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1

Molecular Mechanistic Insights into the Endothelial Receptor Mediated Cytoadherence of Plasmodium falciparum-Infected Erythrocytes  

UK PubMed Central (United Kingdom)

Cytoadherence or sequestration is essential for the pathogenesis of the most virulent human malaria species, Plasmodium falciparum (P. falciparum). Similar to leukocyte-endothelium...Full Text Available

2

var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2  

UK PubMed Central (United Kingdom)

BackgroundThe pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra-vascular host cell...Full Text Available

3

The relationship between the Plasmodium falciparum parasite ratio in childhood and climate estimates of malaria transmission in Kenya  

UK PubMed Central (United Kingdom)

BackgroundPlasmodium falciparum morbid and fatal risks are considerably higher in areas supporting parasite prevalence ≥25%, when compared with low transmission...Full Text Available

4

The Dynamics of Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs230 & Pfs48/45 in a Low Endemic Area in Tanzania  

UK PubMed Central (United Kingdom)

BackgroundNaturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens...Full Text Available

5

Sensitivity of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine in Nigerian children.  

UK PubMed Central (United Kingdom)

The in vivo sensitivity of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine was evaluated in children under 5 years of age in two areas of southern Nigeria in 1987. A modification...Full Text Available

1990-01-01

6

Population genetic analysis of large sequence polymorphisms in Plasmodium falciparum blood-stage antigens  

UK PubMed Central (United Kingdom)

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed...Full Text Available

2010-03-01

7

Hypoglycaemia and severe plasmodium falciparum malaria among pregnant sudanese women in an area characterized by unstable malaria transmission  

UK PubMed Central (United Kingdom)

BackgroundPregnant women are more susceptible to severe Plasmodium falciparum malaria, which can lead to poor maternal and fetal outcomes. Few data exist on the...Full Text Available

8

Diagnosis of Plasmodium falciparum infection using a solid-phase radioimmunoassay for the detection of malaria antigens  

UK PubMed Central (United Kingdom)

A serodiagnostic test has been developed for the detection of Plasmodium falciparum in infected blood. Using parasite antigens and infected red blood cells from in vitro...Full Text Available

1980-01-01

9

Contrasting Population Structures of the Genes Encoding Ten Leading Vaccine-Candidate Antigens of the Human Malaria Parasite, Plasmodium falciparum  

UK PubMed Central (United Kingdom)

The extensive diversity of Plasmodium falciparum antigens is a major obstacle to a broadly effective malaria vaccine but population genetics has rarely been used to guide vaccine design....Full Text Available

10

Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria  

UK PubMed Central (United Kingdom)

There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common...Full Text Available

2008-02-15

11

Blood Group A Antigen Is a Coreceptor in Plasmodium falciparum Rosetting  

UK PubMed Central (United Kingdom)

The malaria parasite Plasmodium falciparum utilizes molecules present on the surface of uninfected red blood cells (RBC) for rosette formation, and a dependency on ABO antigens has...Full Text Available

2000-05-01

12

Age-Related Differences in Naturally Acquired T Cell Memory to Plasmodium falciparum Merozoite Surface Protein 1  

UK PubMed Central (United Kingdom)

Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual, age-related development of protection against high-density...Full Text Available

13

A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray  

UK PubMed Central (United Kingdom)

Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria,...Full Text Available

2010-04-13

14

c-Myc Mediates a Hypoxia-Induced Decrease in Acetylated Histone H4  

UK PubMed Central (United Kingdom)

Global acetylation of histone H4 is a mark of gene transcriptional activation. The c-Myc transcription factor binds to specific DNA sites in cellular chromatin and induces the acetylation of...Full Text Available

2009-10-01

15

Identification of a Novel Inhibitor of Coactivator-associated Arginine Methyltransferase 1 (CARM1)-mediated Methylation of Histone H3 Arg-17*  

UK PubMed Central (United Kingdom)

Methylation of the arginine residues of histones by methyltransferases has important consequences for chromatin structure and gene regulation; however, the molecular mechanism(s) of methyltransferase...Full Text Available

2010-03-05

16

Antagonistic Gcn5-Hda1 interactions revealed by mutations to the Anaphase Promoting Complex in yeast  

UK PubMed Central (United Kingdom)

BackgroundHistone post-translational modifications are critical for gene expression and cell viability. A broad spectrum of histone lysine residues have been identified in yeast...Full Text Available

17

A New Amidohydrolase from Bordetella or Alcaligenes Strain FB188 with Similarities to Histone Deacetylases  

UK PubMed Central (United Kingdom)

The full-length gene encoding the histone deacetylase (HDAC)-like amidohydrolase (HDAH) from Bordetella or Alcaligenes (Bordetella/Alcaligenes) strain...Full Text Available

2004-04-01

18

Polyadenylated H3 histone transcripts and H3 histone variants in alfalfa.  

UK PubMed Central (United Kingdom)

Histone H3 mRNAs were found in polyA(+) fractions of total RNA prepared from alfalfa plants, calli and somatic embryos. The sequence analysis of cDNAs revealed the presence of a polyA tail on independent...Full Text Available

1989-04-25

19

Amino acid sequences that determine the nuclear localization of yeast histone 2B.  

UK PubMed Central (United Kingdom)

Histone-beta-galactosidase protein fusions were used to identify the domain of yeast histone 2B, which targets this protein to the nucleus. Amino acids 28 to 33 in H2B were required for nuclear localization...Full Text Available

1987-11-01

20

Application of the histone deacetylase inhibitors for the treatment of endometriosis: histone modifications as pathogenesis and novel therapeutic target.  

Science.gov (United States)

BACKGROUND Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. We investigated the histone acetylation status in endometriosis and the application of the histone deacetylase inhibitors (HDACIs) for the treatment of endometriosis. METHODS The levels of acetylated histones in the endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were evaluated. The effects of the HDACIs on cell proliferation, the cell cycle, apoptosis of ECSCs and NESCs, and the expression of genes related to these cellular events were investigated. The effects of HDACIs on histone acetylation in chromatin of the promoter region of the cell cycle regulatory genes in ECSCs were also investigated. RESULTS The acetylated histone levels were significantly lower in ECSCs than in NESCs (P endometriosis and that ...

2011-06-29

 
 
 
 
21

Phylogenomic analyses of malaria parasites and evolution of their exported proteins  

UK PubMed Central (United Kingdom)

BackgroundPlasmodium falciparum is the most malignant agent of human malaria. It belongs to the taxon Laverania, which includes other ape-infecting Plasmodium...Full Text Available

22

Efficacy of drug prophylaxis.  

UK PubMed Central (United Kingdom)

With the spread of chloroquine resistant Plasmodium falciparum the control of malaria has become increasingly complex. In recent years, particular concern has arisen over how best to prevent malaria...Full Text Available

1989-01-01

25

Plasticity in patterns of histone modifications and chromosomal proteins in Drosophila heterochromatin  

UK PubMed Central (United Kingdom)

Eukaryotic genomes are packaged in two basic forms, euchromatin and heterochromatin. We have examined the composition and organization of Drosophila melanogaster heterochromatin in...Full Text Available

2011-02-01

26

Ribose metabolism and nucleic acid synthesis in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes infected with Plasmodium falciparum.  

UK PubMed Central (United Kingdom)

The metabolism of pentose-phosphate was investigated in Plasmodium falciparum-infected normal and glucose-6-phosphate dehydrogenase (G6PD)-deficient human red blood cells in vitro. 5'-Phosphoribosyl-1-pyrophosphate...Full Text Available

1986-04-01

27

Primary organization of nucleosomal core particles is invariable in repressed and active nuclei from animal, plant and yeast cells.  

UK PubMed Central (United Kingdom)

A refined map for the linear arrangement of histones along DNA in nucleosomal core particles has been determined by DNA-protein crosslinking. On one strand of 145-bp core DNA, histones are aligned in...Full Text Available

1985-05-24

28

Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial  

British Library Electronic Table of Contents (United Kingdom)

Summary Background There is a need for new artemisinin-based combination therapies that are convenient, effective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria. Methods This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre....

2010-01-01

29

Statistical properties of nucleotide clusters in DNA sequences*  

UK PubMed Central (United Kingdom)

Using the complete genome of Plasmodium falciparum 3D7 which has 14 chromosomes as an example, we have examined the distribution functions for the amount of C or G and A or T consecutively...Full Text Available

2005-05-01

30

Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants  

UK PubMed Central (United Kingdom)

BackgroundIndividuals living in malaria endemic areas generally harbour multiple parasite strains. Multiplicity of infection (MOI) can be an indicator of immune status. However,...Full Text Available

31

Measuring the efficacy of anti-malarial drugs in vivo: quantitative PCR measurement of parasite clearance  

UK PubMed Central (United Kingdom)

BackgroundArtemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries,...Full Text Available

32

Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon  

UK PubMed Central (United Kingdom)

BackgroundImproving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies.MethodsA...Full Text Available

33

Evaluation of the OptiMAL Test for Rapid Diagnosis of Plasmodium vivax and Plasmodium falciparum Malaria  

UK PubMed Central (United Kingdom)

The development of rapid and specific diagnostic tests to identify individuals infected with malaria is of paramount importance in efforts to control the severe public health impact of this disease....Full Text Available

1998-01-01

34

Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial  

UK PubMed Central (United Kingdom)

BackgroundAn artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment...Full Text Available

35

Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women  

UK PubMed Central (United Kingdom)

BackgroundIn sub-Saharan Africa, Plasmodium falciparum malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance...Full Text Available

36

Deletion of the Plasmodium falciparum Merozoite Surface Protein 7 Gene Impairs Parasite Invasion of Erythrocytes?  

UK PubMed Central (United Kingdom)

Merozoite surface proteins have been implicated in the initial attachment to the host red blood cell membrane that begins the process of invasion, an important step in the life cycle of the malaria...Full Text Available

2008-12-01

37

Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates  

UK PubMed Central (United Kingdom)

Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted...Full Text Available

2009-10-01

38

An improved method for undertaking limiting dilution assays for in vitro cloning of Plasmodium falciparum parasites  

UK PubMed Central (United Kingdom)

BackgroundObtaining single parasite clones is required for many techniques in malaria research. Cloning by limiting dilution using microscopy-based assessment for parasite growth...Full Text Available

39

Accumulation of Plasmodium berghei-Infected Red Blood Cells in the Brain Is Crucial for the Development of Cerebral Malaria in Mice?  

UK PubMed Central (United Kingdom)

Cerebral malaria is the most severe complication of human infection with Plasmodium falciparum. It was shown that Plasmodium berghei ANKA-induced cerebral malaria was...Full Text Available

2010-09-01

40

ABO blood group phenotypes influence parity specific immunity to Plasmodium falciparum malaria in Malawian women  

UK PubMed Central (United Kingdom)

BackgroundBlood group O has been significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae in the Gambia, an area...Full Text Available

 
 
 
 
41

Crystal structure of the human centromeric nucleosome containing CENP-A  

British Library Electronic Table of Contents (United Kingdom)

In eukaryotes, accurate chromosome segregation during mitosis and meiosis is coordinated by kinetochores, which are unique chromosomal sites for microtubule attachment. Centromeres specify the kinetochore formation sites on individual chromosomes, and are epigenetically marked by the assembly of nucleosomes containing the centromere-specific histone H3 variant, CENP-A. Although the underlying mechanism is unclear, centromere inheritance is probably dictated by the architecture of the centromeric nucleosome. Here we report the crystal structure of the human centromeric nucleosome containing CENP-A and its cognate ?-satellite DNA derivative (147 base pairs). In the human CENP-A nucleosome, the DNA is wrapped around the histone octamer, consisting of two each of histones H2A, H2B, H4 and CENP...

2011-01-01

42

UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications  

UK PubMed Central (United Kingdom)

Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation...Full Text Available

2009-01-01

43

UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications  

Science.gov (United States)

Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be ...

2009-01-01

44

Structure of the Taz2 domain of p300: insights into ligand binding  

UK PubMed Central (United Kingdom)

CBP and its paralog p300 are histone acetyl transferases that regulate gene expression by interacting with multiple transcription factors via specialized domains. The structure...Full Text Available

2009-12-01

45

Structural Basis for Acetylated Histone H4 Recognition by the Human BRD2 Bromodomain*  

UK PubMed Central (United Kingdom)

Recognition of acetylated chromatin by the bromodomains and extra-terminal domain (BET) family proteins is a hallmark for transcriptional activation and anchoring viral genomes to mitotic chromosomes...Full Text Available

2010-03-05

46

SirT1 brings stemness closer to cancer and aging  

UK PubMed Central (United Kingdom)

Sirtuin 1 acts in various cell processes, deacetylating both chromatin and non-histone proteins, and its role in cancer and aging has long been studied and debated. Here we discuss another aspect of...Full Text Available

47

Role of histone methylation and demethylation in adipogenesis and obesity  

UK PubMed Central (United Kingdom)

Adipocyte differentiation is a complex developmental process that involves the coordinated interplay of numerous transcription factors. PPARγ has emerged as a master regulator of adipogenesis...Full Text Available

2010-01-01

48

Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F  

UK PubMed Central (United Kingdom)

Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug...Full Text Available

49

Isolation and Characterization of a Novel Nuclear Protein from Pollen Mother Cells of Lily  

UK PubMed Central (United Kingdom)

Pollen mother cells of the lily (Lilium speciosum) were found to have a histone-H1-like protein (PMCP) not detected in other tissues. The PMCP appears from the late S-G2...Full Text Available

1990-11-01

50

Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks  

UK PubMed Central (United Kingdom)

The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB...Full Text Available

2011-06-01

51

Coordination of PAD4 and HDAC2 in the regulation of p53 target gene expression  

UK PubMed Central (United Kingdom)

Histone Arg methylation and Lys acetylation have been found to cooperatively regulate the expression of p53 target genes. Peptidylarginine deiminase 4 (PAD4) is an enzyme that citrullinates...Full Text Available

2010-05-27

52

Acetylation of Histones and Transcription-Related Factors  

UK PubMed Central (United Kingdom)

The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies—including...Full Text Available

2000-06-01

53

?H2AX and cancer  

UK PubMed Central (United Kingdom)

Histone H2AX phosphorylation on a serine four residues from the carboxyl terminus (producing γH2AX) is a sensitive marker for DNA double-strand breaks (DSBs). DSBs may lead to cancer...Full Text Available

2008-12-01

54

In vivo phosphorylation of histones H1 and H5 in calf thymus and chicken erythrocytes as studied by /sup 31/P nuclear magnetic resonance spectroscopy  

Energy Technology Data Exchange (ETDEWEB)

The /sup 31/P NMR method was first applied to characterize in vivo phosphorylation of H1 and H5 in calf thymus and chicken erythrocytes as well as in vitro phosphorylation of H1 and H5 by cAMP-dependent protein kinase. The amino acid residues phosphorylated in vivo in the histones were exclusively serine residues, and the mole fraction of phosphoserine was estimated to be 0.34 and 0.27 per molecule of calf thymus H1 and chicken erythrocyte H5, respectively. Interestingly, chicken erythrocyte H1 was not phosphorylated in vivo. Three H1 subtypes from calf thymus H1 varied in the /sup 31/P NMR spectra, and the bisected fragments of calf thymus H1 and chicken erythrocyte H5 exhibited characteristic spectral patterns, indicating that there are considerable diversities of the degree of phosphorylation and phosphorylation sites in very-lysine-rich histones. Furthermore, it was found that the microenvironment of phosphoserine residues phosphorylated in ...

1987-08-01

55

Pharmacokinetic and pharmacodynamic properties of an oral formulation of the histone deacetylase inhibitor Belinostat (PXD101)  

British Library Electronic Table of Contents (United Kingdom)

Purpose The primary objective of this sub-study, undertaken as an extension to the previously reported phase-I study, was to explore the feasibility, tolerability and pharmacokinetics (PK) of belinostat when administered by the oral route. Preliminary pharmacodynamic (PD) studies were also performed to enable comparison of the biological effects of the oral and intravenous formulations. Patients and methods Oral belinostat was administered in a range of doses and schedules (once, twice or thrice daily), on either day 1 or days 1?5, of the second or a subsequent treatment cycle in 15 patients who were included in the phase-I trial of intravenous belinostat. Serial blood samples were collected for PK and PD (histone acetylation) analyses, and the results compared with corresponding analyses ...

2011-01-01

56

Histone deacetylase inhibitors and transforming growth factor-b induce 15-hydroxyprostaglandin dehydrogenase expression in human lung adenocarcinoma cells  

British Library Electronic Table of Contents (United Kingdom)

Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identify gene targets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...

2006-01-01

57

AFM Imaging of SWI/SNF action: mapping the nucleosome remodeling and sliding  

CERN Document Server

We propose a combined experimental (Atomic Force Microscopy) and theoretical study of the structural and dynamical properties of nucleosomes. In contrast to biochemical approaches, this method allows to determine simultaneously the DNA complexed length distribution and nucleosome position in various contexts. First, we show that differences in the nucleo-proteic structure observed between conventional H2A and H2A.Bbd variant nucleosomes induce quantitative changes in the in the length distribution of DNA complexed with histones. Then, the sliding action of remodeling complex SWI/SNF is characterized through the evolution of the nucleosome position and wrapped DNA length mapping. Using a linear energetic model for the distribution of DNA complexed length, we extract the net wrapping energy of DNA onto the histone octamer, and compare it to previous studies.

2007-01-01

58

T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children  

UK PubMed Central (United Kingdom)

BackgroundThe Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against...Full Text Available

59

Evaluation of the rapid diagnostic test SDFK40 (Pf-pLDH/pan-pLDH) for the diagnosis of malaria in a non-endemic setting  

UK PubMed Central (United Kingdom)

BackgroundThe present study evaluated the SD Bioline Malaria Ag 05FK40 (SDFK40), a three-band RDT detecting Plasmodium falciparum-specific parasite lactate dehydrogenase...Full Text Available

60
 
 
 
 
61

The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth  

UK PubMed Central (United Kingdom)

The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available

2007-03-01

62

Synergistic epigenetic reactivation of estrogen receptor-? (ER?) by combined green tea polyphenol and histone deacetylase inhibitor in ER?-negative breast cancer cells  

UK PubMed Central (United Kingdom)

BackgroundThe status of estrogen receptor-α (ERα) is critical to the clinical prognosis and therapeutic approach in breast cancer. ERα-negative breast cancer...Full Text Available

63

Structural Chemistry of Human SET Domain Protein Methyltransferases  

Science.gov (United States)

There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.

2011-08-22

64

Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation  

UK PubMed Central (United Kingdom)

The Sin3-histone deacetylase (HDAC) corepressor complex is conserved from yeast to humans. Mammals possess two highly related Sin3 proteins, mSin3A and mSin3B, which serve as scaffolds tethering HDAC...Full Text Available

2008-03-18

65

SWI/SNF and Asf1 Independently Promote Derepression of the DNA Damage Response Genes under Conditions of Replication Stress  

UK PubMed Central (United Kingdom)

The histone chaperone Asf1 and the chromatin remodeler SWI/SNF have been separately implicated in derepression of the DNA damage response (DDR) genes in yeast cells treated with genotoxins that cause...Full Text Available

66

Gene silencing induced by oxidative DNA base damage: association with local decrease of histone H4 acetylation in the promoter region  

UK PubMed Central (United Kingdom)

Oxidized DNA bases, particularly 7,8-dihydro-8-oxoguanine (8-oxoG), are endogenously generated in cells, being a cause of carcinogenic mutations and possibly interfering with gene expression. We found...Full Text Available

2010-07-01

67

A Role for Set1/MLL-Related Components in Epigenetic Regulation of the Caenorhabditis elegans Germ Line  

UK PubMed Central (United Kingdom)

The methylation of lysine 4 of Histone H3 (H3K4me) is an important component of epigenetic regulation. H3K4 methylation is a consequence of transcriptional activity, but also has been shown to contribute...Full Text Available

2011-03-01

68

Long non-coding RNAs in nervous system function and disease  

British Library Electronic Table of Contents (United Kingdom)

Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases. Epigenetic mechanisms involve chromatin remodeling by relatively generic complexes that catalyze DNA methylation and various types of histone modifications. There is increasing evidence that these complexes are directed to their sites of action by long non-protein-coding RNAs (lncRNAs), of which there are tens if not hundreds of thousands speci...

2010-01-01

69

ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome  

Energy Technology Data Exchange (ETDEWEB)

ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at ...

2011-07-19

70

Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae  

British Library Electronic Table of Contents (United Kingdom)

Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25mg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=...

2007-01-01

71

Anti-plasmodial activity and toxicity of extracts of plants used in traditional malaria therapy in Meru and Kilifi Districts of Kenya  

British Library Electronic Table of Contents (United Kingdom)

The methanol and aqueous extracts of 10 plant species (Acacia nilotica, Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii, Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro anti-plasmodial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of the methanol extracts were toxic to the brine shrimp (LD5050N. macrocalyx had the highest toxicity to brine shrimp nauplii (LD50 21.04+-1.8mg/ml). Methanol extracts of the rest of the plants exhibited mild or no brine shrimp toxicity (LD50>50mg/ml). The aqueo...

2006-01-01

72

Molecular marks for epigenetic identification of developmental and cancer stem cells  

British Library Electronic Table of Contents (United Kingdom)

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, na...

2011-01-01

73

Hepatitis C virus core upregulates the methylation status of the RASSF1A promoter through regulation of SMYD3 in hilar cholangiocarcinoma cells  

British Library Electronic Table of Contents (United Kingdom)

Increasing evidence has been accumulated indicating the important role of epigenetic regulation in tumor genesis. Previously, we observed that the transfection of hepatitis C virus core (HCVc) protein led to malignant transformation in normal biliary cells, and that tumor suppressor gene RASSF1A was downregulated in many hilar cholangiocarcinoma patients by hypermethylation in the promoter region. In the present study, we found SET and MYND domain-containing protein 3 (SMYD3), a novel histone methyltransferase, was overexpressed in cholangiocarcinoma patients especially in those with HCV infection. Transfection of HCVc into hilar cholangiocarcinoma cell lines QBC939 and FRH0201 could upregulate the expression of SMYD3 and promote cell growth, which was consistent with the results of our cl...

2011-01-01

74

Accumulation, Activity and Localization of Cell Cycle Regulatory Proteins and the Chloroplast Division Protein FtsZ in the Alga Scenedesmus quadricauda under Inhibition of Nuclear DNA Replication  

British Library Electronic Table of Contents (United Kingdom)

Synchronized cultures of the green alga Scenedesmus quadricauda were grown in the absence (untreated cultures) or in the presence (FdUrd-treated cultures) of 5-fluorodeoxyuridine, the specific inhibitor of nuclear DNA replication. The attainment of commitment points, at which the cells become committed to nuclear DNA replication, mitosis and cellular division, and the course of committed processes themselves were determined for cell cycle characterization. FdUrd-treated cultures showed nearly unaffected growth and attainment of the commitment points, while DNA replication(s), nuclear division(s) and protoplast fission(s) were blocked. Interestingly, the FdUrd-treated cells possessed a very high mitotic histone H1 kinase activity in the absence of any nuclear division(s). Compared with the ...

2008-01-01

75

Epigenomic disruption: the effects of early developmental exposures.  

Science.gov (United States)

Through DNA methylation, histone modifications, and small regulatory RNAs the epigenome systematically controls gene expression during development, both in utero and throughout life. The epigenome is also a very reactive system; its labile nature allows it to sense and respond to environmental perturbations to ensure survival during fetal growth. This pliability can lead to aberrant epigenetic modifications that persist into later life and induce numerous disease states. Endocrine-disrupting compounds (EDCs) are ubiquitous chemicals that interfere with growth and development. Several EDCs also interfere with epigenetic programming. The investigation of the epigenotoxic effects of bisphenol A (BPA), an EDC used in the production of plastics and resins, has further raised concern over the impact of EDCs on the epigenome. Using the Agouti viable yellow (A(vy)) mouse model, dietary BPA exposure was shown to hypomethylate both the A(vy) and the Cabp(IAP) metastable ...

2010-10-01

76

Enhanced MALDI-TOF MS Analysis of Phosphopeptides Using an Optimized DHAP/DAHC Matrix  

Science.gov (United States)

Selecting an appropriate matrix solution is one of the most effective means of increasing the ionization efficiency of phosphopeptides in matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In this study, we systematically assessed matrix combinations of 2, 6-dihydroxyacetophenone (DHAP) and diammonium hydrogen citrate (DAHC), and demonstrated that the low ratio DHAP/DAHC matrix was more effective in enhancing the ionization of phosphopeptides. Low femtomole level of phosphopeptides from the tryptic digests of ?-casein and ?-casein was readily detected by MALDI-TOF-MS in both positive and negative ion mode without desalination or phosphopeptide enrichment. Compared with the DHB/PA matrix, the optimized DHAP/DAHC matrix yielded superior sample homogeneity and higher phosphopeptide measurement sensitivity, particularly when multiple phosphorylated peptides were assessed. Finally, the DHAP/DAHC matrix was applied to identify phosphorylation sites ...

2010-01-01

77

Structure, Function, and Evolution of Rice Centromeres  

Energy Technology Data Exchange (ETDEWEB)

The centromere is the most characteristic landmark of eukaryotic chromosomes. Centromeres function as the site for kinetochore assembly and spindle attachment, allowing for the faithful pairing and segregation of sister chromatids during cell division. Characterization of centromeric DNA is not only essential to understand the structure and organization of plant genomes, but it is also a critical step in the development of plant artificial chromosomes. The centromeres of most model eukaryotic species, consist predominantly of long arrays of satellite DNA. Determining the precise DNA boundary of a centromere has proven to be a difficult task in multicellular eukaryotes. We have successfully cloned and sequenced the centromere of rice chromosome 8 (Cen8), representing the first fully sequenced centromere from any multicellular eukaryotes. The functional core of Cen8 spans ~800 kb of DNA, which was determined by chromatin immunoprecipitation (ChIP) using an antibody against the rice ...

2010-02-04

78

DNA damage intensity in fibroblasts in a 3-dimensional collagen matrix correlates with the Bragg curve energy distribution of a high LET particle  

International Nuclear Information System (INIS)

The DNA double-strand break (DSB) damage response induced by high energy charged particles on lung fibroblast cells embedded in a 3-dimensional (3-D) collagen tissue equivalents was investigated using antibodies to the DNA damage response proteins gamma-histone 2AX (#gamma#-H2AX) and phosphorylated DNA-PKcs (p-DNA-PKcs). 3-D tissue equivalents were irradiated in positions across the linear distribution of the Bragg curve profiles of 307.7 MeV/nucleon, 556.9 MeV/nucleon, or 967.0 MeV/nucleon "5"6Fe ions at a dose of 0.30 Gy. Patterns of discrete DNA damage streaks across nuclei or saturated nuclear damage were observed, with saturated nuclear damage being more predominant as samples were positioned closer to the physical Bragg peak. Quantification of the DNA damage signal intensities at each distance for each of the examined energies revealed a biological Bragg curve profile with a pattern of DNA damage intensity similar to the physical Bragg curve for the ...

2010-03-01

79

Antimalarial activity of selected Sudanese medicinal plants with emphasis to Maytenus senegalensis  

International Nuclear Information System (INIS)

The aim of the present study is to identify and characterize the antimalrial agents from traitional Sudanese medicinal plants. 49 plants parts representing 26 species from 15 families were extracted and screened for their in vitro antimalrial activity using P. falciparum strain 3D7 which is chloroquine sensitive and Dd2 strain which is chloroquine resistant and pyrimethamine sensitive.The plant species investigated exhibited diverse botanical families. They includes Annonaceae, Aristolochiaceae, Asteraceae, Balantiaceae, Caesalpiniceae, Celasteraceae, Cucurbitaceae, Fabaceae, Graminae, Meliaceae, Myrtaceae, Polygonaceae, Rubiaceae, Rutaceae, and simaroubaceae. The evaluation of these plants for their antimalarial activity and their effect on lymphocyte proliferation was carried out. 57 extracts were tested on the chloroquine sensitive strain (3D7). Where 34 extracts (59%) exhibited significant activity against 3D7 with IC_5_0 values #100 #mu# g/ml), where as ...

80

Local chromatin structure of heterochromatin regulates repeatedDNA stability, nucleolus structure, and genome integrity  

Energy Technology Data Exchange (ETDEWEB)

Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project ...

2007-05-05

 
 
 
 
81

Title of paper: the induction of P-53 independent programmed cell death (apoptosis) with ionizing radiation and 5-fluorouracil (5-FU) in the HT-29 human colon carcinoma cell line  

International Nuclear Information System (INIS)

Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant apoptotic response in cells that have mutated p53 alleles. Materials and Methods: HT-29 cells were assessed for clonogenic survival after being plated at ...

1996-09-01