Displaying publications 1 - 20 of 135 in total

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  1. Lee TY, Muniandy L, Teh LK, Abdullah M, George E, Sathar J, et al.
    Turk J Haematol, 2016 Mar 05;33(1):15-20.
    PMID: 26377036 DOI: 10.4274/tjh.2014.0197
    The diverse clinical phenotype of hemoglobin E (HbE)/β-thalassemia has not only confounded clinicians in matters of patient management but has also led scientists to investigate the complex mechanisms involved in maintaining the delicate red cell environment where, even with apparent similarities of α- and β-globin genotypes, the phenotype tells a different story. The BTB and CNC homology 1 (BACH1) protein is known to regulate α- and β-globin gene transcriptions during the terminal differentiation of erythroid cells. With the mutations involved in HbE/β-thalassemia disorder, we studied the role of BACH1 in compensating for the globin chain imbalance, albeit for fine-tuning purposes.
    Matched MeSH terms: Basic-Leucine Zipper Transcription Factors/genetics*
  2. Al-Absi B, Noor SM, Saif-Ali R, Salem SD, Ahmed RH, Razif MF, et al.
    Tumour Biol., 2017 Apr;39(4):1010428317697573.
    PMID: 28381164 DOI: 10.1177/1010428317697573
    Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was associated with protection against acute lymphoblastic leukemia. In conclusion, our study has shown that ARID5B variants are associated with acute lymphoblastic leukemia in Yemeni children with several gender biases of ARID5B single nucleotide polymorphisms reported.
    Matched MeSH terms: Transcription Factors/genetics*
  3. 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: Transcription Factors/genetics*
  4. Chong ZX, Yong CY, Ong AHK, Yeap SK, Ho WY
    Toxicology, 2023 Aug 15;495:153596.
    PMID: 37480978 DOI: 10.1016/j.tox.2023.153596
    Aryl hydrocarbon receptor (AHR) is a ligand-dependent receptor that belongs to the superfamily of basic helix-loop-helix (bHLH) transcription factors. The activation of the canonical AHR signaling pathway is known to induce the expression of cytochrome P450 enzymes, facilitating the detoxification metabolism in the human body. Additionally, AHR could interact with various signaling pathways such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1α (HIF-1α), nuclear factor ekappa B (NF-κβ), estrogen receptor (ER), and androgen receptor (AR) signaling pathways. Over the past 30 years, several studies have reported that various chemical, physical, or biological agents, such as tobacco, hydrocarbon compounds, industrial and agricultural chemical wastes, drugs, UV, viruses, and other toxins, could affect AHR expression or activity, promoting cancer development. Thus, it is valuable to overview how these factors regulate AHR-mediated carcinogenesis. Current findings have reported that many compounds could act as AHR ligands to drive the expressions of AHR-target genes, such as CYP1A1, CYP1B1, MMPs, and AXL, and other targets that exert a pro-proliferation or anti-apoptotic effect, like XIAP. Furthermore, some other physical and chemical agents, such as UV and 3-methylcholanthrene, could promote AHR signaling activities, increasing the signaling activities of a few oncogenic pathways, such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways. Understanding how various factors regulate AHR-mediated carcinogenesis processes helps clinicians and scientists plan personalized therapeutic strategies to improve anti-cancer treatment efficacy. As many studies that have reported the roles of AHR in regulating carcinogenesis are preclinical or observational clinical studies that did not explore the detailed mechanisms of how different chemical, physical, or biological agents promote AHR-mediated carcinogenesis processes, future studies should focus on conducting large-scale and functional studies to unravel the underlying mechanism of how AHR interacts with different factors in regulating carcinogenesis processes.
    Matched MeSH terms: Basic Helix-Loop-Helix Transcription Factors/genetics
  5. Loo ZX, Kunasekaran W, Govindasamy V, Musa S, Abu Kasim NH
    ScientificWorldJournal, 2014;2014:186508.
    PMID: 25548778 DOI: 10.1155/2014/186508
    Human exfoliated deciduous teeth (SHED) and adipose stem cells (ASC) were suggested as alternative cell choice for cardiac regeneration. However, the true functionability of these cells toward cardiac regeneration is yet to be discovered. Hence, this study was carried out to investigate the innate biological properties of these cell sources toward cardiac regeneration. Both cells exhibited indistinguishable MSCs characteristics. Human stem cell transcription factor arrays were used to screen expression levels in SHED and ASC. Upregulated expression of transcription factor (TF) genes was detected in both sources. An almost equal percentage of >2-fold changes were observed. These TF genes fall under several cardiovascular categories with higher expressions which were observed in growth and development of blood vessel, angiogenesis, and vasculogenesis categories. Further induction into cardiomyocyte revealed ASC to express more significantly cardiomyocyte specific markers compared to SHED during the differentiation course evidenced by morphology and gene expression profile. Despite this, spontaneous cellular beating was not detected in both cell lines. Taken together, our data suggest that despite being defined as MSCs, both ASC and SHED behave differently when they were cultured in a same cardiomyocytes culture condition. Hence, vigorous characterization is needed before introducing any cell for treating targeted diseases.
    Matched MeSH terms: Transcription Factors/genetics
  6. Choo SW, Beh CY, Russell S, White R
    ScientificWorldJournal, 2014;2014:191535.
    PMID: 25389534 DOI: 10.1155/2014/191535
    In Drosophila, protein trap strategies provide powerful approaches for the generation of tagged proteins expressed under endogenous control. Here, we describe expression and functional analysis to evaluate new Ubx and hth protein trap lines generated by the Cambridge Protein Trap project. Both protein traps exhibit spatial and temporal expression patterns consistent with the reported endogenous pattern in the embryo. In imaginal discs, Ubx-YFP is expressed throughout the haltere and 3rd leg imaginal discs, while Hth-YFP is expressed in the proximal regions of haltere and wing discs but not in the pouch region. The Ubx (CPTI000601) line is semilethal as a homozygote. No T3/A1 to T2 transformations were observed in the embryonic cuticle or the developing midgut. The homozygous survivors, however, exhibit a weak haltere phenotype with a few wing-like marginal bristles on the haltere capitellum. Although hth (CPTI000378) is completely lethal as a homozygote, the hth (CPTI000378) /hth (C1) genotype is viable. Using a hth deletion (Df(3R)BSC479) we show that hth (CPTI000378) /Df(3R)BSC479 adults are phenotypically normal. No transformations were observed in hth (CPTI000378), hth (CPTI000378) /hth (C1), or hth (CPTI000378) /Df(3R)BSC479 embryonic cuticles. We have successfully characterised the Ubx-YFP and Hth-YFP protein trap lines demonstrating that the tagged proteins show appropriate expression patterns and produce at least partially functional proteins.
    Matched MeSH terms: Transcription Factors/genetics*
  7. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Transcription Factors/genetics*
  8. Yeap WC, Lee FC, Shabari Shan DK, Musa H, Appleton DR, Kulaveerasingam H
    Plant J, 2017 Jul;91(1):97-113.
    PMID: 28370622 DOI: 10.1111/tpj.13549
    The oil biosynthesis pathway must be tightly controlled to maximize oil yield. Oil palm accumulates exceptionally high oil content in its mesocarp, suggesting the existence of a unique fruit-specific fatty acid metabolism transcriptional network. We report the complex fruit-specific network of transcription factors responsible for modulation of oil biosynthesis genes in oil palm mesocarp. Transcriptional activation of EgWRI1-1 encoding a key master regulator that activates expression of oil biosynthesis genes, is activated by three ABA-responsive transcription factors, EgNF-YA3, EgNF-YC2 and EgABI5. Overexpression of EgWRI1-1 and its activators in Arabidopsis accelerated flowering, increased seed size and oil content, and altered expression levels of oil biosynthesis genes. Protein-protein interaction experiments demonstrated that EgNF-YA3 interacts directly with EgWRI1-1, forming a transcription complex with EgNF-YC2 and EgABI5 to modulate transcription of oil biosynthesis pathway genes. Furthermore, EgABI5 acts downstream of EgWRKY40, a repressor that interacts with EgWRKY2 to inhibit the transcription of oil biosynthesis genes. We showed that expression of these activators and repressors in oil biosynthesis can be induced by phytohormones coordinating fruit development in oil palm. We propose a model highlighting a hormone signaling network coordinating fruit development and fatty acid biosynthesis.
    Matched MeSH terms: Transcription Factors/genetics
  9. Abdul Rahman H, Manzor NF, Tan GC, Tan AE, Chua KH
    Med J Malaysia, 2008 Jul;63 Suppl A:57-8.
    PMID: 19024982
    Angiogenic induction was made to promote angiogenesis by differentiating stem cells towards endothelial cells. However, the stemness property of induced cells has not been revealed yet. Hence, we aim to evaluate the differential mRNA expression of stemness genes in human chorion-derived stem cells (CDSC) after being cultured in EDM50 comprised bFGF and VEGF. Results indicated that CDSC cultured in EMD50 expressed significantly higher mRNA level of Sox-2, FZD9, BST-1 and Nestin. In addition Oct-4, FGF-4 and ABCG-2 were also upregulated. Our finding suggested that CDSC after angiogenic induction enhanced its stem cell properties. This could be contributed for the mechanism of stem cell therapy in ischemic problem.
    Matched MeSH terms: SOXB1 Transcription Factors/genetics*
  10. Hang CY, Kitahashi T, Parhar IS
    J. Comp. Neurol., 2014 Dec 1;522(17):3847-60.
    PMID: 25043553 DOI: 10.1002/cne.23645
    In addition to vision, light information is used to regulate a range of animal physiology. Such nonimage-forming functions of light are mediated by nonvisual photoreceptors expressed in distinct neurons in the retina and the brain in most vertebrates. A nonvisual photoreceptor vertebrate ancient long opsin (VAL-opsin) possesses two functional isoforms in the zebrafish, encoded by valopa and valopb, which has received little attention. To delineate the neurochemical identities of valop cells and to test for colocalization of the valop isoforms, we used in situ hybridization to characterize the expression of the valop genes along with that of neurotransmitters and a neuropeptide known to be present at the sites of valop expression. Double labeling showed that the thalamic valop population coexpresses valopa and valopb. All the thalamic valop cells overlapped with a GABAergic cell mass that continues from the anterior nucleus to the intercalated thalamic nucleus. A novel valopa cell population found in the superior raphe was serotonergic in nature. A valopb cell population in the Edinger-Westphal nucleus was identified as containing thyrotropin-releasing hormone. Valopb cells localized in the hindbrain intermediate reticular formation were noncholinergic in nature (nonmotorneurons). Thus, the presence of valop cell populations in different brain regions with coexpression of neurotransmitters and neuropeptides and the colocalization of valop isoforms in the thalamic cell population indicate regulatory and functional complexity of VAL-opsin in the brain of the zebrafish.
    Matched MeSH terms: Transcription Factors/genetics
  11. Phan MD, Nhu NTK, Achard MES, Forde BM, Hong KW, Chong TM, et al.
    J Antimicrob Chemother, 2017 10 01;72(10):2729-2736.
    PMID: 29091192 DOI: 10.1093/jac/dkx204
    Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958.

    Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins. Mutants were identified using transposon-directed insertion-site sequencing or Illumina WGS. A resistance phenotype was confirmed by MIC and further investigated using RT-PCR. Competitive growth assays were used to measure fitness cost.

    Results: A transposon insertion at nucleotide 41 of the pmrB gene (EC958pmrB41-Tn5) enhanced its transcript level, resulting in a 64- and 32-fold increased MIC of colistin and polymyxin B, respectively. Three spontaneous mutations, also located within the pmrB gene, conferred resistance to both colistin and polymyxin B with a corresponding increase in transcription of the pmrCAB genes. All three mutations incurred a fitness cost in the absence of colistin and polymyxin B.

    Conclusions: This study identified the pmrB gene as the main chromosomal target for induction of colistin and polymyxin B resistance in E. coli.

    Matched MeSH terms: Transcription Factors/genetics*
  12. Lee HC, Md Yusof HH, Leong MP, Zainal Abidin S, Seth EA, Hewitt CA, et al.
    Int J Neurosci, 2019 Sep;129(9):871-881.
    PMID: 30775947 DOI: 10.1080/00207454.2019.1580280
    Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.
    Matched MeSH terms: STAT Transcription Factors/genetics*
  13. Loh SC, Othman AS, Veera Singham G
    Sci Rep, 2019 10 04;9(1):14296.
    PMID: 31586098 DOI: 10.1038/s41598-019-50800-1
    Hevea brasiliensis remains the primary crop commercially exploited to obtain latex, which is produced from the articulated secondary laticifer. Here, we described the transcriptional events related to jasmonic acid (JA)- and linolenic acid (LA)-induced secondary laticifer differentiation (SLD) in H. brasiliensis clone RRIM 600 based on RNA-seq approach. Histochemical approach proved that JA- and LA-treated samples resulted in SLD in H. brasiliensis when compared to ethephon and untreated control. RNA-seq data resulted in 86,614 unigenes, of which 2,664 genes were differentially expressed in JA and LA-induced secondary laticifer harvested from H. brasiliensis bark samples. Among these, 450 genes were unique to JA and LA as they were not differentially expressed in ethephon-treated samples compared with the untreated samples. Most transcription factors from the JA- and LA-specific dataset were classified under MYB, APETALA2/ethylene response factor (AP2/ERF), and basic-helix-loop-helix (bHLH) gene families that were involved in tissue developmental pathways, and we proposed that Bel5-GA2 oxidase 1-KNOTTED-like homeobox complex are likely involved in JA- and LA-induced SLD in H. brasiliensis. We also discovered alternative spliced transcripts, putative novel transcripts, and cis-natural antisense transcript pairs related to SLD event. This study has advanced understanding on the transcriptional regulatory network of SLD in H. brasiliensis.
    Matched MeSH terms: Transcription Factors/genetics
  14. Zaini MN, Patel SA, Syafruddin SE, Rodrigues P, Vanharanta S
    Sci Rep, 2018 08 13;8(1):12063.
    PMID: 30104738 DOI: 10.1038/s41598-018-30499-2
    Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.
    Matched MeSH terms: Basic Helix-Loop-Helix Transcription Factors/genetics*
  15. Abdullah-Zawawi MR, Ahmad-Nizammuddin NF, Govender N, Harun S, Mohd-Assaad N, Mohamed-Hussein ZA
    Sci Rep, 2021 10 04;11(1):19678.
    PMID: 34608238 DOI: 10.1038/s41598-021-99206-y
    Transcription factors (TFs) form the major class of regulatory genes and play key roles in multiple plant stress responses. In most eukaryotic plants, transcription factor (TF) families (WRKY, MADS-box and MYB) activate unique cellular-level abiotic and biotic stress-responsive strategies, which are considered as key determinants for defense and developmental processes. Arabidopsis and rice are two important representative model systems for dicot and monocot plants, respectively. A comprehensive comparative study on 101 OsWRKY, 34 OsMADS box and 122 OsMYB genes (rice genome) and, 71 AtWRKY, 66 AtMADS box and 144 AtMYB genes (Arabidopsis genome) showed various relationships among TFs across species. The phylogenetic analysis clustered WRKY, MADS-box and MYB TF family members into 10, 7 and 14 clades, respectively. All clades in WRKY and MYB TF families and almost half of the total number of clades in the MADS-box TF family are shared between both species. Chromosomal and gene structure analysis showed that the Arabidopsis-rice orthologous TF gene pairs were unevenly localized within their chromosomes whilst the distribution of exon-intron gene structure and motif conservation indicated plausible functional similarity in both species. The abiotic and biotic stress-responsive cis-regulatory element type and distribution patterns in the promoter regions of Arabidopsis and rice WRKY, MADS-box and MYB orthologous gene pairs provide better knowledge on their role as conserved regulators in both species. Co-expression network analysis showed the correlation between WRKY, MADs-box and MYB genes in each independent rice and Arabidopsis network indicating their role in stress responsiveness and developmental processes.
    Matched MeSH terms: Transcription Factors/genetics*; MEF2 Transcription Factors/genetics*
  16. Shahzad H, Giribabu N, Karim K, Kassim N, Muniandy S, Kumar KE, et al.
    Reprod Toxicol, 2017 08;71:42-54.
    PMID: 28431985 DOI: 10.1016/j.reprotox.2017.04.004
    HYPOTHESIS: Quercetin could induce changes to the fluid volume and receptivity development of the uterus during peri-implantation period.

    METHODS: Female rats were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning from day-1 pregnancy. Uterus was harvested at day-4 (following three days quercetin treatment) for morphological, ultra-structural, protein and mRNA expressional changes and plasma sex-steroid levels analyses. In another cohort of rats, implantation rate was determined at day-6 (following five days quercetin treatment).

    RESULTS: Administration of 50mg/kg/day quercetin causes increased in uterine fluid volume and CFTR expression but decreased in γ-ENaC, AQP-5, AQP-9 claudin-4, occludin, E-cadherin, integrin αnβЗ, FGF, Ihh and Msx-1expression in the uterus. Pinopodes were poorly develop, tight junctions appear less complex and implantation rate decreased. Serum estradiol levels increased but serum progesterone levels decreased.

    CONCLUSIONS: Interference in the fluid volume and receptivity development of the uterus during peri-implantation period by quercetin could adversely affect embryo implantation.

    Matched MeSH terms: Transcription Factors/genetics
  17. Lee SH, Wong RR, Chin CY, Lim TY, Eng SA, Kong C, et al.
    Proc Natl Acad Sci U S A, 2013 Sep 10;110(37):15067-72.
    PMID: 23980181 DOI: 10.1073/pnas.1311725110
    Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.
    Matched MeSH terms: GATA Transcription Factors/genetics
  18. Poli A, Abdul-Hamid S, Zaurito AE, Campagnoli F, Bevilacqua V, Sheth B, et al.
    Proc Natl Acad Sci U S A, 2021 08 03;118(31).
    PMID: 34312224 DOI: 10.1073/pnas.2010053118
    Regulatory T cells (Tregs) play fundamental roles in maintaining peripheral tolerance to prevent autoimmunity and limit legitimate immune responses, a feature hijacked in tumor microenvironments in which the recruitment of Tregs often extinguishes immune surveillance through suppression of T-effector cell signaling and tumor cell killing. The pharmacological tuning of Treg activity without impacting on T conventional (Tconv) cell activity would likely be beneficial in the treatment of various human pathologies. PIP4K2A, 2B, and 2C constitute a family of lipid kinases that phosphorylate PtdIns5P to PtdIns(4,5)P 2 They are involved in stress signaling, act as synthetic lethal targets in p53-null tumors, and in mice, the loss of PIP4K2C leads to late onset hyperinflammation. Accordingly, a human single nucleotide polymorphism (SNP) near the PIP4K2C gene is linked with susceptibility to autoimmune diseases. How PIP4Ks impact on human T cell signaling is not known. Using ex vivo human primary T cells, we found that PIP4K activity is required for Treg cell signaling and immunosuppressive activity. Genetic and pharmacological inhibition of PIP4K in Tregs reduces signaling through the PI3K, mTORC1/S6, and MAPK pathways, impairs cell proliferation, and increases activation-induced cell death while sparing Tconv. PIP4K and PI3K signaling regulate the expression of the Treg master transcriptional activator FOXP3 and the epigenetic signaling protein Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). Our studies suggest that the pharmacological inhibition of PIP4K can reprogram human Treg identity while leaving Tconv cell signaling and T-helper differentiation to largely intact potentially enhancing overall immunological activity.
    Matched MeSH terms: Forkhead Transcription Factors/genetics
  19. Low ET, Rosli R, Jayanthi N, Mohd-Amin AH, Azizi N, Chan KL, et al.
    PLoS One, 2014;9(1):e86728.
    PMID: 24497974 DOI: 10.1371/journal.pone.0086728
    Demand for palm oil has been increasing by an average of ∼8% the past decade and currently accounts for about 59% of the world's vegetable oil market. This drives the need to increase palm oil production. Nevertheless, due to the increasing need for sustainable production, it is imperative to increase productivity rather than the area cultivated. Studies on the oil palm genome are essential to help identify genes or markers that are associated with important processes or traits, such as flowering, yield and disease resistance. To achieve this, 294,115 and 150,744 sequences from the hypomethylated or gene-rich regions of Elaeis guineensis and E. oleifera genome were sequenced and assembled into contigs. An additional 16,427 shot-gun sequences and 176 bacterial artificial chromosomes (BAC) were also generated to check the quality of libraries constructed. Comparison of these sequences revealed that although the methylation-filtered libraries were sequenced at low coverage, they still tagged at least 66% of the RefSeq supported genes in the BAC and had a filtration power of at least 2.0. A total 33,752 microsatellites and 40,820 high-quality single nucleotide polymorphism (SNP) markers were identified. These represent the most comprehensive collection of microsatellites and SNPs to date and would be an important resource for genetic mapping and association studies. The gene models predicted from the assembled contigs were mined for genes of interest, and 242, 65 and 14 oil palm transcription factors, resistance genes and miRNAs were identified respectively. Examples of the transcriptional factors tagged include those associated with floral development and tissue culture, such as homeodomain proteins, MADS, Squamosa and Apetala2. The E. guineensis and E. oleifera hypomethylated sequences provide an important resource to understand the molecular mechanisms associated with important agronomic traits in oil palm.
    Matched MeSH terms: Transcription Factors/genetics
  20. Balasubramaniam VR, Hong Wai T, Ario Tejo B, Omar AR, Syed Hassan S
    PLoS One, 2013;8(9):e72429.
    PMID: 24073193 DOI: 10.1371/journal.pone.0072429
    We constructed a novel chicken (Gallus gallus) lung cDNA library fused inside yeast acting domain vector (pGADT7). Using yeast two-hybrid screening with highly pathogenic avian influenza (HPAI) nucleoprotein (NP) from the strain (A/chicken/Malaysia/5858/2004(H5N1)) as bait, and the Gallus gallus lung cDNA library as prey, a novel interaction between the Gallus gallus cellular RNA export adaptor protein Aly/REF and the viral NP was identified. This interaction was confirmed and validated with mammalian two hybrid studies and co-immunoprecipitation assay. Cellular localization studies using confocal microscopy showed that NP and Aly/REF co-localize primarily in the nucleus. Further investigations by mammalian two hybrid studies into the binding of NP of other subtypes of influenza virus such as the swine A/New Jersey/1976/H1N1 and pandemic A/Malaysia/854/2009(H1N1) to human Aly/REF, also showed that the NP of these viruses interacts with human Aly/REF. Our findings are also supported by docking studies which showed tight and favorable binding between H5N1 NP and human Aly/REF, using crystal structures from Protein Data Bank. siRNA knockdown of Aly/REF had little effect on the export of HPAI NP and other viral RNA as it showed no significant reduction in virus titer. However, UAP56, another component of the TREX complex, which recruits Aly/REF to mRNA was found to interact even better with H5N1 NP through molecular docking studies. Both these proteins also co-localizes in the nucleus at early infection similar to Aly/REF. Intriguingly, knockdown of UAP56 in A549 infected cells shows significant reduction in viral titer (close to 10 fold reduction). Conclusively, our study have opened new avenues for research of other cellular RNA export adaptors crucial in aiding viral RNA export such as the SRSF3, 9G8 and ASF/SF2 that may play role in influenza virus RNA nucleocytoplasmic transport.
    Matched MeSH terms: Transcription Factors/genetics
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