WorldWideScience
1

Detection of Ockelbo virus RNA in skin biopsies by polymerase chain reaction.  

UK PubMed Central (United Kingdom)

A sensitive assay based on the polymerase chain reaction for the detection of Ockelbo virus RNA was developed. Two primer pairs from the gene coding for the E2 glycoprotein were chosen. By use of a...Full Text Available

1993-08-01

2

Heparin binding sites on Ross River virus revealed by electron cryo-microscopy  

International Nuclear Information System (INIS)

Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition ...

2005-02-20

3

E2f binding-deficient Rb1 protein suppresses prostate tumor progression in vivo  

UK PubMed Central (United Kingdom)

Mutational inactivation of the RB1 tumor suppressor gene initiates retinoblastoma and other human cancers. RB1 protein (pRb) restrains cell proliferation by binding...Full Text Available

2011-01-11

4

Identification, characterization, and chromosomal localization of the human homolog (hES) of ES/130  

Energy Technology Data Exchange (ETDEWEB)

The chicken extracellular matrix glycoprotein ES/130 is necessary for epithelial-mesenchymal transformation in the developing hear and is also expressed in noncardiac chicken tissues such as limb and notochord. We have identified hES, the human homology of chicken ES/130. Fluorescence in situ hybridization analysis (FISH) localizes hES to human chromosome 20p11.2-p12. FISH analyses of individuals with 20p12 deletions and affected by Alagille syndrome exclude hES as a candidate gene for this disorder. Reverse transcriptase-polymerase chain reaction studies reveal that hES is expressed in both fetal and adult human tissues and that hES expression in the left ventricle is increased in the failing adult heart. Further studies will evaluate how hES mutations may relate to congenital human cardiac and skeletal anomalies as well as cardiac remodeling in the adult. 16 refs., 2 figs.

1996-08-01

5

The LW blood group glycoprotein is homologous to intercellular adhesion molecules.  

UK PubMed Central (United Kingdom)

The LW blood group antigens reside on a 42-kDa erythrocyte membrane glycoprotein that was purified by immunoaffinity and partially sequenced. From this information, a specific PCR-amplified DNA fragment...Full Text Available

1994-06-07

6

Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae  

UK PubMed Central (United Kingdom)

BackgroundThe expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations...Full Text Available

7

Oligodendrocyte-Myelin Glycoprotein and Nogo Negatively Regulate Activity-Dependent Synaptic Plasticity  

UK PubMed Central (United Kingdom)

In the adult mammalian CNS, the growth inhibitors oligodendrocyte-myelin glycoprotein (OMgp) and the reticulon RTN4 (Nogo) are broadly expressed in oligodendrocytes and neurons. Nogo and OMgp...Full Text Available

2010-09-15

8

Myelin associated glycoprotein cross-linking triggers its partitioning into lipid rafts, specific signaling events and cytoskeletal rearrangements in oligodendrocytes  

UK PubMed Central (United Kingdom)

Myelin-associated glycoprotein (MAG) has been implicated in inhibition of nerve regeneration in the CNS. This results from interactions between MAG and the Nogo receptor and gangliosides on...Full Text Available

2004-02-01

9

Microglial Fc Receptors Mediate Physiological Changes Resulting From Antibody Cross-Linking of Myelin Oligodendrocyte Glycoprotein  

UK PubMed Central (United Kingdom)

Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented...Full Text Available

2008-05-30

10

Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols  

UK PubMed Central (United Kingdom)

BackgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence...Full Text Available

11

Detection of glycoproteins in the Acanthamoeba plasma membrane  

International Nuclear Information System (INIS)

In the present study the authors have shown that glycoproteins are present in the plasma membrane of Acanthamoeba castellanii by utilizing different radioactive labeling techniques. Plasma membrane proteins in the amoeba were iodinated by "1"2"5I-lactoperoxidase labeling and the solubilized radiolabeled glycoproteins were separated by lectin-Sepharose affinity chromatography followed by polyacrylamide gel electrophoresis. The periodate/NaB"3H_4 and galactose oxidase/NaB"3H_4 labeling techniques were used for labeling of surface carbohydrates in the amoeba. Several surface-labeled glycoproteins were observed in addition to a diffusely labeled region with M_r of 55,000-75,000 seen on electrophoresis, which could represent glycolipids. The presence of glycoproteins in the plasma membrane of Acanthamoeba castellanii was confirmed by metabolic labeling with ["3"5S]methionine followed by lectin-Sepharose ...

14

Introducing N-glycans into natural products through a chemoenzymatic approach**  

UK PubMed Central (United Kingdom)

The present study describes an efficient chemoenzymatic method for introducing a core N-glycan of glycoprotein origin into various lipophilic natural products. It was found...Full Text Available

2008-11-24

15

Carbohydrate-specified endocytosis: localization of ligand in the lysosomal compartment.  

UK PubMed Central (United Kingdom)

Carbohydrate-directed endocytosis is mediated by a receptor, the hepatic binding protein; it is responsible for the clearance of galactose-terminated glycoproteins from the circulation. This process...Full Text Available

1981-11-01

16

Use of platelet glycoprotein IIb/IIIa inhibitors in diabetics undergoing PCI for non-ST-segment elevation acute coronary syndromes: impact of clinical status and procedural characteristics  

UK PubMed Central (United Kingdom)

BackgroundThe most recent ESC guidelines for percutaneous coronary intervention (PCI) recommend the use of glycoprotein IIb/IIIa inhibitors (GPI) in high risk patients with non-ST-segment...Full Text Available

2010-06-01

17

Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects.  

UK PubMed Central (United Kingdom)

The IgG response to gp41 (envelope glycoprotein of Mr 41,000) of the human immunodeficiency virus (HIV) was studied with eight synthetic peptides derived from three different regions of the protein....Full Text Available

1988-07-01

18

A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins  

UK PubMed Central (United Kingdom)

The Yellow Fever Vaccine 17D (YFV17D) has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) resulting in construction of YFV17D/LASV-GPC recombinant virus. The virus...Full Text Available

2006-02-20

19

Mutation breeding in kalmia juvenile trees derived from shoot tip cultare and kobus seedlings  

International Nuclear Information System (INIS)

Juvenile trees of kalmia derived from shoot tip culture, and seedlings of kobus were irradiated with #gamma#-rays. In kalmia, two mutation lines were obtained which had narrowlong leaves. In kobus two mutation lines were obtained. One mutation line has flowers with 7 to 13 petals. Another mutation line has yellow-green variegated leaves. (author).

20

Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients  

UK PubMed Central (United Kingdom)

BackgroundFamilial Adenomatous Polyposis (FAP) is caused by germline mutations in the APC (Adenomatous Polyposis Coli) gene. The vast majority of APC mutations...Full Text Available

21

Homozygous SLC2A9 Mutations Cause Severe Renal Hypouricemia  

UK PubMed Central (United Kingdom)

Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied...Full Text Available

2010-01-01

22

mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese  

British Library Electronic Table of Contents (United Kingdom)

Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search ...

2006-01-01

23

The early phase change Gene in Maize  

UK PubMed Central (United Kingdom)

Recessive mutations of the early phase change (epc) gene in maize affect several aspects of plant development. These mutations were identified initially because of...Full Text Available

2002-01-01

24

Cloning of the neurodegeneration gene drop-dead and characterization of additional phenotypes of its mutation  

UK PubMed Central (United Kingdom)

Mutations in the Drosophila gene drop-dead (drd) result in early adult lethality and neurodegeneration, but the molecular identity of the drd...Full Text Available

2008-01-01

25

A framework for evolutionary systems biology  

UK PubMed Central (United Kingdom)

BackgroundMany difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often...Full Text Available

26

Wnt3a Induces Myofibroblast Differentiation by Upregulating TGF-? Signaling Through SMAD2 in a ?-Catenin-Dependent Manner  

UK PubMed Central (United Kingdom)

Growing evidence suggests the Wnt family of secreted glycoproteins and their associated signaling pathways, linked to development, are recapitulated during wound repair and regeneration events. However,...Full Text Available

27

Variant influenza virus hemagglutinin that induces fusion at elevated pH.  

UK PubMed Central (United Kingdom)

The hemagglutinin (HA) glycoprotein of influenza virus performs two critical roles during infection: it binds virus to cell surface sialic acids, and under mildly acidic conditions it induces fusion...Full Text Available

1986-02-01

28

The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria.  

UK PubMed Central (United Kingdom)

Angiokeratoma corporis diffusum with glycopeptiduria is a recently recognized inborn error of glycoprotein catabolism resulting from the deficient activity of human alpha-N-acetylgalactosaminidase (E.C....Full Text Available

1994-08-01

29

Serum protein binding and the role of increased alpha 1-acid glycoprotein in moderately obese male subjects.  

UK PubMed Central (United Kingdom)

Serum protein and lipid concentrations as well as the serum protein binding of propranolol, diazepam and phenytoin were measured in normal weight and obese volunteers. Concentrations of alpha 1-acid...Full Text Available

1984-12-01

30

Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat  

UK PubMed Central (United Kingdom)

BackgroundThe dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin...Full Text Available

31

Peptides of human bronchial mucus glycoproteins. Size determination by electron microscopy and by biosynthetic experiments.  

UK PubMed Central (United Kingdom)

Secreted human bronchial mucins, directly collected from macroscopically healthy bronchial mucosa, were prepared in the presence of six proteinase inhibitors, and analysed by electron microscopy. These...Full Text Available

1987-11-15

32

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA  

UK PubMed Central (United Kingdom)

BackgroundAurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently...Full Text Available

33

Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines  

UK PubMed Central (United Kingdom)

BackgroundCD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers....Full Text Available

34

Mechanism of action of an inhibitor of complement-mediated prevention of immune precipitation.  

UK PubMed Central (United Kingdom)

Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients...Full Text Available

1990-06-01

35

Localisation of glycoproteins and glycosaminoglycans during early eye development in the macaque.  

UK PubMed Central (United Kingdom)

The composition of the extracellular matrix (ECM) was examined in the developing lens and optic cup (stages 11-16) of the long-tailed monkey (Macaca fascicularis) using peroxidase immunocytochemistry....Full Text Available

1995-02-01

36

Exercise Decreases Myelin-Associated Glycoprotein Expression in the Spinal Cord and Positively Modulates Neuronal Growth  

UK PubMed Central (United Kingdom)

To successfully grow, neurons need to overcome the effects of hostile environments, such as the inhibitory action of myelin. We have evaluated the potential of exercise to overcome the intrinsic...Full Text Available

2007-07-01

37

Determination of antibody response to influenza virus surface glycoproteins by kinetic enzyme-linked immunosorbent assay.  

UK PubMed Central (United Kingdom)

We modified an existing enzyme-linked immunosorbent assay (ELISA) to be able to use new spectrophotometers which can measure the rate of color development in microtiter wells. This new kinetic-based...Full Text Available

1988-10-01

38

Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV.  

UK PubMed Central (United Kingdom)

The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available

1991-12-01

39

Albumin interacts specifically with a 60-kDa microvascular endothelial glycoprotein.  

UK PubMed Central (United Kingdom)

Confluent monolayers of microvascular endothelial cells, derived from the rat epididymal fat pad and grown in culture, were radioiodinated by using the lactoper-oxidase method. Their radioiodinated...Full Text Available

1988-09-01

40

Aggregation Substance Promotes Adherence, Phagocytosis, and Intracellular Survival of Enterococcus faecalis within Human Macrophages and Suppresses Respiratory Burst  

UK PubMed Central (United Kingdom)

The aggregation substance (AS) of Enterococcus faecalis, encoded on sex pheromone plasmids, is a surface-bound glycoprotein that mediates aggregation between bacteria thereby facilitating...Full Text Available

2000-09-01

41

Abciximab: a reappraisal of its use in coronary care  

UK PubMed Central (United Kingdom)

Platelet reactivity plays a pivotal role in the pathogenesis of ischemic adverse events during and after acute coronary syndromes (ACS), and percutaneous coronary intervention (PCI). Glycoprotein (GP)...Full Text Available

2008-03-01

42

The development of in vitro mutagenicity testing systems using T-lymphocytes  

Energy Technology Data Exchange (ETDEWEB)

This annual report describes progress in studies on hprt mutations induced by radon or Indium 111 along with the corresponding mutation frequency, cloning and molecular spectra in human T-lymphocytes. Parallel studies on the mutation susceptibility between individuals is being investigated by hprt mutation studies on ataxia telangiectasia and xeroderma pigmentosum.

1993-05-01

44

Mutation breeding in leguminous crop plants  

Energy Technology Data Exchange (ETDEWEB)

Since it was introduced in the early 1940's, mutation breeding has been tested on many crops as modern plant breeding. Until now, more than seven hundred varieties have been developed by means of induced mutation, and many of them officially released and approved for registration. Hundreds of papers report the results of mutation breeding, and the characteristics of induced mutation in different kinds of crops were discussed for review purposes (Blixt and Gottschalk 1975, Gottschalk and Wolff 1983). Considering the results already obtained, it can be concluded that the kinds of induced mutation and their utilization vary from crop to crop. This paper summarizes and discusses the mutation characteristics and kinds on the induced mutants of leguminous plants that have been released.

1988-03-01

45

Induced plasmon mutations affecting the growth habit of peanuts, A. hypogaea L  

International Nuclear Information System (INIS)

The effectiveness of the acridines ethidium bromide (EB) and acriflavine in inducing plasmon mutations was compared with the alkylating agents ethyl methanesulphonate (EMS) and diethyl sulphate and to #gamma#-rays. The growth habit (trailing versus bunch) of peanuts (A. hypogaea), controlled by genic-cytoplasmic interactions, was utilized. Breeding tests distinguishing nuclear from plasmon mutations were developed and are described in detail. Plasmon mutations were induced, but there were differences in mutation yields between the cultivars and the mutagens. (Auth.).

1978-01-01

46

Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter.  

UK PubMed Central (United Kingdom)

The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance....Full Text Available

1994-10-01

47

X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis.  

UK PubMed Central (United Kingdom)

In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations...Full Text Available

1993-09-01

48

Tumor-derived extracellular mutations of PTPRT/PTP? are deficient in cell adhesion  

UK PubMed Central (United Kingdom)

Receptor protein tyrosine phosphatase T (PTPRT/PTPρ) is frequently mutated in human cancers including colon, lung, gastric and skin cancers. More than half of the identified tumor-derived...Full Text Available

2008-07-01

49

Transcription induces strand-specific mutations at the 5? end of human genes  

UK PubMed Central (United Kingdom)

A regional analysis of nucleotide substitution rates along human genes and their flanking regions allows us to quantify the effect of mutational mechanisms associated with transcription in germ line...Full Text Available

2008-08-01

50

Rapid detection of epidermal growth factor receptor mutations with multiplex PCR and primer extension in lung cancer  

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available

51

Ocular manifestations of branchio-oculo-facial syndrome: Report of a novel mutation and review of the literature  

UK PubMed Central (United Kingdom)

PurposeTo report unusual ocular manifestations of branchio-oculo-facial syndrome (BOFS) caused by a novel mutation in activating enhancer binding protein 2 alpha (TFAP2A).MethodsFull...Full Text Available

52

Mutational analysis of bacteriophage lambda lysis gene S.  

UK PubMed Central (United Kingdom)

A plasmid carrying the bacteriophage lambda lysis genes under lac control was subjected to hydroxylamine mutagenesis, and mutations eliminating the host lethality of the S gene were selected. DNA sequence...Full Text Available

1986-09-01

53

Mutation analysis of the ferritin L-chain gene in age-related cataract  

UK PubMed Central (United Kingdom)

PurposeTo investigate whether acquired somatic mutations in the iron response element of the ferritin L-chain gene account for the age-related cataract.MethodsThe...Full Text Available

54

Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray  

UK PubMed Central (United Kingdom)

PurposeRetinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations...Full Text Available

55

Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo  

UK PubMed Central (United Kingdom)

Activation-induced cytidine deaminase (AID) protein initiates Ig gene mutation by deaminating cytosines, converting them into uracils. Excision of AID-induced uracils by uracil-N-glycosylase...Full Text Available

2010-12-01

56

Detection of TP53 mutation, loss of heterozygosity and DNA content in fine-needle aspirates of breast carcinoma.  

UK PubMed Central (United Kingdom)

Recent preclinical and clinical data suggest that TP53 status and TP53 mutations may be important in determining tumour aggressiveness and therapy response. In this study we investigate the feasibility...Full Text Available

1998-01-01

57

Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations  

UK PubMed Central (United Kingdom)

Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase...Full Text Available

2011-01-04

58

Comprehensive SNP-chip for retinitis pigmentosa-Leber congenital amaurosis diagnosis: new mutations and detection of mutational founder effects  

UK PubMed Central (United Kingdom)

Fast and efficient high-throughput techniques are essential for the molecular diagnosis of highly heterogeneous hereditary diseases, such as retinitis pigmentosa (RP). We had previously approached RP...Full Text Available

2010-01-01

59

CYP1B1 mutations in Spanish patients with primary congenital glaucoma: phenotypic and functional variability  

UK PubMed Central (United Kingdom)

PurposeTo analyze the contributions of cytochrome P4501B1 (CYP1B1) mutations to primary congenital glaucoma (PCG) in Spanish patients.MethodsWe...Full Text Available

60

Analysis of forward mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in the bacteriophage P22 mnt repressor gene  

Energy Technology Data Exchange (ETDEWEB)

We describe the isolation and genetic characterization of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutations in the phage P22 mnt repressor gene cloned in plasmid pBR322. Mutations in the mnt repressor gene or its operator on this plasmid, pPY98, confer a tetracycline resistance phenotype, whereas the wild-type plasmid confers tetracycline sensitivity. Cells carrying pPY98 were briefly exposed to MNNG to give 20 to 40% survival and a 50- to 100-fold increase in tetracycline-resistant cells. DNA sequence analysis showed that 29 to 30 MNNG-induced mutations were GC-to-AT transitions and one was an AT-to-GC transition. About 80% of the mutations are in three hotspots. This mutation spectrum is consistent with the proposed mechanism of mutagenic action of MNNG, which involves mispairing of an alkylated base, O/sup 6/-methylguanine. The mnt gene may be a useful target ...

1986-04-01

61

A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations  

UK PubMed Central (United Kingdom)

BackgroundSLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 cause...Full Text Available

62

A novel custom high density-comparative genomic hybridization array detects common rearrangements as well as deep intronic mutations in dystrophinopathies  

UK PubMed Central (United Kingdom)

BackgroundThe commonest pathogenic DMD changes are intragenic deletions/duplications which make up to 78% of all cases and point mutations (roughly 20%) detectable...Full Text Available

63

A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells  

UK PubMed Central (United Kingdom)

Frontotemporal lobar degeneration is a progressive neurodegenerative syndrome that is the second most common cause of early-onset dementia. Mutations in the progranulin gene are a major cause of familial...Full Text Available

2011-03-15

64

A cytosine methyltransferase homologue is essential for repeat-induced point mutation in Neurospora crassa  

UK PubMed Central (United Kingdom)

During sexual development, Neurospora crassa inactivates genes in duplicated DNA segments by a hypermutation process, repeat-induced point mutation (RIP). RIP introduces C:G to T:A...Full Text Available

2002-06-25

65

Intravaginal immunization using the recombinant HIV-1 clade-C trimeric envelope glycoprotein CN54gp140 formulated within lyophilized solid dosage forms  

British Library Electronic Table of Contents (United Kingdom)

Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunize...

2011-01-01

66

Detection of Mitochondrial DNA Mutations in Mammary ...  

Science.gov (United States)

... Loss of Heterozygosity in Normal Breast Epithelial Tissue and Benign Breast Lesions in BRCA1/2 Carriers with Breast Cancer. ...

2004-09-01

67

Occurrence of mutations in the epidermal growth factor receptor gene in X-ray-induced rat lung tumors  

International Nuclear Information System (INIS)

Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, ...

2008-02-01

68

Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias  

UK PubMed Central (United Kingdom)

BackgroundGene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.MethodsWe...Full Text Available

69

Vitamin C and a-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats  

British Library Electronic Table of Contents (United Kingdom)

The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated with 17b-estradiol (E2), the antioxidant vitamin C, the estrogen metabolic inhibitor a-naphthoflavone (ANF), or cotreated with E2 + vitamin C or E2 + ANF for up to 8 months. E2 (3 mg) was administered as an subcutaneous implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking water. At necropsy, breast tumor incidence in the E2, E2 + vitamin C and E2 + ANF groups was 82, 29 and 0%, ...

2009-01-01

70

Light-dependent regulation of DEL1 is determined by the antagonistic action of E2Fb and E2Fc.  

Science.gov (United States)

Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single ...

2011-09-01

71

HPV16 E2 could act as down-regulator in cellular genes implicated in apoptosis, proliferation and cell differentiation  

UK PubMed Central (United Kingdom)

BackgroundHuman Papillomavirus (HPV) E2 plays several important roles in the viral cycle, including the transcriptional regulation of the oncogenes E6 and E7, the regulation of the...Full Text Available

72

Package Enhancement Study for the 120-mm M831E2 ...  

Science.gov (United States)

... Descriptors : *AMMUNITION, *CONTAINERS, *CARTRIDGES, *COMBUSTIBLE CARTRIDGE CASES, *CARTRIDGE CASES, *ANTITANK ...

1992-07-01

73

8"+ isomers in N=48 isotones and E2 polarization charges  

International Nuclear Information System (INIS)

... charges energy levels gamma spectra half-life isomeric nuclei kev range

1972-05-01

74

Unusual heterogeneity of the 5'-termini of human adenovirus type 2 early region E2 mRNA.  

UK PubMed Central (United Kingdom)

The 5'-terminal structures of human adenovirus type 2 (Ad2) early region 2 (E2) mRNA were investigated. The E2 transcription unit has several interesting properties, including the presence of a TATA-like...Full Text Available

1984-12-11

75

KMeyeDB: a graphical database of mutations in genes that cause eye diseases  

British Library Electronic Table of Contents (United Kingdom)

KMeyeDB () is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser wi...

2010-01-01

76

Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH  

UK PubMed Central (United Kingdom)

BackgroundThe pre-fusion form of the herpes simplex virus (HSV) fusion protein gB undergoes pH-triggered conformational change in vitro and during viral entry (Dollery...Full Text Available

77

Near-Infrared Fluorescence Labeled Anti-TAG-72 Monoclonal Antibodies for Tumor Imaging in Colorectal Cancer Xenograft Mice  

UK PubMed Central (United Kingdom)

Anti-TAG-72 monoclonal antibodies target the tumor-associated glycoprotein (TAG)-72 in various solid tumors. This study evaluated the use of anti-TAG-72 monoclonal antibodies, both murine CC49...Full Text Available

2009-01-01

78

Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy.  

UK PubMed Central (United Kingdom)

33 patients with advanced malignant melanoma were studied after intravenous administration of 131I-labeled Fab fragments specific for p97, an oncofetal glycoprotein of human melanoma. In all, 47 gamma...Full Text Available

1983-12-01

79

Large T1 oligonucleotides of Moloney leukemia virus missing in an env gene recombinant, HIX, are present on an intracellular 21S Moloney viral RNA species.  

UK PubMed Central (United Kingdom)

HIX, a recombinant derived from Moloney leukemia virus, has an envelope glycoprotein different from that of the Moloney virus. HIX and Moloney viruses share the majority of the large T1 oligonucleotides...Full Text Available

1978-06-01

80

Ewing's sarcoma of the sacrum  

International Nuclear Information System (INIS)

A lytic lesion with softtissue extension in the sacrum of a 47-year old man was needle-biopsied under computed tomographic (CT) guidance using an 18-gauge cutting needle. The cytologic appearance of the lesion and immunohistochemical staining were diagnostic of Ewing's sarcoma. Specifically, a new marker (O13) for the presence of glycoprotein p30/32 mic2 in Ewing's sarcoma was utilized. (orig.).

81

Developmentally regulated expression of a 78 kDa erythroblast membrane glycoprotein immunologically related to the platelet thrombospondin receptor.  

UK PubMed Central (United Kingdom)

We have previously described a monoclonal antibody (FA6-152), obtained by immunizing mice with fetal human erythrocytes [Edelman, Vinci, Villeval, Vainchenker, Henri, Miglierina, Rouger, Reviron, Breton-Gorius,...Full Text Available

1989-09-15

82

Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): common relationship to diminished cell adherence.  

UK PubMed Central (United Kingdom)

Investigations of polymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation, and a severe defect of PMN chemotaxis....Full Text Available

1984-08-01

83

Aarskog-Scott syndrome: Clinical update and report of nine novel mutations of the FGD1 gene  

DEFF Research Database (Denmark)

Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice ...

2010-01-01

85

Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A  

British Library Electronic Table of Contents (United Kingdom)

The penetrance of Lebers hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (Pin vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a seconda...

2008-01-01

86

State II Dissociation Element Formation Following Activator Excision in Maize  

UK PubMed Central (United Kingdom)

Active Activator (Ac) elements undergo mutations to become nonautonomous Dissociation (Ds) elements at a low frequency. To understand...Full Text Available

2007-10-01

87

Some ABCA3 mutations elevate ER stress and initiate apoptosis of lung epithelial cells  

UK PubMed Central (United Kingdom)

BackgroundABCA3 transporter (ATP-binding cassette transporter of the A subfamily) is localized to the limiting...Full Text Available

2011-01-01

88

Ras history  

UK PubMed Central (United Kingdom)

Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an...Full Text Available

2010-07-01

89

Prosthetic rehabilitation of hypophosphatasia: a case report  

UK PubMed Central (United Kingdom)

Hypophosphatasia is a congenital disease characterized by deficiency of serum and tissue non-specific alkaline phosphatase activity. The disease occurs due to mutations in the liver/bone/kidney alkaline...Full Text Available

90

N-acetoxy-N-2-acetylaminofluorene induced frameshift mutations: a comparison between the DNA modification spectrum and the mutation spectrum  

International Nuclear Information System (INIS)

We describe the analysis of forward mutations induced in the tetracycline resistance gene of the plasmid pBR322 by directing the reaction of the carcinogen N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF) to a small restriction fragment (BamHI, SalI) that is located in the proximal part of the antibiotic-resistance gene. Mutant plasmids obtained both in wild type and excision repair deficient (uvrA) bacterial cells are compared. Preliminary data showing the distribution of the -AAF adducts along this restriction fragments are discussed in relation to the observed spectrum of mutations. 20 references, 4 figures.

91

Mutations in RNA Binding Protein Gene Cause Familial Dilated Cardiomyopathy  

UK PubMed Central (United Kingdom)

ObjectivesWe sought to identify a novel gene for dilated cardiomyopathy (DCM).BackgroundDCM is a heritable, genetically...Full Text Available

2009-09-01

93

Misfolded Proteins and Retinal Dystrophies  

UK PubMed Central (United Kingdom)

Many mutations associated with retinal degeneration lead to the production of misfolded proteins by cells of the retina. Emerging evidence suggests that these abnormal proteins cause cell death...Full Text Available

2010-01-01

94

MEDICAL FINAL REVIEW MEMORANDUM OF ORIGINAL BLA  

Science.gov (United States)

... The AAT Z mutation involves a single amino acid substitution (glutamine for lysine) at position 342, resulting in abnormal folding and polymerization of the ...

95

Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism.  

Science.gov (United States)

Objective:? Primary hyperparathyroidism (HPT) is characterised by autonomous secretion of PTH from enlarged parathyroid glands leading, in most patients, to asymptomatic hypercalcaemia. Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder caused by inactivating mutations in the calcium sensing receptor (CaSR) gene; it is characterised by lifelong and usually asymptomatic hypercalcaemia. Establishing the correct diagnosis is important because surgery can be curative in HPT, but ineffective in FHH. There is overlap in the diagnostic criteria for the two disorders and some patients carrying inactivating mutations in the CaSR gene, which is suggestive of FHH, also have HPT with hyperplastic parathyroid glands or adenomas. Design and Patients:? CaSR gene mutations were analyzed and clinical and biochemical parameters evaluated in 139 consecutive out-patients presenting with hypercalcaemia and suspected ...

2011-03-29

96

Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA  

Energy Technology Data Exchange (ETDEWEB)

The Lesch-Nyhan (LN) syndrome is a severe X chromosome-linked disease that results from a deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). The mutations leading to the disease are heterogeneous and frequently arise as de novo events. The authors have identified nucleotide alterations in 15 independently arising HPRT-deficiency cases by direct DNA sequencing of in vitro amplified HPRT cDNA. They also demonstrate that the direct DNA sequence analysis can be automated, further simplifying the detection of new mutations at this locus. The mutations include DNA base substitutions, small DNA deletions, a single DNA base insertion, and errors in RNA splicing. The application of these procedures allows DNA diagnosis and carrier identification by the direct detection of the mutant alleles within individual families affected by LN.

1989-03-01

97

Genomics of human longevity  

UK PubMed Central (United Kingdom)

In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences...Full Text Available

2011-01-12

98

Embryonic Senescence and Laminopathies in a Progeroid Zebrafish Model  

UK PubMed Central (United Kingdom)

BackgroundMutations that disrupt the conversion of prelamin A to mature lamin A cause the rare genetic disorder Hutchinson-Gilford progeria syndrome and a group of laminopathies....Full Text Available

100

Defective gut function in drop-dead mutant Drosophila  

UK PubMed Central (United Kingdom)

Mutation of the gene drop-dead (drd) causes adult Drosophila to die within 2 weeks of eclosion and is associated with reduced rates of defecation...Full Text Available

2009-09-01

101

Cis-regulatory mutations in human disease  

UK PubMed Central (United Kingdom)

Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant...Full Text Available

2009-07-01

102

Abnormal chromosome repair and risk of developing cancer.  

UK PubMed Central (United Kingdom)

Several scientists have proposed that DNA repair deficiencies and the induction of a mutator phenotype are responsible for the generation of multiple mutagenic alterations in cancer cells. I propose...Full Text Available

1993-10-01

103

AEC syndrome - Genetics Home Reference  

Science.gov (United States)

What genes are related to AEC syndrome? AEC syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein known as p63, which plays an...

2011-10-15

104

A child with hyperferritinemia: Case report  

UK PubMed Central (United Kingdom)

Hereditary hyperferritinemia cataract syndrome (HHCS) is a rare condition caused by mutations in the gene coding for the light chain of ferritin; it does not lead to iron overload, but it is associated...Full Text Available

105

Interactions between the chemotherapeutic agent eribulin mesylate (E7389) and P-glycoprotein in CF-1 abcb1a-deficient mice and Caco-2 cells  

British Library Electronic Table of Contents (United Kingdom)

Eribulin is a new anticancer agent currently in Phase III clinical trials for the treatment of metastatic breast cancer. In the current studies, we have investigated the effects of P-glycoprotein (P-gp) on the in vivo disposition of eribulin using CF-1 abcb1a-deficient mice, and the influence of eribulin on P-gp-mediated efflux of digoxin in Caco-2 cells. Eribulin was administered intravenously and orally in both CF-1 wild-type and CF-1 abcb1a-deficient mice. P-gp-mediated efflux of digoxin in Caco-2 cell monolayers was measured in the presence of eribulin. The plasma exposure to eribulin was higher in CF-1 abcb1a-deficient mice than that in CF-1 wild-type mice after intravenous (IV) and oral (PO) administrations. The oral bioavailability of eribulin was 62.3% in CF-1 abcb1a-deficient mice...

2011-01-01

106

Virtual Stove Pipes - NASA  

Science.gov (United States)

Orchestration Layer. Service Delivery . Datacenter. Infrastructure. Systems call API. E2E automated. Automate service-levels. Analyze & ...

107

Spontaneous mutations affecting the host range of the B77 strain of avian sarcoma virus involve type-specific changes in the virion envelope antigen.  

UK PubMed Central (United Kingdom)

Previously it was shown that the host-range gene of the Bratislava strain of avain sarcoma virus (B77 virus) spontaneously mutates with a very high rate. The wild-type B77 virus called B77 virus-II,...Full Text Available

1977-01-01

108

Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression  

UK PubMed Central (United Kingdom)

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations...Full Text Available

109

Mutations induced in the hypoxanthine phosphoribosyl transferase gene by three urban air pollutants: acetaldehyde, benzo[a]pyrene diolepoxide, and ethylene oxide.  

UK PubMed Central (United Kingdom)

Provisional mutational spectra at the hypoxanthine phosphoribosyl transferase (HPRT) locus in vitro have been worked out for acetaldehyde (AA) and benzo[a]pyrene diolepoxide (BPDE) in human (T)-lymphocytes...Full Text Available

1994-10-01

110

Missense mutations in the growth hormone receptor dimerization region in Laron syndrome  

Energy Technology Data Exchange (ETDEWEB)

Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the dimerization domain of the GH receptor. One of ...

1994-09-01

111

Interplay of Reverse Transcriptase Inhibitor Therapy and Gag p6 Diversity in HIV Type 1 Subtype G and CRF02_AG  

UK PubMed Central (United Kingdom)

AbstractThe gag p6 region of HIV-1 has various nonsubstitutionary mutations, including insertions, duplications, deletions, and premature stop codons. Studies have linked gag p6 mutations...Full Text Available

2008-09-01

112

Induction and use of sex linked lethal mutations in the pink bollworm  

International Nuclear Information System (INIS)

The sterile insect release technique can often be improved by removal of females before release. Rearing efficiencies can also be increased if removal of the females occurs at early developmental stages. In order to begin to develop genetic sexing strains for the pink bollworm, Pectinophora gossypiella (Saunders), it was necessary to determine the best dosage of radiation for induction of viable sex linked recessive lethal mutations and to see if stocks containing induced sex linked lethals could be maintained in culture. Sex linked recessive lethal mutations can be detected by distorted sex ratios in the progeny of treated adults. However, in the pink bollworm, highly distorted sex ratios are common even in the absence of induced mutations. Therefore, a visible sex linked trait, purple eye, was used as a marker for the untreated X-chromosomes in crosses. Thus, the presence of a recessive sex linked lethal ...

1987-11-16

113

Homozygosity Mapping Reveals Null Mutations in FAM161A as a Cause of Autosomal-Recessive Retinitis Pigmentosa  

UK PubMed Central (United Kingdom)

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 45 genes. Using homozygosity mapping, we identified a ∼4 Mb homozygous region...Full Text Available

2010-09-10

114

Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals  

International Nuclear Information System (INIS)

Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with ...

115

Effect of UV radiation on the killer phenotype in the wine yeast-saccharomycetes and spontaneous variation of this character  

International Nuclear Information System (INIS)

Spontaneous and ultraviolet-induced changeabilities of wine yeasts from the killer state to sensitive one have been studied. Observed often spontaneous changes of killer and neutral phenotypes under laboratory store conditions as well as high mutation frequency of genetic elements responsible for the killer indication on ultraviolet irradiation testify that often encounterability in nature and in the production of sensitive yeasts is attributed to high frequency of mutation changes of the killer and neutral phenotypes to the sensitive state.

116

Distribution and threshold expression of the tRNA(Lys) mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF).  

UK PubMed Central (United Kingdom)

We investigated the distribution and expression of mutant mtDNAs carrying the A-to-G mutation at position 8344 in the tRNA(Lys) gene in the skeletal muscle of four patients with myoclonus epilepsy and...Full Text Available

1992-12-01

117

Different phenotypes of lattice corneal dystrophy type I in patients with 417C>T (R124C) and 1762A>G (H572R) mutations in TGFBI (BIGH3)  

UK PubMed Central (United Kingdom)

PurposeTo describe clinical data and to characterize mutations in the transforming growth factor beta-induced (TGFBI) gene in patients from three unrelated Chilean...Full Text Available

118

Complementation of areA- regulatory gene mutations of Aspergillus nidulans by the heterologous regulatory gene nit-2 of Neurospora crassa.  

UK PubMed Central (United Kingdom)

Loss-of-function mutations in the regulatory gene areA of Aspergillus nidulans prevent the utilization of a wide variety of nitrogen sources. The phenotypes of nit-2 mutants of Neurospora crassa suggest...Full Text Available

1987-06-01

119

Compensation for a Mutated Auxin Biosynthesis Gene of Agrobacterium Ti Plasmid A66 in Nicotiana glutinosa Does Not Result from Increased Auxin Accumulation 1  

UK PubMed Central (United Kingdom)

Nicotiana glutinosa compensated for a mutated tumor-morphology-shooty (tms) (auxin biosynthesis) locus of Agrobacterlum tumefaciens strain A66 and...Full Text Available

1989-04-01

120

Investigation of lifetimes in the dipole band of {sup 139}Sm  

Energy Technology Data Exchange (ETDEWEB)

Lifetimes have been measured for a dipole band in {sup 139}Sm using DSAM. The deduced B(M1) and B(E2) values as well as B(M1)/B(E2) ratios are compared with calculations in the framework of the TAC (Tilted Axis Cranking) and SPAC (Shears mechanism with Principal Axis Cranking) models. The dipole band in {sup 139}Sm can be considered as a magnetic rotational band with a prolate or triaxial nuclear deformation. (orig.)

2008-09-15

121

Investigation of lifetimes in dipole bands of {sup 142}Gd  

Energy Technology Data Exchange (ETDEWEB)

Lifetimes have been measured for dipole bands in {sup 142}Gd using DSAM. The deduced B(M1) and B(E2) values as well as B(M1)/B(E2) ratios are compared with calculations in the framework of the TAC (Tilted Axis Cranking) and SPAC (shears mechanism with Principal Axis Cranking) models. The dipole bands DB1 to DB4 can be interpreted as magnetic rotational bands. (orig.)

2005-02-01

122

Biochemical changes in human cervical connective tissue after local application of prostaglandin E2  

DEFF Research Database (Denmark)

Intracervical application of prostaglandin E2 in the late first trimester induces (1) softening of the cervix tissue; (2) increase in sulfated glycosaminoglycans (18 +/- 12%, mean +/- SEM); (3) no change in hyaluronic acid and water; (4) decrease in pepsin-extractable collagen, and (5) apparent decrease in collagenase. A high activity of collagenase in combination with a replacement of collagen with sulfated glycosaminoglycans may be of importance for the ripening process.

1983-01-01

123

Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A  

Energy Technology Data Exchange (ETDEWEB)

The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed ...

2008-08-25

124

Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A  

International Nuclear Information System (INIS)

The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate ...

2008-08-25

125

Mutation analysis of KRAS prior to targeted therapy in colorectal cancer: development and evaluation of quality by a European external quality assessment scheme  

British Library Electronic Table of Contents (United Kingdom)

In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to assess them. To ensure the consistency and the quality of KRAS test results in Europe, an interlaboratory control network needs to be set up. This pilot study aimed to identify the variables that need to be assessed in a quality control scheme and to provide a first assessment in a selected set of laboratories. Fourteen different tumor cases were circulated between 13 laboratories by a central laboratory acting as the referent for the mutation status determination. This study illustrated that of...

2011-01-01

126

Mapping of the human cone transducin {alpha}-subunit (GNAT2) gene to 1p13 and negative mutation analysis in patients with Stargardt disease  

Energy Technology Data Exchange (ETDEWEB)

We report localization of the human cone transducin (GNAT2) gene using fluorescence in situ hybridization on chromosome 1 in band p13. The recent assignment of a gene for Stargardt disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. We investigated 66 unrelated patients for mutations in the coding region of the GNAT2 gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. No disease-specific mutations were found, indicating that GNAT2 is probably not involved in the pathogenesis of most cases of Stargardt disease. 19 refs., 1 fig., 1 tab.

1995-01-01

127

Computational mouse atlases and their application to automatic assessment of craniofacial dysmorphology caused by the Crouzon mutation Fgfr2C342Y  

British Library Electronic Table of Contents (United Kingdom)

Abstract Crouzon syndrome is characterized by premature fusion of sutures and synchondroses. Recently, the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of micro-computed tomography (CT) scannings of the skulls of wild-type mice and Crouzon mice were analysed with respect to the dysmorphology caused by Crouzon syndrome. A computational craniofacial atlas was built automatically from the set of wild-type mouse micro-CT volumes using (1) affine and (2) non-rigid image registration. Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landma...

2007-01-01

128

Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens. [Rats, hamsters  

Science.gov (United States)

We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro.

1977-01-01

129

Absence of the A4 peptide in the G4 glycinin subunit of soybean cultivar Enrei is caused by a point mutation in the Gy4 gene  

Scientific Electronic Library Online (English)

Abstract in english Functional properties of soy proteins for food are closely related to the composition of their storage protein subunits. Using base excision sequence scanning (BESS), we show that the absence of the A4 peptide in the G4 glycinin subunit of the soybean (Glycine max L.) cultivar Enrei was caused by the same point mutation in the Gy4 gene as previously reported in the soybean cultivar Raiden. Although the genetic relationship between Raiden and Enrei is not known, the same p (more) oint mutation in their Gy4 genes may indicate that they probably share a related origin. The application of BESS to identify single nucleotide polymorphisms (SNPs) as co-dominant markers for marker-assisted selection (MAS) of a recessive null allele is also discussed.

2005-09-01

130

A miniaturized spatial temperature gradient capillary electrophoresis system with radiative heating and automated sample introduction for DNA mutation detection  

British Library Electronic Table of Contents (United Kingdom)

Abstract A miniaturized spatial temperature gradient CE system with automated sample introduction for DNA mutation detection was established. Continuous electrokinetic sample injection was achieved by combining an automated slotted vial array sample introduction device to the spatial temperature gradient CE system. The temperature gradient was produced by a radiative heating system with a single graphite block heater, and the stability of the temperature gradient was investigated. The temperature variation of each measure point was 0.12 0.21% RSD (n=7) within 6 h. A 14 cm Teflon AF coated silica capillary was used both as the separation channel and as the liquid core waveguide tube of fluorescence signal. Under a temperature gradient from 54.8 to 59.5 C, a low range control mutation standa...

2010-01-01

131

p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin  

UK PubMed Central (United Kingdom)

Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available

2002-06-01

132

aHUS caused by complement dysregulation: new therapies on the horizon  

UK PubMed Central (United Kingdom)

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement...Full Text Available

2011-01-01

133

[Malignant transformation of human fibroblasts by neutrons and by gamma radiation: Relationship to mutations induced  

Energy Technology Data Exchange (ETDEWEB)

A brief overview if provided of selected reports presented at the International Symposium on Molecular Mechanisms of Radiation- and Chemical Carcinogen-Induced Cell Transformation held at Mackinac Island, Michigan on September 19-23, 1993.

1993-12-31

134

Type I Collagen Is a Genetic Modifier of Matrix Metalloproteinase 2 in Murine Skeletal Development  

UK PubMed Central (United Kingdom)

Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone...Full Text Available

2007-06-01

135

Tuberous Sclerosis Complex Activity is Required to Control Neuronal Stress Responses in an mTOR-Dependent Manner  

UK PubMed Central (United Kingdom)

Tuberous Sclerosis Complex (TSC) is a neurogenetic disorder caused by loss-of-function mutations in either the TSC1 or TSC2 genes and frequently results in...Full Text Available

2009-05-06

136

Transposable elements are enriched within or in close proximity to xenobiotic-metabolizing cytochrome P450 genes  

UK PubMed Central (United Kingdom)

BackgroundTransposons, i.e. transposable elements (TEs), are the major internal spontaneous mutation agents for the variability of eukaryotic genomes. To address the general issue...Full Text Available

137

The mitochondrial p53 pathway  

UK PubMed Central (United Kingdom)

p53 is one of the most mutated tumor suppressors in human cancers and as such has been intensively studied for a long time. p53 is a major orchestrator of the cellular response to a broad array...Full Text Available

2009-05-01

138

The erratic mitochondrial clock: variations of mutation rate, not population size, affect mtDNA diversity across birds and mammals  

UK PubMed Central (United Kingdom)

BackgroundDuring the last ten years, major advances have been made in characterizing and understanding the evolution of mitochondrial DNA, the most popular marker of molecular biodiversity....Full Text Available

139

The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template  

UK PubMed Central (United Kingdom)

Mutations in SOX9, a gene essential for chondrocyte differentiation cause the human disease campomelic dysplasia (CD). To understand how SOX9 activates transcription, we characterized...Full Text Available

2010-10-01

140

The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model  

UK PubMed Central (United Kingdom)

Dominant mutations in sarcomere protein genes cause hypertrophic cardiomyopathy, an inherited human disorder with increased ventricular wall thickness, myocyte hypertrophy, and disarray. To understand...Full Text Available

2002-04-15

141

Technical approaches for mouse models of human disease  

UK PubMed Central (United Kingdom)

The mouse is the leading organism for disease research. A rich resource of genetic variation occurs naturally in inbred and special strains owing to spontaneous mutations. However, one can also obtain...Full Text Available

2011-05-01

142

Targeting the p53 Pathway in Ewing Sarcoma  

UK PubMed Central (United Kingdom)

The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53...Full Text Available

2011-01-01

143

T cell-engaging BiTE antibodies specific for EGFR potently eliminate KRAS- and BRAF-mutated colorectal cancer cells  

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available

2010-07-13

144

Species abundance distributions in neutral models with immigration or mutation and general lifetimes  

CERN Document Server

We consider a general, neutral, dynamical model of biodiversity. Individuals have i.i.d. lifetime durations, which are not necessarily exponentially distributed, and each individual gives birth independently at constant rate \\lambda. We assume that types are clonally inherited. We consider two classes of speciation models in this setting. In the immigration model, new individuals of an entirely new species singly enter the population at constant rate \\mu (e.g., from the mainland into the island). In the mutation model, each individual independently experiences point mutations in its germ line, at constant rate \\theta. We are interested in the species abundance distribution, i.e., in the numbers, denoted I_n(k) in the immigration model and A_n(k) in the mutation model, of species represented by k individuals, k=1,2,...,n, when there are n individuals in the total population. In the immigration model, we prove that the ...

2010-01-01

145

Sp1/NF?B/HDAC/miR-29b Regulatory Network in KIT-driven Myeloid Leukemia  

UK PubMed Central (United Kingdom)

SUMMARYThe biologic and clinical significance of KIT overexpression that associates with KIT gain-of- function mutations occurring in subsets...Full Text Available

2010-04-13

146

Sequence variants of the DFNB31 gene among Usher syndrome patients of diverse origin  

UK PubMed Central (United Kingdom)

PurposeIt has been demonstrated that mutations in deafness, autosomal recessive 31 (DFNB31), the gene encoding whirlin, is responsible for nonsyndromic hearing loss...Full Text Available

147

Selection and characterization of ricin toxin A-chain mutations in Saccharomyces cerevisiae.  

UK PubMed Central (United Kingdom)

A DNA sequence encoding the A chain of ricin toxin (RTA) from the castor bean plant, Ricinus communis, was placed under GAL1 promoter control and transformed into Saccharomyces cerevisiae. Induction...Full Text Available

1989-02-01

148

Role of the nac gene product in the nitrogen regulation of some NTR-regulated operons of Klebsiella aerogenes.  

UK PubMed Central (United Kingdom)

A positive, genetic selection against the activity of the nitrogen regulatory (NTR) system was used to isolate insertion mutations affecting nitrogen regulation in Klebsiella aerogenes. Two classes...Full Text Available

1990-12-01

149

Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication  

UK PubMed Central (United Kingdom)

Human cytomegalovirus (HCMV) in clinical material cannot replicate efficiently in vitro until it has adapted by mutation. Consequently, wild-type HCMV differ fundamentally from the passaged strains...Full Text Available

2010-09-01

150

Radiation-induced mutations at mouse hemoglobin loci  

International Nuclear Information System (INIS)

In experiments designed to detect new mutations affecting hemoglobin, we irradiated the male or female parent in reciprocal crosses of two mouse strains that differ in alleles at the hemoglobin (Hba, Hbb) loci as well as at five other specific loci. Offspring were analyzed for hemoglobin properties (electrophoretic pattern, solubility, crystal pattern), serum albumin differences, erythrocyte lysis, reticulocyte count, and external appearance. Five hemoglobin variants were found among the mutants. In three, the genetic contribution from the irradiated father was not expressed with regard to the #alpha#-chain; one carried a tandem duplication (the first known case in the mouse) involving Hbb; and one probably resulted from double nondisjunction of chromosome 7. The finding that major chromosome aberratios can mimic hemoglobin mutations indicates the need, in similar experiments, to follow F_1 screening with thorough cytogenetic analysis. The ...

151

Pten Knockdown in vivo Increases Excitatory Drive onto Dentate Granule Cells  

UK PubMed Central (United Kingdom)

Some cases of autism spectrum disorder (ASD) have mutations in the lipid phosphatase, Pten (phosphatase and tensin homolog on chromosome 10). Tissue...Full Text Available

2011-03-16

152

Production of Infectious Genotype 1b Virus Particles in Cell Culture and Impairment by Replication Enhancing Mutations  

UK PubMed Central (United Kingdom)

With the advent of subgenomic hepatitis C virus (HCV) replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured...Full Text Available

2009-06-01

153

Prenatal diagnosis for recessive dystrophic epidermolysis bullosa in 10 families by mutation and haplotype analysis in the type VII collagen gene (COL7A1).  

UK PubMed Central (United Kingdom)

BACKGROUND: Epidermolysis bullosa (EB) is a group of heritable diseases that manifest as blistering and erosions of the skin and mucous membranes. In the dystrophic forms of EB (DEB), the diagnostic...Full Text Available

1996-01-01

154

Past, present, and future of mutagens in cooked foods.  

UK PubMed Central (United Kingdom)

Mutation assay with Salmonella typhimurium enabled us to detect various types of mutagens in cooked foods. A series of mutagenic heterocyclic amines has been isolated and identified in broiled fish...Full Text Available

1986-08-01

155

Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina  

UK PubMed Central (United Kingdom)

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated...Full Text Available

156

Neurotensin Receptor 1 Is Expressed in Gastrointestinal Stromal Tumors but Not in Interstitial Cells of Cajal  

UK PubMed Central (United Kingdom)

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present...Full Text Available

157

Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae  

UK PubMed Central (United Kingdom)

BackgroundMutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial...Full Text Available

158

Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss  

UK PubMed Central (United Kingdom)

We performed genome-wide homozygosity mapping in a large consanguineous family from Morocco and mapped the autosomal-recessive nonsyndromic hearing loss (ARNSHL) in this family to the DFNB79...Full Text Available

2010-03-12

159

Mutations in CHMP2B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis (ALS)  

UK PubMed Central (United Kingdom)

BackgroundAmyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3–10% of patients....Full Text Available

160

Mutations affecting the development of the peripheral nervous system in Drosophila: a molecular screen for novel proteins.  

UK PubMed Central (United Kingdom)

In our quest for novel genes required for the development of the embryonic peripheral nervous system (PNS), we have performed three genetic screens using MAb 22C10 as a marker of terminally differentiated...Full Text Available

2000-12-01

161

Mutational Analysis of cis-Acting RNA Signals in Segment 7 of Influenza A Virus?  

UK PubMed Central (United Kingdom)

The genomic viral RNA (vRNA) segments of influenza A virus contain specific packaging signals at their termini that overlap the coding regions. To further characterize cis-acting signals...Full Text Available

2008-12-01

162

Mutation Spectrum of EYS in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa  

UK PubMed Central (United Kingdom)

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene (EYS) encoding...Full Text Available

2010-11-01

163

Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration  

UK PubMed Central (United Kingdom)

BackgroundMitochondrial dysfunction, oxidative damage and the accumulation of somatic mutations in mitochondrial DNA (mtDNA) have been associated with certain neurodegenerative disorders....Full Text Available

164

Mapping of the transcription start site (TSS) and identification of SNPs in the bovine neuropeptide Y (NPY) gene  

UK PubMed Central (United Kingdom)

BackgroundNeuropeptide Y is a key neurotransmitter of the central nervous system which plays a vital role in the feed energy homeostasis in mammals. Mutations in the regulatory and...Full Text Available

165

Loss of ?-III spectrin leads to Purkinje cell dysfunction recapitulating the behaviour and neuropathology of SCA5 in humans  

UK PubMed Central (United Kingdom)

Mutations in SPTBN2, the gene encoding β-III spectrin, cause spinocerebellar ataxia type 5 in humans (SCA5), a neurodegenerative disorder resulting in loss of motor...Full Text Available

2010-04-07

166

Lack of association between polymorphisms in C4b-binding protein and atypical haemolytic uraemic syndrome in the Spanish population  

UK PubMed Central (United Kingdom)

Dysregulation of the alternative pathway of complement activation, caused by mutations or polymorphisms in the genes encoding factor H, membrane co-factor protein, factor I or factor B, is associated...Full Text Available

2009-01-01

167

Investigation and prediction of the severity of p53 mutants using parameters from structural calculations  

UK PubMed Central (United Kingdom)

A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important...Full Text Available

2009-08-01

168

Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency.  

UK PubMed Central (United Kingdom)

The lysosomal catabolism of sulfatide requires arylsulfatase A and a specific sphingolipid activator protein, SAP-1. While most patients with metachromatic leukodystrophy have mutations in the gene...Full Text Available

1990-02-01

169

Inferring Stabilizing Mutations from Protein Phylogenies: Application to Influenza Hemagglutinin  

UK PubMed Central (United Kingdom)

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present...Full Text Available

2009-04-01

170

Identification of genetic variation and haplotype structure of the canine ABCA4 gene for retinal disease association studies  

UK PubMed Central (United Kingdom)

Over 200 mutations in the retina specific member of the ATP-binding cassette transporter super-family (ABCA4) have been associated with a diverse group of human retinal diseases....Full Text Available

2010-10-01

171

Identification of a new gene, molR, essential for utilization of molybdate by Escherichia coli.  

UK PubMed Central (United Kingdom)

A mutation in a new gene, molR, prevented the synthesis in Escherichia coli of molybdoenzymes, including the two formate dehydrogenase isoenzymes, nitrate reductase and trimethylamine-N-oxide reductase....Full Text Available

1990-04-01

172

Identification of a Chemically Induced Point Mutation Mediating Herbicide Tolerance in Annual Medics (Medicago spp.)  

UK PubMed Central (United Kingdom)

Background and AimsSulfonylurea (SU) herbicides are used extensively in cereal–livestock farming zones as effective and cheap herbicides with useful levels of residual activity....Full Text Available

2008-05-01

173

ICC-MY coordinate smooth muscle electrical and mechanical activity in the murine small intestine  

UK PubMed Central (United Kingdom)

BackgroundAnimals carrying genetic mutations have provided powerful insights into the role of interstitial cells of Cajal (ICC) in motility. One classic model is...Full Text Available

2010-05-01

174

Highly Conserved Regimes of Neighbor-Base-Dependent Mutation Generated the Background Primary-Structural Heterogeneities along Vertebrate Chromosomes  

UK PubMed Central (United Kingdom)

The content of guanine+cytosine varies markedly along the chromosomes of homeotherms and great effort has been devoted to studying this heterogeneity and its biological implications. Already...Full Text Available

175

Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency.  

UK PubMed Central (United Kingdom)

The DNA sequences were determined for the lipoprotein lipase (LPL) gene from five unrelated Japanese patients with familial LPL deficiency. The results demonstrated that all five patients are homozygotes...Full Text Available

1991-12-01

176

Genetics of the mammalian phenylalanine hydroxylase system. Studies of human liver phenylalanine hydroxylase subunit structure and of mutations in phenylketonuria.  

UK PubMed Central (United Kingdom)

Phenylalanine hydroxylase was purified from crude extracts of human livers which show enzyme activity by usine two different methods: (a) affinity chromatography and (b) immunoprecipitation with an...Full Text Available

1979-08-01

177

Genetic and cellular evidence of vascular inflammation in neurofibromin-deficient mice and humans  

UK PubMed Central (United Kingdom)

Neurofibromatosis type 1 (NF1) results from mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. NF1 patients display diverse clinical manifestations,...Full Text Available

2010-03-01

178

Gene expression profiling of oxidative stress response of C. elegans aging defective AMPK mutants using massively parallel transcriptome sequencing  

UK PubMed Central (United Kingdom)

BackgroundA strong association between stress resistance and longevity in multicellular organisms has been established as many mutations that extend lifespan also show increased...Full Text Available

179

Gene Therapy in the Retinal Degeneration Slow Model of Retinitis Pigmentosa  

UK PubMed Central (United Kingdom)

Human blinding disorders are often initiated by hereditary mutations that insult rod and/or cone photoreceptors and cause subsequent cellular death. Generally, the disease phenotype can be predicted...Full Text Available

2010-01-01

180

GLUE-IT and PEDEL-AA: new programmes for analyzing protein diversity in randomized libraries  

UK PubMed Central (United Kingdom)

There are many methods for introducing random mutations into nucleic acid sequences. Previously, we described a suite of programmes for estimating the completeness and diversity of randomized DNA libraries...Full Text Available

2008-07-01

181

Functional and Behavioral Restoration of Vision by Gene Therapy in the Guanylate Cyclase-1 (GC1) Knockout Mouse  

UK PubMed Central (United Kingdom)

BackgroundRecessive mutations in guanylate cyclase-1 (Gucy2d) are associated with severe, early onset Leber congenital amaurosis-1(LCA1). Gucy2d...Full Text Available

182

FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis  

UK PubMed Central (United Kingdom)

Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull,...Full Text Available

2002-04-01

183

Exome sequencing identifies GRIN2A as frequently mutated in melanoma  

UK PubMed Central (United Kingdom)

The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome...Full Text Available

2011-05-01

184

Evidence of perturbations of cell cycle and DNA repair pathways as a consequence of human and murine NF1-haploinsufficiency  

UK PubMed Central (United Kingdom)

BackgroundNeurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1....Full Text Available

185

EGFR Signaling Through an Akt-SREBP-1-Dependent, Rapamycin-Resistant Pathway Sensitizes Glioblastomas to Anti-Lipogenic Therapy  

UK PubMed Central (United Kingdom)

Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma,...Full Text Available

186

Dissecting the Genetic Components of Adaptation of Escherichia coli to the Mouse Gut  

UK PubMed Central (United Kingdom)

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here...Full Text Available

2008-01-01

187

Developmental abnormalities and epimutations associated with DNA hypomethylation mutations.  

UK PubMed Central (United Kingdom)

A number of aberrant morphological phenotypes were noted during propagation of the Arabidopsis thaliana DNA hypomethylation mutant, ddm1, by repeated self-pollination. Onset of a spectrum of morphological...Full Text Available

1996-10-29

189

Cyst Formation in Kidney via B-Raf Signaling in the PKD2 Transgenic Mice*  

UK PubMed Central (United Kingdom)

The pathogenic mechanisms of human autosomal dominant polycystic kidney disease (ADPKD) have been well known to include the mutational inactivation of PKD2. Although haploinsufficiency...Full Text Available

2009-03-13

190

Construction of a novel bifunctional biogenic amine receptor by two point mutations of the H2-histamine receptor.  

UK PubMed Central (United Kingdom)

BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously...Full Text Available

1995-03-01

191

Congenital woolly hair without P2RY5 mutation  

UK PubMed Central (United Kingdom)

Congenital woolly hair is a disorder with structural defects of the hair shafts. Curled hairs are noticed at birth or soon after birth and often improve with age. Some cases of woolly hairs are associated...Full Text Available

2009-01-01

192

Characterization of a novel missense mutation on murine Pax3 through ENU mutagenesis.  

Science.gov (United States)

N-ethyl-N-nitrosourea (ENU) mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant, including exencephaly, spina bifida and abnormal limbs in homozygotes as well as white belly spotting and occasionally loop-tail in heterozygotes. This novel mutant was named as Sp(xG). Through genome-wide linkage analysis in backcross progenies with microsatellite markers, the Sp(xG) was confined to a region between D1MIT415 and D1MIT7 on chromosome 1, where notable Pax3 gene was located. Direct sequencing revealed that Sp(xG) carried a nucleotide A894G missense transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at amino acid 269 within the highly-conserved homeodomain (HD) DNA recognition module, which was the first point mutation found in this domain in mice. This N269D mutation impaired ...

2011-07-19

193

Chapter 61: Photoreceptor Cell Degeneration in Abcr?/? Mice  

UK PubMed Central (United Kingdom)

Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease. Consistent with the human retinal disorder, deficiency...Full Text Available

2010-01-01

194

COL9A2 and COL9A3 mutations in canine autosomal recessive Oculo-skeletal Dysplasia  

UK PubMed Central (United Kingdom)

Oculo-skeletal dysplasia segregates in two canine breeds, the Labrador retriever and samoyed, in which the causative loci have been termed drd1 and drd2, respectively....Full Text Available

2010-08-01

195

Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.  

UK PubMed Central (United Kingdom)

Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the...Full Text Available

1989-01-01

196

Apolipoprotein E-Mimetics Inhibit Neurodegeneration and Restore Cognitive Functions in a Transgenic Drosophila Model of Alzheimer's Disease  

UK PubMed Central (United Kingdom)

BackgroundMutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production...Full Text Available

197

Anticipation in familial lattice corneal dystrophy type I with R124C mutation in the TGFBI (BIGH3) gene  

UK PubMed Central (United Kingdom)

PurposeTo report the clinical, ophthalmic, and genetic characteristics for lattice corneal dystrophy type I (LCDI) in a Chilean family.MethodsSix...Full Text Available

198

Antagonistic crosstalk between APC and HIF-1?  

UK PubMed Central (United Kingdom)

Most colorectal cancers have mutations in the tumor suppressor APC. The best-understood function of APC is its participation in a protein complex that regulates the availability of β-catenin....Full Text Available

2011-05-15

199

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

200

An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer  

UK PubMed Central (United Kingdom)

Cancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short harpin...Full Text Available

2008-11-28

201

Air pollution induces heritable DNA mutations  

UK PubMed Central (United Kingdom)

Hundreds of thousands of people worldwide live or work in close proximity to steel mills. Integrated steel production generates chemical pollution containing compounds that can induce genetic damage...Full Text Available

2002-12-10

202

Adenomatous Polyposis Coli and Hypoxia-inducible Factor-1? Have an Antagonistic Connection  

UK PubMed Central (United Kingdom)

The tumor suppressor adenomatous polyposis coli (APC) is mutated in the majority of colorectal cancers and is best known for its role as a scaffold in a Wnt-regulated protein complex that determines...Full Text Available

2010-11-01

203

A piggyBac transposon-based genome-wide library of insertionally mutated Blm-deficient murine ES cells  

UK PubMed Central (United Kingdom)

Cultured mouse or human embryonic stem (ES) cells provide access to all of the genes required to elaborate the fundamental components and physiological systems of a mammalian cell. Chemical or insertional...Full Text Available

2009-04-01

204

A new VCAN/versican splice acceptor site mutation in a French Wagner family associated with vascular and inflammatory ocular features  

UK PubMed Central (United Kingdom)

PurposeTo detail the highly variable ocular phenotypes of a French family affected with an autosomal dominantly inherited vitreoretinopathy and to identify the disease gene.MethodsSixteen...Full Text Available

205

A molecular model for the genetic and phenotypic characteristics of the mouse lethal yellow (A{sup y}) mutation  

Energy Technology Data Exchange (ETDEWEB)

Lethal yellow (A{sup y}) is a mutation at the mouse agouti locus in chromosome 2 that causes a number of dominant pleiotropic effects, including a completely yellow coat color, obesity, an insulin-resistant type II diabetic condition, and an increased propensity to develop a variety of spontaneous and induced tumors. Additionally, homozygosity for A{sup y} results in preimplantation lethality, which terminates development by the blastocyst stage. The A{sup y} mutation is the result of a 170-kb deletion that removes all but the promoter and noncoding first exon of another gene called Raly, which lies in the same transcriptional orientation as agouti and maps 280 kb proximal to the 3{prime} end of the agouti gene. The authors present a model for the structure of the A{sub y} allele that can explain the dominant pleiotropic effects associated with this mutation, as well as the recessive lethality, which is unrelated to the ...

1994-03-29

206

A homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, ? cell hyperplasia, and islet cell tumor  

UK PubMed Central (United Kingdom)

ObjectiveThe goal of the study was to investigate the genetic and molecular basis of a novel syndrome of marked hyperglucagonemia and pancreatic α cell hyperplasia...Full Text Available

2009-11-01

207

A Point Mutation in a Domain of Gamma Interferon Receptor 1 Provokes Severe Immunodeficiency  

UK PubMed Central (United Kingdom)

Gamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain...Full Text Available

2001-01-01

208

A DNA transposon-based approach to validate oncogenic mutations in the mouse  

UK PubMed Central (United Kingdom)

Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified...Full Text Available

2008-12-16

209

1,3-Butadiene: linking metabolism, dosimetry, and mutation induction.  

UK PubMed Central (United Kingdom)

There is increasing concern for the potential adverse health effects of human exposures to chemical mixtures. To better understand the complex interactions of chemicals within a mixture, it is essential...Full Text Available

1994-11-01

210

Three novel mutations responsible for Cockayne syndrome group A  

International Nuclear Information System (INIS)

Cockayne syndrome (CS) is a rare autosomal recessive disease, which shows diverse clinical symptoms such as photosensitivity, severe mental retardation and developmental defects. CS cells are hypersensitive to killing by ultraviolet (UV)-irradiation and defective in transcription-coupled repair. Two genetic complementation groups in CS (CS-A and CS-B) have been identified. We analyzed mutations of the CSA gene in 5 CS-A patients and identified 3 types of mutations. Four unrelated CS-A patients (CS2OS, CS2AW, Nps2 and CS2SE) had a deletion including exon 4, suggesting that there is a founder effect on the CSA mutation in Japanese CS-A patients. Patient CS2SE was a compound heterozygote for this deletion and an amino acid substitution at the 106th glutamine to proline (Q106P) in the WD-40 repeat motif of the CSA protein, which resulted in a defective nucleotide excision repair. Patient Mps1 had a large deletion in the ...

2003-02-01

211

Linkage analysis in familial Angelman syndrome  

Energy Technology Data Exchange (ETDEWEB)

Familial Angelman syndrome (AS) can result from mutations in chromosome 15q11q13 that, when transmitted from father to child, result in no phenotypic abnormality but, when transmitted from mother to child, cause AS. These mutations therefore behave neither as dominant nor as recessive mutations but, rather, show an imprinted mode of inheritance. The authors have analyzed two sibling pairs with AS and a larger family with four AS offspring of three sisters with several recently described microsatellite polymorphisms in the AS region. AS siblings inherited the same maternal alleles at the GABRB3 and GABRA5 loci, and the unaffected siblings of AS individuals inherited the other maternal alleles at these loci. In one of the AS sibling pairs, analysis of a recombination event indicates that the mutation responsible for AS is distal to locus D15S63. This result is consistent with a previously described ...

1993-07-01

212

Dual Roles of Nrf2 in Cancer  

UK PubMed Central (United Kingdom)

In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing...Full Text Available

2008-01-01

213

Downregulation of Serum Gonadotropins is as Effective as Estrogen Replacement at Improving Menopause-Associated Cognitive Deficits  

UK PubMed Central (United Kingdom)

While estrogen (E2) is thought to play an important role in age-related cognitive decline, neuronal plasticity, as well as the pathogenesis of Alzheimer disease (AD), the mechanisms by which...Full Text Available

2010-02-01

214

Changes in inflammatory mediators in experimental periodontitis in the rhesus monkey.  

UK PubMed Central (United Kingdom)

Ligature-induced periodontitis was monitored for 6 months in eight Macaca mulatta monkeys to examine clinical status, radiographic bone level, and crevicular fluid (CF) levels of prostaglandin E2 (PGE2),...Full Text Available

1993-04-01

215

E2 transition densities and proton shell structure in /sup 88/Sr, /sup 89/Y, and /sup 90/Zr  

Energy Technology Data Exchange (ETDEWEB)

Electron scattering data have been used to obtain transition charge densities for the low-lying E2 transitions in /sup 88/Sr, /sup 89/Y, and /sup 90/Zr. These charge densities show a characteristic shape indicative of their microscopic constituency, modified by core-polarization effects. A good description of transitions in the even-even nuclei is obtained by using the measured single-particle transitions in /sup 89/Y as effective densities. .ID LV2086 .PG 19 22

1983-01-03

216

Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells  

International Nuclear Information System (INIS)

Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene sequence. The green fluorescence, mean fluorescence intensity, and SARS-CoV S RNA transcripts were found ...

2004-11-26

217

Research work on mutation breeding in Egypt during the 1980s  

International Nuclear Information System (INIS)

The research work carried out on mutation breeding in Egypt during the 1980s is summarized. Several mutations have been developed in bread wheat, maize, rice and barley. A higher yield, tolerance to salinity, shorter types and earliness were obtained after use of different mutagens and growth regulators. Great attention has been paid to the fababean and chickpea, particularly in improving their quality and quantity of protein, and their resistance to insect weevils such as Callosobruchus sp. Tolerance or resistance to broom rape has also been reported. Various grain legumes such as lentil, pea, cowpea, bean, fenugreek and lupin received some attention. Mutation work on fibre crops such as cotton, kenaf and flax has led to some promising results. Zero type, glandless and early maturing mutants were obtained in cotton, and early flowering, high yielding (fibre or oil) mutants in flax. Some attention has been given to oil ...

1990-06-18

218

Production of Infectious Genotype 1b Virus Particles in Cell Culture and Impairment by Replication Enhancing Mutations  

Science.gov (United States)

With the advent of subgenomic hepatitis C virus (HCV) replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured human hepatoma cells, but save for the genotype 2a isolate JFH-1, efficient replication of these HCV RNAs requires replication enhancing mutations (REMs), previously also called cell culture adaptive mutations. These mutations cluster primarily in the central region of non-structural protein 5A (NS5A), but may also reside in the NS3 helicase domain or at a distinct position in NS4B. Most efficient replication has been achieved by combining REMs residing in NS3 with distinct REMs located in NS4B or NS5A. However, in spite of efficient replication of HCV genomes containing such mutations, they do not support production of infectious virus particles. By using the genotype 1b isolate Con1, in this study we ...

2009-06-12

219

Ionizing radiation-induced mutation of human cells with different DNA repair capacities  

Energy Technology Data Exchange (ETDEWEB)

We have observed significant differences in the response to ionizing radiation of two closely related human cell lines, and now compare the effects on these lines of both low and intermediate LET radiation. Compared to TK6, WTK1 has an enhanced X-ray survival, and is also more resistant to cell killing by {alpha}-particles. The hprt locus is more mutable in WTK1 than in TK6 by both X-rays and {alpha}-particles. WTK1 is also more mutable by {alpha}-particles than by X-rays at the hprt locus. X-ray-induced mutation at the heterozygous tk locus in WTK1 is about 25 fold higher than in TK6, while {alpha}-particle-induced mutation is nearly 50 fold higher at this locus. Also, the slowly growing tk- mutants, which comprise the majority of spontaneous and X-ray-induced tk- mutants of TK6, were not induced significantly by {alpha}-particles. Previously, we showed that TK6 has a reduced capacity for recombination compared with WTK1, and therefore, these ...

1994-12-31

220

Detection of basepair substitution mutation at a frequency of 1 x 10(-7) by combining two genotypic selection methods, MutEx enrichment and allele-specific competitive blocker PCR.  

Science.gov (United States)

The detection of rare mutations has many important applications, including risk assessment of drugs and chemicals, measuring environmental exposures to genotoxins, and cancer cell detection. A sensitive genotypic selection method has been developed that combines two different mutant allele selection techniques, MutEx enrichment and allele-specific competitive blocker PCR (ACB-PCR). This method was developed and evaluated for the detection of a CAA --> AAA mutation at codon 61 of the mouse H-ras gene. The MutEx enrichment is based on MutS binding to a mismatched basepair in heteroduplex DNA. The bound MutS protects the mutant allele from degradation during subsequent exonuclease treatment. ACB-PCR preferentially amplifies a mutant allele in a PCR reaction using a primer that has more mismatches to the wild-type allele than the mutant allele. By combining these two approaches, the codon 61 mutation was detected at mutant ...

1998-01-01

221

Deploying perfSONAR-based End-2-End monitoring for production US CMS networking  

Energy Technology Data Exchange (ETDEWEB)

Fermilab is the US Tier-1 Center for CMS data storage and analysis. End-2-End (E2E) circuits are utilized to support high impact data movement into and out of the Tier-1 Center. E2E circuits have been implemented to facilitate the movement of raw experiment data from the Tier-0 Center at CERN, as well as processed data to a number of the US Tier-2 sites. Troubleshooting and monitoring of those circuits presents a significant challenge, since the circuits typically cross multiple research & education networks, each with its own management domain and customized monitoring capabilities. The perfSONAR Monitoring Project was established to facilitate development and deployment of a common monitoring infrastructure across multiple network management domains. Fermilab has deployed perfSONAR across its E2E circuit infrastructure and enhanced the product with several ...

2007-09-01

222

Homology among tet determinants in conjugative elements of streptococci  

Energy Technology Data Exchange (ETDEWEB)

A mutation to tetracycline sensitivity in a resistant strain of Streptococcus pneumoniae was shown by several criteria to be due to a point mutation in the conjugative o(cat-tet) element found in the chromosomes of strains derived from BM6001, a clinical strain resistant to tetracycline and chloramphenicol. Strains carrying the mutation were transformed back to tetracycline resistance with the high efficiency of a point marker by donor deoxyribonucleic acids from its ancestral strain and from nine other clinical isolates of pneumococcus and by deoxyribonucleic acids from Group D Streptococcus faecalis and Group B Streptococcus agalactiae strains that also carry conjugative tet elements in their chromosomes. It was not transformed to resistance by tet plasmid deoxyribonucleic acids from either gram-negative or gram-positive species, except for one that carried transposon TN916, the conjugative tet element present in the ...

1981-10-01

223

Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan  

British Library Electronic Table of Contents (United Kingdom)

Abstract Background & aims: Hepatitis B or C virus infection is considered to be the main cause of hepatocellular carcinoma (HCC) in Japan. Aflatoxin B1 (AFB1) is a carcinogen associated with HCC in regions with high exposure. Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC. Methods: Hepatocyte AFB1-DNA adducts were determined immunohistochemically and direct sequencing of TP53 was done to determine mutations in 188 of 279 patients who underwent hepatic resection for HCC. We assessed hepatitis C virus antibodies (HCV Ab) and HBSAg expression; patients without either were defined as having non-B non-C hepatocellular carcinoma (...

2011-01-01

224

Sequence analysis of the ATM gene in 20 patients with RTOG grade 3 or 4 acute and/or late tissue radiation side effects  

International Nuclear Information System (INIS)

Purpose: Patients with ataxia-telangiectasia (A-T) show greatly increased radiation sensitivity and cancer predisposition. Family studies imply that the otherwise clinically silent heterozygotes of this autosomal recessive disease run a 3.5 to 3.8 higher risk of developing cancer. In vitro studies suggest moderately increased cellular radiation sensitivity of A-T carriers. They may also show elevated clinical radiosensitivity. We retrospectively examined patients who presented with severe adverse reactions during or after standard radiation treatment for mutations in the gene responsible for A-T, ATM, considering a potential means of future identification of radiosensitive individuals prospectively to adjust dosage schedules. Material and Methods: We selected 20 cancer patients (breast, 11; rectum, 2; ENT, 2; bladder, 1; prostate, 1; anus, 1; astrocytoma, 1; Hodgkins lymphoma, 1) with Grade 3 to 4 (RTOG) acute and/or late tissue radiation side effects by reaction ...

1999-07-15

225

An ELISA-based high throughput protein truncation test for inherited breast cancer  

Science.gov (United States)

IntroductionBreast cancer is the most diagnosed and second leading cause of cancer deaths in the U.S. female population. An estimated 5 to 10 percent of all breast cancers are inherited, caused by mutations in the breast cancer susceptibility genes (BRCA1/2). As many as 90% of all mutations are nonsense mutations, causing a truncated polypeptide product. A popular and low cost method of mutation detection has been the protein truncation test (PTT), where target regions of BRCA1/2 are PCR amplified, transcribed/translated in a cell-free protein synthesis system and analyzed for truncated polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. We previously reported a novel High Throughput Solid-Phase PTT (HTS-PTT) based on an enzyme-linked immunosorbent assay (ELISA) format that eliminates the need for radioactivity, SDS-PAGE and subjective interpretation ...

2010-10-04

226

Terminal phalangeal accessory ossification center of the thumb: an additional radiographic finding in Larsen syndrome  

International Nuclear Information System (INIS)

Larsen syndrome is an autosomal-dominant disorder characterized by multiple joint dislocations, vertebral anomalies and dysmorphic facies. Both autosomal-dominant and autosomal-recessive forms of the disorder have been proposed. Individuals with autosomal-dominant Larsen syndrome have characteristic ''cylindrical-shape'' thumbs caused by broad, shortened phalanges. Autosomal-dominant Larsen syndrome results from heterozygosity for mutations in filamin B, a cytoskeletal protein involved in multicellular processes. We report here a patient with a duplicated or accessory distal thumb phalanx and multiple large joint dislocations who was shown to be heterozygous for a filamin B mutation predicting the amino acid substitution G1691S. This adds a new radiographic finding, duplicated or accessory distal phalanx, to the radiographic abnormalities seen in this rare dominant disorder. (orig.)

2006-09-01

227

Studies of human mutation rates  

Energy Technology Data Exchange (ETDEWEB)

November 1989, marked the beginning of a new three-year cycle of DOE grant support, in connection with which the program underwent a major reorganization. This document presents the progress on the three objectives of the present program which are: to isolate by the technique of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), proteins of special interest because of the relative mutability of the corresponding gene, establish the identity of the protein, and, for selected proteins, move to a characterization of the corresponding gene; to develop a more efficient approach, based on 2-D PAGE, for the detection of variants in DNA, with special reference to the identification of mutations in the parents of the individual whose DNA is being examined; and, to continue an effective interface with the genetic studies on the children of atomic bomb survivors in Japan, with reference to both the planning and implementation of new studies at the molecular level.

1990-01-01

228

Somatic mutations detected by immunofluorescence and flow cytometry  

International Nuclear Information System (INIS)

We have at hand the tools for development of both a single amino acid substitution and a gene loss type assay for somatic cell mutations in human red cells. We are close to being able to assess the assays as possible means for screening the human population for individuals who may be a risk of acquiring abnormally high frequencies of mutant cells. The cause for such a high frequency of mutant cells could be a prior exposure of the individual to large amount of mutagen, or it could indicate a member of a vulnerable subpopulation that may have poor DNA repair systems. Either of these cases could well be an indication that the particular individual is at high risk that exposure to mutagens could lead to potential pathology. In the near future we expect to determine the reliability of the assays and to perform experiments to confirm the validity of flow cytometry in measuring real somatic mutagenic events that occur in vivo. (orig./AJ).

229

One-step RNA pathogen detection with reverse transcriptase activity of a mutated thermostable Thermus aquaticus DNA polymerase  

British Library Electronic Table of Contents (United Kingdom)

We describe the cloning and characterization of a mutated thermostable DNA polymerase from Thermus aquaticus (Taq) that exhibits an increased reverse transcriptase activity and is therefore designated for one-step PCR pathogen detection using established real-time detection methods. We demonstrate that this Taq polymerase mutant (Taq M1) has similar PCR sensitivity and nuclease activity as the respective Taq wild-type DNA polymerase. In addition, and in marked contrast to the wild-type, Taq M1 exhibits a significantly increased reverse transcriptase activity especially at high temperatures (>60degreeC). RNA generally hosts highly stable secondary structure motifs, such as hairpins and G-quadruplexes, which complicate, or in the worst case obviate, reverse transcription (RT). Thus, RT at hi...

2010-01-01

230

Mutations at the cysteine codons of the recA gene of Escherichia coli  

International Nuclear Information System (INIS)

Each of the three cysteine residues in the Escherichia coli RecA protein was replaced with a number of other amino acids. To do this, each cysteine codon was first converted to a chain-terminating amber codon by oligonucleotide-directed mutagenesis. These amber mutants were then either assayed for function in different suppressor strains or reverted by a second round of mutagenesis with oligonucleotides that had random sequences at the amber codon. Thirty-three different amino acid substitutions were obtained. Mutants were tested for three functions of RecA: survival following UV irradiation, homologous recombination, and induction of the SOS response. It was found that although none of the cysteines is essential for activity, mutations at each of these positions can affect one or more of the activities of RecA, depending on the particular amino acid substitution. In addition, the cysteine at position 116 appears to be involved in the RecA-promoted cleavage of the ...

231

Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease  

British Library Electronic Table of Contents (United Kingdom)

Lebers hereditary optic neuropathy (LHON), the most frequent mitochondrial disorder, is mostly due to three mitochondrial DNA (mtDNA) mutations in respiratory chain complex I subunit genes: 3460/ND1, 11778/ND4 and 14484/ND6. Despite considerable clinical evidences, a genetic modifying role of the mtDNA haplogroup background in the clinical expression of LHON remains experimentally unproven. We investigated the effect of mtDNA haplogroups on the assembly of oxidative phosphorylation (OXPHOS) complexes in transmitochondrial hybrids (cybrids) harboring the three common LHON mutations. The steady-state levels of respiratory chain complexes appeared normal in mutant cybrids. However, an accumulation of low molecular weight subcomplexes suggested a complex I assembly/stability defect, which was ...

2008-01-01

232

Improving protein quality of soybean through induced mutations  

International Nuclear Information System (INIS)

Soybean is one of the most economical and nutritious food packed with basic nutrients that combat diseases stemming from mal- and under-nutrition. Despite its rich nutritional profile, use of soybean in food has been limited because soybean proteins are often associated with compounds, which could exert a negative impact on the nutritional quality of the protein. Trypsin inhibitor (TI) is one of the important anti-nutritional factors that exert negative effect by causing growth inhibition. Soybean cultivar VLS-2 was irradiated with 250 Gy gamma rays in a gamma cell (200) with 60Co source installed at BARC to induce mutations for low trypsin inhibitor content. Three mutants with lower levels of TI content were identified and can be utilized for developing elite varieties of soybean. (author)

2011-02-22

233

Endogenous expression of Hras(G12V) induces developmental defects and neoplasms with copy number imbalances of the oncogene.  

Science.gov (United States)

We developed mice with germline endogenous expression of oncogenic Hras to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal cranial dimensions, defective dental ameloblasts, and nasal septal deviation, consistent with some of the features of human Costello syndrome. These mice developed papillomas and angiosarcomas, which were associated with Hras(G12V) allelic imbalance and augmented Hras signaling. Endogenous expression of Hras(G12V) was also associated with a higher mutation rate in vivo. Tumor initiation by Hras(G12V) likely requires augmentation of signal output, which in papillomas and angiosarcomas is achieved via increased Hras-gene copy number, which may be favored by a higher mutation frequency in cells expressing the oncoprotein. PMID:19416908

2009-04-29

234

Detection of the first gross CDC73 germline deletion in an HPT-JT syndrome family  

British Library Electronic Table of Contents (United Kingdom)

Abstract Hereditary primary hyperparathyroidism (HPT) may develop as a solitary endocrinopathy (FIHP) or as part of multiple endocrine neoplasia Type 1, multiple endocrine neoplasia Type 2A, or hereditary HPT-jaw tumor syndrome. Inactivating germline mutations of the tumor suppressor gene CDC73 account for 14 and 50% of all FIHP and HPT-JT patients, respectively, and have also been found in almost 20% of apparently sporadic parathyroid carcinoma patients. Although more than 60 independent germline mutations have been described, to date no rearrangement affecting the CDC73 locus has been identified. By means of multiplex-PCR we found a large germline deletion affecting the whole gene in a two-generation HPT-JT family. Subsequently array-CGH and specific PCR analysis determined that the muta...

2011-01-01

235

Amino acid substitution: its use in detection and analysis of genetic variants  

International Nuclear Information System (INIS)

Techniques of chemical analysis, amino acid sequencing and autoradiography are being used to study the frequency of incorporation of normally noncoded amino acids into hemoglobins and seminal fluid proteins. We are studying, by the sequencing of radiolabeled proteins followed by the recovery of ["3H] isoleucine phenylthiohydantoin by high-performance liquid chromatography, the frequency at which normally noncoded isoleucine is incorporated into hemoglobin because of base-substitution mutations versus translational errors. Irradiation increases the isoleucine content of human hemoglobin and the frequency of substitution of isoleucine for specific amino acids in rabbit hemoglobin. Studies to date indicate that these techniques have been developed sufficiently for initial analysis of the potential of drugs and environmental pollutants to induce base-substitution mutations in mammalian somatic cells.

236

APC and KRAS mutations in distal colorectal polyps are related to smoking habits in men: results of a cross-sectional study  

British Library Electronic Table of Contents (United Kingdom)

Background The purpose of this study was (a) to evaluate the association between cigarette smoking and the prevalence of distal colorectal polyps and adenocarcinoma and (b) to analyse genetic alterations representing different molecular pathways of the colorectal carcinogenesis. Methods A total of 623 asymptomatic male (mean age: 53 years; 50?65) car factory workers were included. Information on smoking habits and other lifestyle factors were collected followed by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP) and adenomatous polyps (AP)). Data were analysed using unconditional multiple logistic regression models. Results Smokers had a higher prevalence of AP (OR 2.1; 95% CI 1.2?3.6;...

2011-01-01

237

Sequence of Potentials Lying Between the U(5) and X(5) Symmetries  

CERN Document Server

Starting from the original collective Hamiltonian of Bohr and separating the beta and gamma variables as in the X(5) model of Iachello, an exactly soluble model corresponding to a harmonic oscillator potential in the beta-variable (to be called X(5)-$\\beta^2$) is constructed. Furthermore, it is proved that the potentials of the form $\\beta^{2n}$ (with n being integer) provide a ``bridge'' between this new X(5)-$\\beta^2$ model (occuring for n=1) and the X(5) model (corresponding to an infinite well potential in the beta-variable, materialized for n going to infinity. Parameter-free (up to overall scale factors) predictions for spectra and B(E2) transition rates are given for the potentials $\\beta^2$, $\\beta^4$, $\\beta^6$, $\\beta^8$, corresponding to E(4)/E(2) ratios of 2.646, 2.769, 2.824, and 2.852 respectively, compared to the E(4)/E(2) ratios of 2.000 ...

2004-01-01

238

Butyrate Induces Expression of 17?-Hydroxysteroid Dehydrogenase Type 1 in HT29 and SW707 Colorectal Cancer Cells  

British Library Electronic Table of Contents (United Kingdom)

Epidemiological studies have revealed that butyrate and 17?-estradiol (E2) may decrease the incidence of colorectal cancer (CRC). In peripheral tissue, E2 can be produced locally by 17?-hydroxysteroid dehydrogenase 1 (HSD17B1) estrone (E1) reduction. Using quantitative real-time polymerase chain reaction and western blotting analysis, we found that sodium butyrate significantly upregulates HSD17B1 long and short transcripts and protein levels in HT29 and SW707 CRC cells. Chromatin immunoprecipitation analysis showed that upregulation of these transcript levels correlated with an increase in binding of Polymerase II to proximal and distal promoters of HSD17B1. Moreover, we observed that upregulation of HSD17B1 protein levels was associated with increased conversion of E1 to E2 in HT29 and S...

2011-01-01

239

Studies on the interaction of lidocaine with plasma proteins  

Energy Technology Data Exchange (ETDEWEB)

This study sought to quantitate lidocaine's interaction with alpha-1-acid glycoprotein (AAG), human serum albumin (HSA), and AAG in the presence of HSA, and to determine the extent of displacement of lidocaine from its binding site(s) by selected cardiovascular drugs (dipyridamole, disopyramide and quinidine). Since the limited experimental work reported in this area has involved the use of a single lidocaine concentration, this study involved the evaluation of a range of lidocaine concentrations. Lidocaine interaction with plasma proteins (AAG and HSA) was studied at 37/sup 0/C using an isothermal equilibrium dialysis system and /sup 14/C-lidocaine HCl. A dialysis membrane (M.W. cutoff 12,000 to 14,000) separated the two chambers of each dialysis cell. The extent of /sup 14/C-lidocaine dialysis was studied with respect to both drug and protein concentrations. Aliquots of each chamber of each of the cells were subjected to liquid scintillation counting ...

1985-01-01

240

Some considerations on the processes of axon bundling and the early phases of capillarization in the CNS  

International Nuclear Information System (INIS)

Bundling of axons and capillarization of the neuroepithelium represent two of the numerous important events in brain development. Prerequisite for these two processes is a directed growth in the matrix-containing intercellular space before a final pattern is formed. The formation of the optical nerve in the region of the retina served as example to show that an extracellular substance with adhesive properties, the glycoprotein fibronectin, plays an important role during bundling and directed growth the axons. However, only small amounts of fibronectin are detected in the region of the capillary sprouts that penetrate into the neuroepithelium. In this area other substances, especially basement membrane components are present, e.g. for anchorage and stabilization. Hence, intercellular substances are also involved in the morphogenesis of the brain. Brain development comprises a great number of individual steps. Their knowledge is the prerequisite for an analysis of ...

241

Cerebral biochemical abnormalities in experimental maternal phenylketonuria: gangliosides and sialoglycoproteins  

International Nuclear Information System (INIS)

The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chloropheylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q/sub 1b/ and D_3, was a slower rise in M_1 and D/sub 1a/. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by ("3H) sialic acid released by neuraminidase from periodate-("3H) borohydride labeled glycoproteins, have mobilites of the cell adhesion ...

242

An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial  

British Library Electronic Table of Contents (United Kingdom)

Summary Background Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy. A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists. We investigated the use of an autologous, tumour-derived heat-shock protein (glycoprotein 96)-peptide complex (HSPPC-96; vitespen) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma. Methods In this open-label trial, patients were randomly assigned to receive either vitespen (n=409) or observation alone (n=409) after nephrectomy. Randomisation was done in a one to one ratio by a computer-generated pseudo-random number generator, with a block size of four, and was stratified by performance score, lymph node stat...

2008-01-01

243

Manganese-Induced NF-kB Activation and Nitrosative Stress Is Decreased by Estrogen in Juvenile Mice  

British Library Electronic Table of Contents (United Kingdom)

Manganese toxicity can cause a neurodegenerative disorder affecting cortical and basal ganglia structures with a neurological presentation resembling features of Parkinson's disease. Children are more sensitive to Mn-induced neurological dysfunction than adults, and recent studies from our laboratory revealed a marked sensitivity of male juvenile mice to neuroinflammatory injury from Mn, relative to females. To determine the role of estrogen (E2) in mediating sex-dependent vulnerability to Mn-induced neurotoxicity, we exposed transgenic mice expressing an NF-kB-driven enhanced green fluorescent protein (EGFP) reporter construct (NF-kB-EGFP mice) to Mn, postulating that supplementing male mice with E2 during juvenile development would attenuate neuroinflammatory changes associated with glia...

2011-01-01

244

Final Environmental Impact Statement to construct and operate a facility to receive, store, and dispose of 11e.(2) byproduct material near Clive, Utah (Docket No. 40-8989)  

Energy Technology Data Exchange (ETDEWEB)

A Final Environmental Impact Statement (FEIS) related to the licensing of Envirocare of Utah, Inc.`s proposed disposal facility in Tooele county, Utah (Docket No. 40-8989) for byproduct material as defined in Section 11e.(2) of the Atomic Energy Act, as amended, has been prepared by the Office of Nuclear Material Safety and Safeguards. This statement describes and evaluates the purpose of and need for the proposed action, the alternatives considered, and the environmental consequences of the proposed action. The NRC has concluded that the proposed action evaluated under the National Environmental Policy Act of 1969 (NEPA) and 10 CFR Part 51, is to permit the applicant to proceed with the project as described in this Statement.

1993-08-01

245

Targeted Capture and Next-Generation Sequencing Identifies C9orf75, Encoding Taperin, as the Mutated Gene in Nonsyndromic Deafness DFNB79  

UK PubMed Central (United Kingdom)

Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic...Full Text Available

2010-03-12

246

Signal transduction pathway controlling synthesis of a class of degradative enzymes in Bacillus subtilis: expression of the regulatory genes and analysis of mutations in degS and degU.  

UK PubMed Central (United Kingdom)

The rates of synthesis of a class of both secreted and intracellular degradative enzymes in Bacillus subtilis are controlled by a signal transduction pathway defined by at least four regulatory genes:...Full Text Available

1990-02-01

247

Relationship between O6-alkylguanine-DNA alkyltransferase activity and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation, transformation, and cytotoxicity in C3H/10T1/2 cells expressing exogenous alkyltransferase genes.  

UK PubMed Central (United Kingdom)

While a great deal of evidence has directly implicated the importance of O6-alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this lesion...Full Text Available

1992-12-01

248

Radiation accidents in the Southern Urals (1949-1967) and human genome damage.  

Science.gov (United States)

A series of radioactive catastrophes (from 1948 to 1967) in the Southern Urals in the USSR led to intensive environmental contamination. Radioactive wastes were dispersed over the 20000 km(2) territory of four provinces-Chelyabinsk, Sverdlovsk, Tyumen' and Kurgan-due to the activity of the military facility that was built in 1948 for the production of nuclear bomb plutonium. The results of 50 years of investigations into the consequences of these disasters allow a general picture of the events that occurred to be reconstructed and allow the medical consequences of the irradiation of about half a million residents to be depicted. However, due to the atmosphere of secrecy and inadequate medical procedures, the results of medical studies of radiation victims are scant. The current protocols present a unique opportunity to study the DNA damage at the nucleotide resolution level in the genome of inhabitants of the given region, who presumably received chronic doses of irradiation. Studies ...

2002-11-01

249

Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors  

UK PubMed Central (United Kingdom)

BackgroundSelection of hepatitis B virus (HBV) by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant...Full Text Available

250

ORNL `90  

Energy Technology Data Exchange (ETDEWEB)

This overview of research conducted at ORNL in 1991 presents information on the subjects of biology, physics, and the environment. Specific topics include gene mutations in kidney disease, technology assessments in thermonuclear fusion, submarine hunting technology, ozone-safe refrigerants, optical data storage via surface enhanced raman spectroscopy, and waste mitigating microbes. (GHH)

1990-12-31

251

ORNL '90  

Energy Technology Data Exchange (ETDEWEB)

This overview of research conducted at ORNL in 1991 presents information on the subjects of biology, physics, and the environment. Specific topics include gene mutations in kidney disease, technology assessments in thermonuclear fusion, submarine hunting technology, ozone-safe refrigerants, optical data storage via surface enhanced raman spectroscopy, and waste mitigating microbes. (GHH)

1990-01-01

252

Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C  

UK PubMed Central (United Kingdom)

Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm, and laryngeal muscle weakness. Two unrelated families with CMT2C showed significant...Full Text Available

2010-02-01

253

Mutations at the accommodation gate of the ribosome impair RF2-dependent translation termination  

UK PubMed Central (United Kingdom)

During protein synthesis, aminoacyl-tRNA (aa-tRNA) and release factors 1 and 2 (RF1 and RF2) have to bind at the catalytic center of the ribosome on the 50S subunit where they take part in peptide bond...Full Text Available

2010-09-01

254

Mutations Affecting Motifs of Unknown Function in the Central Domain of Nitrogen Regulatory Protein C  

UK PubMed Central (United Kingdom)

The positive control function of the bacterial enhancer-binding protein NtrC resides in its central domain, which is highly conserved among activators of ς54 holoenzyme. Previous...Full Text Available

1999-09-01

255

Mutational Analysis of the Carboxy-Terminal (YGX)4 Repeat Domain of CpsD, an Autophosphorylating Tyrosine Kinase Required for Capsule Biosynthesis in Streptococcus pneumoniae  

UK PubMed Central (United Kingdom)

In Streptococcus pneumoniae, CpsB, CpsC, and CpsD are essential for encapsulation, and mutants containing deletions of cpsB, cpsC, or cpsD...Full Text Available

2003-05-01

256

Molecular characterization of cap3A, a gene from the operon required for the synthesis of the capsule of Streptococcus pneumoniae type 3: sequencing of mutations responsible for the unencapsulated phenotype and localization of the capsular cluster on the pneumococcal chromosome.  

UK PubMed Central (United Kingdom)

The complete nucleotide sequence of the cap3A gene of Streptococcus pneumoniae, which is directly responsible for the transformation of some unencapsulated, serotype 3 mutants to the encapsulated phenotype,...Full Text Available

1994-10-01

257

Metabolomic analysis of the plant pathogenic fungi Fusarium graminearum and Fusarium culmorum  

Environmental Research Database

DescriptionThis project is part of the BBSRCs special initiative on plant and microbial metabolomics. The project will primarily focus on the trichothecene mycotoxin producing Ascomycete fungus Fusarium graminearum (Fg) which causes ear blight disease of small grain cereals. The project aims to explore the metabolome of various wild-type and single gene deletion Fg strains and to compare some of these with the identical gene mutation in the budding yeast, S. cerevisiae (Sc) and the saprophytic filamentous [continued...

2008-01-31

258

Mechanism of radiation induced carcinogenesis: does a threshold exist?  

International Nuclear Information System (INIS)

Epidemiological studies will not solve the shape of the dose effect curve for stochastic effects in the low dose range. Unicellular processes are necessary for the primary processes so that no threshold dose exists. This is evident for somatic and genetic mutations. Not clearly solved is this question for the complex carcinogenesis. These processes develop with manifold interacting molecular and cellular steps. (orig.).

1996-10-23

259

Mapping of the human cone transducin {alpha} subunit (GNAT2) gene to 1p13 and mutation analysis in patients with Stargardt`s disease  

Energy Technology Data Exchange (ETDEWEB)

Transducin {alpha} subunits are members of a large family of G-proteins and play an important role in phototransduction in rod and cone photoreceptors. We report the localization of the human cone {alpha} transducin (GNAT2) gene using fluorescence in situ hybridization (FISH) on chromosome 1 in band p13. The recent assignment of a gene for Stargardt`s disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. Stargardt`s disease is characterized by degeneration in late childhood or early adulthood of the macula of the retina, a region rich in cones. We screened patients with Stargardt`s disease, with or without peripheral cone involvement as monitored by the full-field ERG, for mutations in this gene. We investigated 66 unrelated patients including 22 with peripheral cone dysfunction for mutations in the coding region of the GNAT2 gene using polymerase ...

1994-09-01

260

Induced mutation in narrow-leafed lupin improvement: An example of herbicide tolerance  

International Nuclear Information System (INIS)

Spontaneous mutation has been discovered and utilized in domestication of narrow-leafed lupin (Lupinus angustifolius L.). As the result of the domestication, lupin has become a dominant grain legume crop in Western Australia. Facing the new challenge of developing herbicide tolerance cultivars, chemical mutagenesis has been used to create new tolerance to herbicide. This paper reports the characterization of two lupin mutants (Tanjil-AZ-33 and Tanjil-AZ-55) that are highly tolerant to metribuzin herbicide. A dose response study over 8 doses revealed that Tanjil-AZ-33 was 6 times more tolerant to metribuzin than the original parental cultivar Tanjil by measure of LD50. This mutant Tanjil-AZ-33 is the most tolerant germplasm in narrow-leafed lupin. Both mutants also maintain the high resistance to the disease anthracnose as cv Tanjil. Seed yield based on small field plots (3.6 m"2) under irrigation was 4.2 t/ha for Tanjil-AZ-33 and 1.9 t/ha for Tanjil when the ...

2008-08-12

261

Induced mutation in Lupinus mutabilis sweet in Peru  

International Nuclear Information System (INIS)

Mutagenesis of Lupinus mutabilis was started at the UNA LM (Peru) to obtain mutants with low alkaloid content and early germination. Varieties SCG 25 and Lib 020 were irradiated with gamma radiation. The optimum dose for the SCG 25 variety was 15 Krad and for Lib 020 15 to 20 Krad. The relation between the plant height and radiation dose fits the quadratic polynomial model.

1984-04-01

262

High yielding mutants in sesamum  

International Nuclear Information System (INIS)

Mutation breeding in one of the cultigens TMV-5 in Sesamum is undertaken with 5 kr, 10 kr, 15 kr, 20 kr, 60 kr and 80 kr, dosages of gamma-rays. 60 kr and 80 kr dosages were found to be lethal from the complete failure of seed germination. The mutagen had a heterotic effect on the different characters and the promising variants obtained in this programme are proposed to be maintained by pureline breeding for their possible release as new varieties. (author).

263

Handling boundary constraints for numerical optimization by particle swarm flying in periodic search space  

CERN Document Server

The periodic mode is analyzed together with two conventional boundary handling modes for particle swarm. By providing an infinite space that comprises periodic copies of original search space, it avoids possible disorganizing of particle swarm that is induced by the undesired mutations at the boundary. The results on benchmark functions show that particle swarm with periodic mode is capable of improving the search performance significantly, by compared with that of conventional modes and other algorithms.

2005-01-01

264

Genetic and somatic effects in animals maintained on tritiated water  

Energy Technology Data Exchange (ETDEWEB)

The possible genetic (dominant lethal mutations (DLM) and cytogenetic changes in the regenerating liver) and somatic (hematopoietic stem cell changes, growth and nonspecific life time shortening) effects in mice maintained on tritiated water (HTO) over two generations was investigated. Results to date are summarized. (ACR)

1981-01-01

265

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

266

Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype.  

UK PubMed Central (United Kingdom)

APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V6421, V642F and V642G have been discovered in APP695. Here we show that...Full Text Available

1996-02-01

267

Evolution of Hepatitis B Virus in a Chronic HBV-Infected Patient over 2 Years  

UK PubMed Central (United Kingdom)

Mutations in full-length HBV isolates obtained from a chronic HBV-infected patient were evaluated at three time points: 1 day, 6 months, and 31 months. While 5 nucleotides variation, and an 18 bp...Full Text Available

2011-01-01

268

Evaluation of radiation induced sesame mutants as affected by some micro nutrients  

International Nuclear Information System (INIS)

Tow experiments were carried out in 1981 and 1982 growth seasons at the greenhouse of the department of agriculture for soils and water researches, atomic energy authority, at inshas, to investigate the responses of two mutation derived lines of sesame and the local cultivar giza 25 to the application of micro nutrients. The possible effect of radiation on germination and growth of sesame seed was also studied in a separate experiment conducted in 1985 season, at inshas.

269

Ephrin B1 Regulates Bone Marrow Stromal Cell Differentiation and Bone Formation by Influencing TAZ Transactivation via Complex Formation with NHERF1?  

UK PubMed Central (United Kingdom)

Mutations of ephrin B1 in humans result in craniofrontonasal syndrome. Because little is known of the role and mechanism of action of ephrin B1 in bone, we examined the function of osteoblast-produced...Full Text Available

2010-02-01

270

Effect of mutations in HNF-1#alpha# and HNF-1#beta# on the transcriptional regulation of human sucrase-isomaltase in Caco-2 cells  

International Nuclear Information System (INIS)

Mutations in transcription factors hepatocyte nuclear factors (HNF)-1#alpha# and HNF-1#beta# cause maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. HNF-1#alpha# and HNF-1#beta# mutations are well studied in some tissues, but the mechanism by which HNF-1#alpha# and HNF-1#beta# mutations affect sucrase-isomaltase (SI) transcription in the small intestine is unclear. We studied the effects of 13 HNF-1#alpha# mutants and 2 HNF-1#beta# mutants on human SI gene transcription, which were identified in subjects with MODY3 and MODY5, respectively. Transactivation activity of 11 HNF-1#alpha# and 2 HNF-1#beta# mutants was significantly lower than that of wild (wt)-HNF-1#alpha# and wt-HNF-1#beta#. Furthermore, in co-expression studies with mutant (mu)-HNF-1#alpha#/ wt-HNF-1#beta# and wt-HNF-1#alpha#/mu-HNF-1#beta#, the combination of mu-HNF-1#alpha# (P379fsdelCT and T539fsdelC)/wt-HNF-1#beta# impaired SI ...

2004-12-03

271

Disruption of the ATP-binding Cassette B7 (ABTM-1/ABCB7) Induces Oxidative Stress and Premature Cell Death in Caenorhabditis elegans*  

UK PubMed Central (United Kingdom)

X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild anemia and ataxia. XLSA/A is caused by mutations in the ABCB7 gene, which encodes...Full Text Available

2011-06-17

272

Development of radiological emergency preparedness technology  

Energy Technology Data Exchange (ETDEWEB)

Large-scale field tracer experiments have been conducted on Ulchin, Wolsung and Daeduk sites for the purpose of validating FADAS and of analyzing the environmental characteristics around the nuclear sites. The most influential factor in atmospheric dispersion is the meteorological condition. During the experiment, meteorological data were measured on the release point and the selected positions among sampling points. Once radioactive materials are released to the atmosphere, members of public may be exposed through the environmental media such as air, soil and foods. Therefore, to protect the public, adequate countermeasures should be taken at due time for those exposure pathways. both processes, of justification and optimization are applied to a countermeasure simultaneously for decision-making. The work scope of Biological research for the radiation protection had contained the search of biological microanalytic methods for assessing the health effect by {gamma}-radiation and toxic ...

2000-04-01

273

Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels  

UK PubMed Central (United Kingdom)

Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived...Full Text Available

2009-01-01

274

Comparison of the genetic effects of equimolar doses of ENU and MNU: While the chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia, both elicit very high mutation rates in differentiating spermatogonia  

UK PubMed Central (United Kingdom)

Mutagenic, reproductive, and toxicity effects of two closely related chemicals, ethylnitrosourea (ENU) and methylnitrosourea (MNU), were compared at equimolar and near-equimolar doses in the...Full Text Available

2007-03-01

275

Comparative analysis of the ATRX promoter and 5' regulatory region reveals conserved regulatory elements which are linked to roles in neurodevelopment, alpha-globin regulation and testicular function  

UK PubMed Central (United Kingdom)

BackgroundATRX is a tightly-regulated multifunctional protein with crucial roles in mammalian development. Mutations in the ATRX gene cause ATR-X syndrome, an X-linked...Full Text Available

276

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene  

UK PubMed Central (United Kingdom)

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%....Full Text Available

277

The gamma transition from the 55/22"+[402] state to the 77/22"+[404] state in "1"7"7Ta  

International Nuclear Information System (INIS)

An experimental investigation of the 70.5 keV #gamma#-ray transition from the 55/22"+[402] state to the 77/22"+[404] ground state in "1"7"7Ta was made. The half-life and magnetic moment of the initial state were found to be 73+-5 ns and 4.7+-0.5 #mu#sub(N) respectively. The E2/M1 mixing ratio of the transition was determined to be -0.10+-0.04. The reduced transition probabilities, B(E2) and B(M1), were found to be 2.9+-2.3e"2.fm"4 and (1.1+-0.1)x10"-"4#mu#sub(N)"2, respectively, and the M1 penetration parameter was determined to be 6+-2. The Coriolis mixing amplitude of the 75/22"+[402] state in the 77/22"+[404] ground state was determined from the B(E2) value to be -0.011+-0.004. It was found that the experimental value of the Coriolis matrix element <5/2"+/j-/7/2"+>sub(exp) was one-tenth of that calculated using ...

278

Penetration effect in the M1 component of "1"7"7Ta #gamma#-transition with energy of 70.45 keV  

International Nuclear Information System (INIS)

The magnetic #beta#-spectrometer of the #pi# #sq root#2 type with 0.07% pulse resolution is used to measure the intensities of interval conversion electrons on L- and M-subshells of 70.45 keV "1"7"7 Ta gamma-transition. The results are analyzed and the values of mixing parameter #sigma#(E2/M1) and penetration parameter #lambda# are obtained.

279

On the spectral sequence from Khovanov homology to Heegaard Floer homology  

CERN Document Server

Ozsvath and Szabo show that there is a spectral sequence whose E^2 term is the reduced Khovanov homology of L, and which converges to the Heegaard Floer homology of the (orientation reversed) branched double cover of S^3 along L. We prove that the E^k term of this spectral sequence is an invariant of the link L when k>2. If L is a transverse link, then we show that Plamenevskaya's transverse invariant gives rise to a transverse invariant of L in each of these higher terms.

2008-01-01

280

Computer tomography of orbita in children  

Energy Technology Data Exchange (ETDEWEB)

The experiences are described of the examination of orbita in children using computer tomography (CT). Over a period of four years 42 examinations were performed of children in the age ranging between 7 months and 15 years, i.e., 2.7 percent of all CT examinations performed. The highest diagnostic yield was in orbita tumours. The possibilities of CT are demonstrated on examples.

1983-07-01

281

Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root.  

Science.gov (United States)

Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by ...

2007-06-24

282

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders  

British Library Electronic Table of Contents (United Kingdom)

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E2 patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.

2011-01-01

283

A pre-clinical model of double versus single unit unrelated cord blood transplantation  

UK PubMed Central (United Kingdom)

Cord blood transplantation (CBT) with units containing total nucleated cell (TNC) dose e;2.5×107/kg is associated with improved engraftment and decreased transplant-related...Full Text Available

2010-08-01

284

Nuclear structure of light Ca and heavy Cr isotopes  

Energy Technology Data Exchange (ETDEWEB)

In the present thesis, the shell structure in exotic nuclei has been investigated. The focus of the work was on finding new experimental data in neutron-rich Cr and proton-rich Ca isotopes. The investigation of light Ca isotopes concentrated on the nucleus {sup 36}Ca which was produced in a knockout reaction from a radioactive {sup 37}Ca beam. For {sup 36}Ca, the excitation energy of the first 2{sup +} state has been measured for the first time. Furthermore, momentum distributions were analyzed using a Monte-Carlo simulation of the knockout reaction. This analysis yielded the contributions of neutrons from individual orbitals to the total knockout cross section. In principle, these may be used to calculate spectroscopic factors, but such a calculation is hampered by difficulties of present knockout-reaction models in predicting precise single-particle cross sections. The measured branching ratio to the ground and excited states, on the other hand, is close to the predicted value. A ...

2007-07-01

285

SLC9A9 mutations, gene expression, and protein-protein interactions in rat models of attention-deficit/hyperactivity disorder  

British Library Electronic Table of Contents (United Kingdom)

Abstract SLC9A9 (solute carrier family 9, member 9, also known as Na+/H+ exchanger member (NHE9)) is a membrane protein that regulates the luminal pH of the recycling endosome, an essential organelle for synaptic transmission and plasticity. SLC9A9 has been implicated in human attention deficit hyperactivity disorder (ADHD) and in rat studies of hyperactivity. We examined the SLC9A9 gene sequence and expression profile in prefrontal cortex, dorsal striatum and hippocampus in two genetic rat models of ADHD. We report two mutations in a rat model of inattentive ADHD, the WKY/NCrl rat, which affect the interaction of SLC9A9 with calcineurin homologous protein (CHP). We observed an age-dependent abnormal expression of SLC9A9 in brains of this inattentive model and in the Spontaneous Hypertensi...

2011-01-01

286

Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity  

British Library Electronic Table of Contents (United Kingdom)

Coutinho MF, Encarnao M, Gomes R, da Silva Santos L, Martins S, Sirois-Gagnon D, Bargal R, Filocamo M, Raas-Rothschild A, Tappino B, Laprise C, Cury GK, Schwartz IV, Artigals O, Prata MJ, Alves S. Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity. Mucolipidosis II (ML II alpha/beta), or I-cell disease, is a rare genetic disease in which activity of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) is absent. GlcNAc-phosphotransferase is a multimeric enzyme encoded by two genes, GNPTAB and GNPTG. A spectrum of mutations in GNPTAB has been recently reported to cause ML II alpha/beta. Most of these mutations were found to be private or rare. ...

2011-01-01

287

Negative Ames-test of cis-di(thiocyanato)-N,N'-bis(4,4'-dicarboxy-2,2'-bipyridine)Ru(II), the sensitizer dye of the nanocrystalline TiO{sub 2} solar cell  

Energy Technology Data Exchange (ETDEWEB)

Dye-sensitized nanocrystalline TiO{sub 2} solar cells are currently under development. Since these cells contain an electrolyte solution we reviewed the health and safety aspects in view of indoor applications, where personal contact cannot be excluded. Only small amounts of chemicals are present in each cell and so there is no danger of acute toxicity. However, long-term effects often can be caused by incidental contact with minute amounts. For this reason we have tested cis-di(thiocyanato)-bis(4,4'-dicarboxy-2,2'-bipyridine)Ru(II), the sensitizer dye in the Ames test. The dye was not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

2000-01-01

288

Induction of mutation in Trichoderma viride for conversion of natural cellulose into glucose  

Energy Technology Data Exchange (ETDEWEB)

The production of cellulolytic enzymes from fungi has been extensively studied. Several mutants of Trichoderma reesei were selected. Most of the studies were carried out on T. reesei, T. viride, T. harzianum, Penicillium funiculosum, Altemaria alternata. Aspergillus phoenicis, A. ustus, A. tamarii, A. japonicus, and A. niger. T. koningii is one of the most active producers of the so-called C, factor, which is indispensable for the rapid and extensive attack on crystal-line cellulose. However, Trichodenna is known to excrete only small amounts of {beta}-glucosidase. Therefore, Trichoderma is supplemented with {beta}-glucosidase from Aspergillus to increase the saccharification rate of cellulose to glucose as the main sugar. Induction of mutations in Trichodenna spp. rather than T. viride as a tool for the enhancement of {beta}-glucosidase activity was reported. Unfortunately, T. reesei is a poor producer of {beta}-glucosidase. On the other hand, T. harzianum M{sub ...

1991-12-31

289

Improvement of banana through biotechnology and mutation breeding  

International Nuclear Information System (INIS)

Protocols were standardized for in vitro propagation of several elite and diverse banana accessions using shoot tip explants. Tissue culture raised plants were field planted at multiple locations. Studies were undertaken for the induction of mutations using multiple shoot cultures of six selected cultivars, Shreemanti (AAA), Basrai (AAA), Lal Kela (AAA), Rasthali (AAB), Karibale Monthan (ABB) and a wild diploid (BB). These shoot cultures were irradiated at different doses of gamma rays (0-100 Gy) and subcultured thrice (up to M_1V_3) to separate shimeras, followed by induction of rooting (M_1V_4). In general, the rate of multiplication had a negative association with the dose of gamma rays. Enhanced multiplication of shoots was noticed at lower doses. The proliferation of shoots was arrested beyond 50 Gy and a dose of 70 Gy was completely lethal for all the genotypes studied. The rooted plantlets were hardened in the green house and in the early stages of field ...

1998-10-01

290

Development of radiological emergency preparedness and biological dosimetry technology  

Energy Technology Data Exchange (ETDEWEB)

Large-scale field tracer experiments have been conducted on Ulchin and Wolsung nuclear sites for the purpose of validating FADAS and of analyzing the environmental characteristics around the nuclear site. The most influential factor in atmospheric dispersion is the meteorological condition. During the experiment, meteorological data were measured on the release point and the selected positions among sampling points. Once radioactive materials are released to the atmosphere, members of public may be exposed through the environmental media such as air, soil and foods. Therefore, to protect the public, adequate countermeasures should be taken at due time for those exposure pathways. Both processes of justification and optimization are applied to a countermeasure simultaneously for decision-making. The work scope of biological research for the radiation protection had contained the search of biological microanalytic methods for the assessment of health effect by radiation and toxic agents, ...

1999-04-01

291

Construction and evaluation of a double mutant of Shigella flexneri as a candidate for oral vaccination against shigellosis.  

Science.gov (United States)

Based on studies on the genetic and molecular basis of Shigella flexneri invasive properties, we have constructed and evaluated a double mutant of S. flexneri serotype 5 for utilization as a live attenuated oral vaccine against shigellosis. The first mutation, icsA, blocks intracellular spread of bacteria as well as cell-to-cell infection. It affects the capacity of the invasive pathogen to form large abscesses in epithelia. The second mutation, iuc, eliminates production of the siderophore aerobactin thus impairing growth of the bacterium within tissues. This double mutant, SC5700 appeared safe when administered intragastrically to macaque monkeys as three doses (5 x 10(10) c.f.u. each) at weekly intervals. Protection against a challenge by the wild type isolate (M90T) was observed 4 weeks after the last vaccine inoculation. Duration of carriage was considerably reduced as compared to the control group in which all animals had developed severe ...

1989-10-01

292

Characterization of the heterokaryotic and vegetative diploid phases of Magnaporthe grisea  

Energy Technology Data Exchange (ETDEWEB)

The heterokaryotic and vegetative diploid phases of Magnaporthe grisea, a fungal pathogen of grasses, have been characterized. Hyphal tip cells and conidia (vegetative spores) taken from these heterokaryons are auxotrophs with phenotypes identical to one or the other of the parents. M. grisea heterokaryons have completely septate hyphae with a single nucleus per cell. Heterokaryons have been utilized for complementation and dominance testing of mutations that affect nutritional characteristics of the fungus. Heterokaryons growing on minimal medium spontaneously give rise to fast-growing sectors that have the genetic properties expected of unstable heterozygous diploids. In fast-growing sectors, most hyphal tip cells are unstable prototrophs. The conidia collected from fast-growing sectors include stable and unstable prototrophs, as well as auxotrophs that exhibit a wide range of phenotypes, including many recombinant classes. Genetic linkage in meiosis has been ...

1984-01-01

293

Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport  

DEFF Research Database (Denmark)

Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that ...

2006-01-01

294

Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the human papillomavirus type 31 life cycle  

British Library Electronic Table of Contents (United Kingdom)

The E6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. E6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. In this study, we investigated the consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16 E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV 31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not alter binding to another ?-helical domain protein, E6AP. When HPV 31 genomes containing mutations a...

2007-01-01

295

Alteration of alpha 1 Na+,K(+)-ATPase "8"6Rb"+ influx by a single amino acid substitution  

International Nuclear Information System (INIS)

The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase alpha subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension.

296

Inborn Errors of Metabolism Presenting in Childhood  

British Library Electronic Table of Contents (United Kingdom)

Abstract Neurodegenerative and neurometabolic disorders may cause significant morbidity and mortality in children. Imaging is important in early diagnosis of metabolic disorders and in determining the extent of brain injury. Especially after the development of new techniques such as diffusion-weighted magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), neuroimaging plays more important role in the diagnosis and management of these disorders. In these disorders, usually a mutation causes a clinically significant block in one or more metabolic pathways. This blockage usually results in either a deficiency of the product or in an accumulation of substrate with damage induced by either storage or toxicity. The presenting symptoms are usually nonspecific. In some of the ...

2011-01-01

297

Effect of ionizing radiation and chemical mutagens on vegetatively reproducing plants. Deistvie ioniziruyushchikh izluchenii i khimicheskikh mutagenov na vegetativno razmnozhaemye rasteniya  

Energy Technology Data Exchange (ETDEWEB)

A study is made of plant sensitivity to mutagens during the processing of seeds. An examination is made of problems concerned with modification mutability, the nature of plant restoration following irradiation. Particular attention is given to mutation changes. A presentation is made of several features of mutant changes initially selected by separate indicators. An examination is made of the possible study of mutant indicator genetics. General data on the forms and varieties produced by the mutagenesis method are given. The book is designed for breeding specialists and geneticists engaged in the study of mutagenesis. 439 references, 27 figures, 66 table.

1981-01-01

298

The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3  

Energy Technology Data Exchange (ETDEWEB)

Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse ...

1996-08-01

299

GLUE-IT and PEDEL-AA: new programmes for analyzing protein diversity in randomized libraries.  

Science.gov (United States)

There are many methods for introducing random mutations into nucleic acid sequences. Previously, we described a suite of programmes for estimating the completeness and diversity of randomized DNA libraries generated by a number of these protocols. Our programmes suggested some empirical guidelines for library design; however, no information was provided regarding library diversity at the protein (rather than DNA) level. We have now updated our web server, enabling analysis of translated libraries constructed by site-saturation mutagenesis and error-prone PCR (epPCR). We introduce GLUE-Including Translation (GLUE-IT), which finds the expected amino acid completeness of libraries in which up to six codons have been independently varied (according to any user-specified randomization scheme). We provide two tools for assisting with experimental design: CodonCalculator, for assessing amino acids corresponding to given randomized codons; and AA-Calculator, for finding ...

2008-04-28

300

Apoptotic pathways as regulators of recombination  

International Nuclear Information System (INIS)

Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 domain that is known to interfere with the ability to suppress PCD (BCL-X L ...

2003-08-17

301

Alteration of nucleoside diphosphate binding specificity of E. coli elongation factor Tu (EF-Tu) by single amino acid substitution at position 138  

International Nuclear Information System (INIS)

A single amino acid substitution (Asp #-># Asn) at position 138 of E. coli EF-Tu was induced in the tufA gene by an M13 phage oligonucleotide site-directed mutagenesis protocol. The mutated tufA gene was then subcloned in a plasmid vector and expressed in maxicells. The properties of ["3"5S]methionine labelled mutant and wild type EF-Tu's were compared by in vitro assays. Mutant and wild-type EF-Tu's bound EF-Ts with approximately equal affinities. The 138-Asn mutation greatly reduced the protein's affinity for GDP; however, this mutation dramatically increased the proteins affinity for XDP. The mutant protein forms a stable complex with phe-tRNA and XTP, which binds to ribosomes; whereas, it does not form a complex with phe-tRNA and GTP. These results suggest that in EF-Tu x NDP complexes amino acid residue 138 must interact with the substituent on C-2 of the purine ring. Thus in wild-type EF-Tu Asp-138 would H-bond to ...

1987-06-07

302

Strength functions of primary transitions following thermal neutron capture in strontium  

Energy Technology Data Exchange (ETDEWEB)

The primary E1, M1 and E2 ..gamma..-radiation in /sup 87,88,89/Sr observed after thermal neutron capture was compared with the predictions of single particle and giant resonance models. The nuclei feature a wide range of neutron binding energies between 6.3 and 11.1 MeV, which makes a 5.5 MeV spectrum of primary transition energies available for investigation. The (n, ..gamma..) reaction was used to estimate the parameters of the spin-flip M1 giant resonance in strontium. The total energy weighted M1 strength of this resonance exceeds the results of shell model and random phase approximation calculations for /sup 90/Zr by a factor of 3-4. The E1 strengths were found to agree with the established giant dipole resonance model. The few data on primary E2 transitions do not allow to differentiate between the giant quadrupole resonance and the single particle models.

1989-04-01

303

Strength functions of primary transitions following thermal neutron capture in strontium  

International Nuclear Information System (INIS)

The primary E1, M1 and E2 #gamma#-radiation in "8"7","8"8","8"9Sr observed after thermal neutron capture was compared with the predictions of single particle and giant resonance models. The nuclei feature a wide range of neutron binding energies between 6.3 and 11.1 MeV, which makes a 5.5 MeV spectrum of primary transition energies available for investigation. The (n, #gamma#) reaction was used to estimate the parameters of the spin-flip M1 giant resonance in strontium. The total energy weighted M1 strength of this resonance exceeds the results of shell model and random phase approximation calculations for "9"0Zr by a factor of 3-4. The E1 strengths were found to agree with the established giant dipole resonance model. The few data on primary E2 transitions do not allow to differentiate between the giant quadrupole resonance and the single particle models. (orig.).

304

Preferential induction of cytochrome P450 1A1 over cytochrome P450 1B1 in human breast epithelial cells following exposure to quercetin  

British Library Electronic Table of Contents (United Kingdom)

Estrogen metabolism is suggested to play an important role in estrogen-induced breast carcinogenesis. Epidemiologic studies suggest that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Phytoestrogens are biologically active plant compounds that structurally mimic 17b-estradiol (E2). We hypothesize that phytoestrogens, may provide protection against breast carcinogenesis by altering the expression of estrogen-metabolizing enzymes cytochrome P450 1A1 (Cyp1A1) and 1B1 (Cyp1B1). Cyp1A1 and Cyp1B1 are responsible for the metabolism of E2 to generate 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2), respectively. Studies suggest that 2-OHE2 and 2-methoxyestradiol may protect against breast carcinogenesis, while 4-OHE2 is carcinogenic in rodent models....

2008-01-01

305

Feynman integral treatment of the Bargmann potential  

International Nuclear Information System (INIS)

A method based on path integral formulation is given for obtaining exact solution of the s states for the Bargmann potentialV(r)=1ka"2#beta#(#beta#-1)e"-"2"r"/"a1-e"-"r"/"a"2-Ae"-"r"/"a1-e"-"r"/"a,where #beta# and k are parameters. The exact energy spectrum and the normalised s-state eigenfunctions are obtained from the poles of the Green function and their residues, respectively. The results are compared with their of Schrodinger formalism, special cases are also discussed.

2005-06-01

306

Asymmetric rotor model for decoupled bands in transitional odd-mass nuclei  

International Nuclear Information System (INIS)

The high-spin states in transitional odd-mass nuclei are studied in terms of an odd quasi-particle coupled to an asymmetric rotor with a variable moment of inertia (VMI). In order to take into account the VMI, the basis states are expanded in terms of the core eigenfunctions. Excitation energies, quadrupole moments, magnetic moments, B(E2) values and B(M1) values are calculated and compared with the experimental data for nuclei in Au and La regions. On comparison with other descriptions it is found that the treatment with VMI provides a more satisfactory explanation of the data. (Auth.).

307

A combinatorial spanning tree model for knot Floer homology  

CERN Document Server

We iterate Manolescu's unoriented skein exact triangle in knot Floer homology with coefficients in the fraction field of the group ring (Z/2Z)[Z]. The result is a spectral sequence which converges to a stabilized version of delta-graded knot Floer homology. The (E_2,d_2) page of this spectral sequence is an algorithmically computable chain complex expressed in terms of spanning trees, and we show that there are no higher differentials. This gives the first combinatorial spanning tree model for knot Floer homology.

2011-01-01

308

Magnetic moment of the three-quasiparticle state in /sup 177/Ta  

Energy Technology Data Exchange (ETDEWEB)

An experimental investigation was made of the ..gamma..-transitions feeding or de-exciting the 1355 keV isomeric state in /sup 177/Ta. The E2/M1 mixing ratios for the 311 keV interband transition from the isomer and for the 271 keV and the 295 keV intraband transitions within the rotational band on the isomer were determined to be delta = 0.29sup(+0.11)sub(-0.06), 0.25sup(+0.05)sub(-0.03) and 0.30sup(+0.06)sub(-0.08), respectively, employing combined measurements of the linear polarization and angular distribution of the ..gamma..-ray with the aid of conversion electron measurements. Spin and parity assignments of the isomer were confirmed to be 21/2/sup -/. The half-life of the isomer was remeasured to be Tsub(1/2) = 5.0 +- 0.2 ..mu..s and the magnetic moment was found to be ..mu.. = 0.080 +- 0.014 ..mu..sub(N). The gsub(K) and gsub(R) factors for the band on the isomer were deduced separately to be gsub(K=21/2/sup -/) = ...

1982-06-07

309

Magnetic moment of the three-quasiparticle state in "1"7"7Ta  

International Nuclear Information System (INIS)

An experimental investigation was made of the #gamma#-transitions feeding or de-exciting the 1355 keV isomeric state in "1"7"7Ta. The E2/M1 mixing ratios for the 311 keV interband transition from the isomer and for the 271 keV and the 295 keV intraband transitions within the rotational band on the isomer were determined to be delta = 0.29sup(+0.11)sub(-0.06), 0.25sup(+0.05)sub(-0.03) and 0.30sup(+0.06)sub(-0.08), respectively, employing combined measurements of the linear polarization and angular distribution of the #gamma#-ray with the aid of conversion electron measurements. Spin and parity assignments of the isomer were confirmed to be 21/2"-. The half-life of the isomer was remeasured to be Tsub(1/2) = 5.0 +- 0.2 #mu#s and the magnetic moment was found to be #mu# = 0.080 +- 0.014 #mu#sub(N). The gsub(K) and gsub(R) factors for the band on the isomer were deduced separately to be gsub(K=21/2"-) = 0.062sup(+0.011)sub(-0.008) and gsub(R) = ...

310

In vivo footprinting of the human [alpha]-globin locus upstream regulatory element by guanine and adenine ligation-mediated polymerase chain reaction  

Energy Technology Data Exchange (ETDEWEB)

A major regulatory element required for expression of the human [alpha]-globin genes is located 40 kb upstream of the embryonic [zeta]-globin gene. To understand how this and other locus control region (LCR) elements contribute to high-level expression in erythroid cells, we have performed high-resolution, in vivo dimethyl sulfate footprinting. In addition, we have modified the dimethyl sulfate-based ligation-mediated polymerase chain reaction in vivo footprinting procedure to permit the assessment of interactions at guanine and adenine residues, rather than guanines alone. In vivo footprinting of the human [alpha]-LCR element carried on chromosome 16 in a mouse erythroleukemia cell environment revealed protein occupancy at GATA-1, AP-1/NF-E2, and CACC/GGTGG motifs, specific differences compared with in vitro protein binding, and distinct changes in one region upon dimethyl sulfoxide-induced cellular maturation. No protein contacts were ...

1992-05-01

311

Effects of postoperative adjuvant chemotherapy and radiotherapy on ovarian function in women undergoing treatment for soft tissue sarcoma  

Energy Technology Data Exchange (ETDEWEB)

Ovarian function was evaluated in 11 women 16 to 43 years of age at treatment who received doxorubicin, cyclophosphamide, and high doses of methotrexate with or without radiotherapy in adjuvant therapy of soft tissue sarcoma. Five women (16-33 yr old) who received chemotherapy alone or combined with radiotherapy only at sites distant from the ovaries (chest wall, thigh, and leg) had minimal menstrual irregularities or temporary cessation of menses during therapy; cyclic menses returned promptly after therapy. Gonadotropin levels (expressed as means +/- SD (follicle-stimulating hormone (FSH), 10 +/- 5 mlU/ml; luteinizing hormone (LH), 10 +/- 4 mlU/ml) and 17 beta-estradiol (E2) levels (means +/- SD, 208 +/- 147 pg/ml) were normal. By contrast, 4 older women (ages 36-43 yr) who received similar treatment developed persistent amenorrhea with postmenopausal levels of gonadotropin (FSH, 108 +/- 29 mlU/ml; LH, 72 +/- 19 mlU/ml) and ...

1981-12-01

312

Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1.  

Science.gov (United States)

Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into human corneal ...

2011-08-26

313

Therapeutic efficacy of intralesional 131I-labelled hyaluronectin in grafted human glioblastoma  

Energy Technology Data Exchange (ETDEWEB)

The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN). 131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 {mu}Ci/{mu}gHN, 1 {mu}g chloramine-T/{mu}gHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the tumour. On day 4 the radioactivity concentrated in the tumour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 {mu}Ci 131I-HN was injected into the tumour, resulting in a delivery of 6.8 Gy over a 7-day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free ...

2000-07-01

314

The role of the mesenchyme in mouse neural fold elevation. II. Patterns of hyaluronate synthesis and distribution in embryos developing in vitro  

Energy Technology Data Exchange (ETDEWEB)

Hyaluronate (HA) distribution patterns were examined in the cranial mesenchyme underlying the mesencephalic neural folds of mouse embryos maintained in roller tube culture. Using standard image-processing techniques, the digitized images of Alcian blue-stained or 3H-glucosamine-labeled sections digested with an enzyme specific for HA, were subtracted from adjacent, undigested sections. The resultant difference picture images (DPI) accurately depicted the distribution of stained or labeled HA within the cranial mesenchyme. 3H-glucosamine-labeled HA was distributed uniformly throughout the cranial mesenchyme as 12, 18, and 24 hr of culture. By contrast, the mesenchyme was uniformly stained with Alcian blue at 12 hr, but stain intensity decreased in the central regions of the mesenchyme at 18 and 24 hr. HA distribution patterns were also examined in the cranial mesenchyme of embryos cultured in the presence of diazo-oxo-norleucine (DON), a glutamine analogue that inhibits ...

1990-06-01

315

Platelet fibrinogen binding in Basset Hound Hereditary Thrombopathy  

Energy Technology Data Exchange (ETDEWEB)

Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10/sup -5/M ADP in the presence of /sup 125/I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- 3971 molecules of ...

1986-03-01

316

Photoaffinity labeling of ATP and NAD"+ binding sites on recombinant human interleukin 2  

International Nuclear Information System (INIS)

Interleukin 2 (IL-2) is a T-cell-derived lymphokine critical in the activation and proliferation of T cells, B cells, and lymphokine-activated killer cells. It is a glycoprotein of #approx#15,500 daltons that is synthesized and secreted after activation by antigen or mitogen. By using the analogs 8-azidoadensoine 5'-[#gamma#-"3"2P]triphosphate ([#gamma#-"3"2P]8N_3ATP) and nicotinamide 2-azidoadenine [adenylate-"3"2P]dinucleotide ([#alpha#-"3"2P]2N_3NAD"+) as photoaffinity probes, the authors have detected specific, metal ion-requiring nucleotide binding sites on recombinant human IL-2 (rhIL-2). The specificity of these nucleotide interactions with rhIL-2 was demonstrated by saturation effects and by competition by the parent nucleotides at physiologically relevant concentrations. Saturation of photoinsertion into rhIL-2 occurred at 50 #mu#M [#gamma#-"3"2P]8N_3ATP. Saturation of photoinsertion with [#alpha#-"3"2P]2N_3NAD"+ was observed at 180 #mu#M. The extent of ...

317

Olfactomedin 4 suppresses prostate cancer cell growth and metastasis via negative interaction with cathepsin D and SDF-1.  

Science.gov (United States)

The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through ...

2011-04-05

318

Functional and physical molecular size of the chicken hepatic lectin determined by radiation inactivation and sedimentation equilibrium analysis  

Energy Technology Data Exchange (ETDEWEB)

Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified binding protein yielded a lower limit molecular weight of 79,000 +/- 7,000. However, the ...

1990-03-05

319

Development of an assay for a biomarker of pregnancy and early fetal loss  

Energy Technology Data Exchange (ETDEWEB)

Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodies that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with ...

1987-10-01

320

Characterization of hyaluronate binding proteins isolated from 3T3 and murine sarcoma virus transformed 3T3 cells  

Energy Technology Data Exchange (ETDEWEB)

A hyaluronic acid binding fraction was purified from the supernatant media of both 3T3 and murine sarcoma virus (MSV) transformed 3T3 cultures by hyaluronate and immunoaffinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the hyaluronate affinity-purified fraction into three major protein bands of estimated molecular weight (M/sub r,e/) 70K, 66K, and 56K which contained hyaluronate binding activity and which were termed hyaluronate binding proteins (HABP). Hyaluronate affinity chromatography combined with immunoaffinity chromatography, using antibody directed against the larger HABP, allowed a 20-fold purification of HABP. Fractions isolated from 3T3 supernatant medium also contained additional binding molecules in the molecular weight range of 20K. This material was present in vanishingly small amounts and was not detected with a silver stain or with (/sup 35/S)methionine label. The three protein species isolated by hyaluronate affinity ...

1987-06-02

321

The effects of chemicals in the presence of cellophane on X-ray-induced point mutation and gene conversion in Aspergillus midulans  

International Nuclear Information System (INIS)

The presence of washed or unwashed cellophane alone or together with a bleomycin, mitomycin C or hydrochlorothiazide, ('Esidrex') showed no appreciable effect on survival of either unirradiated or irradiated conidia. Irradiation for a period of 20min reduced the survival of conidia to 20%. The growth of irradiated conidia in the presence of bleomycin, mitomycin C or Esidrex is associated with a 2- to 3-fold increase in the frequency of gene convertants, but was not accompanied by an increase in point mutants. When conidia were grown on cellophane but otherwise treated as before the frequency of gene convertants was increased 8-fold, but induction of point mutants was negligible. This effect was the same for irradiated and unirradiated conidia. The environment created by the cellophane in contract with the medium appears to affect the action of each of the three compounds synergistically. (author).

322

The DFNA5 gene, responsible for hearing loss and involved in cancer, encodes a novel apoptosis-inducing protein  

British Library Electronic Table of Contents (United Kingdom)

DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection ...

2011-01-01

323

Sodium-driven motor of the polar flagellum in marine bacteria Vibrio  

British Library Electronic Table of Contents (United Kingdom)

The Na+-driven bacterial flagellar motor is a molecular machine powered by an electrochemical potential gradient of sodium ions across the cytoplasmic membrane. The marine bacterium Vibrio alginolyticus has a single polar flagellum that enables it to swim in liquid. The flagellar motor contains a basal body and a stator complexes, which are composed of several proteins. PomA, PomB, MotX, and MotY are thought to be essential components of the stator that are required to generate the torque of the rotation. Several mutations have been investigated to understand the characteristics and function of the ion channel in the stator and the mechanism of its assembly around the rotor to complete the motor. In this review, we summarize recent results of the Na+-driven motor in the polar flagellum of ...

2011-01-01

324

Prostate cancer immunology - an update for Urologists  

British Library Electronic Table of Contents (United Kingdom)

A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the...

2011-01-01

325

New Public Management et professions dans l'Etat : au-dela des oppositions, quelles recompositions ?  

British Library Electronic Table of Contents (United Kingdom)

More and more reforms in public administrations are being conducted that are based on the principles and instruments of ''new public management''. They have set off protest and collective actions by several professional groups in various sectors (health, education, justice, social work, research...), whence questions about the future of professional groups in public services, in particular about their autonomy, which these reforms threaten. The opposition between this new public management and certain professional groups, is not the final explanation to draw from an analysis of this situation. Should these changes be seen as the decline of professional groups and of their autonomy, as a mutation of professional models, an overhaul of professionalism, etc.? These questions, which current ev...

2011-01-01

326

Molecular analysis of polymerase gamma gene and mitochondrial polymorphism in fertile and subfertile men  

British Library Electronic Table of Contents (United Kingdom)

Summary CAG trinucleotide repeat length in the nuclear polymerase gamma gene (POLg) has been shown to be associated with men with reduced fertility. The present study investigated the frequency of CAG repeat length genotypes and three exonuclease motifs of the POLg in relation to the frequency of mitochondrial nucleotide substitutions. DNA from semen samples of 93 normozoospermic men and 192 non-normozoospermic men was isolated and the specific regions of the genes were amplified by polymerase chain reactions (PCR) and sequenced to identify mutations. The genotypic frequencies of pooled POLg CAG repeat lengths, =10/!=10 heterozygotes and !=10/!=10 homozygotes, were significantly different between normozoospermic and non-normozoospermic men (p p POLg genotype. Of the 17 men with non-synonym...

2006-01-01

327

Metabolic engineering of carotenoid accumulation by creating a metabolic sink  

British Library Electronic Table of Contents (United Kingdom)

Carotenoids are highly beneficial for human nutrition and health because they provide essential nutrients and important antioxidants in our diets. However, many food crops, especially the major staple crops contain only trace to low amounts of carotenoids. Although significant progress has been made in developing food crops rich in carotenoids by altering the expression of carotenoid biosynthetic genes, in many cases it has proved to be difficult to reach the desired levels of carotenoid enrichment. The recent identification and characterization of a novel gene mutation in cauliflower reveals that creating a metabolic sink to sequester carotenoids is an important mechanism to control carotenoid accumulation in plants. The successful demonstration of increased carotenoid accumulation in ass...

2007-01-01

328

Identification of a functional nuclear export signal in the green fluorescent protein asFP499  

International Nuclear Information System (INIS)

The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified _1_9_4LRMEKLNI_2_0_1 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES.

2006-04-21

329

IAEA RESEARCH CONTRACTS FIRST ANNUAL REPORT. Technical reports Series No. 4  

Science.gov (United States)

Summaries are included of research contracts which expired prior to Dec. 31, 1960. The contracts were concerned with investigations of: electrophysiological responses of biological systems in nerve cells to irradiation with small doses of ionizing radiations; the mode of the protective action of certain sulfhydryl compounds against radiation effects on the synthesis of deoxyribonucleic acid, using tritium-labeled thymidine; development of a bubble chamber method of monitoring and dosimetry for Low fast neutron fluxes; effects of incorporated radioisotopes on the stability of genetic materials; interrelation of root and leaf absorption of radioisotopes in herbaceous plants; uptake of radioactive wastes by lowland rice from soils contaminated by irrigation water, and decontamination of the rice; and comparison between mutation rates induced by acute and chronic gamma irradiations. (B.O.G.)

1961-01-01

330

Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts  

British Library Electronic Table of Contents (United Kingdom)

Mutations in sclerostin function or expression cause sclerosing bone dysplasias, involving decreased antagonism of Wnt/Lrp5 signaling. Conversely, deletion of the VHL tumor suppressor in osteoblasts, which stabilize HIF-a isoforms and thereby enables HIF-a/b-driven gene transcription, increases bone mineral content and cross-sectional area compared to wild-type controls. We examined the influence of cellular hypoxia (1% oxygen) upon sclerostin expression and canonical Wnt signaling. Osteoblasts and osteocytes cultured under hypoxia revealed decreased sclerostin transcript and protein, and increased expression and nuclear localization of activated b-catenin. Similarly, both hypoxia and the hypoxia mimetic DFO increased b-catenin gene reporter activity. Hypoxia and its mimetics increased exp...

2010-01-01

331

Genetic testing for hereditary cancer: Effects of alexithymia and coping strategies on variations in anxiety before and after result disclosure  

British Library Electronic Table of Contents (United Kingdom)

This study assessed the impact of the results of genetic testing for hereditary cancer from a multifactorial health psychology perspective, considering that emotional expression plays a key role in psychological adjustment. Measures of dispositional and transactional coping strategies, anxiety and alexithymia were filled out by 77 participants in a longitudinal study design. Statistical analyses were performed using general linear models and partial least squares path modelling, low-constraint methods that are particularly useful in the behavioural sciences. While anxiety levels prior to the result announcement were predictive of the distress experienced by noncarriers, considerable variability was observed for mutation carriers. Some subjects who had lower anxiety levels before the test d...

2011-01-01

332

Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters  

British Library Electronic Table of Contents (United Kingdom)

Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animals exhibiting altered valu...

2011-01-01

333

Functional and Oncologic Outcomes of Partial Adrenalectomy for Pheochromocytoma in Patients With von Hippel-Lindau Syndrome After at Least 5 Years of Followup  

British Library Electronic Table of Contents (United Kingdom)

PurposeAlthough the safety and feasibility of partial adrenalectomy in patients with von Hippel-Lindau syndrome have been established, long-term outcomes have not been examined. In this study we evaluate the recurrence and functional outcomes in a von Hippel-Lindau syndrome cohort treated for pheochromocytoma with partial adrenalectomy with a followup of at least 5 years. Materials and MethodsWe reviewed the records of patients with von Hippel-Lindau syndrome treated with partial adrenalectomy for pheochromocytoma at the National Cancer Institute. Demographic, germline mutation status, surgical indication, oncologic and functional outcome data were collected. Local recurrence was defined as radiographic evidence of recurrent tumor on the ipsilateral side of partial adrenalectomy. Patients ...

2010-01-01

334

Effects of chemicals in the presence of cellophane on X-ray-induced point mutation and gene conversion in Aspergillus midulans  

Energy Technology Data Exchange (ETDEWEB)

The presence of washed or unwashed cellophane alone or together with a bleomycin, mitomycin C or hydrochlorothiazide, ('Esidrex') showed no appreciable effect on survival of either unirradiated or irradiated conidia. Irradiation for a period of 20min reduced the survival of conidia to 20%. The growth of irradiated conidia in the presence of bleomycin, mitomycin C or Esidrex is associated with a 2- to 3-fold increase in the frequency of gene convertants, but was not accompanied by an increase in point mutants. When conidia were grown on cellophane but otherwise treated as before the frequency of gene convertants was increased 8-fold, but induction of point mutants was negligible. This effect was the same for irradiated and unirradiated conidia. The environment created by the cellophane in contract with the medium appears to affect the action of each of the three compounds synergistically.

1984-08-01

335

Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder - a preliminary study  

British Library Electronic Table of Contents (United Kingdom)

Please cite this paper as: Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder - a preliminary study. Experimental Dermatology 2008; 17: 203-207. Abstract: Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6-/- mice. Three groups were fed a specific di...

2008-01-01

336

Cyclosporine metabolic side effects: association with the WNK4 system  

British Library Electronic Table of Contents (United Kingdom)

Abstract Background- Cyclosporine is used for treatment of transplanted patients and for immune-mediated diseases. Cyclosporine is known to cause a combination of metabolic side effects including hypertension, hyperkalemia, hypercalciuria and hypomagnesemia. These side effects except for hypomagnesemia are the cardinal features of familial hyperkalemia and hypertension (FHHt), also called pseudohypoaldosteronism type II (PHA II). FHHt is caused by mutations in the kinases WNK1 and WNK4 resulting in an increase in renal Na-Cl cotransporter (NCC) apical distribution and function. Therefore, we studied whether cyclosporine-s metabolic side effects are mediated by WNK4 and NCC. Design- Sprague-Dawley (SD) rats were treated by cyclosporine 25-mg-kg-1 subcutaneously for 14-days. Blood pressure, ...

2011-01-01

337

Characteristics of radiation-induced neoplastic transformation in vitro  

Energy Technology Data Exchange (ETDEWEB)

Data are presented to support the hypothesis that the initial step in the morphologic transformation of irradiated rodent (BALB/3T3) cells is a frequent cellular event involving a large fraction of the irradiated population. This process appears to involve DNA damage, but not to represent a targeted mutation in specific structural gene(s). Morphologic transformation and immortalization appear to be distinct steps in the overall process of transformation. In contradistinction to rodent cells, immortalization is a very rare event in human diploid cells which is induced at extremely low frequencies. The hypothesis is presented that immortality develops among clones of cells bearing stable chromosomal rearrangements which emerge during the proliferation of a population of radiation damaged cells.

1986-01-01

338

An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes  

Energy Technology Data Exchange (ETDEWEB)

The authors have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken {beta}-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.

1988-08-01

339

Amphiphysin (Amph) maps to the proximal region of mouse chromosome 13  

Energy Technology Data Exchange (ETDEWEB)

Amphiphysin is a protein concentrated in neuronal synapses and peripherally associated with neurotransmitter vesicles. It is expressed in many neurons of the central and peripheral nervous systems, in the adrenal medulla, in the anterior and posterior pituitary, in cell lines of the endocrine pancreas, and in spermatocytes. Its subcellular localization and tissue distribution indicate a potential involvement in mechanisms of regulated exocytosis. A role in the dynamic organization of the membrane-associated cytoskeleton is suggested by structural homology to the products of two yeast genes, RVS161 and RVS167, whose mutation results in an abnormal actin distribution, disturbs budding morphology, and impairs cell entry into stationary phase. Limited stretches of sequence similarity, including an SH3 domain, are also shared with other actin-binding proteins. Amphiphysin is the dominant autoantigen in paraneoplastic Stiff-Man syndrome, a neurological autoimmune ...

1995-07-20

340

A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in a-synuclein transgenic C. elegans  

British Library Electronic Table of Contents (United Kingdom)

Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...

2008-01-01

341

A PAC containing the human mitochondrial DNA polymerase gamma gene (POLG) maps to chromosome 15q25  

Energy Technology Data Exchange (ETDEWEB)

The human mitochondrial DNA (mtDNA) is a closed circular, 16,569-bp double-stranded DNA, encoding 13 genes whose protein products are subunits of the oxidative phosphorylation system required for synthesis of most of the ATP consumed by eukaryotic cells. Point mutations of the mtDNA that cause multi-tissue, loss-of-energy syndromes, called mitochondrial encephalomyopathies (e.g., MERRF and MELAS), have been identified. In addition, large-scale deletions of the human mtDNA have been identified and are the molecular bases for the neonatal and adolescent onset loss-of-energy syndromes Pearson and Kearns-Sayer, respectively. 5 refs., 1 fig.

1997-03-01

342

The BAIKAL Neutrino Experiment: From NT200 to NT200+  

CERN Document Server

The Baikal Neutrino Telescope has been operating in its NT200 configuration since April, 1998. The telescope has been upgraded in April, 2005, to the 10 Mton scale detector NT200+. It's main physics goal is the detection of signals from high energy neutrino cascades. NT200+ reaches a 3-year sensitivity of 2 \\times 10^{-7}cm^{-2}s^{-1}sr^{-1}GeV for an all-flavor diffuse cosmic E^{-2} neutrino flux for energies 10^2 TeV \\div 10^5 TeV. Desgin and sensitivity of NT200+ are described. NT200+ is forming the basic building block of a future km3-scale (Gigaton-Volume) Baikal Telescope. Research and development work on that next stage detector has started.

2006-01-01

343

Rotational structures in {sup 177}Ta  

Energy Technology Data Exchange (ETDEWEB)

High-spin states in {sup 177}Ta were produced using the {sup 170}Er({sup 11}B, 4{ital n}) reaction at 55 and 60 MeV. Considerable extensions have been made to the previously known level scheme, and new structures have been found. {ital B}({ital M}1)/{ital B}({ital E}2) ratios have been extracted for strongly coupled bands. The behavior of the different rotational cascades, in particular the anomalous crossing frequency observed in the [541]1/2{sup {minus}} proton {ital h}{sub 9/2} band and the occurrence of ``identical bands,`` is discussed. Comparisons are made with projected shell model calculations.

1995-09-01

344

Rotational structures in "1"7"7Ta  

International Nuclear Information System (INIS)

High-spin states in "1"7"7Ta were produced using the "1"7"0Er("1"1B, 4n) reaction at 55 and 60 MeV. Considerable extensions have been made to the previously known level scheme, and new structures have been found. B(M1)/B(E2) ratios have been extracted for strongly coupled bands. The behavior of the different rotational cascades, in particular the anomalous crossing frequency observed in the [541]1/2"- proton h_9_/_2 band and the occurrence of ''identical bands,'' is discussed. Comparisons are made with projected shell model calculations.

345

Reliability data update method for emergency diesel generator of Daya Bay Nuclear Power Plant  

British Library Electronic Table of Contents (United Kingdom)

In the field of Living Probabilistic Safety Assessment (LPSA) the reliability data updating is an important factor. In risk analysis equipment failure data is needed to estimate the frequencies of events contributing to risk posed by a facility. Five years data of emergency diesel generator (EDG) of Daya Bay Nuclear Power Plant (NPP) has been studied in this paper. The data updating process has been done by using two methods, i.e., the classical method and Bayesian method. The aim of using these methods is to calculate the operational failure rate (@l) and demand failure probability (p). The results show that the operational failure rate is 1.7E-3 per hour and the demand failure probability is 2.4E-2 demand per day for Daya Bay NPP. By comparing the results obtain from classical and Bayesi...

2011-01-01

346

Real-time imaging for neutron radiography at KURRI  

International Nuclear Information System (INIS)

For neutron radiography (NR), photographic techniques have been mainly used for many years. To observe a dynamic event and to test many samples, the real-time neutron radiography (i.e. neutron television - NTV) system has been introduced at the E-2 experimental tube of the Kyoto University Research Reactor (KUR). The NTV system has been practically applied to penetrating the side plates containing boron burnable poison to test MTR type reactor fuel, to investigation of moving objects and to neutron computed tomography (NCT). New approaches using some advanced neutron converters, a high sensitive and resolution TV camera and a high performance image processing system are being undertaken for standard indicators, visualization on air-water two-phase flow, NCT and so on. (author).

1987-07-01

347

Charged particle decay from giant monopole resonance in sup 28 Si  

Energy Technology Data Exchange (ETDEWEB)

Proton and alpha decay from the giant resonance region of {sup 28}Si excited with a 129 MeV alpha particle beam has been measured in coincidence with inelastic alpha particles detected at 0{degree}. The angular correlation data show the presence of decay from both {ital E}0 and {ital E}2 giant resonances. The {ital E}0 giant resonance decays primarily through the {alpha}{sub 0}, {alpha}{sub 1}, {ital p}{sub 0}, and {ital p}{sub 1,2} channels with the branching ratios 18{plus minus}6 %, 24{plus minus}8 %, 23{plus minus}9 %, and 18{plus minus}8 %, respectively. Substantial direct decay is observed.

1990-04-01

348

Balance with Unbounded Complexes  

CERN Document Server

Given a double complex $X$ there are spectral sequences with the $E_2$ terms being either H$_I$ (H$_{II}(X))$ or H$_{II}($H$_I (X))$. But if $H_I(X)=H_{II}(X)=0$ both spectral sequences have all their terms 0. This can happen even though there is nonzero (co)homology of interest associated with $X$. This is frequently the case when dealing with Tate (co)homology. So in this situation the spectral sequences may not give any information about the (co)homology of interest. In this article we give a different way of constructing homology groups of $X$ when H$_I(X)=$H$_{II}(X)=0$. With this result we give a new and elementary proof of balance of Tate homology and cohomology.

2011-01-01

349

Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root  

British Library Electronic Table of Contents (United Kingdom)

Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17b-estradiol (E2), although glycyrrhizin di...

2007-01-01

350

Radiation effects on shoot tip culture of chrysanthemum, 2  

International Nuclear Information System (INIS)

(1) Young chrysanthemums were planted after being irradiated at the time of shoot tip culture and the influence of irradiation was evaluated from the point of view of establishment of mutants. (2) Two cultivars, Kin-tenryu and Tenryu-no-asa were used in this experiment. The percentage of cultivars healthy enough to transplant on June 10, 1972 showed a decrease in proportion to the increase of dosage. Some plants of cultivar Kin-tenryu died after being transplanted. (3) Few plants of either cultivar could overwinter, and in particular no plant irradiated by gamma-rays of 20 kR. (4) Plant height showed a tendency of inhibition in both cultivars. (5) Three chlorophyll mutants showing chimera appeared. One of them was in the cultivar Tenryu-no-asa irradiated by 10 kR at 3 days after planting; two of them were in the cultivar Tenryu-no-asa irradiated by 10 kR at 5 days after planting. One mutant exhibiting malformation of entire leaves appeared in the cultivar Kin-tenryu irradiated by 20 kR ...

351

One-step RNA pathogen detection with reverse transcriptase activity of a mutated thermostable Thermus aquaticus DNA polymerase.  

Science.gov (United States)

We describe the cloning and characterization of a mutated thermostable DNA polymerase from Thermus aquaticus (Taq) that exhibits an increased reverse transcriptase activity and is therefore designated for one-step PCR pathogen detection using established real-time detection methods. We demonstrate that this Taq polymerase mutant (Taq M1) has similar PCR sensitivity and nuclease activity as the respective Taq wild-type DNA polymerase. In addition, and in marked contrast to the wild-type, Taq M1 exhibits a significantly increased reverse transcriptase activity especially at high temperatures (>60 degrees C). RNA generally hosts highly stable secondary structure motifs, such as hairpins and G-quadruplexes, which complicate, or in the worst case obviate, reverse transcription (RT). Thus, RT at high temperatures is desired to weaken or melt secondary structure motifs. To demonstrate the ability of Taq M1 for RNA detection of pathogens, we performed TaqMan probe-based ...

2010-02-01

352

Novel method for differentiation between Trastuzumab and host adaptive response.  

Science.gov (United States)

Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human ...

2011-06-08

353

Magnetic resonance imaging of cerebral anomalies in subjects with resistance to thyroid hormone  

Energy Technology Data Exchange (ETDEWEB)

Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of six contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl`s ...

1995-06-19

354

Association of attention-deficit disorder and the dopamine transporter gene  

Energy Technology Data Exchange (ETDEWEB)

Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter, including methylphenidate, amphetamine, pemoline, and bupropion, led us to consider the dopamine transporter as a primary candidate gene for ADHD. To avoid effects of population stratification and to avoid the problem of classification of relatives with other psychiatric disorders as affected or unaffected, we used the haplotype-based haplotype relative risk (HHRR) method to test for association between a VNTR polymorphism at the dopamine transporter locus (DAT1) and DSM-III-R-diagnosed ADHD (N = 49) and undifferentiated attention-deficit disorder (UADD) (N = 8) in trios composed of father, mother, and affected offspring. HHRR analysis revealed significant association ...

1995-04-01

355

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 ...

2011-07-19

356

A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses  

International Nuclear Information System (INIS)

We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinant AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results ...

2010-09-01

357

A single amino acid substitution (R441A) in the receptor-binding domain of SARS coronavirus spike protein disrupts the antigenic structure and binding activity  

International Nuclear Information System (INIS)

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not bind to soluble and ...

2006-05-26

358

Regulation of sulfated glycosaminoglycan production by prostaglandin E2 in cultured lung fibroblasts  

Energy Technology Data Exchange (ETDEWEB)

Prostaglandin E2 (PGE2) has been shown to increase the synthesis of hyaluronic acid in cultured fibroblasts by increasing the activity of hyaluronate synthetase, a group of plasma membrane-bound synthetic enzymes. We examined whether PGE2 also increased the activity of those enzyme systems involved in the synthesis of sulfated glycosaminoglycan in the human embryonic lung fibroblast. Exposure of cells to PGE2 resulted in dose-dependent increases in glucosamine incorporation into all sulfated glycosaminoglycan subtypes. PGE2 at 10(-7) mol/L increased total glycosaminoglycan per dish to 21.6 +/- 3.1 micrograms versus 12.0 +/- 2.5 micrograms in control untreated cultures. Stimulation of endogenous PGE2 production by bradykinin had a similar effect on glycosaminoglycan synthesis. To examine whether PGE2 affected sulfated glycosaminoglycan protein core production, cells were labeled with tritiated glucosamine in the presence of cycloheximide. Under ...

1989-08-01

359

p53 protein in aggressive and non-aggressive basal cell carcinoma.  

Science.gov (United States)

Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm, with a generally favorable clinical behavior. Sometimes, indeed, it recurs after therapy and/or metastasizes. As point mutations in the coding sequence of the p53 tumor suppressor gene have been implicated in the progression of many human tumors, we studied the expression of p53 protein on this neoplasia. We tested immunohistochemically the positivity for p53 protein (NCL-p53-CM1, YLEM) on 19 cases of morphologically "non aggressive" BCC (BCC1) and on 19 "aggressive" BCC (BCC2), all with one or more relapses and 3 with distant metastases also. Results were related to clinico-pathological and follow-up data. All but one BCC2 were found positive for p53 protein. Conversely, only 2 cases of BCC1 exhibited low immunoreactivity for p53 protein, with high statistical differences between the two groups. No correlation was found between the immunoreactivity, age of patients, and site of the lesions. The ...

1993-10-01

360

Vibrational spectroscopy of bacteriorhodopsin mutants: light-driven proton transport involves protonation changes of aspartic acid residues 85, 96, and 212  

Energy Technology Data Exchange (ETDEWEB)

Fourier transform infrared (FTIR) difference spectra have been obtained for the bR----K, bR----L, and bR----M photoreactions in bacteriorhodopsin mutants in which Asp residues 85, 96, 115, and 212 have been replaced by Asn and by Glu. Difference peaks that had previously been attributed to Asp COOH groups on the basis of isotopic labeling were absent or shifted in these mutants. In general, each COOH peak was affected strongly by mutation at only one of the four residues. Thus, it was possible to assign each peak tentatively to a particular Asp. From these assignments, a model for the proton-pumping mechanism of bR is derived, which features proton transfers among Asp-85, -96, and -212, the chromophore Schiff base, and other ionizable groups within the protein. The model can explain the observed COOH peaks in the FTIR difference spectra of bR photointermediates and could also account for other recent results on site-directed mutants of bR.

1988-11-15

361

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 ...

1996-09-01

362

The mouse formin (Fmn) gene: Genomic structure, novel exons, and genetic mapping  

Energy Technology Data Exchange (ETDEWEB)

Mutations in the mouse formin (Fmn) gene, formerly known as the limb deformity (ld) gene, give rise to recessively inherited limb deformities and renal malformations or aplasia. The Fmn gene encodes many differentially processed transcripts that are expressed in both adult and embryonic tissues. To study the genomic organization of the Fmn locus, we have used Fmn probes to isolate and characterize genomic clones spanning 500 kb. Our analysis of these clones shows that the Fmn gene is composed of at least 24 exons and spans 400 kb. We have identified two novel exons that are expressed in the developing embryonic limb bud as well as adult tissues such as brain and kidney. We have also used a microsatellite polymorphism from within the Fmn gene to map it genetically to a 2.2-cM interval between D2Mit58 and D2Mit103. 36 refs., 6 figs., 1 tab.

1997-02-01

363

The Origin of Life from Primordial Planets  

CERN Document Server

The origin of life and the origin of the universe represent two of the most important problems of science. Both are resolved by hydro-gravitational dynamics (HGD) cosmology (Gibson 1996, Schild 1996, Gibson 2009ab), which predicts frozen primordial hydrogen-helium gas planets in clumps as the dark matter of galaxies. Merging Earth-mass planets formed stars, moons and comets to incubate and cosmically seed the first life. Cometary panspermia (Hoyle and Wickramasinghe 1981, 1982; Wickramasinghe et al. 2009) occurs naturally by HGD mechanisms. Comets and moons are fragments from mergers of stardust covered frozen gas planets in their step-wise growth to star mass. Supernovae from stellar over-accretion of planets produce stardust (C, N, O, P etc.) chemical fertilizer. Planets collect this infected radioactive dust gravitationally, to provide liquid water domains in contact with life nutrients seeded with life prototypes. The first mutating, evolving, life from HGD ...

2010-01-01

364

The 2001 Superoutburst of WZ Sagittae  

CERN Document Server

We report the results of a worldwide campaign to observe WZ Sagittae during its 2001 superoutburst. After a 23-year slumber at V=15.5, the star rose within 2 days to a peak brightness of 8.2, and showed a main eruption lasting 25 days. The return to quiescence was punctuated by 12 small eruptions, of ~1 mag amplitude and 2 day recurrence time; these "echo outbursts" are of uncertain origin, but somewhat resemble the normal outbursts of dwarf novae. After 52 days, the star began a slow decline to quiescence. Periodic waves in the light curve closely followed the pattern seen in the 1978 superoutburst: a strong orbital signal dominated the first 12 days, followed by a powerful /common superhump/ at 0.05721(5) d, 0.92(8)% longer than P_orb. The latter endured for at least 90 days, although probably mutating into a "late" superhump with a slightly longer mean period [0.05736(5) d]. The superhump appeared to follow familiar rules for such phenomena in dwarf novae, with ...

2002-01-01

365

S1 nuclease analysis of #alpha#-globin gene expression in preleukemic patients with acquired hemoglobin H disease after transfer to mouse erythroleukemia cells  

International Nuclear Information System (INIS)

The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse erythroleukemia cell can genetically complement the #alpha#-globin ...

366

Role of accelerator mass spectrometry in biological dosimetry  

International Nuclear Information System (INIS)

Understanding risks from exposures to carcinogens and other chemicals depends upon measurement of their dose to target tissues and their reactivity with critical macromolecules. The authors have used AMS detection of radio-isotopes to assess doses and reactivities at low, environmentally relevant doses. Several biomedical investigations show the effectiveness of quantification of biologically important events at extremely high sensitivity with AMS. Specifically, they have measured the addition of environmental carcinogens such as 2-amino-3,8-dimethylimidazo[4,5-f]-quinoaxaline (MelQx), a chemical found in cooked food, to DNA at concentrations relevant to human exposure. Other low level detection problems in biology, such as immunoassay assessment of small environmental chemicals, is being developed with attomole sensitivity. AMS also aids the assessment of genotoxic risks from chemicals by quantifying the binding of labeled chemicals to DNA. The very toxic and potent carcinogen, ...

1992-04-05

367

Polymorphisms in the p53 gene in thyroid tumours and blood samples of children from areas in Belarus  

International Nuclear Information System (INIS)

We present changes in the p53 gene in a group of 70 thyroid tumours and 40 blood samples obtained from children from Belarus. Three thyroid tumours show a polymorphism in exon 6 (codon 213) and 5 tumours show a polymorphism in intron 6, 37 bp upstream to the 5'-end of exon 7. Only one patient has a mutation in exon 7 (codon 258) resulting in an amino acid substitution in the protein p53. The distribution of polymorphisms in the 40 blood samples was as follows: three patients had a polymorphism in exon 6 and two persons had a polymorphism in intron 6. One polymorphism in intron 6 was also found in the group of 30 healthy children from Belarus. The fact that the differences in the sequence in p53 found in the tumours was also seen in the blood of these patients demonstrates that they are polymorphisms not induced by radiation exposure. It is difficult to conclude, if the polymorphisms found by us could be associated with the predisposition to radiation-induced ...

368

Polymorphism in HTR3D shows different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy  

British Library Electronic Table of Contents (United Kingdom)

Aims: Serotonin (5-hydroxytryptamine 3; 5-HT3) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT3 antagonists are part of the `gold standard' antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT3 receptor subunit genes with the occurrence of CINV. Materials & methods: A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT3 receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis. Results: A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assu...

2010-01-01

369

Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex  

International Nuclear Information System (INIS)

The nuclear pore complexes (NPCs) reversibly disassemble and reassemble during mitosis. Disassembly of the NPC is accompanied by phosphorylation of many nucleoporins although the function of this is not clear. It was previously shown that in the transmembrane nucleoporin gp210 a single serine residue at position 1880 is specifically phosphorylated during mitosis. Using amino acid substitution combined with live cell imaging, time-lapse microscopy and FRAP, we investigated the role of serine 1880 in binding of gp210 to the NPC in vivo. An alanine substitution mutant (S1880A) was significantly more dynamic at the NPC compared to the wild-type protein, suggesting that serine 1880 is important for binding of gp210 to the NPC. Moreover a glutamate substitution (S1880E) closely mimicking phosphorylated serine specifically interfered with incorporation of gp210 into the NPC and compromised its post-mitotic recruitment to the nuclear envelope of daughter nuclei. Our findings are consistent ...

2007-07-15

370

Organisms posses enzymes that function in the repair of DNA damaged by radiations, chemicals and metabolic events  

International Nuclear Information System (INIS)

This report briefly describes the studies on the mechanism of in vivo DNA repairing by the author in Research Reactor Institute, Kyoto Univ. for the past 30 years. First, the ability of UV radiation to induce transformation was investigated with viral DNA. The formation of thymine-thymine dimer was found harmful to organisms and such dimers were removable by UV-radiation at a low frequency. The mutability was determined in three different E.coli strains with mutator gene, mutT, mutS or mutL. The ability to excise 8-oxoguanin developed in primer DNA was deficient in mutT and miss-pairing left after DNA replication could not be recovered in mutL and mutS strains. Further, DNA repairing mechanism was investigated in other microorganisms; single-strand cleavage caused by exposure to BNCB radiation (boron-neutron-captured beam) could not be repaired in E. coli. Whereas for Deinococcus radiodurans, of which survival rate was not decreased by #gamma#-ray radiation at 5 ...

1998-01-01

371

Mutations in cyr1 and pat1 reveal pheromone-induced G1 arrest in the fission yeast Schizosaccharomyces pombe  

DEFF Research Database (Denmark)

Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non-dividing cells. Here we overcome this problem by using two mutants that bypass the nutritional requirements and respond to the M-factor mating pheromone in rich medium. The first mutant lacks the cyr1 gene which encodes adenylate cyclase and these cells contain no measurable amounts of cAMP. When M-factor is added to a growing h+ cyr1- strain it causes a transient G1 arrest of cell division, transcription of mat1-Pm, and elongation of the cells to form shmoos. The second mutant contains the temperature-sensitive pat1-114 allele. At 30 degrees C this mutant was previously shown not only to bypass the nutritional signal but also to stop growing in a state derepressed for pheromone-controlled functions. We now report that an h+ pat1-114 strain ...

1994-01-01

372

Mitochondrial genetic damage induced in yeast by a photoactivated furocoumarin in combination with ethidium bromide or ultraviolet light  

International Nuclear Information System (INIS)

Ethidium bromide (EB) and ultraviolet light (UV) in combination are known to produce a synergistic induction of 'petite' mutants in yeast. Two other agents were combined with EB, 3-Carbethoxypsoralene (3 CPs) activated by 365 nm light or #gamma# rays. EB in combination with 3 CPs also resulted in an enhanced production of 'petite' mutants. After the photoaddition of 3 CPs in exponential phase cells, recovery of the 'petite' mutation during dark liquid holding was inhibited by the presence of EB producing an enhanced number of 'petite' mutants. The behavior of mitochondrial antibiotic resistance markers after individual and combined treatments with EB and 3 CPs indicates a random loss of markers after EB and a preferential loss of a certain region for the 3 CPs photoaddition. The combination of the two agents leads to an additivity of total drug marker losses rather than a synergistic loss. The combination of EB with #gamma# rays produced no enhancement in 'petite' ...

373

Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model  

British Library Electronic Table of Contents (United Kingdom)

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...

2011-01-01

374

Long-term Retinal Function and Structure Rescue Using Capsid Mutant AAV8 Vector in the rd10 Mouse, a Model of Recessive Retinitis Pigmentosa  

British Library Electronic Table of Contents (United Kingdom)

The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the ? subunit of rod cGMP-phosphodiesterase (PDE?). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDE? was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed tha...

2011-01-01

375

Isolation of fetal DNA from nucleated erythrocytes in maternal blood  

Energy Technology Data Exchange (ETDEWEB)

Fetal nucleated cells within maternal blood represent a potential source of fetal genes obtainable by venipuncture. The authors used monoclonal antibody against the transferrin receptor (TIR) to identify nucleated erythrocytes in the peripheral blood of pregnant women. Candidate fetal cells from 19 pregnancies were isolated by flow sorting at 12 1/2-17 weeks gestation. The DNA in these cells was amplified for a 222-base-pair (bp) sequence present on the short arm of the Y chromosome as proof that the cells were derived from the fetus. The amplified DNA was compared with standardized DNA concentrations. In the case of the female fetus, DNA prepared from samples at 32 weeks of gestation and cord blood at delivery also showed the presence of the Y chromosomal sequence, suggesting Y sequence mosaicism or translocation. In 10/12 cases where the 222-bp band was absent, the fetuses were female. Thus, they were successful in detecting the Y chromosomal sequence in 75% of the male-bearing ...

1990-05-01

376

Identification of the binding domain for NADP"+ of human glucose-6-phosphate dehydrogenase by sequence analysis of mutants  

International Nuclear Information System (INIS)

Human erythrocyte glucose-6-phosphate is normally quite stable in the presence of 10 #mu#M NADP"+. Certain glucose-6-phosphate dehydrogenase variants lose virtually all their activity at this concentration of NADP"+ but are reactivated by 200 #mu#M NADP"+. Such variants presumably have a defect in their NADP"+-binding site. The authors analyzed the sequence of cDNA or genomic DNA from seven unrelated patients with hemolytic anemia due to the inheritance of variants that are reactivated by NADP"+. Six patients had substitutions of one of three adjacent amino acids, and the seventh patient had another amino acid substitution 23 residues downstream. These amino acids are highly conserved, all being present in rat and all but one being found also in Drosophila. The anomalous electrophoretic behavior of some of the variants can be explained by their loss of ability to bind NADP"+. The conclude that the region in which these mutations occur defines the binding domain for ...

377

Homology analyses of the protein sequences of fatty acid synthases from chicken liver, rat mammary gland, and yeast  

Energy Technology Data Exchange (ETDEWEB)

Homology analyses of the protein sequences of chicken liver and rat mammary gland fatty acid synthases were carried out. The amino acid sequences of the chicken and rat enzymes are 67% identical. If conservative substitutions are allowed, 78% of the amino acids are matched. A region of low homologies exists between the functional domains, in particular around amino acid residues 1059-1264 of the chicken enzyme. Homologies between the active sites of chicken and rat and of chicken and yeast enzymes have been analyzed by an alignment method. A high degree of homology exists between the active sites of the chicken and rat enzymes. However, the chicken and yeast enzymes show a lower degree of homology. The DADPH-binding dinucleotide folds of the {beta}-ketoacyl reductase and the enoyl reductase sites were identified by comparison with a known consensus sequence for the DADP- and FAD-binding dinucleotide folds. The active sites of all of the enzymes are primarily in hydrophobic regions of ...

1989-11-01

378

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci  

International Nuclear Information System (INIS)

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F_1 offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of #alpha#-chains normally found in all SEC mice. The deficient #alpha#-chain synthesis caused these mice to exhibit an #alpha#-thalassemia similar to human #alpha#-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with #alpha#-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining #beta#-chain structure) produced twice as much SEC as 101 #beta#-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its ...

379

Genotoxic effects of sunlight-activated waste waters  

Energy Technology Data Exchange (ETDEWEB)

Natural sunlight induces a genotoxic response in cultured CHO cells pre-treated with shale oil retort process water. Near ultraviolet light (NUV) component of the solar spectrum is the apparent radiation responsible for photoactivation. Cultured human skin fibroblasts are acutely sensitive to the genotoxic effects of photoactivated process water. The mutagenic potential of photoactivated process water in human cells is the same as that witnessed for an equivalent killing dose of the potent skin carcinogen FUV. DNA repair processes are involved in modulating genotoxic effects of this photo-induced process. The exact magnitude of the potential health-related and environmental risks resulting from photoactivation of retort process waters and other oil shale by-products is unassessed at this time. Our demonstration that a significant rate of mutation occurs in cultured human cells exposed to high dilutions of process waters and fluences of NUV comparable to that ...

1981-01-01

380

Evolutionary dynamics of Newcastle disease virus  

International Nuclear Information System (INIS)

A comprehensive dataset of NDV genome sequences was evaluated using bioinformatics to characterize the evolutionary forces affecting NDV genomes. Despite evidence of recombination in most genes, only one event in the fusion gene of genotype V viruses produced evolutionarily viable progenies. The codon-associated rate of change for the six NDV proteins revealed that the highest rate of change occurred at the fusion protein. All proteins were under strong purifying (negative) selection; the fusion protein displayed the highest number of amino acids under positive selection. Regardless of the phylogenetic grouping or the level of virulence, the cleavage site motif was highly conserved implying that mutations at this site that result in changes of virulence may not be favored. The coding sequence of the fusion gene and the genomes of viruses from wild birds displayed higher yearly rates of change in virulent viruses than in viruses of low virulence, suggesting that an ...

2009-08-15

381

Endonuclease IV of Escherichia coli is induced by paraquat  

International Nuclear Information System (INIS)

The addition of paraquat (methyl viologen) to a growing culture of Escherichia coli K-12 led within 1 hr to a 10- to 20-fold increase in the level of endonuclease IV, a DNase for apurinic/apyrimidinic sites. The induction was blocked by chloramphenicol. Increases of 3-fold or more were also seen with plumbagin, menadione, and phenazine methosulfate. H_2O_2 produced no more than a 2-fold increase in endonuclease IV activity. The following agents had no significant effect: streptonigrin, nitrofurantoin, tert-butyl hydroperoxide, #gamma# rays, 260-nm UV radiation, methyl methanesulfonate, mitomycin C, and ascorbate. Paraquat, plumbagin, menadione, and phenazine methosulfate are known to generate superoxide radical anions via redox cycling in vivo. A mutant lacking superoxide dismutase was unusually sensitive to induction by paraquat. In addition, endonuclease IV could be induced by merely growing the mutant in pure O_2. The levels of endonuclease IV in uninduced or paraquat-treated cells ...

382

Effect of chronic fractionated low-dose gamma irradiation on division potential of human embryonic cells in vitro  

Energy Technology Data Exchange (ETDEWEB)

We investigated the in vitro phenotypic transformation of human embryo (HE) cells that were repeatedly irradiated (7.5 cGy once a week) throughout their life-span. Irradiation was repeated until the cells had accumulated 195 cGy (equivalent to the 26th passage). Samples of cells were assayed for survival by colony formation, as well as for mutation at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus and for transformation by focus formation. The life-span (mean number of population doublings) of multiply irradiated cells with a total dose of 97.5 cGy was slightly but significantly prolonged over that of controls. After HE cells had accumulated 195 cGy, the maximum number of divisions increased to 130-160% of the number in non-irradiated control cells. Transformed foci were not observed until cells had accumulated 97.5 cGy, and then increased with the increasing accumulation of radiation. However, no cells showed immortality or expressed a malignant ...

1991-12-01

383

Development of a novel mouse tk{sup +/-} embryonic stem cell line for use in mutagenicity studies  

Energy Technology Data Exchange (ETDEWEB)

A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mouse model for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 figs., 1 tab.

1996-12-31

384

Current status of a hepatitis C vaccine: encouraging results but significant challenges ahead  

DEFF Research Database (Denmark)

Persistent hepatitis C virus (HCV) infection affects 170 million people worldwide. Acute HCV infection is often asymptomatic, but many infected individuals develop persistent infections that may lead to development of end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma. Thus, an HCV vaccine that could significantly lower the chronicity rate would have a major impact on the disease burden. Unfortunately, HCV is a highly mutable virus, and escape mutations can undermine vaccine-induced virus-specific immunity. Also, HCV exists as multiple genotypes, and so genotype-specific vaccines might be required to achieve broad protection. Finally, vaccine development has been hampered by the lack of a small animal model and cell culture systems, but these are currently being established. Despite these obstacles, several vaccine candidates tested in the chimpanzee HCV model have shown some encouraging results.

2007-01-01

385

Characterization of mal recombination plasmids cloned in Streptococcus pneumoniae  

Energy Technology Data Exchange (ETDEWEB)

The malM locus of Streptococcus pneumoniae was cloned into one of the two PstI sites of the multicopy S. pneumoniae plasmid pMV158. To eliminate chromosomal transformants in the simultaneous selection for tetracycline resistance (coded by pMV158) and maltose utilization, the host cells contained a chromosomal deletion of the mal gene cluster. Two clones were isolated; one with a 3.3 kb insert (pLS70) which behaved like wild type with respect to maltose utilization, and another with a 2.9 kb insert (pLS69) which behaved as though it contained a down promoter mutation. Preliminary mapping of these clones by restriction analysis placed the 0.4kb deletion on a HindIII fragment in the interior of the chromosomal insert. The recombinant plasmids were able to transform over 50% of a recipient population to Mal/sup +/. Enzyme measurements of the clones indicated an overproduction of amylomaltase, constituting up to 10% of the total cellular protein, and supported the ...

1981-01-01

386

Antioxidant and toxicity tests of roasted noni (Morinda citrifolia) leaf infusion  

British Library Electronic Table of Contents (United Kingdom)

Summary The antioxidant properties and toxicity profile of roasted noni (Morinda citrifolia L.) leaf infusion were evaluated. The 2,2-diphenylpicrylhydrazyl (DPPH) radical scavenging activity was greater than green tea infusion (81.6 +- 0.9% vs. 57.5 +- 1.8%, P < 0.001). The mean quercetin and kaempferol contents of roasted noni leaf infusion, as prepared by the consumer, were 0.24 +- 0.01 and 0.14 +- 0.01 mg mL-1, respectively. Tannic acid content was 10 +- 1 mg mL-1. The infusion was non-mutagenic in the reverse mutation test in Salmonella typhimurium and did not induce primary DNA damage in E. coli PQ37. Further, no significant primary DNA damage was induced by 5,15-dimethylmorindol, which was the only detectable anthraquinone in noni leaves. The infusion was not cytotoxic in the 24 h b...

2009-01-01

387

Analysis of the 5{prime} region of PMS2 reveals heterogeneous transcripts and a novel overlapping gene  

Energy Technology Data Exchange (ETDEWEB)

The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published PMS2 cDNA sequence lack an upstream in-frame stop codon preceding the presumptive initiating methionine. To evaluate the 5` terminus of the PMS2 coding region further, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5` genomic segment of the PMS2 locus. The PMS2 gene transcripts were found to have heterogeneous but colinear 5` termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5-kDa polypeptide was found to initiate transcriptionally within PMS2 from the opposite strand. 23 refs., 5 figs., 2 tabs.

1995-09-20

388

Aging, tumor suppression and cancer: High-wire act!  

Energy Technology Data Exchange (ETDEWEB)

Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy--protecting ...

2004-08-15

389

Absence of linkage of apparently single gene mediated ADHD with the human syntenic region of the mouse mutant coloboma  

Energy Technology Data Exchange (ETDEWEB)

Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best ...

1995-12-18

390

A single amino acid substitution results in a retinoblastoma protein defective in phosphorylation and oncoprotein binding  

International Nuclear Information System (INIS)

The authors have previously identified a small-cell lung cancer cell line (NCI-H209) that expresses an aberrant, underphosphorylated form of the retinoblastoma protein RB1. Molecular analysis of RB1 mRNA from this cell line revealed a single point mutation within exon 21 that resulted in a nonconservative amino acid substitution (cysteine to phenylalanine) at codon 706. Stable expression of this mutant RB1 cDNA in a human cell line lacking endogenous RB1 demonstrated that this amino acid change was sufficient to inhibit phosphorylation. In addition, this cysteine-to-phenylalanine substitution also resulted in loss of RB1 binding to the simian virus 40 large tumor and adenovirus E1A transforming proteins. These results confirm the importance of exon 21 coding sequences and suggest that the cysteine residue at codon 706 may play a role in achieving a specific protein conformation essential for protein-protein interactions.

391

5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects  

Science.gov (United States)

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C{sup {r_arrow}}T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C{sup {r_arrow}}T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C{sup {r_arrow}}T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD. 13 refs., 1 fig., 1 tab.

1996-06-28

392

UMCP-BG and E collaboration in nuclear power engineering in the framework of DOE-Utility Nuclear Power Engineering Education Matching Grant Program  

Energy Technology Data Exchange (ETDEWEB)

The DOE-Utility Nuclear Power Engineering Education Matching Grant Program has been established to support the education of students in Nuclear Engineering Programs to maintain a knowledgeable workforce in the United States in order to keep nuclear power as a viable component in a mix of energy sources for the country. The involvement of the utility industry ensures that this grant program satisfies the needs and requirements of local nuclear energy producers and at the same time establishes a strong linkage between education and day-to-day nuclear power generation. As of 1997, seventeen pairs of university-utility partners existed. UMCP was never a member of that group of universities, but applied for the first time with a proposal to Baltimore Gas and Electric Company in January 1999 [1]. This proposal was generously granted by BG&E [2,3] in the form of a gift in the amount of $25,000 from BG&E's Corporate ...

2000-03-01

393

The Structural and Optical Properties of GaAs1-xPx /GaAs  

International Nuclear Information System (INIS)

GaAs1-xPx p-n junction structures were grown on the epi-ready n-type GaAs(100) substrate by solid source MBE system for different phosphor compositions. To obtain the lattice-match sample structure was applied graded growth procedure. The structural and optical properties of the sample structures with different P concentration were investigated by using X-ray diffraction (XRD), spectroscopic ellipsometry (SE). In addition, The range of lattice parameters in the graded epilayer and phosphorous composition were determined from the HRXRD rocking curve simulation. We analyse dielectric function spectra of disordered GaAs1-xPx junction structures measured using spectroscopic ellipsometry at room temperature in the 0.6-4.7 eV photon energy region. The critical energy points such as band gap energy and spin-orbit-split energy of these structures were determined using SE data. It is detected that E0, E1 ,E2 energies of the GaAs1-xPx p-n junction ...

2008-08-25

394

Structure of the triplet of low-lying states in sup 101 Mo  

Energy Technology Data Exchange (ETDEWEB)

The properties of the triplet of low-lying states in {sup 101}Mo have been studied through spectroscopy of the {gamma} radation following thermal neutron capture in {sup 100}Mo and {beta}-decay of {sup 101}Nb and through a measurement of the proton angular distributions in the {sup 100}Mo(d, p) reaction with 14 MeV deuteron energy. The half-lives of the 13.5 keV state and the 57.0 keV 5/2{sup +} state have been measured as 226(7) and 133(7) ns, respectively. These values and the quadrupole/dipole mixing ratios of the 13.5 keV and 43.5 keV transitions yield spin and parity 3/2{sup +} for the 13.5 keV level. The E2 components in the 13.5 (3/2{sup +}->1/2{sup +}) and 43.5 keV (5/2{sup +}->3/2{sup +}) transitions are {le} 8x10{sup -4} and 54(9)%, respectively. The possibility of an additional state near to the 57.0 keV level is discussed. IBFM/PTQM calculations, taking into consideration the transitional character of the {sup 100}Mo boson ...

1991-06-01

395

Structure of the triplet of low-lying states in "1"0"1Mo  

International Nuclear Information System (INIS)

The properties of the triplet of low-lying states in "1"0"1Mo have been studied through spectroscopy of the #gamma# radation following thermal neutron capture in "1"0"0Mo and #beta#-decay of "1"0"1Nb and through a measurement of the proton angular distributions in the "1"0"0Mo(d, p) reaction with 14 MeV deuteron energy. The half-lives of the 13.5 keV state and the 57.0 keV 5/2"+ state have been measured as 226(7) and 133(7) ns, respectively. These values and the quadrupole/dipole mixing ratios of the 13.5 keV and 43.5 keV transitions yield spin and parity 3/2"+ for the 13.5 keV level. The E2 components in the 13.5 (3/2"+#->#1/2"+) and 43.5 keV (5/2"+#->#3/2"+) transitions are #<=# 8x10"-"4 and 54(9)%, respectively. The possibility of an additional state near to the 57.0 keV level is discussed. IBFM/PTQM calculations, taking into consideration the transitional character of the "1"0"0Mo boson core, account for the ...

396

Shell-model predictions for electromagnetic properties of N = 50 nuclei  

Energy Technology Data Exchange (ETDEWEB)

Predictions for E2, M1, and M4 transition rates and moments, together with examples of transition-charge densities, are presented for states of N = 50 nuclei. These predictions are based on one-body spectroscopic amplitudes obtained from the wave functions of a new N = 50 shell-model calculation which incorporates the 0f/sub 5/2/, 1p/sub 3/2/, 1p/sub 1/2/, and 0g/sub 9/2/ single-particle orbits and an empirically determined effective Hamiltonian for this space. The predictions are compared with experimental data, first in order to evaluate how well the model space, as applied by this Hamiltonian, accounts for observations, and then to assess the importance of configurations excluded from the model space and to determine the values of the operator renormalizations (effective charges and effective g factors) which optimally map the theoretical results onto the corresponding experimental values.

1988-12-01

397

Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-Agonist Azagly-Nafarelin as a removable implant "Gonazon"; a preclinical trial  

British Library Electronic Table of Contents (United Kingdom)

Downregulation of anterior pituitary GnRH-receptors by application of a slow release GnRH-implant offers an effective and reversible alternative to surgical castration of the male dog. Aim of the present study was to test the efficacy and the underlying mechanisms of a new non-biodegradable controlled-release device implant (Gonazon, Intervet, containing 18.5mg of the GnRH-agonist Azagly-Nafarelin). Eight male beagle dogs were implanted s.c. at the para-umbilical region. In four dogs implant removal was after 180 days (group 1), in the other four dogs after 365 days (group 2). Eleven weeks after implantation availability of LH was reduced (p<0.0001) by 70%. After an initial increase lasting for about 4 days, testosterone (T) and estradiol (E2) concentrations decreased (p<0.0001) to basal l...

2009-01-01

398

On-line video image processing system for real-time neutron radiography  

Energy Technology Data Exchange (ETDEWEB)

The neutron radiography system installed at the E-2 experimental hole of the KUR (Kyoto University Reactor) has been used for some NDT applications in the nuclear field. The on-line video image processing system of this facility is introduced in this paper. A 0.5 mm resolution in images was obtained by using a super high quality TV camera developed for X-radiography viewing a NE-426 neutron-sensitive scintillator. The image of the NE-426 on a CRT can be observed directly and visually, thus many test samples can be sequentially observed when necessary for industrial purposes. The video image signals from the TV camera are digitized, with a 33 ms delay, through a video A/D converter (ADC) and can be stored in the image buffer (32 KB DRAM) of a microcomputer (Z-80) system. The digitized pictures are taken with 16 levels of gray scale and resolved to 240 x 256 picture elements (pixels) on a monochrome CRT, with the capability also to display 16 ...

1983-09-15

399

Multilayered Nano-Microcomposite Ti-Al-N/TiN/Al_2O_3 Coatings. Their Structure and Properties  

International Nuclear Information System (INIS)

This paper presents the first results on formation and study of structure and properties of micro- and nanocomposite combined coatings. By means of modeling the deposition processes (deposition conditions, current density-discharge, plasma composition and density, voltage) we formed the three-layer nanocomposite coatings of Ti-Al-N/Ti-N/Al_2O_3. The coating composition, structure and properties were studied using physical and nuclear-physical methods. The Rutherford proton and helium ion backscattering, scanning electron microscopy with microanalysis, grazing incidence X-ray diffraction, as well as nanohardness tests (hardness) were used. Measurements of wear resistance and corrosion resistance in NaCl, HCl and H_2SO_4 solutions were also performed. For testing mechanical properties such characteristics of layered structures as hardness H, elastic modulus E: H"3/E"2 etc. were measured. It is demonstrated that the formed three-layer ...

2011-07-01

400

Magnetic moments of C isotopes studied with antisymmetrized molecular dynamics  

International Nuclear Information System (INIS)

We studied the magnetic dipole moments #mu# of even-odd C isotopes, ranging from proton-rich to neutron-rich nuclei, with antisymmetrized molecular dynamics (AMD). The results are in good agreement with the experimental data. In the "9C ground state the total intrinsic spin of the protons is found to be nonzero (S_p#not =#0), which is unusual in even-odd nuclei. The interesting point is that the spin-orbit force breaks slightly the coupling off of intrinsic spins of the even nucleon group in isospin T=3/2 nuclei. This result is consistent with the newly measured #mu# data that, when combined with "9Li data, indicate an unusual left-angle #sigma# right-angle value larger than unity. A #mu# moment -1.05#mu#_N of "1"7C is theoretically predicted. We also show a good reproduction of E2 transition data. copyright 1996 The American Physical Society.

401

High-spin structure of odd $^{71-81}$Ga isotopes with shell model  

CERN Document Server

The recently measured experimental data of Argonne National Laboratory for high-spin states in neutron-rich $^{71,73,75,77}$Ga isotopes have been interpreted in the framework of large-scale shell model. Calculations have been performed in $f_{5/2}pg_{9/2}$ model space with two recent effective shell model interactions, JUN45 and jj44b. We also predict high-spin states for $^{79,81}$Ga, where very little is known experimentally. The calculated results show that existence of band structure built on top of the 3/2$^-$, 5/2$^-$ and 9/2$^+$ levels in $^{71-77}$Ga. The collective structure reflected in experimental data is not well reproduced in calculated values. The calculated positive parity states in $^{71,73,75}$Ga are higher in energy in comparison to experimental finding, while for $^{77,79}$Ga, the positive parity states are in better agreement. Both the interactions predict, leading configuration of $\\pi(f_{5/2}^3)$ and $\\pi(p_{3/2}f_{5/2}^2)$ for $^{79,81}$Ga. The ...

2011-01-01

402

Electron momentum spectroscopy of H_2 and D_2: Ionization to ground and excited final states  

International Nuclear Information System (INIS)

The symmetric noncoplanar (e,2e) cross sections (momentum profiles) of H_2 and D_2 for the transitions to the 2p#sigma#_u and 2s#sigma#_g excited ion states have been measured, relative to the ground-state ion transition, using a high-sensitivity multichannel momentum-dispersive electron momentum spectrometer (EMS) at an impact energy of 1200 eV. Newly calculated plane-wave impulse approximation (PWIA) cross sections, based on a full-configuration-interaction H_2 wave function, are compared to the experimental results. These calculations are in better agreement with the experimental results for the transition to the 2s#sigma#_g ion state than the earlier theoretical work of Liu and Smith, Jr. [Phys. Rev. A 31, 3003 (1985)] which has been found to be in error. Nevertheless, significant discrepancies between the relative experimental and theoretical cross sections are observed for the transitions to excited ion states, suggesting a failure of the ...

403

Cytotoxic Naphtho--pyrones from the Mangrove Endophytic Fungus Aspergillus tubingensis (GX1-5E)  

British Library Electronic Table of Contents (United Kingdom)

Abstract Four new dimeric naphtho--pyrones, named rubasperone D (1), rubasperone E (2), rubasperone F (3), and its atropisomer rubasperone G (4), together with four known monomeric naphtho--pyrones, TMC 256 A1 (5), rubrofusarin B (6), fonsecin (7), and flavasperone (8), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1-5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D- and 2D-NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF-7, MDA-MB-435, Hep3B, Huh7, SNB19, and U87-MG with IC50 values between 19.92 and 47.98-M. Compounds 1, 6, and 8 also showed mild cytotoxic activity.

2011-01-01

404

An on-line video image processing system for real-time neutron radiography  

International Nuclear Information System (INIS)

The neutron radiography system installed at the E-2 experimental hole of the KUR (Kyoto University Reactor) has been used for some NDT applications in the nuclear field. The on-line video image processing system of this facility is introduced in this paper. A 0.5 mm resolution in images was obtained by using a super high quality TV camera developed for X-radiography viewing a NE-426 neutron-sensitive scintillator. The image of the NE-426 on a CRT can be observed directly and visually, thus many test samples can be sequentially observed when necessary for industrial purposes. The video image signals from the TV camera are digitized, with a 33 ms delay, through a video A/D converter (ADC) and can be stored in the image buffer (32 KB DRAM) of a microcomputer (Z-80) system. The digitized pictures are taken with 16 levels of gray scale and resolved to 240 x 256 picture elements (pixels) on a monochrome CRT, with the capability also to display 16 ...

1983-09-01

405

Alignments, additivity, and signature inversion in odd-odd "1"7"0Ta: A comprehensive high-spin study  

International Nuclear Information System (INIS)

High-spin states (I < or approx. 50(#Planck constant#/2#pi#)) of the odd-odd nucleus "1"7"0Ta have been investigated with the "1"2"4Sn("5"1V,5n) reaction. The resolving power of Gammasphere has allowed for the observation of eleven rotational bands (eight of which are new) and over 430 transitions (#approx#350 of which are new) in this nucleus. Many interband transitions have been observed such that the relative spins and excitation energies of the 11 bands have been established. This is an unusual circumstance in an odd-odd study. Configurations have been assigned to most of these bands based upon features such as alignment properties, band crossings, B(M1)/B(E2) ratios, and the additivity of Routhians. A systematic study of the frequency at which normal signature ordering occurs in the #pi#h_9_/_2#nu#i_1_3_/_2 band has been performed and it is found that its trend is opposite to that observed in the #pi#h_1_1_/_2#nu#i_1_3_/_2 bands. A ...

2010-06-01

406

A novel small-molecule inhibitor of NF-#kappa#B signaling  

International Nuclear Information System (INIS)

The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by ...

2008-04-18

407

Evolution of improved varieties of sesame through induced mutations  

International Nuclear Information System (INIS)

Sesame varieties/genotypes showed a good response to radiation with gamma rays and treatments with EMS. In M_1 both gamma rays and EMS influenced germination, seedling height, survival of plants and pollen fertility/sterility, producing deleterious effects on these characters. Compared to black seeded genotypes, white seeded ones are more susceptible to radiation. Both gamma rays and EMS produced various types of morphological variations in M_2 generation. These were dwarf plant mutants, mottled and fleshy leaved mutants (sterile), fasciated stem, flower colour, altered phyllotaxy, early, uniculm, capsule size variations, multiple capsule/leaf axil, seed coat colour variations, indehiscent and semi-indehiscent type mutants. Moreover, studies on quantitative characters including seed yield revealed the induction of mutants in both positive and negative directions for such traits which made a good scope of selection of desirable mutants in M_2 generation. Mutants selected in M_2 were ...

2001-01-01

408

The radioecological risk of decommissioning of nuclear submarines. Possible accidents and normal conditions  

International Nuclear Information System (INIS)

In the report the results of the estimations of radiological risk of various stages of decommissioning of nuclear submarines are presented. At occurrence on nuclear submarine the heavy failure, relating to the class hypotetical volume of acting of radionuclides in atmosphere can reach 1.6E(15) Bq. Results of estimations probable doses on an axis of a trace of a radioactive loop show, that at distribution of radionuclides during atmospheric carry to 'agreed' settlement (500-1000 m) the maximum doses on its territory can make: about 6.0E(-3) Sv (for the whole body); 3.0E(-3) Gy for the leather (basal layer); 6.3E(-2) Gy for the lungs (acute exposure) and up to 1.8 Gy for the thyroid gland. Hypotetical failure for the estimation of the greatest possible radioecological consequences for hydrobiocenosis is considering, connected with single discharge of liquid radioactive waste (LRW) in water area. At navigating failure of the tanker with LRW in ...

2000-05-01

409

Two Functional S100A4 Monomers Are Necessary for Regulating Nonmuscle Myosin-IIA and HCT116 Cell Invasion.  

Science.gov (United States)

S100A4, a member of the Ca(2+)-activated S100 protein family, regulates the motility and invasiveness of cancer cells. Moreover, high S100A4 expression levels correlate with poor patient survival in several cancers. Although biochemical, biophysical, and structural data indicate that S100A4 is a noncovalent dimer, it is unknown if two functional S100A4 monomers are required for the productive recognition of protein targets and the promotion of cell invasion. To address this question, we created covalently linked S100A4 dimers using a glycine rich flexible linker. The single-chain S100A4 (sc-S100A4) proteins exhibited wild-type affinities for calcium and nonmuscle myosin-IIA, retained the ability to regulate nonmuscle myosin-IIA assembly, and promoted tumor cell invasion when expressed in S100A4-deficient colon carcinoma cells. Mutation of the two calcium-binding EF-hands in one monomer, while leaving the other monomer intact, caused a 30-60-fold reduction in ...

2011-07-13

410

Structure-function studies on inhibitory activity of Bungarus multicinctus protease inhibitor-like protein on matrix metalloprotease-2, and invasion and migration of human neuroblastoma SK-N-SH cells.  

Science.gov (United States)

In view of the findings that several Kunitz-type protein inhibitors suppress tumor invasion and metastasis, the aim of the present study is to explore whether Bungarus multicinctus protease inhibitor-like protein-2 (PILP-2) and PILP-3 exhibit anti-tumor activity. Although approximately 28% of amino acid substitutions occurred between PILP-2 and PILP-3, molecular modeling suggested that PILP-2 and PILP-3 shared similar folded structures. Unlike PILP-2, PILP-3 showed a notable activity in abolishing migration and invasion of human neuroblastoma SK-N-SH cells. The ability of PILP-3 to inhibit matrix metalloprotease-2 (MMP-2) activity was higher than that of PILP-2. Pull-down assay revealed protein-protein interaction between PILP-3 and MMP-2. In contrast to mutation on N-terminal region, replacement of amino acids at C-terminus attenuated notably the ability of PILP-3 to inhibit cell invasion, cell migration and MMP-2 activity as well as the binding capability of ...

2009-08-23

411

Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha  

Energy Technology Data Exchange (ETDEWEB)

The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific ...

2008-07-23

412

Structural Insights into the Interaction of the Evolutionarily Conserved ZPR1 Domain Tandem with Eukaryotic EF1A, Receptors, and SMN Complexes  

Energy Technology Data Exchange (ETDEWEB)

Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based mutational and complementation analyses reveal ...

2007-01-01

413

Spark decomposition of SF/sub 6/: Chemical and biological studies  

Energy Technology Data Exchange (ETDEWEB)

Gas-insulated systems employing SF/sub 6/ are utilized in a variety of applications in power delivery systems. Because electric arcs, sparks or corona can decompose SF/sub 6/ into byproducts having chemical properties different from SF/sub 6/, environmental concerns arise regarding inadvertent human exposures to electrically-decomposed SF/sub 6/. Biological assays in our laboratory using mammalian cell culture systems have revealed that spark-decomposed SF/sub 6/ produces cell death, and the extent of cell killing increases with increasing spark energy. Chemical analysis of spark-decomposed SF/sub 6/ has identified the major decomposition pathways and byproducts, but biological testing of individual or byproduct mixtures has indicated that these major decomposition products do not contribute, in a significant fashion, to the cell lethality seen in our assays. Further experiments have suggested that S/sub 2/F/sub 10/ may be produced under our decomposition conditions and that this ...

1987-01-01

414

Safety evaluation of Propionibacterium freudenreichii ET-3 culture.  

Science.gov (United States)

Propionibacterium freudenreichii ET-3 culture, a cell-free product of whey fermentation using P. freudenreichii ET-3 (7025), has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA), and therefore, has potential use in the food and supplement industries. Although currently used as a food ingredient in Japan, the safety of this novel ingredient has not been previously evaluated through traditional toxicity testing. Therefore, here we report the results of standard toxicological testing performed on P. freudenreichii ET-3 culture. In a 4-week oral toxicity study, administration of 6000mg/kg body weight/day P. freudenreichii ET-3 culture was without compound-related adverse effects on clinical signs, body weights, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, and gross and microscopic findings in male and female Sprague-Dawley rats. Furthermore, in vitro mutagenicity testing ...

2011-03-22

415

Relationship of DNA repair processes to mutagenesis and carcinogenesis in mammalian cells. Progress report, November 1, 1979-October 31, 1980  

International Nuclear Information System (INIS)

The objective of this research is to determine the role of DNA repair in mutagenesis and carcinogenesis in mammalian cells. Use of the host-cell reactivation viral suicide enrichment procedure was initiated in the isolation of repair-deficient mutants. Lightly mutagenized BHK cells were infected with irradiated Herpes simplex virus (HSV); several radiation-sensitive strains were isolated among the survivors of the infection. The characterization of these strains is progressing and the enrichments are continuing. That alterations in the frequency of mutation of C3H/10T 1/2 cells, occurring as a result of holding the cells in a confluent state following treatment with ethylmethane sulfonate, parallel the alterations in the frequency of neoplastic transformation was found. The repair capabilities of BHK cells were found to be intermediate in comparison to repair-proficient and -deficient human cells with regard to the reactivation of HSV treated with various ...

416

New discoveries in prostate cancer pathogenesis  

International Nuclear Information System (INIS)

Background. Through PSA screening the rate of prostate cancers detected at an early stage has increased significantly; thus a decrease in mortality can be expected in the near future. Despite all scientific efforts, however, the molecular mechanisms underlying the development and progression of prostate cancer remain poorly understood. Prostate cancer is a disease of aging men and epidemiological evidence supports a major contribution to its development through diet, lifestyle and environmental factors. Genetic instability is the basic phenomenon of tissue cell cancerisation. This instability can be hereditary or due to mutations and other chromosomal aberrations acquired during life. In recent years a large number of interesting data have been collected which show the relationships between focal atrophy and genetic instability of the prostate epithelia. Atrophy can be the result of prostatitis, ischemia as well as of oxidative stress (diet). Several chromosomal ...

417

Mucociliary transport and upper airway disease  

International Nuclear Information System (INIS)

Mucociliary transport so critical in nasal, paranasal sinus, and middle ear physiology is impaired in chronic sinsusitis and otitis media by factors such as increased mucus viscoelasticity, decreased ciliary area, and primary or secondary ciliary immotility. We reviewed the pathophysiology of primary ciliary dyskinesia, otitis media with effusion, chronic sinusitis, and allergic rhinitis in terms of mucociliary transport. Subjects with primary ciliary dyskinesia may experience recurrent middle ear infection, chronic airway infection, predominantly lower-lobe bronchiectasis, male sterility, or situs inversus. Primary ciliary dyskinesia is sometimes difficult to diagnose in cases without situs inversus. Nasal nitric oxide concentration in such patients decreases, although why is unclear. Mutations may involve dynein arm intermediate chain 1 (DNAI1) or dynein arm heavy chain 5 (DNAH5). Mucociliary clearance decreases more in those with otitis media with effusion than ...

2010-05-01

418

Molecular targeted treatment and radiation therapy for rectal cancer  

Energy Technology Data Exchange (ETDEWEB)

Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have ...

2009-06-15

419

Late-onset Stargardt-like macular dystrophy maps to chromosome 1p13  

Energy Technology Data Exchange (ETDEWEB)

Stargardt`s disease (MIM 248200), originally described in 1909, is an autosomal recessive condition of childhood, characterized by a sudden and bilateral loss of central vision. Typically, it has an early onset (7 to 12 years), a rapidly progressive course and a poor final outcome. The central area of the retina (macula) displays pigmentary changes in a ring form with depigmentation and atrophy of the retinal pigmentary epithelium (RPE). Perimacular yellowish spots, termed fundus flavimaculatus, are observed in a high percentage of patients. We have recently reported the genetic mapping of Stargardt`s disease to chromosome 1p13. On the other hand, considering that fundus flavimaculatus (MIM 230100) is another form of fleck fundus disease, with a Stargardt-like retinal aspect but with a late-onset and a more progressive course, we decided to test the hypothesis of allelism between typical Stargardt`s disease and late-onset autosomal recessive fundus flavimaculatus. Significant pairwise ...

1994-09-01

420

Deficiency of the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT) dysregulates neurogenesis.  

Science.gov (United States)

Neuronal transcription factors play vital roles in the specification and development of neurons, including dopaminergic (DA) neurons. Mutations in the gene encoding the purine biosynthetic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause the resulting intractable and largely untreatable neurological impairment of Lesch-Nyhan disease (LND). The disorder is associated with a defect in basal ganglia DA pathways. The mechanisms connecting the purine metabolic defect and the central nervous system (CNS) phenotype are poorly understood but have been presumed to reflect a developmental defect of DA neurons. We have examined the effect of HPRT deficiency on the differentiation of neurons in the well-established human (NT2) embryonic carcinoma neurogenesis model. We have used a retrovirus expressing a small hairpin RNA (shRNA) to knock down HPRT gene expression and have examined the expression of a number of transcription factors essential for neuronal ...

2009-08-11

421

Cytogenetic effects of protracted gamma exposures from conception of male mice  

Energy Technology Data Exchange (ETDEWEB)

In order to gain an overall picture of the genetic effects of an increased level of background radiation it is necessary to study the results of protracted exposures to embryonic and immature germ-cell stages as well as to stages found in the mature organism. For this purpose, litters produced by female mice, kept in a 10 or 20 rad/day /sup 60/Co ..gamma..-irradiation field, were kept in the same fields from conception until about 60 days later, having absorbed doses of 526 and 1078 rad respectively. Tests on exposed female offspring showed them to be sterile. Eight weeks after removal from the gamma field, mean testis masses of males in the 20 rad/day series were only half normal but those receiving 10 rad/day were little affected. Frequencies of translocations in spermatocytes at diakinesis/metaphase I were only slightly increased in the exposed series, differences not being significant. Estimated rates of translocation induction were around 5 x 10sup(-6) per rad, about one-third of ...

1982-01-01

422

Alterations in heart looping induced by overexpression of the tight junction protein Claudin-1 are dependent on its C-terminal cytoplasmic tail.  

Science.gov (United States)

In vertebrates, the positioning of the internal organs relative to the midline is asymmetric and evolutionarily conserved. A number of molecules have been shown to play critical roles in left-right patterning. Using representational difference analysis to identify genes that are differentially expressed on the left and right sides of the chick embryo, we cloned chick Claudin-1, an integral component of epithelial tight junctions. Here, we demonstrate that retroviral overexpression of Claudin-1, but not Claudin-3, on the right side of the chick embryo between HH stages 4 and 7 randomizes the direction of heart looping. This effect was not observed when Claudin-1 was overexpressed on the left side of the embryo. A small, but reproducible, induction of Nodal expression in the perinodal region on the right side of the embryo was noted in embryos that were injected with Claudin-1 retroviral particles on their right sides. However, no changes in Lefty,Pitx2 or cSnR expression were observed. ...

2006-02-24

423

{sup 18}F-labeled styrylpyridines as PET agents for amyloid plaque imaging  

Energy Technology Data Exchange (ETDEWEB)

Positron emission tomography (PET) imaging of {beta}-amyloid (A{beta}) plaques in the brain is a potentially valuable tool for studying the pathophysiology of Alzheimer's disease (AD). It may also be applicable for measuring the effectiveness of therapeutic drugs aimed at lowering A{beta} plaques in the brain. We have successfully reported a series of {sup 18}F-labeled fluoropegylated stilbenes for PET imaging studies. Encouraging results clearly demonstrated the usefulness of {sup 18}F-labeled stilbenes as potential A{beta} plaque-imaging agents. In the present study, we applied a similar approach to a styrylpyridine backbone structure. Among all derivatives examined (E)-2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-5-(4-dimethylaminostyryl) -pyridine (2) displayed high binding affinity in postmortem AD brain homogenates (K {sub i}=2.5{+-}0.4 nM, with [{sup 125}I]IMPY as radioligand). No-carrier-added [{sup 18}F]2 was successfully prepared ...

2007-01-15

424

Thermoluminescence emission of X-irradiated Eu"2"+ doped KBr single crystals  

International Nuclear Information System (INIS)

In this paper we discuss the results of thermoluminescence (TL) studies carried out on freshly quenched crystals of KBr doped with #approx# 50 ppm of Eu"2"+ ions which were X-irradiated at room temperature. The TL glow curve of this phosphor material consists of three glow peaks at 355, 376 and 398 K whose intensities increased as a function of X-irradiation time. The TL glow peaks were analyzed by the total curve-fitting method in order to obtain the characteristic parameters; activation energy, pre-exponential factor and kinetic order. The spectral character of the emission recorded during thermoluminescence was found to be the same for all glow peaks and consists of a broad band centered at #approx# 420 nm. It is proposed that the model of the TL process most consistent with our experimental results is one in which the Eu"2"+ impurity acts as an electron trap during the irradiation process and that the radiation induced center (partner of an center) and the V_k center (partner of an ...

425

Studies on the mechanism of action of enterotoxin-induced fluid secretion in the gut  

International Nuclear Information System (INIS)

The mechanism of action of Clostridium difficile enterotoxin A (CA), of Escherichia coli enterotoxin (STa) and of cholera toxin (CT), which are known to cause severe diarrhea, were studied in a preparation of ligated jejunal loops of anesthetized rats in vivo. The toxins were administered intraluminally. Pharmacological agents, which were tested for their potency to influence toxin-related effects, were administered subcutaneously. Net fluid transport was determined gravimetrically, prostaglandin (PG) E_2-output into the lumen, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) contents in the mucosa were measured by radioimmunoassay, serotonin-(5-HT)-output into the lumen was determined by high performance liquid chromatography. The histopathological effects of CA and CT were examined by light- and scanning electron microscopy. All three toxins caused net fluid secretion (FS). 5-HT_2-(ketanserin) and ...

1992-01-01

426

Lung studies with spiral CT. pitch 1 versus pitch 2; Confronto tra diversi parametri (pitch 1 e 2) nello studio del polmone con Tomografia Computerizzata spirale  

Energy Technology Data Exchange (ETDEWEB)

In Spiral CT, the pitch is the ratio of the distance to tabletop travels per 360 degrees rotation to nominal slice width, expressed in mm. Performing Spiral CT examination with pitch 2 allows to reduce examination time, exposure and contrast dose, and X-ray tube overload. The authors investigated the yield of pitch 2 in lung parenchyma studies, particular relative to diagnostic image quality. [Italian] Nella Tomografia Computerizzata (TC) spirale il rapporto tra la distanza percorsa dal lettino portapaziente in una rotazione e lo spessore nominale dello strato, entrambi espressi in millimetri, si definische pitch. Se i due valori del rapporto coincidono si avra' pitch uguale a 1, mentre raddoppiando la distanza percorsa dal lettino portapaziente, per il medesimo spessore nominale, conseguentemente raddoppia il pitch (pitch 2). Eseguire gli esami TC spirale utilizzando pitch 2, consente di ridurre la durata dell'esame, la dose di esposizione, il consumo mdc e ...

1999-03-01

427

Level structures of  

Energy Technology Data Exchange (ETDEWEB)

Using Gammasphere data on prompt gamma rays from spontaneous fission of 252Cf, we propose energy-level schemes for 110,111,112, & 113Rh (Z=45). The fission-gamma data complement earlier studies of others on beta decay of fission products in that prompt fission gammas mainly populate yrast or near-yrast levels, while beta decay populates lower-spin levels. For the odd-A rhodium nuclei studied here, their ground bands and collective sidebands are compared with model calculations using triaxial-shaped nucleus with one odd quasi-proton. The energies and E2 transition rates are best fit by a shape slightly to the prolate side of maximum triaxiality, namely, gamma = 28 deg. The model calculations also show a K=1/2+ band with energies not in good agreement with a corresponding experimental band. The experimental 1/2+ band is regarded as an intruder band from a prolate-driving proton orbital 1/2[431] above the Z=50 closed shell. This intruder band, ...

2003-08-19

428

HVDC submarine power cables systems state of the art and future developments  

Energy Technology Data Exchange (ETDEWEB)

The paper begins with an introduction on the reasons that lead to the use of HVDC submarine cable links. The main aspects for the choice of direct current are presented as well as the advantages deriving from the utilization of submarine cables. The second part is dedicated to a discussion on the various type of insulation that could be used in power cables and their possible application to HVDC submarine cables. In the following there is a description of the main characteristics and technical details of some particular project that at present time (1995) are in progress. Two projects are briefly presented: Spain-Morocco, a 26 km long interconnection for the transmission, in a first phase, of 700 MW from Spain to Morocco at 400 kV a.c. by means of three cables, plus one spare, of the fluid filled type. The cables are designed for a future change to d.c. 450 kV, allowing a transmission of 500 MW each (i.e., 2 GW total). One of the peculiarities ...

1995-12-31

429

Goals and activities of the JICA technical cooperation project on reduction of seismic risk in Romania  

International Nuclear Information System (INIS)

Japan International Cooperation Agency (JICA) Technical Cooperation Project on Reduction of Seismic Risk for Buildings and Structures started in Romania on October 1, 2002. The aim of the Project is to strengthen the capacity of earthquake disaster related activities in Romania. The Project approval is the result of four years of intensive efforts made by professionals from Technical University of Civil Engineering Bucharest (UTCB), Ministry of Transport, Constructions and Tourism (MTCT), Romania, National Building Research Institute (INCERC) Bucharest, JICA, Building Research Institute (BRI), Tsukuba, and National Institute for Land, Infrastructure and Management (NILIM), Tsukuba, Japan. The duration of the Project is five years. The implementing agency is the National Center for Seismic Risk Reduction (NCSRR) as a public institution of national interest under MTCT. The activities are carried out by NCSRR in partnership with UTCB and INCERC. During the Project period, 29 young ...

2007-04-26

430

Electromagnetic structure of decuplet baryons towards the chiral regime  

Science.gov (United States)

The electromagnetic properties of the baryon decuplet are calculated in quenched QCD on a 20{sup 3}x40 lattice with a lattice spacing of 0.128 fm using the fat-link irrelevant clover fermion action with quark masses providing a pion mass as low as 300 MeV. Magnetic moments and charge radii are extracted from the electric and magnetic form factors for each individual quark sector. From these, the corresponding baryon properties are constructed. We present results for the higher-order moments of the spin-3/2 baryons, including the electric-quadrupole moment E2 and the magnetic-octupole moment M3. The world's first determination of a nonzero M3 form factor for the {delta} baryon is presented. With these results we provide a conclusive analysis which shows that decuplet baryons are deformed. We compare the decuplet-baryon results from a similar lattice calculation of the octet baryons. We establish that the environment sensitivity is far ...

2009-09-01

431

Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity  

International Nuclear Information System (INIS)

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 ...

2008-05-01

432

Behaviour of silicon released during alteration of nuclear waste glass in compacted clay  

Energy Technology Data Exchange (ETDEWEB)

Long term integrated in situ experiments are performed in the HADES underground research facility (Mol, Belgium) in order to study the coupled reactivity between the different components of an underground repository for vitrified high level radioactive waste (HLW): glass, compacted clay, and stainless steel containers, at 90 degrees C and under gamma irradiation. Studies pertaining to the behaviour of silicon, a major element released during glass alteration, are presented here. Data collected from the integrated experiment, from simplified tests, and from modelling are put together, giving complementary information. The integrated experiment is used to investigate overall reactivity, whereas diffusion experiments coupled with modelling focused on the precipitation of silica in clay media. In the integrated in situ experiment, a bentonite clay (FoCa7) mixed with 5 wt.% of powdered glass frit was put in contact with U/Th-doped SON68 reference glass specimens for 1.2 years. One of the ...

2007-02-15

433

Absence of isoscalar monopole strength in {sup 56}Fe and {sup 58}Ni  

Energy Technology Data Exchange (ETDEWEB)

Measurements with 240 MeV {alpha} particle inelastic scattering with excellent peak/background ratios at small scattering angles including 0{degrees} were made on {sup 56}Fe and {sup 58}Ni using the multipole-dipole-multipole spectrometer at Texas A&M University. Beam was delivered to the spectrometer through a beam analysis system having two bends of 88{degrees} and 87{degrees} respectively. A slit placed after the first 88{degrees} bend was used to define the beam. Slits placed after the second bend (87{degrees}) were used to eliminate slit scattered particles. Comparison of the results of a multiple peak fit to the{sup 58}Ni spectra after continuum subtraction to DWBA calculations revealed about 32% of the E0 EWSR and 58% of the E2 EWSR in the peak, in agreement with previous works. Fits to the angular distribution of the continuum for E{sub x} = 25 MeV show that <15% of the E0 EWSR is present in the continuum. Hence 50% of the EO ...

1995-10-01

434

Tissue structure, nuclear organization and gene expression in normal and malignant breast  

Energy Technology Data Exchange (ETDEWEB)

Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the nucl2048 These connections are made via membrane-bound receptors and transmitted to the nucleus, where ...

2000-01-27

435

Monitoring of DNA and cytogenetic damage in lymphocytes from persons with skin cancer diseases  

International Nuclear Information System (INIS)

There is a lot of interest in the studies that would help to understand whether there is a casual association between cancer and various types of molecular or cytogenetic damage detected in human cells. One major oncogenesis process is activation of proto-oncogenes by point mutations or chromosomal translocation. There are substantial evidence that indicates that the loss of heterozygosity of certain chromosomes is involved in human cancerogenesis. Our study aimed to elicit the possible association between cancer and DNA and cytogenetic abnormalities induced in lymphocytes of people bearing various categories of skin cancer cells. Fresh blood was collected by venipuncture from 25 individuals (including nine prior to cancer treatment). All patients were nonsmoking males, however 42.3 % of them were former smokers. Blood samples were divided into two parts and in the first part of samples cytogenetic studies were performed immediately, while from the second part ...

2004-11-01

436

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 investigates how ...

2007-05-05

437

National Ignition Facility Incorporates P2/E2 in Aqueous Parts Cleaning of Optics Hardware  

Energy Technology Data Exchange (ETDEWEB)

When completed, Lawrence Livermore National Laboratory's (LLNL) National Ignition Facility (NIF) will be the world's largest laser with experimental capabilities applicable to stockpile stewardship, energy research, science and astrophysics. As construction of the conventional facilities nears completion, operations supporting the installation of specialized laser equipment have come online. Playing a critical role in the precision cleaning of mechanical parts from the NIF beamline are three pieces of aqueous cleaning equipment. Housed in the Optics Assembly Building (OAB), adjacent to NIF's laser bay, are the large mechanical parts gross cleaner (LMPGC), the large mechanical parts precision cleaner (LMPPC), and the small mechanical parts gross and precision cleaner (SMPGPC). These aqueous units, designed and built by Sonic Systems, Inc., of Newtown, Pennsylvania, not only accommodate parts that vary greatly in size, weight, geometry, surface finish and ...

2001-07-27

438

Emission of {sup 14}C by the Almirante Alvaro Alberto Nuclear Power Plant 1 and 2 and their local effects on the environmental levels; Emissao de {sup 14}C pelas unidades 1 e 2 da Central Nuclear Almirante Alvaro Alberto (CNAAA) e seu efeito local nos niveis ambientais  

Energy Technology Data Exchange (ETDEWEB)

{sup 14}C is a is a long-lived beta-emitting nuclide (T{sub 1/2} = 5730 years) produced naturally in the upper atmosphere as a result of reactions between neutrons and stable {sup 14}N({sup 14}N(n,p){sup 14}C). Although in a lesser extent, nuclear power plants produce {sup 14}C as well during their routine operation. Since it is converted in {sup 14}CO{sub 2} and mixed throughout the atmosphere, it is incorporated into plant tissues, via photosynthesis process, and hence in food chain. Because of the biological importance of {sup 14}C and long half-life, it is of interest to quantify the amounts released by nuclear industry. The Brazilian nuclear central named Nuclear Central Admiral Alvaro Alberto (CNAAA) has two nuclear reactors of PWR type in operation, Angra I (657 MWe) and Angra II (1350 MWe), and one under construction, Angra III (1309 MWe PWR). The aim of this study was to determine the strength of the sources and the {sup 14}C content in the environment through analyses of air, ...

2006-07-01