Displaying publications 121 - 140 of 262 in total

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  1. Fulltext Non-tenera Contamination and the Economic Impact of SHELL Genetic Testing in the Malaysian Independent Oil Palm Industry
    Ooi LC, Low ET, Abdullah MO, Nookiah R, Ting NC, Nagappan J, et al.
    Front Plant Sci, 2016;7:771.
    PMID: 27446094 DOI: 10.3389/fpls.2016.00771
    Oil palm (Elaeis guineensis) is the most productive oil bearing crop worldwide. It has three fruit forms, namely dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), which are controlled by the SHELL gene. The fruit forms exhibit monogenic co-dominant inheritance, where tenera is a hybrid obtained by crossing maternal dura and paternal pisifera palms. Commercial palm oil production is based on planting thin-shelled tenera palms, which typically yield 30% more oil than dura palms, while pisifera palms are female-sterile and have little to no palm oil yield. It is clear that tenera hybrids produce more oil than either parent due to single gene heterosis. The unintentional planting of dura or pisifera palms reduces overall yield and impacts land utilization that would otherwise be devoted to more productive tenera palms. Here, we identify three additional novel mutant alleles of the SHELL gene, which encode a type II MADS-box transcription factor, and determine oil yield via control of shell fruit form phenotype in a manner similar to two previously identified mutant SHELL alleles. Assays encompassing all five mutations account for all dura and pisifera palms analyzed. By assaying for these variants in 10,224 mature palms or seedlings, we report the first large scale accurate genotype-based determination of the fruit forms in independent oil palm planting sites and in the nurseries that supply them throughout Malaysia. The measured non-tenera contamination rate (10.9% overall on a weighted average basis) underscores the importance of SHELL genetic testing of seedlings prior to planting in production fields. By eliminating non-tenera contamination, comprehensive SHELL genetic testing can improve sustainability by increasing yield on existing planted lands. In addition, economic modeling demonstrates that SHELL gene testing will confer substantial annual economic gains to the oil palm industry, to Malaysian gross national income and to Malaysian government tax receipts.
    Matched MeSH terms: Transcription Factors
  2. Fulltext MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network
    Samad AFA, Sajad M, Nazaruddin N, Fauzi IA, Murad AMA, Zainal Z, et al.
    Front Plant Sci, 2017;8:565.
    PMID: 28446918 DOI: 10.3389/fpls.2017.00565
    Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions.
    Matched MeSH terms: Transcription Factors
  3. Fulltext Transcriptional regulation of Lonicera japonica Thunb. during flower development as revealed by comprehensive analysis of transcription factors
    Wang T, Yang B, Guan Q, Chen X, Zhong Z, Huang W, et al.
    BMC Plant Biol, 2019 May 14;19(1):198.
    PMID: 31088368 DOI: 10.1186/s12870-019-1803-1
    BACKGROUND: Lonicera japonica Thunb. flower has been used for the treatment of various diseases for a long time and attracted many studies on its potential effects. Transcription factors (TFs) regulate extensive biological processes during plant development. As the restricted reports of L. japonica on TFs, our work was carried out to better understand the TFs' regulatory roles under different developmental stages in L. japonica.

    RESULTS: In this study, 1316 TFs belonging to 52 families were identified from the transcriptomic data, and corresponding expression profiles during the L. japonica flower development were comprehensively analyzed. 917 (69.68%) TFs were differentially expressed. TFs in bHLH, ERF, MYB, bZIP, and NAC families exhibited obviously altered expression during flower growth. Based on the analysis of differentially expressed TFs (DETFs), TFs in MYB, WRKY, NAC and LSD families that involved in phenylpropanoids biosynthesis, senescence processes and antioxidant activity were detected. The expression of MYB114 exhibited a positive correlation with the contents of luteoloside; Positive correlation was observed among the expression of MYC12, chalcone synthase (CHS) and flavonol synthase (FLS), while negative correlation was observed between the expression of MYB44 and the synthases; The expression of LSD1 was highly correlated with the expression of SOD and the total antioxidant capacity, while the expression of LOL1 and LOL2 exhibited a negative correlation with them; Many TFs in NAC and WRKY families may be potentially involved in the senescence process regulated by hormones and reactive oxygen species (ROS). The expression of NAC19, NAC29, and NAC53 exhibited a positive correlation with the contents of ABA and H2O2, while the expression of WRKY53, WRKY54, and WRKY70 exhibited a negative correlation with the contents of JA, SA and ABA.

    CONCLUSIONS: Our study provided a comprehensive characterization of the expression profiles of TFs during the developmental stages of L. japonica. In addition, we detected the key TFs that may play significant roles in controlling active components biosynthesis, antioxidant activity and flower senescence in L. japonica, thereby providing valuable insights into the molecular networks underlying L. japonica flower development.

    Matched MeSH terms: Transcription Factors
  4. α-Mangostin and its derivatives against estrogen receptor alpha
    Mardianingrum R, Yusuf M, Hariono M, Mohd Gazzali A, Muchtaridi M
    J Biomol Struct Dyn, 2020 Nov 06.
    PMID: 33155528 DOI: 10.1080/07391102.2020.1841031
    Estrogen receptor alpha (ERα) acts as the transcription factor and the main therapeutic target against breast cancer. One of the compounds that has been shown to act as an ERα is α-mangostin. However, it still has weaknesses due to its low solubility and low potent activity. In this study, α-mangostin was modified by substituting -OH group at C6 using benzoyl derivatives through a step by step in silico study, namely pharmacokinetic prediction (https://preadmet.bmdrc.kr/adme/), pharmacophore modeling (LigandScout 4.1), molecular docking simulation (AutoDock 4.2), molecular dynamics simulation (AMBER 16) and a binding free energy analysis using MM-PBSA method. From the computational studies, three compounds which are derived from α-mangostin (AMB-1 (-9.84 kcal/mol), AMB-2 (-6.80 kcal/mol) and AMB-10 (-12.42 kcal/mol)) have lower binding free energy than α-mangostin (-1.77 kcal/mol), as evidenced by the binding free energy calculation using the MM-PBSA method. They can then be predicted to have potent activities as ERα antagonists.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Transcription Factors
  5. Role of NF-kβ factor Rel2 during Plasmodium falciparum and bacterial infection in Anopheles dirus
    Khan MB, Liew JW, Leong CS, Lau YL
    Parasit Vectors, 2016 Sep 29;9(1):525.
    PMID: 27688040
    Anopheles mosquitoes transmit malaria which is one of the world's most threatening diseases. Anopheles dirus (sensu stricto) is among the main vectors of malaria in South East Asia. The mosquito innate immune response is the first line of defence against malaria parasites during its development. The immune deficiency (IMD) pathway, a conserved immune signaling pathway, influences anti-Plasmodium falciparum activity in Anopheles gambiae, An. stephensi and An. albimanus. The aim of the study was to determine the role of Rel2, an IMD pathway-controlled NF-kappaβ transcription factor, in An. dirus.
    Matched MeSH terms: Transcription Factors
  6. Fulltext The rare primary Low Grade Papillary Adenocarcinoma of Nasopharynx: a diagnostic challenge and management
    Noor Dina, H., Gendeh, B.S.
    Medicine & Health, 2015;10(2):137-140.
    MyJurnal
    Low Grade Papillary Nasopharyngeal Adenocarcinoma (LGPAC) is a very rare tumour of mucosal origin compared to a higher incidence of well differentiated keratinized/non-keratinized nasopharyngeal carcinoma. It is an epithelial tumour with glandular differentiation. Its papillary figure seen histologically, is also seen in metastatic papillary thyroid carcinoma. This has caused a significant challenge to the Pathologist to differentiate primary papillary nasopharyngeal adenocarcinoma and metastatic tumour. Thyroid Transcription Factor-1 (TTF-1) is also expressed in subsets of papillary nasopharyngeal adenocarcinoma, which is valuable as a diagnostic tool. LGPAC is a benign-like malignant neoplasm. An early diagnosis with a complete tumour removal via conventional excision or endoscopic approach has offered a good prognosis with low risk of recurrence.
    Matched MeSH terms: Transcription Factors
  7. Fulltext Physicochemical and structural properties of Asian Swamp Eel (Monopterus albus) skin gelatin as compared to bovine gelatin
    Rosli, N., Sarbon, N.M.
    International Food Research Journal, 2015;22(2):699-706.
    MyJurnal
    The aims of this study are to report on the extraction and characterization of Asian swamp eel (Monopterus albus) skin gelatin. The characterization conducted were includes chemical composition, pH, gel strength, viscosity, thermal property, color and structure determination of extracted eel skin gelatin. Eel skin contains 70.28% moisture, 11.07% protein, 4.21% fat, and 5.01% ash. The chemical composition of eel skin gelatin (yield of 12.75%) was 18.8% moisture, 67.64% protein, 0.34% fat and 1.08% ash, with a pH of 4.62 and gel strength of 215.96 g (± 9.62 g). Although viscosity (2.8 cPa/min) profile of eel skin gelatin showed lower than that of bovine gelatin, the higher melting temperature (35 °C) of eel skin gelatin indicating its higher stability than bovine gelatin with FTIR spectrum similar to that of typical bovine gelatin. Eel skin gelatin has a 71.4 (± 1.14), a +3.2 (± 0.29), and a +7.52 (± 0.29) for L*, a* and b* value respectively, indicate a darker and less yellow colour. These findings show promising potential for the application of eel skin gelatin as an alternative to commercial gelatin.
    Matched MeSH terms: Basic Helix-Loop-Helix Transcription Factors
  8. Fulltext The CRISPR Growth Spurt: from Bench to Clinic on Versatile Small RNAs
    Bayat H, Omidi M, Rajabibazl M, Sabri S, Rahimpour A
    J Microbiol Biotechnol, 2017 Feb 28;27(2):207-218.
    PMID: 27840399 DOI: 10.4014/jmb.1607.07005
    Clustered regulatory interspaced short palindromic repeats (CRISPR) in association with CRISPR-associated protein (Cas) is an adaptive immune system, playing a pivotal role in the defense of bacteria and archaea. Ease of handling and cost effectiveness make the CRISPR-Cas system an ideal programmable nuclease tool. Recent advances in understanding the CRISPR-Cas system have tremendously improved its efficiency. For instance, it is possible to recapitulate the chronicle CRISPR-Cas from its infancy and inaugurate a developed version by generating novel variants of Cas proteins, subduing off-target effects, and optimizing of innovative strategies. In summary, the CRISPR-Cas system could be employed in a number of applications, including providing model systems, rectification of detrimental mutations, and antiviral therapies.
    Matched MeSH terms: Transcription Factors
  9. Fulltext Appropriate planning, thorough examinations and decent implementations for a predictable prognosis in the management of a severely worn dentition: a case report
    Siti Mariam Ab Ghani, Lillywhite, Graeme
    Compendium of Oral Science, 2014;1(1):30-39.
    MyJurnal
    The management of patients with severely worn dentition is challenging due to the loss of occlusal vertical dimension and tooth structure creating an uneven plane of occlusion. This case report describes the importance of every step of the conventional and improvised methods in treating tooth wear patients. Stages from the initial work-up of tooth wear assessment, substantial surgical crown lengthening, the controlled method of increasing vertical dimension, the precise method of crown preparations, advanced impression techniques till the cementation procedure of final restorations.

    The whole treatment was in a reorganized approach such that the new inter-cuspal position (ICP) coincided with the retruded axial position (RAP). When restoring worn dentition, cl inician should always have a proper planning, decent implementation for each stages thus guarantee excellent performances. However maintenance and recall visits are the main keys to long term success.
    Matched MeSH terms: Transcription Factors
  10. Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells
    Tan SA, Goya L, Ramanathan S, Sulaiman SF, Alam M, Navaratnam V
    Food Res Int, 2014 Oct;64:387-395.
    PMID: 30011665 DOI: 10.1016/j.foodres.2014.06.040
    Extract from papaya leaves, a waste material from fruit farms in Malaysia was previously reported to possess remarkable antioxidative activities. In this study, papaya leaf extract was separated into fractions of different polarities [petroleum ether (PE), ethyl acetate (EA), n-butanol (NB) and water (W) fractions]. The aim of this research was to determine the most active fraction in terms of its chemopreventive effects towards oxidative stress and the chemical constituents involved. The cytoprotective nature of the papaya fractions was observed against t-BOOH-induced oxidative stress on HepG2 liver cell line. ROS assay indicated that only PE and EA effectively reduced the increment of radical due to the pro-oxidant, t-BOOH. Nevertheless, PE was a stronger ROS scavenger by demonstrating ROS reducing activity in a dose-dependent manner to the basal level. This fraction was also found to inhibit cell death caused by t-BOOH toxicity, attenuating lactate dehydrogenase enzyme leakage by more than 90% (p<0.05). In addition, gene expression of phase II antioxidant enzymes (hmox-1 and nqo-1) and their transcription factor (nrf-2) were shown to be upregulated upon PE treatment during a time-course study. A GC-MS fingerprint of the active fraction was subsequently obtained with standardization using the marker compound; α-tocopherol, a well known antioxidant. However, this pure compound was not as effective as its corresponding PE concentrations in ROS reduction. Hence, PE of papaya leaf extract was a strong antioxidant and cytoprotectant with tremendous potential to be harnessed into the next therapeutic remedy against oxidative stress of the liver.
    Matched MeSH terms: Transcription Factors
  11. Fulltext Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis
    Ab Mutalib NS, Othman SN, Mohamad Yusof A, Abdullah Suhaimi SN, Muhammad R, Jamal R
    PeerJ, 2016;4:e2119.
    PMID: 27350898 DOI: 10.7717/peerj.2119
    Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.
    Matched MeSH terms: Transcription Factors
  12. Fulltext Zerumbone-Loaded Nanostructured Lipid Carrier Induces Apoptosis of Canine Mammary Adenocarcinoma Cells
    Foong JN, Selvarajah GT, Rasedee A, Rahman HS, How CW, Beh CY, et al.
    Biomed Res Int, 2018;2018:8691569.
    PMID: 30410940 DOI: 10.1155/2018/8691569
    Canine mammary gland tumor (CMT) is the most common tumor in intact female dog. Zerumbone (ZER) has promising anticancer properties, but plagued with poor water solubility, poor absorption, bioavailability, and delivery to target tissues. To solubilize, ZER was loaded into nanostructured lipid carrier (NLC) to produce ZER-loaded NLC (ZER-NLC). The objectives of this study were to determine the antiproliferative effect and the mode of cell death induced by ZER-NLC and ZER on a canine mammary gland tumor (CMT) adenocarcinoma primary cell line. There was no significant difference (p>0.05) between ZER-NLC and ZER treatments in the inhibition of CMT cell proliferation; thus, the loading of ZER into NLC did not compromise the cytotoxic effect of ZER. Microscopically, ZER-NLC- and ZER-treated CMT cells showed apoptotic cell morphology. ZER-NLC and ZER treatments significantly downregulated the antiapoptotic Bcl-2 and upregulated the proapoptotic Bax gene expressions in CMT cells. Both ZER-NLC and ZER-treated CMT cells showed significant (p<0.0001) increases in caspase-8, -9, and -3/7 protein activities. In conclusion, ZER-NLC induced CMT cell death via regulation of Bcl-2 and Bax gene expressions and caspase activations, indicating the involvement of both the intrinsic and extrinsic pathways of apoptosis. This study provided evidences for the potential of ZER-NLC as an anticanine mammary gland adenocarcinoma chemotherapy.
    Matched MeSH terms: Transcription Factors
  13. Reconstruction of the transcriptional regulatory network in arabidopsis thaliana aliphatic glucosinolate biosynthetic pathway
    Khalidah-Syahirah Ashari, Zeti-Azura Mohamed-Hussein, Muhammad-Redha Abdullah-Zawawi, Sarahani Harun
    Sains Malaysiana, 2018;47:2993-3002.
    Aliphatic glucosinolate is an important secondary metabolite responsible in plant defense mechanism and carcinogenic
    activity. It plays a crucial role in plant adaptation towards changes in the environment such as salinity and drought.
    However, in many plant genomes, there are thousands of genes encoding proteins still with putative functions and
    incomplete annotations. Therefore, the genome of Arabidopsis thaliana was selected to be investigated further to identify
    any putative genes that are potentially involved in the aliphatic glucosinolate biosynthesis pathway, most of its gene are
    with incomplete annotation. Known genes for aliphatic glucosinolates were retrieved from KEGG and AraCyc databases.
    Three co-expression databases i.e., ATTED-II, GeneMANIA and STRING were used to perform the co-expression network
    analysis. The integrated co-expression network was then being clustered, annotated and visualized using Cytoscape plugin,
    MCODE and ClueGO. Then, the regulatory network of A. thaliana from AtRegNet was mapped onto the co-expression
    network to build the transcriptional regulatory network. This study showed that a total of 506 genes were co-expressed
    with the 61 aliphatic glucosinolate biosynthesis genes. Five transcription factors have been predicted to be involved
    in the biosynthetic pathway of aliphatic glucosinolate, namely SEPALLATA 3 (SEP3), PHYTOCHROME INTERACTING FACTOR
    3-like 5 (AtbHLH15/PIL5), ELONGATED HYPOCOTYL 5 (HY5), AGAMOUS-like 15 (AGL15) and GLABRA 3 (GL3). Meanwhile,
    three other genes with high potential to be involved in the aliphatic glucosinolates biosynthetic pathway were identified,
    i.e., methylthioalkylmalate-like synthase 4 (MAML-4) and aspartate aminotransferase (ASP1 and ASP4). These findings
    can be used to complete the aliphatic glucosinolate biosynthetic pathway in A. thaliana and to update the information
    on the glucosinolate-related pathways in public metabolic databases.
    Matched MeSH terms: Transcription Factors
  14. Fulltext Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase
    Ahmad B, Serpell CJ, Fong IL, Wong EH
    Front Mol Biosci, 2020;7:76.
    PMID: 32457917 DOI: 10.3389/fmolb.2020.00076
    Obesity is now a widespread disorder, and its prevalence has become a critical concern worldwide, due to its association with common co-morbidities like cancer, cardiovascular diseases and diabetes. Adipose tissue is an endocrine organ and therefore plays a critical role in the survival of an individual, but its dysfunction or excess is directly linked to obesity. The journey from multipotent mesenchymal stem cells to the formation of mature adipocytes is a well-orchestrated program which requires the expression of several genes, their transcriptional factors, and signaling intermediates from numerous pathways. Understanding all the intricacies of adipogenesis is vital if we are to counter the current epidemic of obesity because the limited understanding of these intricacies is the main barrier to the development of potent therapeutic strategies against obesity. In particular, AMP-Activated Protein Kinase (AMPK) plays a crucial role in regulating adipogenesis - it is arguably the central cellular energy regulation protein of the body. Since AMPK promotes the development of brown adipose tissue over that of white adipose tissue, special attention has been given to its role in adipose tissue development in recent years. In this review, we describe the molecular mechanisms involved in adipogenesis, the role of signaling pathways and the substantial role of activated AMPK in the inhibition of adiposity, concluding with observations which will support the development of novel chemotherapies against obesity epidemics.
    Matched MeSH terms: Transcription Factors
  15. Fulltext Proline Homeostasis in Saccharomyces cerevisiae: How Does the Stress-Responsive Transcription Factor Msn2 Play a Role?
    Mat Nanyan NSB, Takagi H
    Front Genet, 2020;11:438.
    PMID: 32411186 DOI: 10.3389/fgene.2020.00438
    Overexpression of MSN2, which is the transcription factor gene in response to stress, is well-known to increase the tolerance of the yeast Saccharomyces cerevisiae cells to a wide variety of environmental stresses. Recent studies have found that the Msn2 is a feasible potential mediator of proline homeostasis in yeast. This result is based on the finding that overexpression of the MSN2 gene exacerbates the cytotoxicity of yeast to various amino acid analogs whose uptake is increased by the active amino acid permeases localized on the plasma membrane as a result of a dysfunctional deubiquitination process. Increased understanding of the cellular responses induced by the Msn2-mediated proline incorporation will provide better comprehension of how cells respond to and counteract to different kinds of stimuli and will also contribute to the breeding of industrial yeast strains with increased productivity.
    Matched MeSH terms: Transcription Factors
  16. Fulltext WDR5, ASH2L, and RBBP5 control the efficiency of FOS transcript processing
    Teoh PL, Sharrocks AD
    Cell Mol Biol Lett, 2014 Jun;19(2):215-32.
    PMID: 24715476 DOI: 10.2478/s11658-014-0190-8
    H3K4 trimethylation is strongly associated with active transcription. The deposition of this mark is catalyzed by SET-domain methyltransferases, which consist of a subcomplex containing WDR5, ASH2L, and RBBP5 (the WAR subcomplex); a catalytic SET-domain protein; and additional complexspecific subunits. The ERK MAPK pathway also plays an important role in gene regulation via phosphorylation of transcription factors, co-regulators, or histone modifier complexes. However, the potential interactions between these two pathways remain largely unexplored. We investigated their potential interplay in terms of the regulation of the immediate early gene (IEG) regulatory network. We found that depletion of components of the WAR subcomplex led to increased levels of unspliced transcripts of IEGs that did not necessarily reflect changes in their mature transcripts. This occurs in a manner independent from changes in the H3K4me3 levels at the promoter region. We focused on FOS and found that the depletion of WAR subcomplex components affected the efficiency of FOS transcript processing. Our findings show a new aspect of WAR subcomplex function in coordinating active transcription with efficient pre-mRNA processing.
    Matched MeSH terms: Transcription Factors/antagonists & inhibitors; Transcription Factors/genetics; Transcription Factors/metabolism*
  17. Fulltext Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats
    Teo CH, Soga T, Parhar IS
    Front Endocrinol (Lausanne), 2017;8:225.
    PMID: 28936198 DOI: 10.3389/fendo.2017.00225
    Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH) acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH). The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH) in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin-which has been shown to be affected by circadian proteins such as Bmal1-in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.
    Matched MeSH terms: ARNTL Transcription Factors
  18. Reduced phosphorylated Foxp3 levels in Crimean Congo haemorrhagic fever
    Gazi U, Baykam N, Karasartova D, Tosun O, Akdogan O, Yapar D, et al.
    Trop Biomed, 2022 Dec 01;39(4):587-591.
    PMID: 36602220 DOI: 10.47665/tb.39.4.016
    Crimean-Congo haemorrhagic fever (CCHF) is a severe human infection which can lead to fatal consequences. Acute CCHF patients were previously shown to exhibit frequencies of regulatory T-cell (Treg) but lower Treg-mediated suppressive activities than the healthy counterparts. This study aims is to investigate the phosphorylation levels of Foxp3 protein (master regulator of Treg cells) in CCHF patients. Blood samples collected from 18 CCHF patients and nine healthy volunteers were used to isolate peripheral blood mononuclear cells (PBMCs). Total and phosphorylated Foxp3 expression levels in the isolated PBMC samples were monitored by western blot and quantified using ImageJ software. Total Foxp3 expression levels in CCHF patients displayed decreasing trend, but not significantly. In contrast, significantly lower expression levels of phosphorylated Foxp3 were reported in CCHF patients. Our results suggest a possible association between Foxp3 dephosphorylation and CCHF pathogenesis. Nevertheless, more studies are required to evaluate the effect of Foxp3 dephosphorylation on Treg function, which would not only help to enlighten the CCHF pathogenesis but also contribute to the development of effective treatment strategies.
    Matched MeSH terms: Forkhead Transcription Factors
  19. The Novel Role of the B-Cell Lymphoma/Leukemia 11A (BCL11A) Gene in β-Thalassaemia Treatment
    Mahmoud Ahmed NH, Lai MI
    Cardiovasc Hematol Disord Drug Targets, 2023;22(4):226-236.
    PMID: 36734897 DOI: 10.2174/1871529X23666230123140926
    β-thalassaemia is a genetic disorder resulting in a reduction or absence of β-globin gene expression. Due to the high prevalence of β-thalassaemia and the lack of available treatment other than blood transfusion and haematopoietic stem cell (HSC) transplantation, the disease represents a considerable burden to clinical and economic systems. Foetal haemoglobin has an appreciated ameliorating effect in β-haemoglobinopathy, as the γ-globin chain substitutes the β-globin chain reduction by pairing with the excess α-globin chain in β-thalassaemia and reduces sickling in sickle cell disease (SCD). BCL11A is a critical regulator and repressor of foetal haemoglobin. Downregulation of BCL11A in adult erythroblasts and cell lines expressing adult haemoglobin led to a significant increase in foetal haemoglobin levels. Disruption of BCL11A erythroid enhancer resulted in disruption of the BCL11A gene solely in the erythroid lineages and increased γ-globin expression in adult erythroid cells. Autologous haematopoietic stem cell gene therapy represents an attractive treatment option to overcome the immune complications and donor availability associated with allogeneic transplantation. Using genome editing technologies, the disruption of BCL11A to induce γ- globin expression in HSCs has emerged as an alternative approach to treat β-thalassaemia. Targeting the +58 BCL11A erythroid enhancer or BCL11A binding motif at the γ-gene promoter with CRISPR-Cas9 or base editors has successfully disrupted the gene and the binding motif with a subsequent increment in HbF levels. This review outlines the critical role of BCL11A in γ-globin gene silencing and discusses the different genome editing approaches to downregulate BCL11A as a means for ameliorating β-thalassaemia.
    Matched MeSH terms: Transcription Factors
  20. Fulltext Discovery of candidate genes for nonsyndromic cleft lip palate through genome-wide linkage analysis of large extended families in the Malay population
    Mohamad Shah NS, Salahshourifar I, Sulong S, Wan Sulaiman WA, Halim AS
    BMC Genet, 2016 Feb 11;17:39.
    PMID: 26868259 DOI: 10.1186/s12863-016-0345-x
    BACKGROUND: Nonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large extended families from the Malay population.

    RESULTS: A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1.

    CONCLUSIONS: We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.

    Matched MeSH terms: Transcription Factors/genetics; Forkhead Transcription Factors/genetics
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