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Simulation of live-cell imaging system reveals hidden uncertainties in cooperative binding measurements

Watabe M, Arjunan SNV, Chew WX, Kaizu K, Takahashi K

Phys Rev E, 2019 Jul;100(1-1):010402.
PMID: 31499827 DOI: 10.1103/PhysRevE.100.010402

We propose a computational method to quantitatively evaluate the systematic uncertainties that arise from undetectable sources in biological measurements using live-cell imaging techniques. We then demonstrate this method in measuring the biological cooperativity of molecular binding networks, in particular, ligand molecules binding to cell-surface receptor proteins. Our results show how the nonstatistical uncertainties lead to invalid identifications of the measured cooperativity. Through this computational scheme, the biological interpretation can be more objectively evaluated and understood under a specific experimental configuration of interest.

Matched MeSH terms: Receptors, Cell Surface
The clinical utility of CD163 in viral diseases

Yap YJ, Wong PF, AbuBakar S, Sam SS, Shunmugarajoo A, Soh YH, et al.

Clin Chim Acta, 2023 Feb 15;541:117243.
PMID: 36740088 DOI: 10.1016/j.cca.2023.117243

Macrophage activation and hypercytokinemia are notable presentations in certain viral infections leading to severe disease and poor prognosis. Viral infections can cause macrophage polarization into the pro-inflammatory M1 or anti-inflammatory M2 phenotype. Activated M1 macrophages usually restrict viral replication whereas activated M2 macrophages suppress inflammation and promote tissue repair. In response to inflammatory stimuli, macrophages polarize to the M2 phenotype expressing hemoglobin scavenger CD163 surface receptor. The CD163 receptor is shed as the soluble form, sCD163, into plasma or tissue fluids. sCD163 causes detoxification of pro-oxidative hemoglobin which produces anti-inflammatory metabolites that promote the resolution of inflammation. Hence, increased CD163 expression in tissues and elevated circulatory levels of sCD163 have been associated with acute and chronic inflammatory diseases. CD163 and other macrophage activation markers have been commonly included in the investigation of disease pathogenesis and progression. This review provides an overview of the involvement of CD163 in viral diseases. The clinical utility of CD163 in viral disease diagnosis, progression, prognosis and treatment evaluation is discussed.

Matched MeSH terms: Receptors, Cell Surface/genetics
Small Molecules for Active Targeting in Cancer

Kue CS, Kamkaew A, Burgess K, Kiew LV, Chung LY, Lee HB

Med Res Rev, 2016 Apr;36(3):494-575.
PMID: 26992114 DOI: 10.1002/med.21387

For the purpose of this review, active targeting in cancer research encompasses strategies wherein a ligand for a cell surface receptor expressed on tumor cells is used to deliver a cytotoxic or imaging cargo. This area of research is more than two decades old, but in those 20 and more years, how many receptors have been studied extensively? What kinds of the ligands are used for active targeting? Are they mostly naturally occurring molecules such as folic acid, or synthetic substances developed in campaigns for medicinal chemistry efforts? This review outlines the most important receptor or ligand combinations that have been used in active targeting to answer these questions, and therefore to address the most important one of all: is research in active targeting affording diminishing returns, or is this an area for which the potential far exceeds progress made so far?

Matched MeSH terms: Receptors, Cell Surface
Kesan masa pengeraman nanozarah zink oksida yang dihasilkan menggunakan afrons gas koloid

Saifful Kamaluddin Muzakir, Shahidan Radiman

Sains Malaysiana, 2011;40:1123-1127.

Nanozarah zink oksida telah disintesis menggunakan afrons gas koloid sebagai acuan. Zink sulfat (ZnSO4.7H2O) dan gas ammonia digunakan sebagi bahan tindak balas. Masa pengeraman yang dikaji adalah 2 jam dan 18 jam. Daripada analisis mikroskop elektron imbasan, morfologi nanohelaian dapat diperhatikan dengan ketebalan helaian 125 nm hingga 200 nm. Daripada analisis spektroskopi ultra lembayung-boleh nampak, saiz purata yang dianggarkan bagi sampel nanozarah zink oksida yang disintesis dengan masa pengeraman 2 jam adalah 2.03 nm dan 2.1 nm untuk sampel yang dieramkan selama 18 jam.

Matched MeSH terms: Receptors, Cell Surface
Soil erosion potential at sungai bilut catchment, Raub, Pahang using integration of rusle and GIS

Tukimat Lihan, Nur Fatin Khodri, Muzzneena Ahmad Mustapha, Zulfahmi Ali Rahman, Wan Mohd Razi Idris

Sains Malaysiana, 2018;47:2241-2249.

Aktiviti guna tanah di kawasan lembangan adalah salah satu faktor yang mendorong kepada kemerosotan kualiti air
sungai akibat daripada hakisan tanih. Potensi hakisan tanih di kawasan lembangan Sungai Bilut, Raub, Pahang yang
menjadi sumber bekalan air minuman utama di daerah Raub boleh ditentukan dengan menggunakan integrasi model
Semakan Semula Persamaan Kehilangan Tanih Universal (RUSLE) dan Sistem Maklumat Geografi (GIS). Kajian ini
bertujuan untuk menentukan potensi hakisan tanih dan faktor utama yang mempengaruhi kadar hakisan tanih. Kajian ini
melibatkan penggunaan data sekunder yang terdiri daripada data hujan, data siri tanih dan topografi bagi menghasilkan
faktor kehakisan hujan (R), kebolehhakisan tanih (K), serta panjang dan kecuraman cerun (LS). Faktor litupan tumbuhan
(C) dan amalan pemuliharaan (P) pula dijana daripada imej satelit Landsat 8 (2014). Keputusan kajian menunjukkan
nilai faktor R di kawasan kajian ialah 8927.68-9775.18 MJ mm ha-1 jam-1 tahun-1, nilai K ialah 0.036-0.500 tan jam-1
MJ-1 mm-1, nilai LS ialah 0-514, nilai C ialah 0.03-0.80 dan nilai P ialah 0.1-0.7. Kawasan yang mempunyai potensi
hakisan sangat rendah hingga rendah meliputi 81%, manakala potensi hakisan tanih sederhana hingga sangat tinggi
meliputi 19% daripada keseluruhan kawasan kajian. Model yang dihasilkan mempunyai ketepatan sebanyak 81%. Faktor
utama yang mempengaruhi berlakunya hakisan tanih di kawasan kajian adalah faktor topografi, litupan tumbuhan dan
kebolehhakisan tanih. Keputusan menunjukkan analisis integrasi RUSLE dan GIS berpotensi dalam penentuan potensi
hakisan tanih untuk kawasan luas yang mempunyai pelbagai jenis guna tanah, topografi dan jenis tanih.

Matched MeSH terms: Receptors, Cell Surface
Enlightening the role of high mobility group box 1 (HMGB1) in inflammation: Updates on receptor signalling

Paudel YN, Angelopoulou E, Piperi C, Balasubramaniam VRMT, Othman I, Shaikh MF

Eur J Pharmacol, 2019 Sep 05;858:172487.
PMID: 31229535 DOI: 10.1016/j.ejphar.2019.172487

High mobility group box 1 (HMGB1) is a ubiquitous protein, released passively by necrotic tissues or secreted actively by stressed cells. Extracellular HMGB1 is a typical damage-associated molecular pattern (DAMP) molecule which generates different redox types through binding with several receptors and signalling molecules, aggravating a range of cellular responses, including inflammation. HMGB1 is reported to participate in the pathogenesis of inflammatory diseases, through the interaction with pivotal transmembrane receptors, including the receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4). This review aims to highlight the role of HMGB1 in the innate inflammatory response describing its interaction with several cofactors and receptors that coordinate its downstream effects. Novel and underexplored HMGB1 binding molecules that have been actively involved in HMGB1-mediated inflammatory diseases/conditions with therapeutic potential are further discussed.

Matched MeSH terms: Receptors, Cell Surface/metabolism*
Gonadotropin-inhibitory hormone mediates behavioral stress responses

Ubuka T, Parhar IS, Tsutsui K

Gen Comp Endocrinol, 2018 09 01;265:202-206.
PMID: 29510150 DOI: 10.1016/j.ygcen.2018.03.004

Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.

Matched MeSH terms: Receptors, Cell Surface/metabolism
Fulltext Overview of the Microenvironment of Vasculature in Vascular Tone Regulation

Loh YC, Tan CS, Ch'ng YS, Yeap ZQ, Ng CH, Yam MF

Int J Mol Sci, 2018 Jan 02;19(1).
PMID: 29301280 DOI: 10.3390/ijms19010120

Hypertension is asymptomatic and a well-known "silent killer", which can cause various concomitant diseases in human population after years of adherence. Although there are varieties of synthetic antihypertensive drugs available in current market, their relatively low efficacies and major application in only single drug therapy, as well as the undesired chronic adverse effects associated, has drawn the attention of worldwide scientists. According to the trend of antihypertensive drug evolution, the antihypertensive drugs used as primary treatment often change from time-to-time with the purpose of achieving the targeted blood pressure range. One of the major concerns that need to be accounted for here is that the signaling mechanism pathways involved in the vasculature during the vascular tone regulation should be clearly understood during the pharmacological research of antihypertensive drugs, either in vitro or in vivo. There are plenty of articles that discussed the signaling mechanism pathways mediated in vascular tone in isolated fragments instead of a whole comprehensive image. Therefore, the present review aims to summarize previous published vasculature-related studies and provide an overall depiction of each pathway including endothelium-derived relaxing factors, G-protein-coupled, enzyme-linked, and channel-linked receptors that occurred in the microenvironment of vasculature with a full schematic diagram on the ways their signals interact. Furthermore, the crucial vasodilative receptors that should be included in the mechanisms of actions study on vasodilatory effects of test compounds were suggested in the present review as well.

Matched MeSH terms: Receptors, Cell Surface/metabolism
Fulltext Two Genetically Distinct Plasmodium knowlesi Duffy Binding Protein Alpha Region II (PkDBPαII) Haplotypes Demonstrate Higher Binding Level to Fy(a+b+) Erythrocytes than Fy(a+b--) Erythrocytes

Liew CC, Lau YL, Fong MY, Cheong FW

Am J Trop Med Hyg, 2020 05;102(5):1068-1071.
PMID: 32189613 DOI: 10.4269/ajtmh.19-0836

Invasion of human erythrocytes by merozoites of Plasmodium knowlesi involves interaction between the P. knowlesi Duffy binding protein alpha region II (PkDBPαII) and Duffy antigen receptor for chemokines (DARCs) on the erythrocytes. Information is scarce on the binding level of PkDBPαII to different Duffy antigens, Fya and Fyb. This study aims to measure the binding level of two genetically distinct PkDBPαII haplotypes to Fy(a+b-) and Fy(a+b+) human erythrocytes using erythrocyte-binding assay. The binding level of PkDBPαII of Peninsular Malaysian and Malaysian Borneon haplotypes to erythrocytes was determined by counting the number of rosettes formed in the assay. Overall, the Peninsular Malaysian haplotype displayed higher binding activity than the Malaysian Borneon haplotype. Both haplotypes exhibit the same preference to Fy(a+b+) compared with Fy(a+b-), hence justifying the vital role of Fyb in the binding to PkDBPαII. Further studies are needed to investigate the P. knowlesi susceptibility on individuals with different Duffy blood groups.

Matched MeSH terms: Receptors, Cell Surface/genetics*; Receptors, Cell Surface/immunology; Receptors, Cell Surface/metabolism
Periodontal management in a primary polycythemia rubra vera patient: A case report

Hassan FW, Mohd N

Spec Care Dentist, 2021 Jan;41(1):92-97.
PMID: 33125720 DOI: 10.1111/scd.12537

BACKGROUND/AIM: Polycythemia rubra vera (PRV) is a myeloproliferative disease, which is characterized by the proliferation of all three major hematopoietic groups (erythrocytes, leucocytes and platelets). This hematological condition presented with different clinical manifestations depending on the thrombohemorrhagic status of the patient. It is suggested patient with preexisting PRV may suffer complication during periodontal treatment. Thus, this case would therefore demonstrate periodontal management outcome in PRV patient.
CASE PRESENTATION: A 60-year-old Malay gentleman presented to the Periodontic Clinic, Universiti Kebangsaan Malaysia. He was a known case of primary PRV for the past 5 years. Intraoral examination showed generalized periodontal deep pockets ranging from 5 to 10 mm. He was diagnosed as Stage III Grade C periodontitis. Nonsurgical periodontal therapy was provided, followed by surgical correction of residual periodontal deep pockets on teeth 17, 11, and 23. He was reviewed at 4-month intervals for supportive periodontal therapy after stabilization of his periodontal condition.
CONCLUSION: Polycythemia rubra vera (PRV) patients should have preoperative therapeutic control for more than 4 months and have been treated with myelosuppressive agents prior to periodontal surgery. Good oral hygiene and periodical supportive periodontal therapy are the key factors for successful periodontal treatment outcomes in well-controlled PRV patients.

Matched MeSH terms: Receptors, Cell Surface
Fulltext Roles of Sema4D and Plexin-B1 in tumor progression

Ch'ng ES, Kumanogoh A

Mol. Cancer, 2010;9:251.
PMID: 20858260 DOI: 10.1186/1476-4598-9-251

Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.

Matched MeSH terms: Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism*
Fulltext Erythrocyte-binding assays reveal higher binding of Plasmodium knowlesi Duffy binding protein to human Fya+/b+ erythrocytes than to Fya+/b- erythrocytes

Fong MY, Cheong FW, Lau YL

Parasit Vectors, 2018 Sep 26;11(1):527.
PMID: 30257710 DOI: 10.1186/s13071-018-3118-8

BACKGROUND: The merozoite of the zoonotic Plasmodium knowlesi invades human erythrocytes via the binding of its Duffy binding protein (PkDBPαII) to the Duffy antigen on the eythrocytes. The Duffy antigen has two immunologically distinct forms, Fya and Fyb. In this study, the erythrocyte-binding assay was used to quantitatively determine and compare the binding level of PkDBPαII to Fya+/b+ and Fya+/b- human erythrocytes.
RESULTS: In the erythrocyte-binding assay, binding level was determined by scoring the number of rosettes that were formed by erythrocytes surrounding transfected mammalian COS-7 cells which expressed PkDBPαII. The assay result revealed a significant difference in the binding level. The number of rosettes scored for Fya+/b+ was 1.64-fold higher than that of Fya+/b- (155.50 ± 34.32 and 94.75 ± 23.16 rosettes, respectively; t(6) = -2.935, P = 0.026).
CONCLUSIONS: The erythrocyte-binding assay provided a simple approach to quantitatively determine the binding level of PkDBPαII to the erythrocyte Duffy antigen. Using this assay, PkDBPαII was found to display higher binding to Fya+/b+ erythrocytes than to Fya+/b- erythrocytes.

Matched MeSH terms: Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism*
Inhibitory effects of xanthones on platelet activating factor receptor binding in vitro

Jantan I, Juriyati J, Warif NA

J Ethnopharmacol, 2001 May;75(2-3):287-90.
PMID: 11297865

Nine naturally occurring xanthones were investigated for their platelet activating factor (PAF) receptor binding inhibitory effects using rabbit platelets. 2-(3-methylbut-2-enyl)-1,3,5-trihydoxyxanthone, macluraxanthone, 1,3,5-trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)xanthone, 6-deoxyjacareubin and 2-(3-methylbut-2-enyl)-1,3,5,6-terahydroxyxanthone showed strong inhibition with IC50 values of 4.8, 11.0, 21.0, 29.0 and 44.0 microM, respectively. The prenyl group at C-2, the dimethylprop-2-enyl group at C-4 and the hydroxyl group at C-5 are all beneficial to the binding of xanthones to the PAF receptor. The results revealed that xanthones can represent a new class of natural PAF receptor antagonists.

Matched MeSH terms: Receptors, Cell Surface*
Competitive binding of gangliosides and glycophorin to wheat germ agglutinin

Lee PM, Lee KH

Biochem Biophys Res Commun, 1989 Apr 28;160(2):780-7.
PMID: 2719696

Gangliosides and glycophorin are receptors for wheat germ agglutinin. The competitive binding of these molecules to wheat germ agglutinin is studied by electron spin resonance spectroscopy with spin labels attached to the oligosaccharide chains of gangliosides. Evidence shows that glycophorin is more accessible to wheat germ agglutinin binding than gangliosides. The interactions of gangliosides and glycophorin in liposomes is disrupted on low level binding of WGA.

Matched MeSH terms: Receptors, Cell Surface*
Fulltext In vitro invasion inhibition assay using antibodies against Plasmodium knowlesi Duffy binding protein alpha and apical membrane antigen protein 1 in human erythrocyte-adapted P. knowlesi A1-H.1 strain

Muh F, Lee SK, Hoque MR, Han JH, Park JH, Firdaus ER, et al.

Malar J, 2018 Jul 27;17(1):272.
PMID: 30049277 DOI: 10.1186/s12936-018-2420-4

BACKGROUND: The rapid process of malaria erythrocyte invasion involves ligand-receptor interactions. Inducing antibodies against specific ligands or receptors that abrogate the invasion process is a key challenge for blood stage vaccine development. However, few candidates were reported and remain to be validated for the discovery of new vaccine candidates in Plasmodium knowlesi.
METHODS: In order to investigate the efficacy of pre-clinical vaccine candidates in P. knowlesi-infected human cases, this study describes an in vitro invasion inhibition assay, using a P. knowlesi strain adapted to in vitro growth in human erythrocytes, PkA1-H.1. Recombinant proteins of P. knowlesi Duffy binding protein alpha (PkDBPα) and apical membrane antigen 1 (PkAMA1) were produced in Escherichia coli system and rabbit antibodies were generated from immune animals.
RESULTS: PkDBPα and PkAMA1 recombinant proteins were expressed as insoluble and produced as a functional refolded form for this study. Antibodies against PkDBPα and PkAMA1 specifically recognized recombinant proteins and native parasite proteins in schizont-stage parasites on the merozoite organelles. Single and combination of anti-PkDBPα and anti-PkAMA1 antibodies elicited strong growth inhibitory effects on the parasite in concentration-dependent manner. Meanwhile, IgG prevalence of PkDBPα and PkAMA1 were observed in 13.0 and 46.7% in human clinical patients, respectively.
CONCLUSION: These data provide support for the validation of in vitro growth inhibition assay using antibodies of DBPα and AMA1 in human-adapted P. knowlesi parasite PkA1-H.1 strain.

Matched MeSH terms: Receptors, Cell Surface/immunology*
The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index

Ng HF, Chin KF, Chan KG, Ngeow YF

Genome, 2015 Jun;58(6):315-21.
PMID: 26284904 DOI: 10.1139/gen-2015-0028

suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity.

Matched MeSH terms: Receptors, Cell Surface/genetics*; Receptors, Cell Surface/metabolism
In vitro inhibitory effect of rubraxanthone isolated from Garcinia parvifolia on platelet-activating factor receptor binding

Jantan I, Pisar MM, Idris MS, Taher M, Ali RM

Planta Med, 2002 Dec;68(12):1133-4.
PMID: 12494345

Rubraxanthone and isocowanol isolated from Garcinia parvifolia Miq. were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets using 3H-PAF as a ligand. Rubraxanthone showed a strong inhibition with IC 50 value of 18.2 microM. The IC 50 values of macluraxanthone, 6-deoxyjacareubin, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone, 2-(3-methylbut-2-enyl)-1,3,5,6-tetrahydroxyxanthone and 1,3,5-trihydroxy-6,6'-dimethylpyrano(2',3':6,7)-4-(1,1-dimethylprop-2-enyl)-xanthone were also determined for comparison. In the course of our study on structure-activity relationship of xanthones, the results revealed that a geranyl group substituted at C-8 was beneficial to the binding while a hydroxylated prenyl group at C-4 resulted in a significant loss in binding to the PAF receptor.

Matched MeSH terms: Receptors, Cell Surface/antagonists & inhibitors; Receptors, Cell Surface/metabolism*
Potential combinatorial effects of recombinant atypical chemokine receptors in breast cancer cell invasion: A research perspective

Chew AL, Tan WY, Khoo BY

Biomed Rep, 2013 Mar;1(2):185-192.
PMID: 24648916

Apart from their major function in the coordination of leukocyte recruitment, chemokines, in cooperation with their receptors, have been implicated in the progression of various diseases including different types of cancer, affecting survival, proliferation and metastasis. A complex network of chemokines and receptors exists in the tumor microenvironment and affects tumor development in various ways where chemokines activate typical signalling pathways by binding to the respective receptors. The identification and characterization of a group of atypical chemokine receptors [D6, Duffy antigen receptor for chemokines (DARC), ChemoCentryx chemokine receptor (CCX-CKR) and CXCR7] which appear to use unique biochemical properties to regulate the biological activities of these chemokines, is useful in the effort to therapeutically manipulate chemokines in a broad spectrum of diseases in which these chemokines play a critical role. The aim of this review was to investigate the combinatorial effect of two reported atypical chemokine receptors, D6 and DARC, on breast cancer cell invasion to understand their role and therapeutic potential in cancer treatment. In this regard, findings of the present review should be confirmed via the construction of recombinant D6 and DARC clones as well as the expression of the respective recombinant proteins using the Pichia pastoris (P. pastoris) expression system is to be performed in a future study in order to support findings of the current review.

Matched MeSH terms: Receptors, Cell Surface
Fulltext Genetic Diversity, Natural Selection and Haplotype Grouping of Plasmodium knowlesi Gamma Protein Region II (PkγRII): Comparison with the Duffy Binding Protein (PkDBPαRII)

Fong MY, Rashdi SA, Yusof R, Lau YL

PLoS One, 2016;11(5):e0155627.
PMID: 27195821 DOI: 10.1371/journal.pone.0155627

BACKGROUND: Plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in Southeast Asia. This parasite invades the erythrocytes of humans and of its natural host, the macaque Macaca fascicularis, via interaction between the Duffy binding protein region II (PkDBPαRII) and the Duffy antigen receptor on the host erythrocytes. In contrast, the P. knowlesi gamma protein region II (PkγRII) is not involved in the invasion of P. knowlesi into humans. PkγRII, however, mediates the invasion of P. knowlesi into the erythrocytes of M. mulata, a non-natural host of P. knowlesi via a hitherto unknown receptor. The haplotypes of PkDBPαRII in P. knowlesi isolates from Peninsular Malaysia and North Borneo have been shown to be genetically distinct and geographically clustered. Also, the PkDBPαRII was observed to be undergoing purifying (negative) selection. The present study aimed to determine whether similar phenomena occur in PkγRII.
METHODS: Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkγRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00) programmes. Genetic differentiation between the PkγRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright's FST fixation index in DnaSP (version 5.10.00). Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3).
RESULTS: A total of 78 PkγRII sequences was obtained. Comparative analysis showed that the PkγRII have similar range of haplotype (Hd) and nucleotide diversity (π) with that of PkDBPαRII. Other similarities between PkγRII and PkDBPαRII include undergoing purifying (negative) selection, geographical clustering of haplotypes, and high inter-population genetic differentiation (FST index). The main differences between PkγRII and PkDBPαRII include length polymorphism and no departure from neutrality (as measured by Tajima's D statistics) in the PkγRII.
CONCLUSION: Despite the biological difference between PkγRII and PkDBPαRII, both generally have similar genetic diversity level, natural selection, geographical haplotype clustering and inter-population genetic differentiation index.

Matched MeSH terms: Receptors, Cell Surface/genetics*
Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma

Khor GH, Froemming GR, Zain RB, Abraham TM, Lin TK

Asian Pac J Cancer Prev, 2016;17(1):219-23.
PMID: 26838213

BACKGROUND: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers.
OBJECTIVES: The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters.
MATERIALS AND METHODS: Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM.
RESULTS: MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001).
CONCLUSIONS: CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication.

Matched MeSH terms: Receptors, Cell Surface/genetics*

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