were confirmed in a country wide survey where 70% and 72% of the 201 Ae. aegypti analysed possessed the mutations at residues 1016 and 1269 respectively. The highest mutated frequency combination was found to be heterozygous alleles (VG/FC) at both residues 1016 and 1269 (37.8%), followed by homozygous mutation at allele 1269 (24.4%) and homozygous mutation at allele 1016 (22.9%). The kdr- type of resistance among the vector is likely to undermine the effectiveness of pyrethroids treated materials against these mosquitoes.

Matched MeSH terms: Mutant Proteins/genetics
Fulltext Recombinant proteins from new constructs of SAG1 and GRA7 sequences and their usefulness to detect acute toxoplasmosis

Kotresha D, Poonam D, Muhammad Hafiznur Y, Saadatnia G, Nurulhasanah O, Sabariah O, et al.

Trop Biomed, 2012 Mar;29(1):129-37.
PMID: 22543613 MyJurnal

In this study we have cloned unreported gene fragments of Toxoplasma gondii GRA7 and SAG1 and expressed the corresponding recombinant proteins, followed by evaluation of their usefulness for the serological diagnosis of toxoplasmosis. Both recombinant proteins were expressed efficiently in insoluble form, purified by single step Ni-NTA affinity chromatography and their antigenicity to detect toxoplasma specific IgG antibodies were determined by immunoblotting. A total of 60 serum samples from three groups of individuals based on their anti-toxoplasma antibody profiles were tested, namely (I) IgM+, IgG+ (n=20), (II) IgM-, IgG+ (n=20) and (III) IgM-, IgG- (n=20). Both recombinant proteins exhibited high sensitivity (100%) with sera from Group I. rGRA7 and rSAG1 reacted 40% and 80% respectively with Group II sera. The specificity of the recombinant proteins based on reactivities with Group III sera were 100% and 80% with rGRA7 and rSAG1 respectively. Thus rGRA7 was found to be better at discriminating probable acute from chronic phases of toxoplasmosis, and it also showed higher specificity.

Matched MeSH terms: Recombinant Proteins/genetics
Fulltext Phagocytic activity and pro-inflammatory cytokines production by the murine macrophage cell line J774A.1 stimulated by a recombinant BCG (rBCG) expressing the MSP1-C of Plasmodium falciparum

Rapeah S, Dhaniah M, Nurul AA, Norazmi MN

Trop Biomed, 2010 Dec;27(3):461-9.
PMID: 21399587 MyJurnal

Macrophages are involved in innate immunity against malaria due to their ability to phagocytose infected erythrocytes and produce inflammatory cytokines, which are important for controlling parasite growth during malaria infection. In this study, the ability of a recombinant BCG (rBCG) vaccine expressing the 19-kDa C-terminus of merozoite surface protein-1 (MSP1-C) of Plasmodium falciparum, to stimulate the phagocytic activity and secretion of pro-inflammatory cytokines by the macrophage cell line J774A.1 was measured at varying times. The results demonstrate the ability of the rBCG construct to activate the inflammatory action of macrophages, which is important as a first-line of defence in clearing malaria infections.

Matched MeSH terms: Recombinant Proteins/genetics
Fulltext Characterization of vancomycin-resistant Enterococcus isolates from broilers in Selangor, Malaysia

Getachew YM, Hassan L, Zakaria Z, Saleha AA, Kamaruddin MI, Che Zalina MZ

Trop Biomed, 2009 Dec;26(3):280-8.
PMID: 20237442 MyJurnal

Vancomycin-resistant Enterococcus (VRE) is an emerging nosocomial pathogen in humans. The use of antibiotics in human therapy and in the production of food animals has been incriminated in the emergence of this organism. The present study describes the distribution of VRE species, the vancomycin-resistant genes detected, the vancomycin resistance pattern observed, and the genetic diversity of the isolates found in live broiler chickens in Malaysia. Overall 140 VRE were isolated with species comprising Enterococcus faecalis (48%), Enterococcus faecium (25.7%), Enterococcus gallinarum (12.1%), Enterococcus casseliflavus (1.4%) and other Enterococcus species (12.8%). Vancomycin resistance gene vanA and intrinsic genes vanC1 and vanC2/3 were detected in the study population. VanA was detected in 15 (63.9%) of E. faecium, 23 (22.4%) of E. faecalis and in 3 (17.6%) E. gallinarum isolates. E-test was conducted on randomly selected 41 of the isolates and the minimum inhibition concentration (MIC) of vancomycin for five (11.9%) of tested isolates is more than 256 μg/ml. Genotypic analysis using random amplified polymorphic DNA (RAPD) showed genetic diversity within the Enterococcus species.

Matched MeSH terms: Bacterial Proteins/genetics
Fulltext Overexpression of WNT2 and TSG101 genes in colorectal carcinoma

Ma XR, Edmund Sim UH, Pauline B, Patricia L, Rahman J

Trop Biomed, 2008 Apr;25(1):46-57.
PMID: 18600204 MyJurnal

Colorectal carcinoma (CRC) arises as a result of mutational activation of oncogenes coupled with inactivation of tumour suppressor genes. Mutations in APC, K-ras and p53 have been commonly reported. In a previous study by our group, the tumour susceptibility gene 101 (TSG101) were found to be persistently upregulated in CRC cases. TSG101 was reported to be closely related to cancers of the breast, brain and colon, and its overexpression in human papillary thyroid carcinomas and ovarian carcinomas had previously been reported. The wingless-type MMTV integration site family member 2 (WNT2) is potentially important in the Wnt/beta-catenin pathway and upregulation of WNT2 is not uncommon in human cancers. In this study, we report the investigation for mutation(s) and expression pattern(s) of WNT2 and TSG101, in an effort to further understand their role(s) in CRC tumourigenesis. Our results revealed no mutation in these genes, despite their persistent upregulation in CRC cases studied.

Matched MeSH terms: DNA-Binding Proteins/genetics*
Fulltext Functional Insights into Silymarin as an Antiviral Agent against Enterovirus A71 (EV-A71)

Lalani S, Masomian M, Poh CL

Int J Mol Sci, 2021 Aug 15;22(16).
PMID: 34445463 DOI: 10.3390/ijms22168757

Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent.

Matched MeSH terms: Capsid Proteins/genetics
Fulltext Increased prevalence of pfdhfr and pfdhps mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from Jazan Region, Southwestern Saudi Arabia: important implications for malaria treatment policy

Madkhali AM, Al-Mekhlafi HM, Atroosh WM, Ghzwani AH, Zain KA, Abdulhaq AA, et al.

Malar J, 2020 Dec 02;19(1):446.
PMID: 33267841 DOI: 10.1186/s12936-020-03524-x

BACKGROUND: Despite significant progress in eliminating malaria from the Kingdom of Saudi Arabia, the disease is still endemic in the southwestern region of the country. Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used in Saudi Arabia since 2007 as a first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to artemisinin and sulfadoxine-pyrimethamine (SP) resistance in P. falciparum parasites circulating in Jazan region, southwestern Saudi Arabia.
METHODS: A total of 151 P. falciparum isolates were collected between April 2018 and March 2019 from 12 of the governorates in Jazan region. Genomic DNA was extracted from dried blood spots and amplified using nested PCR. Polymorphisms in the propeller domain of the P. falciparum k13 (pfkelch13) gene and point mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by sequencing.
RESULTS: No mutations in the pfkelch13 propeller domain were found in any of the 151 isolates. However, point mutations in the pfdhfr and pfdhps genes were detected in 90.7% (137/151) of the isolates. The pfdhfr double mutations N51I + S108N (i.e. ACICNI haplotype) and triple mutations N51I + C59R + S108N (i.e. ACIRNI haplotype) were detected in 47% and 37.8% of the isolates, respectively. Moreover, the pfdhps single mutation at codon A437G and double mutations A437G + K540E (i.e. SGEAAI haplotype) were observed in 4.6% and 51.7% of the isolates, respectively. Interestingly, 23.8%, 25.1 and 12.6% of the isolates had quintuple, quadruple and triple mutated combined pfdhfr-pfdhps genotypes, respectively. Furthermore, significant associations were found between the prevalence of mutant haplotypes and the age, gender and nationality of the patients (P

Matched MeSH terms: Protozoan Proteins/genetics*
Fulltext Phylogenetic analyses uncover a novel clade of transferrin in nonmammalian vertebrates

Mohd-Padil H, Mohd-Adnan A, Gabaldón T

Mol Biol Evol, 2013 Apr;30(4):894-905.
PMID: 23258311 DOI: 10.1093/molbev/mss325

Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups.

Matched MeSH terms: Fish Proteins/genetics*
Fulltext Regulation of Proteolytic Activity to Improve the Recovery of Macrobrachium rosenbergii Nodavirus Capsid Protein

Selvaraj BA, Mariatulqabtiah AR, Ho KL, Ng CL, Yong CY, Tan WS

Int J Mol Sci, 2021 Aug 13;22(16).
PMID: 34445426 DOI: 10.3390/ijms22168725

The causative agent of white tail disease (WTD) in the giant freshwater prawn is Macrobrachium rosenbergii nodavirus (MrNV). The recombinant capsid protein (CP) of MrNV was previously expressed in Escherichia coli, and it self-assembled into icosahedral virus-like particles (VLPs) with a diameter of approximately 30 nm. Extensive studies on the MrNV CP VLPs have attracted widespread attention in their potential applications as biological nano-containers for targeted drug delivery and antigen display scaffolds for vaccine developments. Despite their advantageous features, the recombinant MrNV CP VLPs produced in E. coli are seriously affected by protease degradations, which significantly affect the yield and stability of the VLPs. Therefore, the aim of this study is to enhance the stability of MrNV CP by modulating the protease degradation activity. Edman degradation amino acid sequencing revealed that the proteolytic cleavage occurred at arginine 26 of the MrNV CP. The potential proteases responsible for the degradation were predicted in silico using the Peptidecutter, Expasy. To circumvent proteolysis, specific protease inhibitors (PMSF, AEBSF and E-64) were tested to reduce the degradation rates. Modulation of proteolytic activity demonstrated that a cysteine protease was responsible for the MrNV CP degradation. The addition of E-64, a cysteine protease inhibitor, remarkably improved the yield of MrNV CP by 2.3-fold compared to the control. This innovative approach generates an economical method to improve the scalability of MrNV CP VLPs using individual protease inhibitors, enabling the protein to retain their structural integrity and stability for prominent downstream applications including drug delivery and vaccine development.

Matched MeSH terms: Capsid Proteins/genetics*
Genes associated with amyloid-beta-induced inflammasome-mediated neuronal death identified using functional gene trap mutagenesis approach

Yap JKY, Pickard BS, Gan SY, Chan EWL

Int J Biochem Cell Biol, 2021 07;136:106014.
PMID: 34022435 DOI: 10.1016/j.biocel.2021.106014

Alzheimer's disease is an irreversible neurodegenerative disease, which accounts for most dementia cases. Neuroinflammation is increasingly recognised for its roles in Alzheimer's disease pathogenesis which, in part, links amyloid-beta to neuronal death. Neuroinflammatory signalling can be exhibited by neurons themselves, potentially leading to widespread neuronal cell death, although neuroinflammation is commonly associated with glial cells. The presence of the inflammasomes such as nucleotide-binding leucine-rich repeat receptors protein 1 in neurons accelerates amyloid-beta -induced neuroinflammation and has been shown to trigger neuronal pyroptosis in murine Alzheimer's disease models. However, the pathways involved in amyloid-beta activation of inflammasomes have yet to be elucidated. In this study, a gene trap mutagenesis approach was utilised to resolve the genes functionally involved in inflammasome signalling within neurons, and the mechanism behind amyloid-beta-induced neuronal death. The results indicate that amyloid-beta significantly accelerated neuroinflammatory cell death in the presence of a primed inflammasome (the NLR family pyrin domain-containing 1). The mutagenesis screen discovered the atypical mitochondrial Ras homolog family member T1 as a significant contributor to amyloid-beta-induced inflammasome -mediated neuronal death. The mutagenesis screen also identified two genes involved in transforming growth factor beta signalling, namely Transforming Growth Factor Beta Receptor 1 and SNW domain containing 1. Additionally, a gene associated with cytoskeletal reorganisation, SLIT-ROBO Rho GTPase Activating Protein 3 was found to be neuroprotective. In conclusion, these genes could play important roles in inflammasome signalling in neurons, which makes them promising therapeutic targets for future drug development against neuroinflammation in Alzheimer's disease.

Matched MeSH terms: NLR Proteins/genetics
Phylogenetic and genetic analyses of the emerging Nipah virus from bats to humans

Shi J, Sun J, Hu N, Hu Y

Infect Genet Evol, 2020 11;85:104442.
PMID: 32622923 DOI: 10.1016/j.meegid.2020.104442

Little is known about the genetic features of Nipah virus (NiV) associated with virulence and transmission. Herein, phylogenetic and genetic analyses for all available NiV strains revealed sequence variations between the two genetic lineages of NiV with pathogenic differences, as well as among different strains within Bangladesh lineage. A total of 143 conserved amino acid differences, distributed among viral nucleocapsid (N), phosphoprotein (P), matrix protein (M), fusion protein (F) and glycoprotein (G), were revealed. Structural modeling revealed one key substitution (S3554N) in the viral G protein that might mediate a 12-amino-acid structural change from a loop into a β sheet. Multiple key amino acids substitutions in viral G protein were observed, which may alter viral fitness and transmissibility from bats to humans.

Matched MeSH terms: Viral Proteins/genetics*
Fulltext Solar rhythm in the regulation of photoperiodic flowering of long-day and short-day plants

Yeang HY

J Exp Bot, 2013 Jul;64(10):2643-52.
PMID: 23645867 DOI: 10.1093/jxb/ert130

In photoperiodic flowering, long-day (LD) plants are induced to flower seasonally when the daylight hours are long, whereas flowering in short-day (SD) plants is promoted under short photoperiods. According to the widely accepted external coincidence model, flowering occurs in LD Arabidopsis when the circadian rhythm of the gene CONSTANS (CO) peaks in the afternoon, when it is light during long days but dark when the days are short. Nevertheless, extending this explanation to SD flowering in rice, Oriza sativa, requires LD and SD plants to have 'opposite light requirements' as the CO orthologue in rice, HEADING-DATE1 (Hd1), promotes flowering only under short photoperiods. This report proposes a role of the plant's solar rhythm in promoting seasonal flowering. The interaction between rhythmic genes entrained to the solar clock and those entrained to the circadian clock form the basis of an internal coincidence model that explains both LD and SD flowering equally well. The model invokes no presumption of opposite light requirements between LD and SD plants, and further argues against any specific requirement of either light or darkness for SD flowering. Internal coincidence predicts the inhibition of SD flowering of the rice plant by a night break (a brief interruption of light), while it also provides a plausible explanation for how a judiciously timed night break promotes Arabidopsis flowering even on short days. It is the timing of the light transitions (sunrise and sunset) rather than the duration of light or darkness per se that regulates photoperiod-controlled flowering.

Matched MeSH terms: Plant Proteins/genetics
Fulltext Combination of VP3 and CD147-knockdown enhance apoptosis and tumor growth delay index in colorectal tumor allograft

Ismail R, Allaudin ZN, Abdullah R, Mohd Lila MA, Nik Abd Rahman NM, Abdul Rahman SO

BMC Cancer, 2016 07 13;16:461.
PMID: 27411985 DOI: 10.1186/s12885-016-2530-8

BACKGROUND: Cancer therapies that kill cancer cells without affecting normal cells is the ultimate mode of treating cancers. The VP3, an avian virus-derived protein, can specifically initiate cell death through several signal transduction pathways leading to apoptosis. In cancer, chemoresistance and cell survivability implicate the cell surface protein, CD147.
METHODS: In this study, transfection of VP3 and silencing of CD147 genes was achieved through the treatment of tumors with pVIVO1-GFP/VP3 (VP3), psiRNA-CD147/2 (shCD147/2), and their combination of CT26 colon cancer cell-induced in mice. The effectiveness of tumor-treatment was ascertained by electrophoresis, TUNEL assay, and flow cytometry analysis. While histopathological and biochemical analysis were used as toxic side effect identification.
RESULTS: The tumor growth delay index (TGDI) after treatment with VP3, shCD147/2, and their combination treatments increased by 1.3-, 1.2-, 2.0- and 2.3-fold respectively, over untreated control. The VP3-shCD147/2 combination treatment was more efficacious then either VP3 or shCD147/2 alone in the retardation of mouse CT26 colorectal cell tumor allograft.
CONCLUSION: The antitumor effect of the combination treatment is the result of synergistic effects of VP3 and shCD147/2 on the tumor cells resulting in apoptosis. Thus, the study shows that combination of VP3 and shCD147/2 treatment can be developed into a potential approach for anticolorectal cancer treatment regimen.

Matched MeSH terms: Capsid Proteins/genetics*
Effect of gamma radiation on the expression of mRNA growth factors in glycerol cryopreserved human amniotic membrane

Yatim RM, Kannan TP, Ab Hamid SS

Cell Tissue Bank, 2016 Dec;17(4):643-651.
PMID: 27535136

Human amniotic membrane (HAM) due to its high biocompatibility, low immunogenicity, anti-microbial, anti-viral properties as well as the presence of growth factors has been used in various clinical applications. The growth factors play an important role in wound healing. The current study aimed to explore the effect of 15 kGy gamma radiation dose on selected growth factors and receptors mRNA present in HAM. Eight growth factors, namely, EGF, HGF, KGF, TGF-α, TGF-β1, TGF-β2, TGF-β3 and bFGF and two growth factor receptors, HGFR and KGFR were evaluated in this study. The total RNA was extracted and converted to complimentary DNA using commercial kits. Subsequently, the mRNA expressions of these growth factors were evaluated using real-time PCR and the results were statistically analyzed using REST-MCS software. This study confirmed the presence of these mRNA growth factors and receptors in fresh, glycerol cryopreserved and irradiated glycerol cryopreserved HAM. In glycerol cryopreserved HAM, the results showed up-regulation of HGF and bFGF and down-regulation of EGF, HGFR, KGF, KGFR, TGF-α, TGF-β1, TGF-β2 and TGF-β3 relative to the fresh HAM which acted as the control, whereas in irradiated glycerol cryopreserved HAM, the results showed up-regulation of EGF, HGF, KGF, KGFR, TGF-β1, TGF-β2 and TGF-β3 and down-regulation of HGFR, TGF-α and bFGF relative to the glycerol cryopreserved HAM which acted as the control. However, these mRNA expressions did not show any statistical significant difference compared to the control groups. This study concluded that a dose of 15 kGy of gamma radiation did not affect the mRNA expression for the growth factors' and receptors' in the glycerol cryopreserved HAM.

Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics*
Global and Targeted Proteomics of Prostate Cancer Cell Secretome: Combination of 2-Dimensional Image-Converted Analysis of Liquid Chromatography and Mass Spectrometry and In Silico Selection Selected Reaction Monitoring Analysis

Nurdin A, Hoshi Y, Yoneyama T, Miyauchi E, Tachikawa M, Watanabe M, et al.

J Pharm Sci, 2016 Nov;105(11):3440-3452.
PMID: 27665127 DOI: 10.1016/j.xphs.2016.08.013

Prostate-specific antigen is currently the only protein biomarker routinely used as a diagnostic tool for early detection and treatment monitoring of prostate cancer. However, it remains questionable whether prostate-specific antigen-based screening can sensitively and selectively identify the presence and progression status of primary and metastatic prostate cancers. Hence, the purpose of this study was to identify potential biomarker candidates in the secretome of primary and metastatic prostate cancer cells by using a combination of global and targeted proteomics. Quantitative comparisons among secretome proteins derived from androgen-responsive primary cancer cells (P-22Rv1), androgen-irresponsive bone metastatic cancer cells (M-PC-3), and noncancerous prostate cells (N-PNT2) were performed using 2-dimensional image-converted analysis of liquid chromatography and mass spectrometry followed by in silico selection selected reaction monitoring analysis. Mediator of RNA polymerase II transcription subunit 13-like, insulin-like growth factor-binding protein 2, and hepatocyte growth factor were identified as highly secreted proteins from P-22Rv1 cells compared with N-PNT2 cells. Prostate-associated microseminoprotein, proactivator polypeptide, collagen-α-1 (VI) chain, and neuropilin-1 were identified as predominantly secreted proteins in M-PC-3 cells compared with N-PNT2 cells. These proteins in biological fluids are considered to be candidate biomarkers of primary and/or metastatic prostate cancer.

Matched MeSH terms: Neoplasm Proteins/genetics*
Fulltext Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

Permuth JB, Pirie A, Ann Chen Y, Lin HY, Reid BM, Chen Z, et al.

Hum Mol Genet, 2016 08 15;25(16):3600-3612.
PMID: 27378695 DOI: 10.1093/hmg/ddw196

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P P≥5.0 ×10 - 7) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 × 10 - 5; PSKAT-o = 9.23 × 10 - 4) and KRT13 (PAML = 1.67 × 10 - 4; PSKAT-o = 1.07 × 10 - 5), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease.

Matched MeSH terms: Neoplasm Proteins/genetics

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