23s rrna mutation: Topics by WorldWideScience.org

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

BackgroundThe genus Vibrio is a diverse group of Gram-negative bacteria comprised of 74 species. Furthermore, the genus has and is expected to continue expanding...Full Text Available

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

Regulation of human ribosomal RNA transcription.

Rapid in situ hybridization technique using 16S rRNA segments for detecting and differentiating the closely related gram-positive organisms Bacillus polymyxa and Bacillus macerans

We have used a cell-free polymerase I transcription system derived from HeLa cells to study the regulation of human rRNA synthesis. Analysis of deletion mutants spanning the start site of transcription at nucleotide +1 indicates that the control region affecting initiation of human rRNA synthesis is contained within sequences from nucleotides -158 to +18. This promoter region can be subdivided into (i) a central segment of approximately 40 base pair that is required for transcription and (ii) flanking sequences that influence the efficiency of transcription in vitro. We have examined the in vitro transcriptional activity of the human extract under various conditions that are thought to modulate rRNA synthesis in vivo. Cell-free extracts prepared from HeLa cells infected with adenovirus 2 synthesize human rRNA at levels greatly decreased relative to uninfected cell extracts. By contrast, in vitro ...

1983-06-01

Emergence of Klebsiella pneumoniae Coproducing KPC-2 and 16S rRNA Methylase ArmA in Poland ?

A rapid, sensitive, inexpensive in situ hybridization technique, using 30-mer 16S rRNA probes, can

1992-01-01

Nucleotide sequence of a Euglena gracilis chloroplast gene coding for the 16S rRNA: homologies to E. coli and Zea mays chloroplast 16S rRNA.

A Klebsiella pneumoniae epidemic strain that coproduced carbapenemase KPC-2 (K. pneumoniae carbapenemase 2) and 16S rRNA methylase ArmA has emerged in Poland. Four...Full Text Available

2011-01-01

The nucleotide sequence and organization of nuclear 5S rRNA genes in yellow lupine

The nucleotide sequence of 16S rDNA from Euglena gracilis chloroplasts has been determined representing the first complete sequence of an algal chloroplast rRNA gene. The structural part of the 16S...Full Text Available

1982-10-25

Fast evolving 18S rRNA sequences from Solenogastres (Mollusca) resist standard PCR amplification and give new insights into mollusk substitution rate heterogeneity

We have isolated a genomic clone containing 'Lupinus luteus' 5S ribosomal RNA genes by screening with 5S rDNA probe clones that were hybridized previously with the initiator methionine tRNA preparation (contaminated) with traces of rRNA or its degradation products). The clone isolated contains ten repeat units of 342 bp with 119 bp fragment showing 100% homology to the 5S rRNA from yellow lupine. Sequence analysis indicates only point heterogeneities among the flanking regions of the genes. (author). 6 refs, 3 figs.

1993-01-01

Norwegian Open Research Archives (NORA)

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Yeast ribosomal protein L1 is required for the stability of newly synthesized 5S rRNA and the assembly of 60S ribosomal subunits.

Protein S inherited qualitative deficiency: novel mutations and phenotypic influence.

Ribosomal protein L1 from Saccharomyces cerevisiae binds 5S rRNA and can be released from intact 60S ribosomal subunits as an L1-5S ribonucleoprotein (RNP) particle. To understand the nature of the...Full Text Available

1993-05-01

PAX6 Mutations and Clinical Features of Congenital Aniridia

PMID:20880255

2010-12-01

KoreaScience (Korea)

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2008-11-01

Identification of pork derivatives in food products by species-specific polymerase chain reaction (PCR) for halal verification

British Library Electronic Table of Contents (United Kingdom)

Pork identification in four types of food products, which are sausages and the casings, bread and biscuits, using species-specific polymerase chain reaction (PCR) detection of a conserved region in the mitochondrial (mt) 12S ribosomal RNA (rRNA) gene was developed. Genomic DNA of the food products were successfully extracted except for the casing samples, where no genomic DNA was detected. The extracted genomic DNA was then subjected to PCR amplification targeting the specific regions of the 12S rRNA gene. The genomic DNA from the food products were found to be of good quality and produced clear PCR products on the amplification of 12S rRNA gene of 387 base pairs (bp) from pork species. The species-specific PCR identification yielded excellent results for identification of pork derivatives...

2007-01-01

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Worlds within worlds: evolution of the vertebrate gut microbiota

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Use of synthetic oligonucleotide DNA probes for identification and direct detection of Bacteroides forsythus in plaque samples.

Here we use published 16S rRNA gene sequences to compare the bacterial assemblages associated with humans, other mammals, other metazoa, and free-living microbial communities spanning a range...Full Text Available

2008-10-01

Seasonal and Spatial Variability of Bacterial and Archaeal Assemblages in the Coastal Waters near Anvers Island, Antarctica

Oligonucleotide DNA probes complementary to the hypervariable region of the 16S rRNA of Bacteroides forsythus were tested for their specificity and sensitivity against reference and clinical isolates...Full Text Available

1991-10-01

Scintillation proximity assay for measurement of RNA methylation

A previous report of high levels of members of the domain Archaea in Antarctic coastal waters prompted us to investigate the ecology of Antarctic planktonic prokaryotes. rRNA hybridization...Full Text Available

1998-07-01

Improved Understanding of the Bacterial Vaginal Microbiota of Women before and after Probiotic Instillation

Methylation of RNA by methyltransferases is a phylogenetically ubiquitous post-transcriptional modification that occurs most extensively in transfer RNA (tRNA) and ribosomal RNA (rRNA). Biochemical...Full Text Available

2009-03-01

Detection of Atopobium vaginae in Postmenopausal Women by Cultivation-Independent Methods Warrants Further Investigation

The vaginal bacterial microbiota of 19 premenopausal women was examined by PCR-denaturing gradient gel electrophoresis (DGGE) and sequencing of the V2-V3 region of the 16S rRNA gene. Ten of the women...Full Text Available

2003-01-01

Association of Unique, Isolated Treponemes with Bovine Digital Dermatitis Lesions?

2004-04-01

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

This study used a PCR-based approach targeting 16S rRNA gene fragments to determine the occurrence and association of the three bovine digital dermatitis (BDD) treponeme phylogroups within lesions found...Full Text Available

2009-03-01

Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients

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).

Homozygous SLC2A9 Mutations Cause Severe Renal Hypouricemia

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

The early phase change Gene in Maize

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

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

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

A framework for evolutionary systems biology

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

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

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

Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene

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

Mutation breeding in leguminous crop plants

Udgivelsesdato: 2006/8

2006-01-01

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

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

The Morphology, Ontogeny, and Small Subunit rRNA Gene Sequence Analysis of Diophrys parappendiculata n. sp. (Protozoa, Ciliophora, Euplotida), a New Marine Ciliate from Coastal Waters of Southern China

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

British Library Electronic Table of Contents (United Kingdom)

ABSTRACT. The morphology, morphogenesis, and phylogeny of Diophrys parappendiculata n. sp., a large marine ciliate isolated from the coastal waters of Daya Bay, southern China, were investigated. This new species is characterized by a combination of its large size, appendiculata-pattern of ciliature, and bipartite adoral zone of membranelles. The main stages of morphogenesis during binary fission were also recorded and described. Comparisons of morphological characteristics with similar congeners support the validity of the new species. The small subunit rRNA gene sequence of D. parappendiculata is 96.3-99.94% similar to those of four other congeners; it differs in four nucleotides from that of Diophrys appendiculata (i.e. structural similarity was 99.94%). Phylogenetic analysis indicates ...

2011-01-01

Oxidation of Elemental Sulfur by Fusarium solani Strain THIF01 Harboring Endobacterium Bradyrhizobium sp.

British Library Electronic Table of Contents (United Kingdom)

Nineteen fungal strains having an ability to oxidize elemental sulfur in mineral salts medium were isolated from deteriorated sandstones of Angkor monuments. These fungi formed clearing zone on agar medium supplemented with powder sulfur due to the dissolution of sulfur. Representative of the isolates, strain THIF01, was identified as Fusarium solani on the basis of morphological characteristics and phylogenetic analyses. PCR amplification targeting 16S rRNA gene and analyses of full 16S rRNA gene sequence indicated strain THIF01 harbors an endobacterium Bradyrhizobium sp.; however, involvement of the bacterium in the sulfur oxidation is still unclear. Strain THIF01 oxidized elemental sulfur to thiosulfate and then sulfate. Germination of the spores of strain THIF01 was observed in a liqui...

2010-01-01

Extraribosomal functions associated with the C terminus of the 37/67?kDa laminin receptor are required for maintaining cell viability

Discrimination of Listeria monocytogenes from other Listeria species by ligase chain reaction.

The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly....Full Text Available

2010-05-01

Detection of Atopobium vaginae in postmenopausal women by cultivation-independent methods warrants further investigation.

A ligase chain reaction assay based on a single-base-pair difference in the V9 region of the 16S rRNA gene (16S rDNA) was developed to distinguish between Listeria monocytogenes and other Listeria species....Full Text Available

1992-11-01

Application of a Newly Developed ARB Software-Integrated Tool for In Silico Terminal Restriction Fragment Length Polymorphism Analysis Reveals the Dominance of a Novel pmoA Cluster in a Forest Soil

We sequenced 16S rRNA genes from the vaginal swab contents of a postmenopausal woman with asymptomatic bacterial vaginosis (BV). Sequences from Atopobium vaginae were the most commonly detected. In a survey of 35 other postmenopausal women, this organism was detected in 44% with BV but not in any subjects deemed healthy. PMID:15071062

2004-04-01

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

TRF-CUT, an ARB-implemented tool, was developed to predict in silico the terminal restriction fragments of aligned small-subunit rRNA gene or functional gene sequences. Application of this new tool...Full Text Available

2005-03-01

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

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

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

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

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

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

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

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

Mutational analysis of bacteriophage lambda lysis gene S.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells

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

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

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

Detection of Mitochondrial DNA Mutations in Mammary ...

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

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

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

2004-09-01

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

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

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

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

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

Source tracking of Escherichia coli by 16S-23S intergenic spacer region denaturing gradient gel electrophoresis (DGGE) of the rrnB ribosomal operon.

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

This research validates a novel approach for source tracking based on denaturing gradient gel electrophoresis (DGGE) analysis of DNA extracted from Escherichia coli isolates. Escherichia coli from different animal sources and from river samples upstream from, at, and downstream of a combined sewer overflow were subjected to DGGE to determine sequence variations within the 16S-23S intergenic spacer region (ISR) of the rrnB ribosomal operon. The ISR was analyzed to determine if E. coli isolates from various animal sources could be differentiated from each other. DNA isolated from the E. coli animal sources was PCR amplified to isolate the rrnB operon. To prevent amplification of all 7 E. coli ribosomal operons by PCR amplification using universal primers, sequence-specific primers were utilized for the rrnB operon. Another primer set was then used to prepare samples of the 16S-23S ISR for DGGE. Comparison ...

2007-10-01

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The vacuolar processing enzyme (VPE) mutation suppresses an HR-like cell death induced by the double knockout mutant of vacuolar Ca2+-ATPases in Arabidopsis

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

KoreaScience (Korea)

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2011-06-01

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

State II Dissociation Element Formation Following Activator Excision in Maize

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

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

2007-10-01

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

2011-01-01

Ras history

Prosthetic rehabilitation of hypophosphatasia: a case report

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

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

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

Mutations in RNA Binding Protein Gene Cause Familial Dilated Cardiomyopathy

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.

Mutation frequency in hprt gene in children accidentally exposed to ionizing radiations; Frequencia de mutacao no gene hprt em criancas acidentalmente expostas as radiacoes ionizantes

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

2009-09-01

Misfolded Proteins and Retinal Dystrophies

No abstract prepared

1995-09-01

MEDICAL FINAL REVIEW MEMORANDUM OF ORIGINAL BLA

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

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

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

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

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

Genomics of human longevity

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

Embryonic Senescence and Laminopathies in a Progeroid Zebrafish Model

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

Detection of genetic mutations in repetitive DNA sequences in somatic human cells after low-dose irradiation

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

Defective gut function in drop-dead mutant Drosophila

... 3-89701-147-6 0949-2224 245 p. animal cells dna genetic radiation effects

1998-03-01

Cis-regulatory mutations in human disease

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

Abnormal chromosome repair and risk of developing cancer.

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

AEC syndrome - Genetics Home Reference

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

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A child with hyperferritinemia: Case report

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

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

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

Prostaglandin E₂ Signals Through PTGER2 to Regulate Sclerostin Expression

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 ...

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

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.

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

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

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

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

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

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

Direct observation of polymerization in the oleic acid-ozone heterogeneous reaction system by photoelectron resonance capture ionization aerosol mass spectrometry

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

British Library Electronic Table of Contents (United Kingdom)

High molecular weight products of the ozonolysis reaction of particle-phase 9-octadecenoic acid (oleic acid) have been studied by photoelectron resonance capture ionization (PERCI) mass spectrometry (MS). Oleic acid particles ( Formula Not Shown , Formula Not Shown ) were reacted with ozone (1.8x10-4atm) in a flow reactor at reaction times of 8 and 23s. Particles were sampled on-line with a differentially pumped particle inlet and chemically analyzed by PERCI-MS. PERCI is a soft ionization method that permits the direct measurement of relatively high molecular weight compounds, facilitating molecular identification. In addition to cyclic oxygenates, such as secondary ozonides and geminal diperoxides that were reported previously, we demonstrate the formation of polymers at the particle sur...

2006-01-01

Molecular phylogenetic relationships and phenotypic diversity in miniaturized toadlets, genus Brachycephalus (Amphibia: Anura: Brachycephalidae)

British Library Electronic Table of Contents (United Kingdom)

Toadlets of the genus Brachycephalus are endemic to the Atlantic rainforests of southeastern and southern Brazil. The 14 species currently described have snout-vent lengths less than 18mm and are thought to have evolved through miniaturization: an evolutionary process leading to an extremely small adult body size. Here, we present the first comprehensive phylogenetic analysis for Brachycephalus, using a multilocus approach based on two nuclear (Rag-1 and Tyr) and three mitochondrial (Cyt b, 12S, and 16S rRNA) gene regions. Phylogenetic relationships were inferred using a partitioned Bayesian analysis of concatenated sequences and the hierarchical Bayesian method (BEST) that estimates species trees based on the multispecies coalescent model. Individual gene trees showed conflict and also va...

2011-01-01

Molecular environment of the IIId subdomain of the IRES element of hepatitits C virus RNA on the human 40S ribosomal subunit

British Library Electronic Table of Contents (United Kingdom)

The molecular environment of the key subdomain IIId of the internal ribosome entry site (IRES) element of hepatitis C virus (HCV) RNA in the binary complex with the human 40S ribosomal subunit was studied. To this end, HCV IRES derivatives bearing perfluorophenylazido groups activatable by mild UV at nucleotides G263 or A275 in the subdomain IIId stem were used. They were prepared by the complementary addressed modification of the corresponding RNA transcript with alkylating oligodeoxyribonucleotide derivatives. None of the RNA derivatives were shown to be crosslinked to the 18S rRNA. It was found that the photoreactive groups of the IRES G263 and A275 nucleotides are crosslinked to ribosomal proteins S3a, S14, and S16. For the IRES derivative with the photoreactive group in nucleotide G26...

2009-01-01

Methanogen community structure in the rumens of farmed sheep, cattle and red deer fed different diets

British Library Electronic Table of Contents (United Kingdom)

Abstract Development of inhibitors and vaccines that mitigate rumen-derived methane by targeting methanogens relies on knowledge of the methanogens present. We investigated the composition of archaeal communities in the rumens of farmed sheep (Ovis aries), cattle (Bos taurus) and red deer (Cervus elaphus) using denaturing gradient gel electrophoresis (DGGE) to generate fingerprints of archaeal 16S rRNA genes. The total archaeal communities were relatively constant across species and diets, and were less variable and less diverse than bacterial communities. There were diet- and ruminant-species-based differences in archaeal community structure, but the same dominant archaea were present in all rumens. These were members of three coherent clades: species related to Methanobrevibacter ruminan...

2011-01-01

100

Functional adaptation of microbial communities from jet fuel-contaminated soil under bioremediation treatment: simulation of pollutant rebound

British Library Electronic Table of Contents (United Kingdom)

Abstract To investigate the link between the functionality and the diversity of microbial communities under strong selective pressure from pollutants, two types of mesocosms that simulate natural attenuation and phytoremediation were generated using soil from a site highly contaminated with jet fuel and under air-sparging treatment. An increase in the petroleum hydrocarbon concentration from 4900 to 18-500-mg-kg-1-dw soil simulated a pollutant rebound (postremediation pollutant reversal due to residual contamination). Analysis of soil bacterial communities by denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene fragments showed stronger changes and selection for a phylogenetically diverse microbial population in the mesocosms with pollutant-tolerant willow trees. Enumerat...

2011-01-01

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101

Distinctive Responses of Metabolically Active Microbiota to Acidification in a Thermophilic Anaerobic Digester

British Library Electronic Table of Contents (United Kingdom)

Acidification is one of the most common and serious problems inducing process failure in anaerobic digesters. The production of volatile fatty acids (VFAs) mainly triggers acidic shock. However, little is known about the bacteria involved in the processes of acidogenic metabolism, such as fermentation and reductive acetogenesis. Here, the metabolic responses of a methanogenic community to the acidification and resulting process deterioration were investigated using transcriptional profiling of both the 16S rRNA and formyltetrahydrofolate synthetase (FTHFS) genes. The 16S rRNA-based analyses demonstrated that the dynamic shift of bacterial populations was closely correlated with reactor performance, especially with VFA accumulation levels. The pH drop accompanied by an increase in VFAs stim...

2011-01-01

102

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

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

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

103

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

2008-08-25

104

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

105

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

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

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

106

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

107

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

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

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

108

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

109

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

110

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

aHUS caused by complement dysregulation: new therapies on the horizon

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

111

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

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

112

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

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

113

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

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

114

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

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

115

The mitochondrial p53 pathway

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

116

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

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

117

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

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

118

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

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

119

Technical approaches for mouse models of human disease

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

120

Targeting the p53 Pathway in Ewing Sarcoma

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

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121

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

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

122

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

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

123

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

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

124

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

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

125

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

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

126

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

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

127

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

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

128

Radiation-induced mutations at mouse hemoglobin loci

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

129

Pten Knockdown in vivo Increases Excitatory Drive onto Dentate Granule Cells

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 ...

130

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

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

131

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

2009-06-01

132

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

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

133

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

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

134

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

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

135

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

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

136

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

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

137

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

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

138

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

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

139

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

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

140

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

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

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141

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

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

142

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

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

143

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

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

144

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

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

145

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

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

146

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

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

147

Inferring Stabilizing Mutations from Protein Phylogenies: Application to Influenza Hemagglutinin

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

148

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

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

149

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

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

150

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

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

151

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

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

152

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

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

153

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

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

154

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

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

155

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

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

156

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

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

157

Gene Therapy in the Retinal Degeneration Slow Model of Retinitis Pigmentosa

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

158

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

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

159

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

2008-07-01

160

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

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

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161

Exome sequencing identifies GRIN2A as frequently mutated in melanoma

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

162

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

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

163

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

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

164

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

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

165

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

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

166

Developmental abnormalities and epimutations associated with DNA hypomethylation mutations.

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

167

Detection of genetic mutations in repetitive DNA sequences in somatic human cells after low-dose irradiation; Nachweis genetischer Veraenderungen in repetitiven DNA-Sequenzen in somatischen menschlichen Zellen nach Bestrahlung im niedrigen Dosisbereich

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

168

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

No abstract prepared

1998-03-01

169

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

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

170

Congenital woolly hair without P2RY5 mutation

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

171

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

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

172

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

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

173

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

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

174

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

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

175

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

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

176

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

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

177

Antagonistic crosstalk between APC and HIF-1?

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

178

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

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

179

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

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

180

Air pollution induces heritable DNA mutations

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

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181

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

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

182

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

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

183

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

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

184

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

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

185

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

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

186

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

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

187

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

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

188

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

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

189

Three novel mutations responsible for Cockayne syndrome group A

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

190

Linkage analysis in familial Angelman syndrome

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

191

The mitochondrial genome of the entomophagous endoparasite Xenosvesparum (Insecta: Strepsiptera)

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

192

Report on a survey in fiscal 1999. Survey on industrial utilization of microorganism reaction mechanisms under anaerobic condition; 1999 nendo kenki jokenka ni okeru biseibutsu hanno kiko no kogyoteki riyo ni kansuru chosa hokokusho

In this study, the nearly complete sequence (14,519 bp) of the mitochondrial DNA (mtDNA) of the entomophagous endoparasite Xenos vesparum (Insecta: Strepsiptera) is described. All protein coding genes (PCGs) are in the arrangement known to be ancestral for insects, but three tRNA genes (trnA, trnS(gcu), and trnL(uag)) have transposed to derived positions and there are three tandem copies of trnH, each of which is potentially functional. All of these rearrangements except for that of trnL(uag) is within the short span between nad3 and nad4 and there are numerous blocks of unassignable sequence in this region, perhaps as remnants of larger scale predisposing rearrangements. X. vesparum mtDNA nucleotide composition is strongly biased toward As and Ts, as is typical for insect mtDNAs. There is also significant strand skew in the distribution of these nucleotides, with the J-strand being richer in A than T and in C than G, and the N-strand showing an opposite skew for complementary pairs of ...

2005-12-01

193

Identification of culturable and originally non-culturable endophytic bacteria isolated from shoot tip cultures of banana cv. Grand Naine

Industrial utilization of reaction mechanisms of microorganisms under anaerobic condition permits structuring energy saving type production processes. The present survey has investigated features of new microorganisms under anaerobic condition and the status of researches thereon inside and outside the country, and discussed their future applications. Chapter 1 compares anaerobic microorganisms and functions of microorganism under anaerobic condition with those aerobic to describe their general features, and describes the purpose of this survey and the summary of the investigations. Chapter 2 surveys the current status of technologies to utilize microorganisms under anaerobic condition. Chapter 3 outlines metabolic characteristics of the anaerobic microorganisms, and extracts functions effective for material production by different anaerobic microorganisms to describe their applicability. Chapter 4 evaluates the system classification for the anaerobic microorganisms utilizing the basic ...

2000-03-01

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In this article we describe the identification of endophytic bacteria belonging to three groups isolated from shoot tip cultures of banana cv. Grand Naine in a recent study (Thomas et?al. 2008) based on partial 16S rRNA gene sequence homology analysis. The first group included banana stocks that displayed obvious colony growth on MS based tissue culture medium during the first in?vitro passage. The second group constituted stocks that were tissue index-negative for cultivable bacteria initially but turned index-positive after a few to several (4?8) in?vitro passages while the third group formed one sub-stock that turned index-positive after about 18 passages. The organisms belonged to about 20 different genera comprising of ?, ?, ?-proteobacteria, Gram-positive firmicutes and actinobacteri...

2008-01-01

195

Two and 8-azido photoaffinity probes. 1. Enzymatic synthesis, characterization, and biological properties of 2- and 8-azido photoprobes of 2-5A and photolabeling of 2-5A binding proteins

Research work on mutation breeding in Egypt during the 1980s

The 2- and 8-azido trimer 5'-triphosphate photoprobes of 2-5A have been enzymatically synthesized from [#gamma#-"3"2P]2-azidoATP and [#alpha#-"3"2P]8-azidoAPT by 2-5A synthetase from rabbit reticulocyte lysates. Identification and structural determination of the 2- and 8-azido adenylate trimer 5'-triphosphates were accomplished by enzymatic hydrolyses with T2 RNase, snake venom phosphodiesterase, and bacterial alkaline phosphatase. Hydrolysis products were identified by HPLC and PEI-cellulose TLC analyses. The 8-azido photoprobe of 2-5A displaces p_3A_4["3"2P]pCp from RNase L with affinity equivalent to p_3A_3. The 8-azido photoprobe also activates RNase L to hydrolyze poly(U)["3"2P]pCp 50% at 7 /times/ 10/sup /minus/9/ M in core-cellulose assays. The 2- and 8-azido photoprobes and authentic p_3A_3 activate RNase L to cleave 28S and 18S rRNA to specific cleavage products at 10/sup /minus/9/ M in rRNA cleavage assays. The nucleotide binding ...

196

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

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

197

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

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

198

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.

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

199

Homology among tet determinants in conjugative elements of streptococci

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

200

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

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

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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

202

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

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

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

203

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

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

204

Studies of human mutation rates

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

205

Somatic mutations detected by immunofluorescence and flow cytometry

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

206

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

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).

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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

208

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

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

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 ...

209

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

210

Improving protein quality of soybean through induced mutations

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

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

211

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

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

212

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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

213

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

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

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.

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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

215

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

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.

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

216

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.

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

217

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

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

218

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

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

219

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

220

ORNL `90

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

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

221

ORNL '90

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

1990-01-01

222

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

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

223

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

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

224

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

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

225

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.

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

226

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

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

227

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

228

Mechanism of radiation induced carcinogenesis: does a threshold exist?

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

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

229

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

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

230

Induced mutation in Lupinus mutabilis sweet in Peru

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

231

High yielding mutants in sesamum

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

232

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

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).

233

Genetic and somatic effects in animals maintained on tritiated water

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

234

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

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

235

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

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

236

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

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

237

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

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

238

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

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.

239

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

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

240

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

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

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

241

Development of radiological emergency preparedness technology

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

242

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

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

243

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

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

244

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

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

245

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

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

246

Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes

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

247

Microbial community analysis of ambient temperature anaerobic digesters

In previous work the authors showed that on photolysis of Escherichia coli ribosomes in the presence of ({sup 3}H)tetracycline (TC) the major protein labeled is S7, and they presented strong evidence that such labeling takes place from a high-affinity site related to the inhibitory action of TC. In this work they use single protein omission reconstitution (SPORE) experiments to identify those proteins that are important for high-affinity TC binding to the 30S subunit, as measured by both cosedimentation and filter binding assays. With respect to both sedimentation coefficients and relative Phe-tRNA{sup Phe} binding, the properties of the SPORE particles they obtain parallel very closely those measured earlier, with the exception of the SPORE particle lacking S13. A total of five proteins, S3, S7, S8, S14, and S19, are shown to be important for TC binding, with the largest effects seen on omission of proteins S7 and S14. Determination of the protein compositions of the corresponding ...

1990-06-05

248

Mapping a nucleolar targeting sequence of an RNA binding nucleolar protein, Nop25

This paper reported on a study in which designs for Chinese and Indian fixed-dome anaerobic digesters were modified in an effort to produce smaller and more affordable digesters. While these types of systems are common in tropical regions of developing countries, they have not been used in colder climates because of the low biogas yield during the winter months. Although there is evidence that sufficient biogas production can be maintained in colder temperatures through design and operational changes, there is a lack of knowledge about the seasonal changes in the composition of the microbial communities in ambient temperature digesters. More knowledge is needed to design and operate systems for maximum biogas yield in temperate climates. The purpose of this study was to cultivate a microbial community that maximizes biogas production at psychrophilic temperatures. The study was conducted on a 300 gallon experimental anaerobic digester on the campus of Ohio State University. ...

2010-07-01

249

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

Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of lysine and arginine residues in the subdomain resulted in the loss ...

2006-06-10

250

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

251

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

252

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

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

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

253

Improvement of banana through biotechnology and mutation breeding

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

254

Development of radiological emergency preparedness and biological dosimetry technology

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

255

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

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

256

Characterization of the heterokaryotic and vegetative diploid phases of Magnaporthe grisea

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

257

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

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

258

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

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

259

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

260

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

Inborn Errors of Metabolism Presenting in Childhood

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.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

261

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

262

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

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

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

263

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

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

264

Apoptotic pathways as regulators of recombination

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

265

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

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

266

Biogeochemistry of the compost bioreactor components of a composite acid mine drainage passive remediation system

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

267

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

The compost bioreactor ('anaerobic cell') components of three composite passive remediation systems constructed to treat acid mine drainage (AMD) at the former Wheal Jane tin mine, Cornwall, UK were studied over a period of 16 months. While there was some amelioration of the preprocessed AMD in each of the three compost bioreactors, as evidenced by pH increase and decrease in metal concentrations, only one of the cells showed effective removal of the two dominant heavy metals (iron and zinc) present. With two of the compost bioreactors, concentrations of soluble (ferrous) iron draining the cells were significantly greater than those entering the reactors, indicating that there was net mobilisation (by reductive dissolution) of colloidal and/or solid-phase ferric iron compounds within the cells. Soluble sulfide was also detected in waters draining all three compost bioreactors which was rapidly oxidised, in contrast to ferrous iron. Oxidation and hydrolysis of iron, together with ...

2005-02-01

268

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

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).

269

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

270

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

271

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

272

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

273

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

274

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

275

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

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

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

276

Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts

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

277

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

278

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

279

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

280

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

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

281

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

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

1984-08-01

282

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

283

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

284

Characteristics of radiation-induced neoplastic transformation in vitro

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

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

285

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

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

286

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

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

287

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

288

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

Radiation effects on shoot tip culture of chrysanthemum, 2

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

289

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

(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 ...

290

Novel method for differentiation between Trastuzumab and host adaptive response.

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

291

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

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

292

Association of attention-deficit disorder and the dopamine transporter gene

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

293

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

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

294

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

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

295

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

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

296

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

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

297

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

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

298

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

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

299

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

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

300

The Origin of Life from Primordial Planets

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

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

301

The 2001 Superoutburst of WZ Sagittae

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

302

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

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

303

Role of accelerator mass spectrometry in biological dosimetry

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 ...

304

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

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

305

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

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 ...

306

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

307

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

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

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

308

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

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

309

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

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

310

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

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' ...

311

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

312

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

313

Isolation of fetal DNA from nucleated erythrocytes in maternal blood

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

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

314

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

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

315

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

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 ...

316

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

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

317

Genotoxic effects of sunlight-activated waste waters

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 ...

318

Evolutionary dynamics of Newcastle disease virus

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

319

Endonuclease IV of Escherichia coli is induced by paraquat

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

320

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

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 ...

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

321

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

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

322

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

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

323

Characterization of mal recombination plasmids cloned in Streptococcus pneumoniae

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

324

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

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

325

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

326

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

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

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

327

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

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

328

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

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

329

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

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.

330

Evolution of improved varieties of sesame through induced mutations

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

331

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

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

332

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.

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

333

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

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

334

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

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

335

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

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

336

Safety evaluation of Propionibacterium freudenreichii ET-3 culture.

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

337

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

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

338

New discoveries in prostate cancer pathogenesis

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 ...

339

Mucociliary transport and upper airway disease

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 ...

340

Molecular targeted treatment and radiation therapy for rectal cancer

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

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341

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

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

342

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

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

343

Cytogenetic effects of protracted gamma exposures from conception of male mice

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

344

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

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

345

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

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

346

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

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

347

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

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

348