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).
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
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
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 mutationderived 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.
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
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 ...
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 ...
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
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
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 ...
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
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
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
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.
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.
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.).
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.
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 ...
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 ...
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
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
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
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
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
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
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
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
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
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
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
PurposeTo analyze the contributions of cytochrome P4501B1 (CYP1B1) mutations to primary congenital glaucoma (PCG) in Spanish patients.MethodsWe...Full Text Available
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 ...
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
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
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
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
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, ...
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
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...
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 ...
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...
Active Activator (Ac) elements undergo mutations to become nonautonomous Dissociation (Ds) elements at a low frequency. To understand...Full Text Available
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
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
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.
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
... The AAT Z mutation involves a single amino acid substitution (glutamine for lysine) at position 342, resulting in abnormal folding and polymerization of the ...
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 ...
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.
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
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
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
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
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
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...
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
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
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
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
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 ...
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
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 ...
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
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 ...
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.
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
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
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
Nicotiana glutinosa compensated for a mutated tumor-morphology-shooty (tms) (auxin biosynthesis) locus of Agrobacterlum tumefaciens strain A66 and...Full Text Available
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 ...
The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate ...
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...
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.
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...
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.
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.
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...
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
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
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.
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
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
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
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
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
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
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
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
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
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
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 ...
SUMMARYThe biologic and clinical significance of KIT overexpression that associates with KIT gain-of- function mutations occurring in subsets...Full Text Available
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
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
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
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
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 ...
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
With the advent of subgenomic hepatitis C virus (HCV) replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured...Full Text Available
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
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
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
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
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
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
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
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
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
BackgroundMitochondrial dysfunction, oxidative damage and the accumulation of somatic mutations in mitochondrial DNA (mtDNA) have been associated with certain neurodegenerative disorders....Full Text Available
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
There are many methods for introducing random mutations into nucleic acid sequences. Previously, we described a suite of programmes for estimating the completeness and diversity of randomized DNA libraries...Full Text Available
BackgroundRecessive mutations in guanylate cyclase-1 (Gucy2d) are associated with severe, early onset Leber congenital amaurosis-1(LCA1). Gucy2d...Full Text Available
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
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
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
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
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
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
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
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
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
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
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 ...
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
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
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
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
PurposeTo report the clinical, ophthalmic, and genetic characteristics for lattice corneal dystrophy type I (LCDI) in a Chilean family.MethodsSix...Full Text Available
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
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
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
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
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
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
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
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 ...
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
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
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
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
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 (...
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 ...
U.v.-visible-absorption and e.p.r. spectroscopy were used to study the type 2 and type 3 copper centres in the mercury derivative of laccase. After treatment with peroxide the mercury derivative of...Full Text Available
The mutagenic and cytotoxic activity of two newly synthesized doxorubicin derivatives and of one daunorubicin derivative were studied in V79 Chinese hamster cells and bacteria (Salmonella typhimurium...Full Text Available
Binary mixtures of dipyrone and pitophenone hydrochloride are assayed by zero-crossing second- and third-derivative spectrophotometry and by ratio-spectra first- and second-derivative spectrophotometry. In the first method, calibration plots are linear at 266.5 and 302.5 nm (dipyrone, second derivative), and 257 and 286 nm (pitophenone second derivative) and 242 and 278.3 nm (dipyrone third derivative), and 228.5 and 300 nm (pitophenone, third-derivative). By the second method, lines of regression are linear at 235 and 262 nm (dipyrone, first derivative), and 229.5 and 288.5 nm (pitophenone, first-derivative), and 249.7 and 268 nm (dipyrone, second derivative), and 280.5 and 300 nm (pitophenone, second-derivative). In all methods calibration curves follow the Beer's law up to 40 ...
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.)
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.
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).
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...
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 ...
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 ...
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)
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
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...
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.
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;...
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
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
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
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 ...
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
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)
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)
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
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
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
In Streptococcus pneumoniae, CpsB, CpsC, and CpsD are essential for encapsulation, and mutants containing deletions of cpsB, cpsC, or cpsD...Full Text Available
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
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...
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.).
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 ...
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 ...
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.
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).
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.
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)
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
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
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
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
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 ...
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
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 ...
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
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
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
Various physics applications involve the computation of the standard hypergeometric function {sub 2}F{sub 1} and its derivatives. Because it is not an intrinsic in the common programming languages, automatic differentiation tools will either differentiate through the code that computes {sub 2}F{sub 1} if that code is available or require the user to provide a hand-written derivative code. We present options for the derivative computation in the context of an ionization problem and compare the approach implemented in the Diamant library to standard methods.
The usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. {sup 125}I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a-e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a-c), iodophenoxyethyl ethylenediamine derivatives (9,14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a-e, 6a-c, 8, 13, 17) by this method. (author).
The usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. "1"2"5I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a-e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a-c), iodophenoxyethyl ethylenediamine derivatives (9,14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a-e, 6a-c, 8, 13, 17) by this method. (author).
In developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The alpha,alpha-dimethylester derivative, amide derivatives and diamine derivatives, which were stable to hydrolysis, showed low blood activity levels following intravenous administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be useful as potential ...
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...
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. ...
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.
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 ...
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 ...
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, ...
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 ...
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 ...
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 ...
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...
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.
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 ...
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.
UV, first, second and third derivative spectrophotometric methods have been developed for the determination of ezetimibe in pharmaceutical formulation. The solutions of standard and sample were prepared...Full Text Available
Three photaffinity labeled derivatives of epothilone D were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building...Full Text Available
The excess molar volumes V_m"E for binary liquid mixtures containing dipropylene glycol monomethyl ether or dipropylene glycol monobutyl ether and methanol, 1-propanol, 1-pentanol and 1-heptanol have been measured as a function of composition using a continuous dilution dilatometer at T=(288.15, 298.15, and 308.15) K and atmospheric pressure over the whole concentration range. The excess volume results allowed the following mixing quantities to be reported in all range of concentrations or at equimolar concentrations: #alpha#, volume expansivity; (#partial deriv#V_m"E/#partial deriv#T)_p; (#partial deriv#H"E/#partial deriv#P)_T at T=298.15 K. The obtained results have been compared at T=298.15 K with the calculated values by using the Flory theory of liquid mixtures. The theory predicts the #alpha#, and #alpha#"E values rather well, while the calculated values of (#partial ...
Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore...Full Text Available
Ring opening dynamics of diarylethene derivative (BTF6) in n-hexane are studied by femtosecond transient absorption and time resolved spontaneous fluorescence techniques. Cyclo-reversion time constant is obtained.
Some of most used indicators in marine ecology are nucleic acid-derived indices. They can be divided by target levels in three groups: 1) at the organism level as ecophysiologic indicators, indicators...Full Text Available
Platelet-derived growth factor (PDGF) is a potent moderator of soft tissue repair through induction of the inflammatory phase of repair and subsequent enhanced collagen deposition. We examined the effect...Full Text Available
The ultraviolet photoelectron spectra of benzoic acid and 20 of its derivatives are presented. The low-energy regions of these spectra are deconvoluted and assigned using chemical substitution effects. 5 figures, 3 tables.
A series of N-alkylamide epoxides have shown considerable selective activity against insects. The N-ethyl and 7,11-dichloro-N-ethyl derivatives showed particularly pronounced activity, and this paper...Full Text Available
In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two...Full Text Available
BackgroundDespite numerous treatments available for deteriorated cutaneous wound healing such as a diabetic foot, there is still the need for more effective therapy. Adipose-derived...Full Text Available
The consequences of structural modifications at the 5'-OH ribofuranotide moiety of quinoline modified B12 derivatives are discussed in regard of the coordination chemistry, the electrochemical properties and the biological behaviour of the compound. PMID:21850334
In this article, we report anticancer activity of 14 anthracenedione derivatives separated from the secondary metabolites of the mangrove endophytic fungi Halorosellinia sp. (No. 1403)...Full Text Available
Anaerobic reactions of Rhus vernicifera laccase and its type-2 copper-depleted derivatives with hexacyanoferrate(II) were investigated by absorption and e.s.r. spectroscopy. When native laccase was...Full Text Available
BackgroundBacterial constituents, such as Gram-negative derived lipopolysaccharide (LPS), can initiate inflammatory bone loss through induction of host-derived inflammatory...Full Text Available
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 ...
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 ...
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 ...
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 ...
This paper is concerned with the study of insurance related derivatives on financial markets that are based on non-tradable underlyings, but are correlated with tradable assets. We calculate exponential utility-based indifference prices, and corresponding derivative hedges. We use the fact that they can be represented in terms of solutions of forward-backward stochastic differential equations (FBSDE) with quadratic growth generators. We derive the Markov property of such FBSDE and generalize results on the differentiability relative to the initial value of their forward components. In this case the optimal hedge can be represented by the price gradient multiplied with the correlation coefficient. This way we obtain a generalization of the classical 'delta hedge' in complete markets.
Kaluza-Klein higher derivative induced gravity is studied for its application in the inflationary universe. The stability of an inflationary solution in a $D+4$-dimensional anisotropic space is analyzed carefully. We show that there is two nontrivial constraints derived from the static assumptions on the $D$-dimensional scale factor $d$ and scalar field $\\psi$. We find that a physical inflationary solution is consistent with the above constraints. In addition, a compact formula for the non-redundant $4+D$ dimensional Friedmann equation is also derived for convenience. Possible implications are also discussed in this paper.
Let $\\A$ be an irreducible Coxeter arrangement and $\\bfk$ be a multiplicity of $\\A$. We study the derivation module $D(\\A, \\bfk)$. Any two-dimensional irreducible Coxeter arrangement with even number of lines is decomposed into two orbits under the action of the Coxeter group. In this paper, we will {explicitly} construct a basis for $D(\\A, \\bfk)$ assuming $\\bfk$ is constant on each orbit. Consequently we will determine the exponents of $(\\A, \\bfk)$ under this assumption. For this purpose we develop a theory of universal derivations and introduce a map to deal with our exceptional cases.
This paper studies the pricing of variance swap derivatives with stochastic volatility by the control variate method. A closed form solution is derived for the approximate model with deterministic volatility, which plays the key role in the paper, and an efficient control variate technique is therefore proposed when the volatility obeys the log-normal process. By the analysis of moments for the underlying processes, the optimal volatility function in the approximate model is constructed. The numerical results show the high efficiency of our method; the results coincide with the theoretical results. The idea in the paper is also applicable for the valuation of other types of variance swap, options with stochastic volatility and other financial derivatives with multi-factor models.
The authors investigate anomalous terms in finite superconformal transformations in N = 4 SU(2)-extended superconformal algebras (SCA). Based on the superspace formalism they obtain super Schwarzian derivatives for the N = 4 SCA. Solutions for global superconformal transformations with the vanishing super-Schwarzian derivatives are given.
A hydrocarbon composition having a major portion of a hydrocarbon preferably a lubricating oil such as mineral oil and at least a friction-reducing amount usually 0.01 to 10 weight percent of an amine or amine derivative of a hydrocarbon-soluble polymerized fatty acid e.g. a dimeramine derived from a dicarboxylic acid containing at least 12 carbon atoms such as 9(10)-carboxy stearic acid has improved antifriction and flue economy properties.
The thermodynamic characteristics of adsorption of proline and its hydroxy derivatives on the surface of graphitized thermal carbon black (GTCB) were calculated. The arrangement of hydroxyl groups in the amino acid molecule was shown to influence their adsorption on GTCB. The influence of internal rotation angles in proline and its hydroxy derivative molecules on their adsorption on GTCB was studied.
The thermodynamic characteristics of adsorption of proline and its hydroxy derivatives on the surface of graphitized thermal carbon black (GTCB) were calculated. The arrangement of hydroxyl groups in the amino acid molecule was shown to influence their adsorption on GTCB. The influence of internal rotation angles in proline and its hydroxy derivative molecules on their adsorption on GTCB was studied.
A formula for calculating the Dirac S-matrix for central Lorentz scalar and vector potentials is derived by use of a new amplitude-phase method. The derivation also makes use of certain invariants of the reduced 2-spinor radial Dirac equations.
A formula for calculating the Dirac S-matrix for central Lorentz scalar and vector potentials is derived by use of a new amplitude-phase method. The derivation also makes use of certain invariants of the reduced 2-spinor radial Dirac equations.
A consistent mathematical derivation is given for the Sommerfeld fine structure electromagnetic coupling 1/?-bar 0=?0-bar 1/137.036. Following 't Hooft's holographic principle two complimentary forms of the derivation are given both leading to the E(?) theoretical value, namely ?-bar 0=(20)(1/?)4=137.082039311. The experimental value is subsequently found by projection as ?-bar 0(exp)=137/[cos(?/?-bar 0)]-bar 137.036.
Platinum and ruthenium in carbon supported Pt and Pt-Ru catalysts were determined by direct and derivative spectrophotometric methods. Complexes of platinum and ruthenium with SnCl(3)(-) ligands (tin(II) chloride in HCl) were used to determine both metals in solutions obtained after digestion of the samples of the catalysts. Platinum in the Pt/C catalyst can be determined in solutions obtained by digestion of the samples in aqua regia. Derivative spectrophotometry was used to determine both metals in the presence of each other in solutions obtained after digestion of samples of the Pt-Ru/C catalyst in the mixture of HCl+HNO(3) (6:1). The first derivative at 377 nm (;zero-crossing' point of ruthenium) and the second-derivative values at 495 nm (;zero-crossing' point of platinum) were used to estimate the concentration of platinum and ruthenium, respectively. PMID:18967441
Y-zeolite supported catalysts were applied to the hydrocracking of coal-derived liquids. By the introduction of two-stage upgrading consisting of hydrotreating and hydrocracking, Wandoan coal-derived middle distillate was hydrocracked over Ni-Mo/Y-zeolite, producing a high gasoline fraction yield. Zeolite supported catalysts gave little hydrocracked compounds in the hydroprocessing of coal-derived heavy oils, even after hydrotreatment. The reaction inhibitors which seriously poison the active sites of zeolites were found to be small nitrogen-containing molecules. In the hydroprocessing of coal-derived heavy oils, zeolite supported catalysts were inferior to alumina supported catalysts. This is due to the high hydrocracking but low hydrogenation activity of zeolite supported catalysts. 22 refs., 5 figs., 11 tabs.
Derivative spectrophotometry and bivariate calibration algorithm were used for study of run of photooxidation of levomepromazine hydrochloride (LV). The actual concentrations of LV and its main degradation product levomepromazine sulphoxide (LV-SO) were calculated using data provided by applied methods. The direct reading of absorbance values at 302nm and 334nm were employed for quantification of LV and LV-SO, respectively, in the case of bivariate method. The derivative spectrophotometric method is based on transformation of zero-order spectra into first derivative. The values of first derivative at 334nm were used for quantification of LV while at 278nm for assay of LV-SO. The obtained quantitative data were applied for investigation of kinetics of photodegradation of LV.
Two-component mixtures of dorzolamide hydrochloride and timolol maleate were assayed by first derivative and ratio derivative spectrophotometric methods. The first method, derivative spectrophotometry, by the zero-crossing measurements, was used due to the drugs closely overlapping absorption spectra. Linear calibration graphs of first derivative values at 250.3 nm for dorzolamide hydrochloride and 315.8 nm for timolol maleate. The second method, is based on ratio first derivative spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 242.9 and at 223.5 nm were selected to determine dorzolamide and timolol maleate in the binary mixture. Calibration graphs were established for 8.0-30.0 microg ml(-1) for dorzolamide hydrochloride and 3.0-24.6 microg ml(-1) for timolol maleate in binary mixture. Good linearity, precision and selectivity ...
In developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The #alpha#,#alpha#-dimethylester derivative (1e), amide derivatives (2a-c) and diamine derivatives (3a, b, 4), which were stable to hydrolysis, showed low blood activity levels following i.v. administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be ...
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).
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 ...
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 ...
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...
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...
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...
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...
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.
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.)
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...
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...
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...
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 ...
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.
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...
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, ...
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.
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.
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 ...
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...
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.
A simple formulation is presented for torsion analysis of hollow tubes with polygonal shapes. Thicknesses of segments of cross section can be different. Governing equations in term of Prandtl's stress function are used to derive the formulas. The derived formulas are so simple that computations can be carried out with a pocket calculator. Several examples are presented to show the accuracy and efficiency of the formulation. The obtained results are verified by accurate finite element solutions. It will be seen that the derived formulas can be useful for analysis of thin-walled and moderately thick-walled hollow tubes.
Using an ab initio pseudopotential method within a generalized gradient approximation of the density functional theory, the structural, electronic, and phonon properties of SrS in the B1 (NaCl) and B2 (CsCl) structures have been studied. The calculated lattice constants, static bulk modulus, and first-order pressure derivative of the bulk modulus are reported for both the B1 and B2 structures and compared with previous experimental and theoretical calculations. Electronic band structures and densities of states have been derived for SrS. Subsequently, a linear-response approach to the density functional theory is used to derive the phonon frequencies and densities of states.
According to enactment of reduced dose limit based on ICRP-60, the calculation of Derived Release Limits(DRL) on Wolsung NPPs was carried out. There are two methods of determination on DRL; that is MPC(Maximum Permissible Concentration) method and system analysis method. In order to use the system analysis method, lots of environmental data are necessary and complicated exposure pathway are considered. So we intend to apply MPC method that is sort of simple. In addition the calculated results were compared with derived release limit on Canadian nuclear power plant.
Using some modification of the standard fermion technique we derive factorized formula for spin operator matrix elements (form-factors) between general eigenstates of the Hamiltonian of quantum Ising chain in a transverse field of finite length. The derivation is based on the approach recently used to derive factorized formula for Z_N-spin operator matrix elements between ground eigenstates of the Hamiltonian of the Z_N-symmetric superintegrable chiral Potts quantum chain. The obtained factorized formulas for the matrix elements of Ising chain coincide with the corresponding expressions obtained by the Separation of Variables Method.
The adsorption and corrosion inhibition behavior of three selected thiosemicarbazone derivatives, namely 3-pyridinecarboxaldehyde thiosemicarbazone (META), isonicotinaldehyde thiosemicarbazone (PARA) and 2-pyridinecarboxaldehyde thiosemicarbazone (ORTHO) at the nickel surface were studied electrochemically by Tafel and impedance methods and computationally by carrying out Monte Carlo searches of configurational space on nickel/thiosemicarbazone derivative system. Electrochemical measurements showed that the inhibition efficiency of these compounds increased with increase in their concentration. The recorded inhibition efficiencies of the three tested thiosemicarbazone increase in the order: META>PARA>ORTHO. Polarization studies showed that these compounds act as mixed-type inhibitors for n...
The symmetry properties of the Coulomb potential allow for a dynamical spin-1/2 description of any fixed n level of a hydrogenlike atom in a time-dependent sufficiently weak electric and/or magnetic field. An explicit expression for the time dependence of the l,m amplitudes pertaining to a general n level is derived. The derivation follows on purely algebraic operations. Based on the derivation, we give analytical n-independent solutions to established and proposed schemes for driving the atom into a high angular-momentum state.
... Each beam finite element was derived using Hamilton's principle and the following basic assumptions: the beam has an arbitrary amount of pretwist ...
... Values of absorption maxima, X.nax, and associated molar extinction coefficients, c, as well as values of the n-octanol/water partition coefficient( ...
Using the operator approach we reexamine the two-dimensional model describing a massive Fermi field interacting via derivative couplings with two massless Bose fields, one scalar and the other pseudoscalar. Performing a canonical transformation on the Bose field algebra, the Fermi field operator is written in terms of the Mandelstam soliton operator and the derivative-coupling (DC) model is mapped into the massive Thirring model with two vector-current-scalar-derivative interactions (Schroer-Thirring model). The DC model with massless fermions can be mapped into the massless Rothe-Stamatescu model with a Thirring interaction (massless Rothe-Stamatescu-Thirring model). Within the present approach the weak equivalence between the fermionic sector of the DC model and the massive Thirring model is exhibited compactly.
Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer,...Full Text Available
A representation of tensors and spinors at a point of space-time as spin and conformally weighted functions on the unit sphere is derived. Methods for performing algebraic operations on tensors and spinors in this representation are discussed. (author).
Hyaluronan (HA), a non-sulfated glycosaminoglycan, is widely used in the clinic for viscosurgery, viscosupplementation, and treatment of osteoarthritis. Four decades of chemical modification...Full Text Available
The synthesis of 3-O-sulphamoyl derivatives of 1,2:5,6-di-O-isopropylidene-#alpha#-D-glucofuranose, 1,2-O-isopropylidene-#alpha#-D-glucofuranose, and 5,6-di-O-acetyl-1,2-O-isopropylidene-#alpha#-D-glucofuranose is described. A study of the reactions of carbohydrate chlorosulphates with azide has demonstrated the relative case with which certain chlorosulphonyloxy groups may be converted into azidosulphates. These azidosulphates could have potential synthetic value if a facile method for their conversion into sulphamoyl (aminosulphate) derivatives were available, since some sulphamoyl carbohydrates have been shown to possess antibiotic and antitrypanosomal activity. This report deals with the application of sodium borohydride and platinum oxide-hydrogen to the reduction of some 3-O-azidosulphate glucofuranose derivatives. "1H-n.m.r. spectra and infrared spectra were used.
Mono- and disubstituted novel derivatives of the heptaene nystatin analog 28,29-didehydronystatin A1 (S44HP, 1) were obtained by chemical modification of the exocyclic C-16 carboxyl and/or an amino group of mycosamine moiety. The strategy of preparation of mono- and double-modified polyene macrolides was based on the use of intermediate hydrophobic N-Fmoc (9-fluorenylmethoxycarbonyl) derivatives that facilitated the procedures of isolation and purification of new compounds. The antifungal activity of the new derivatives was first tested in vitro against yeasts and filamentous fungi, allowing the selection of the most active compounds that were subsequently tested for acute toxicity in mice. 2-(N,N-dimethylamino)ethylamide of 1 (2) and 2-(N,N-dimethylamino)ethylamide of N-fructopyranosyl-28...
Robert A. Martock. Cleveland State University, Cleveland, Ohio. Synthesis and Structural Characterization of a. Novel Indium Mercapto Derivative. [Clln(SCH. 2 ...
Reactive blue 2 (RB-2) had been characterized as a relatively potent ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) inhibitor with some selectivity for NTPDase3. In search for the pharmacophore and to analyze structure-activity relationships we synthesized a series of truncated derivatives and analogs of RB-2, including 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinones, 1-amino-2-methyl-4-arylaminoanthraquinones, 1-amino-4-bromoanthraquinone 2-sulfonic acid esters and sulfonamides, and bis-(1-amino-4-bromoanthraquinone) sulfonamides, and investigated them in preparations of rat NTPDase1, 2, and 3 using a capillary electrophoresis assay. Several 1-amino-2-sulfo-4-ar(alk)ylaminoanthraquinone derivatives inhibited E-NTPDases in a concentration-dependent manner. The 2-sulfonate group ...
will be derived from biochemical analyses of molluscs, ostracodes, foraminifera and corals. The corals will allow us to compare marine and estuarine trends, examine the linkage...
Wall thickness measurement of pipe is very important of the structural integrity of the industrial plant. However, the radiography method has an advantage because the ability of penetrating the insulated pipe. This will have economic benefit for industry. Moreover, the era of digital radiography has more advantages because the speed of radiographic work, less exposure time and no chemical used for film development. Either the conventional radiography or digital radiology, the wall thickness measurement is using the tangential radiography technique (TRT). In case, of a large diameter, pipe (more than inches) the determination maximum penetration wall thickness must be taken into the consideration. This paper is revisited the mathematical derivation of the determination of wall thickness measurement based on tangential radiography technique (TRT). The mathematical approach used in this derivation is the Pythagoras theorem and geometrical ...
and the estimated parameter covariance matrix is. 5. (25) where p in this case is the number of elements in the vector . The parameter standard errors, ?, ...
... The phenol and cresylic acid stream is flashed in a thin film evaporator over a concentrated sulfuric acid mixture to remove pyridine type substances ...
BackgroundThe monolignol biosynthetic pathway interconnects with the biosynthesis of other secondary phenolic metabolites, such as cinnamic acid derivatives, flavonoids and condensed...Full Text Available
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...
Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide...Full Text Available
This study was carried out to determine the rate and types of injuries experienced by boardsailors. Results derive from: (a) a review of hospital medical records for water sports injuries, and (b) a...Full Text Available
The effects of temperatures, durations of treatment, and derivations from spermatophores or spermaries on in vitro acrosome reaction of the spermatozoa in the Chinese mitten crab Eriocheir sinensis...Full Text Available
this, however, was a real environmental threat since various drums containing jet fuel, Bunker C, diesel and other petroleum derivatives were on fire. The CAPECO...
major radius of the toroidal containment volume. The containment time was calculated using equation (4) as derived in references 16 and 17. The solid ...
Nowadays it is accepted that natural flavonoids present in fruits and plant-derived-foods are relevant, not only for technological reasons and organoleptic properties, but also because of their potential...Full Text Available
... The third series used a correlated parameter covariance matrix derived from a generic database of modeling uncertainty for space structures [5-1 ...
We develop and investigate numerically a thermodynamically consistent model of two-dimensional multicomponent vesicles in an incompressible viscous fluid. The model is derived using an energy...Full Text Available
... The solution used on the size Large helmet war an arbitrary one; as discussed above, the developers added a standard deviation to ... 4 O. i3a: o.04. ...
Density functional theory calculations were performed to study the effects of different substituents and bridge groups on the heats of formation (HOFs), thermal stability, and detonation properties for a series of diiminotetrazole derivatives. The isodesmic reaction method was employed to calculate the HOFs of the derivatives using total energies obtained from electronic structure calculations. The bond dissociation energies and bond orders for the weakest bonds were analyzed to investigate the thermal stability of the diiminotetrazole derivatives. The detonation velocities and pressures were evaluated by using the semiempirical Kamlet-Jacobs equations, based on the theoretical densities and HOFs. These results provide basic information for the molecular design of novel high-energy density...
Necessary conditions are derived for compact aggregates of solid matter to develop from loose local clumps of dust grains in a contracting protostellar cloud.
To test whether the dose addition and independent action models can predict the combined toxicity of the mixtures of phenol and aniline derivatives, six phenolic and two aniline derivatives were selected as the test components. The inhibition toxicity of the derivatives and their mixtures to Vibrio qinghaiensis sp.-Q67 indicated that all dose?response relationships could be effectively described by the Weibull function with correlation coefficients greater than 0.99. The combined toxicity of two equivalent-effect concentration ratio mixtures and eight uniform design concentration ratio mixtures could be predicted successfully by the dose addition model within 95% confidence intervals. However, it was also well predicted by the independent action model, especially at lower concentrations.
As presented in [4], the Sigma-Point Consider Filter (SPCF) algorithm extends ... lines of the derivative-free, Sigma-Point Kalman Filter algorithm given in ...
We have recently introduced several important improvements in the measurement of distillation curves for complex fluids. This new method is a significant improvement over current approaches, with features including a composition-explicit data channel for each distillate fraction (for both qualitative and quantitative analysis), trace chemical analysis of each distillate fraction, and a corrosivity assessment of each distillate fraction. In the present contribution, we present the application of the advanced distillation curve method to a bio-derived crude oil prepared from swine manure. One motivation behind the work was to precisely measure the distillation curve of the oil derived from swine manure with our advanced distillation apparatus and compare the bio-derived oil to traditional pe...
The avermectins were introduced in 1981 and constitute a potent new class of anthelmintic agents. They are naturally-derived products of microbial action displaying an exceptionally wide range of antiparasitic...Full Text Available
(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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
The rare earth antimonates RE_3Sb_5O_1_2 constitute an isostructural series, where the rare earth site symmetry is S_4. The spectroscopic properties of pure or doped compounds of this family are studied in order to derive their energy level schemes and to simulate them through the crystal field theory, by using the approximated D_2_d potential. The paramagnetic susceptibilities are calculated with the derived wavefunctions and compared to experiment.
The purpose of work is systematical studying of benzo (B) of thiophene-1,1-dioxides and their 2,3-di-hydro derivatives behaviour in the reactions of electrophflic, radical, nucleophilic nitration, reduction of nitro group, embodiment of synthesis of N-amino derivatives, investigation of sulfur containing hetero-cyclic compounds, including of residues of some steroids
Some acylhydrazine derived ONO donor Schiff bases and their Co(II) and Ni(II) complexes have been prepared having the same metal ion (cation) but different anions. These synthesized metal(II)...Full Text Available
The synthesis of novel b-functionalized derivatives of the clinically used photosensitizer Temoporfin has been achieved by nucleophilic addition reactions to a corresponding diketo chlorin. The b-substituted dihydroxychlorin products exhibit a strong absorption in the red spectral region, a high singlet oxygen quantum yield, and were found to be highly effective in in vitro assays against HT-29 tumor cells.
Dwarf galaxies are generally faint. To derive their age and metallicity distributions, it is critical to optimize the use of any collected photon. Koleva et al., using full spectrum fitting, have found strong population gradients in some dwarf elliptical galaxies. Here, we show that the population profiles derived with this method are consistent and more precise than those obtained with spectrophotometric indices. This allows studying fainter objects in less telescope time.
Reduction of wavefunction which transforms as scalar field imaginary mass system has been derived in terms of irreducible representation of proper, orthochronous, inhomogeneous Lorentz group and it has been shown that only transformation properties of wavefunction are needed in the derivation while the reality condition and wave equations only restrict the number of independent representations. The properties of energy and momentum of tachyons have been analysed and it has been shown that the tachyons are unidirectional in space. (author).
The reduction of four-vector and electromagnetic fields produced by spin-1 tachyons has been derived in terms of standard helicity representations of inhomogeneous Lorentz group, and the conditions for these superluminal electromagnetic fields to satisfy the Maxwell's field equations have been derived. 16 refs.
The transport of Rn through activated charcoal was modelled for a charcoal canister used for surface emanation measurements. Derived Rn concentration distributions in full and half charcoal charges were compared with measured Rn profiles. The distributions were also compared with an empirical expression for the measured profiles. Close agreement was observed between the measured, empirically generated and derived profiles. The influence of temperature and humidity on Rn accumulation and transport is also discussed.
We investigate the q-deformation of the BRST algebra, the algebra of the ghost, matter and gauge fields on one spacetime point using the result of the bicovariant differential calculus. There are two nilpotent operations in the algebra, the BRST transformation #delta#_B and the derivative d. We show that one can define the covariant commutation relations among the fields and their derivatives consistently with these two operations as well as the *-operation, the antimultiplicative inner involution. (orig.).
CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in vitro. The present study examined the...Full Text Available
Dithiolato-nickel complexes with multisulfur ligands derived from benzenehexathiolate have been synthesized. The properties of the monomeric and polymeric complexes have been characterized by ESR spectroscopic and magnetochemical data and by electrical conductivity measurements. The prepared complexes are paramagnetic and have characteristic absorptions between 800 and 1000 nm. (orig.).
This paper outlines the development of an organizational model which will be used to determine the influence of supervisory and management functions in a nuclear power plant (NPP) on risk. A theoretical conceptualization, derived from the empirical literature, is used to describe the organizational structure of NPPs. The parameters and variables associated with this dynamic, process-oriented model are detailed. Applications of the model and preliminary insights derived from this conceptualization are discussed.
The complex formation of zirconium with biphenyl mono- and biscatecholyazo derivatives has been studied spectrophotometrically. The composition of the complexes, form and charge of complex-forming zirconium ions have been established. A procedure is suggested for calculation of molar absorptivities and stability constants for each of the complexes formed simultaneously in the system. Possible complex formation schemes have been studied. The data obtained were used to develop a spectrophotometric method of determining zirconium in the presence of large amounts of copper.
A method is proposed for deriving hydrolized polyacrylonitrile from a water-based alkali solution. This process is meant to improve the thermal stability of clay drilling solutions by employing the hydrolized product to treat aliphatic non-water-soluble C/sub 8/-C/sub 16/ spirits in an organic dispersant during the presence of acidity and while the solution is being heated.
Phospholipid vesicles were found to be lysed by exposure to free radicals derived from irradiated glycine and galactose. The decomposition yield increased with vesicle concentration, and attained values of 0.0006 vesicles destroyed per radical added. Ionic charge at the phospholipid end groups was found to be more important than degree of unsaturation in determining this yield. Radicals derived from irradiated serine and alanine had no detectable lytic action at the vesicle concentrations tested.
The yeast phosphatidylinositol transfer protein (Sec14p) is required for biogenesis of Golgi-derived transport vesicles and cell viability, and this essential Sec14p requirement is abrogated by inactivation...Full Text Available
Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we...Full Text Available
Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from...Full Text Available
An evaluation of eastern shale oil (ESO) residue as an asphalt additive to reduce oxidative age hardening and moisture susceptibility was conducted by Western Research Institute (WRI). The ESO residue, have a viscosity of 23.9 Pa{lg_bullet}s at 60{degree}C (140{degree}F), was blended with three different petroleum-derived asphalts, ASD-1, AAK-1, and AAM-1, which are known to be very susceptible to oxidative aging. Rheological and infrared analyses of the unaged and aged asphalts and the blends were then conducted to evaluate oxidative age hardening. In addition, the petroleum-derived asphalts and the blends were coated onto three different aggregates, Lithonia granite (RA), a low-absorption limestone (RD), and a siliceous Gulf Coast gravel (RL), and compacted into briquettes. Successive freeze-thaw cycling was then conducted to evaluate the moisture susceptibility of the prepared briquettes. The rheological analyses of the unaged ...
Explicit analytical formulas are derived for the stress intensity factors at the tips of a main crack and of a microcrack for the two-dimensional case of a collinear microcrack. This configuration is used to derive an estimate of the toughness degradation due to microcracks linking up with an advancing main crack. The implications of this estimate for theoretical predictions of the toughening due to stress-induced microcracking are discussed.
We present a simple and intuitive derivation of the track parameter covariance matrix due to multiple Coulomb scattering for use in track fitting with the Kalman filter. We derive all the covariance matrix elements for two experimentally relevant track parameterizations (i.e. x and y slopes and intercepts, and direction cosines and intercepts) in the presence of thin scatterers and absence of magnetic fields. We further comment on how to account for thick and/or continuous scattering centers.
In the positive column of a neon glow discharge, two different types of ionization waves occur simultaneously. The low-dimensional chaos arising from the nonlinear interaction between the two waves is controlled by a continuous feedback technique. The control strategy is derived from the time-delayed autosynchronization method. Two spatially displaced points of observation are used to obtain the control information, using the propagation characteristics of the chaotic wave.
We have identified a plasmid-like element within mitochondria of Neurospora crassa strain stp-B1. It is derived from the EcoRI-4 and EcoRI-6 regions of the mitochondrial DNA, and an additional 124 bp...Full Text Available
The available measurements on the cosmic-ray antiproton/proton ratio show an excess of antiprotons above predictions derived in the framework of the standard picture of cosmic-ray origin and propagation. Calculations are performed of the production from collisions of cosmic rays with the interstellar gas under the condition of distributed reacceleration. It could be shown that the calculated antiproton/proton ratio is enhanced compared to that derived from the leaky box model, but it remains difficult to bring it into agreement with the data by reasonable astrophysical assumptions. 15 references.
A transition from petroleum~derived jet fuels to blends with Fischer-Tropsch (F~T) fuels, and ultimately fully synthetic hydro-isomerized F-T fuels has raised concern about the fate of plasticizers in nitrile-butadiene rubber a-rings that are contacted by the fuels as this transition occurs. The partitioning of plasticizers and fuel molecules between nitrile a-rings and petroleum-derived, synthetic, and additized-synthetic jet fuels has been measured. Thermal desorption of o-rings soaked in the various jet fuels followed by gas chromatographic analysis with a mass spectrometric detector showed many of the plasticizer and stabilizer compounds were removed from the o-rings regardless of the contact fuel. Fuel molecules were observed to migrate into the o-rings for the petroleum-derived fuel as did both the fuel and additive for a synthetic F-T jet fuel additized with benzyl alcohol, but less for the unadditized synthetic ...
An ignition timing control apparatus is described for an internal combustion engine having a reference ignition timing comprising: sensing means for sensing vibrations including knocks of the engine; knock signal deriving means for deriving knock signals from the output of the sensing means; correction magnitude determining means for determining from the knock signals derived by the knock signal deriving means of ignition timing correction magnitude for suppressing the occurrence of knock; displacement magnitude determining means for determining from at least one of an output of the knock signal deriving means and an output of the correction magnitude determining means as a displacement magnitude for the reference ignition timing corresponding to the octane rating of a fuel used in the engine; and ignition timing determining means for setting the reference ignition timing at an ...
The Kadomtsev-Petviashvili equation describes nonlinear dispersive waves which travel mainly in one direction, generalizing the Korteweg-de Vries equation for purely uni-directional waves. In this Letter we derive an improved KP-equation that has exact dispersion in the main propagation direction and that is accurate in second order of the wave height. Moreover, different from the KP-equation, this new equation is also valid for waves on deep water. These properties are inherited from the AB-equation (E. van Groesen, Andonowati, 2007 ) which is the unidirectional improvement of the KdV equation. The derivation of the equation uses the variational formulation of surface water waves, and inherits the basic Hamiltonian structure.
The radiative heat loss from a surface is determined by its total hemispherical emittance, which consequently plays an important role in aerospace and solar applications. This study compares emittances measured calorimetrically with values derived from near normal incidence spectral reflectance measurements. This optical derivation is based on a number of assumptions which limit the accuracy if not sufficiency fulfilled. These assumptions include sample specularity, a straybody character beyond the range of measurement, only small variations of emittance with temperature, and a perfectly smooth sample surface. The comparison of calorimetrically and optically derived emittance performed in this study not only quantifies the errors introduced by insufficient fulfillment of the assumptions but also identifies which assumption causes the dominant error. The calorimetric emissometer, constructed for this study and based on a ...
The space derivation term of a wave equation is accurately calculated using Fourier transform method, and the wave equation only relating to time derivative in time-space domain is derived. Solving this equation with the aid of central difference method brings the numerical recursion formula for forward modeling or reverse time migration of seismic wave field in the medium in which seismic velocity varies. The key to this method lies in introducing two auxiliary wave fields relating to velocity and spacial frequency of Fourier transform respectively after multi-dimensional Fourier transform respectively after multi-dimensional Fourier transform of space vector is made. Theoretically, this method is suitable to the forward modeling and migration of seismic wave field in complex area where seismic velocity and structure shape vary arbitrarily. Theoretical results proved this method satisfactory.
A nonlinear partial differential equation modeling the propagation of a vertical hydraulic fracture first derived by Nordgren is studied. When properly posed, Nordgren's derivation constitutes a Stefan problem and requires another boundary condition-namely, that the velocity of the fluid at the crack tip equals the velocity of crack propagation. With this addition, Nordgren's similarity solution in the no-leakoff case is perfected by a power-series solution. New shut-in solutions are derived in the large-and-no-leakoff cases where the crack of the large-leakoff shut-in solution retracts and the crack of the no-leakoff shut-in solution extends forever. This study ignores the effect of crack-tip rock strength on crack propagation.
Three analogs of lidocaine (benzyl carbamyl, benzyl nitrile and methyl nitrile) were synthesized and examined for cardiovascular and central activity. The benzyl carbamyl analog was more potent than lidocaine in lowering blood pressure but possessed only slight local anesthetic, antiarrhythmic and CNS-depressant activity. At 40 mg/kg the benzyl nitrile derivative was superior to lidocaine in protecting against chloroform-induced arrhythmias. The methyl nitrile analog was less active than the benzyl nitrile analog in most parameters examined. The benzyl nitrile derivative and lidocaine had similar potencies on blood pressure depression, local anesthetic activity and ability to protect against calcium chloride-induced arrhythmias. Unlike the benzyl carbamyl derivative both lidocaine and the benzyl nitrile compounds appear to depress the cardiovascular system via a common mechanism. PMID:515167
3-Azido-..beta..-lactams react with the derivatives of trivalent phosphorus acids under mild conditions with the formation of 3-phosphoranediylamino-1,4-diaryl-2-azetidinones, which are readily hydrolyzed with the elimination of alcohol (thiol) to 3-phosphoranylamino-1,4-diaryl-2-azetidinones. The phosphine imide compounds obtained from the aryl alkyl phosphites are hydrolyzed with the elimination of phenols. 3-Phosphoranediylamino-1,4-diaryl-2-azetidinones react readily with alkyl and acyl halides with the formation of 3-(N-alkylphosphoryl-amino)- and 3-(N-acylphosphorylamino)-1,4-diaryl-2-azetidinones, respectively.
3-Azido-#beta#-lactams react with the derivatives of trivalent phosphorus acids under mild conditions with the formation of 3-phosphoranediylamino-1,4-diaryl-2-azetidinones, which are readily hydrolyzed with the elimination of alcohol (thiol) to 3-phosphoranylamino-1,4-diaryl-2-azetidinones. The phosphine imide compounds obtained from the aryl alkyl phosphites are hydrolyzed with the elimination of phenols. 3-Phosphoranediylamino-1,4-diaryl-2-azetidinones react readily with alkyl and acyl halides with the formation of 3-(N-alkylphosphoryl-amino)- and 3-(N-acylphosphorylamino)-1,4-diaryl-2-azetidinones, respectively.
A relationship between partial derivatives of the associated Legendre function of the first kind with respect to its degree, Formula Not Shown , and to its order, Formula Not Shown , is established for Formula Not Shown . This relationship is used to deduce four new closed-form representations of Formula Not Shown from those found recently for Formula Not Shown by the author [R. Szmytkowski, On the derivative of the associated Legendre function of the first kind of integer degree with respect to its order (with applications to the construction of the associated Legendre function of the second kind of integer degree and order), J. Math. Chem. 46 (2009) 231]. Several new expressions for the associated Legendre function of the second kind of integer degree and order, Formula Not Shown , suita...
Racemic and enantiomerically pure b-amino-a-trifluoromethyl alcohols were obtained via sequential nucleophilic trifluoromethylation of selected a-imino ketones, derived from arylglyoxals, and subsequent removal of the MeO or Ph(Me)CH substituent, respectively, located at the N-atom. The obtained products, containing a primary amino group, were used for the synthesis of imidazole N-oxides bearing a trifluoromethyl group as a part of the N(1)-alkyl chain. Imidazole N-oxides with an electron-withdrawing ester group at C(4) underwent spontaneous isomerization under the reaction conditions, and the corresponding imidazol-2-ones derivatives were isolated as final products.
1,3-Dienes derived from steroidal D-ring C17-ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2- or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands it is possible to synthesize either the C20 (R)- or the C20 (S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Since the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.
The purpose of this work is the elucidation of the f"n electronic structure of neutral mono base adducts derived from tris(#eta#"5-cyclopentadienyl)-lanthanide(III) (Cp_2Ln). The available data on related compounds like bis adducts and anionic mono adducts of the same moiety was also analyzed. The first aim was to derive the experimental crystal field splitting pattern from optical, magnetooptical and magnetochemical measurements and to reproduce it using an empirical Hamiltonian operator. The eigenvalues and eigenvectors obtained in this manner were used for a quantitative interpretation of the magnetochemical, EPR- and NMR-spectroscopic properties. For the latter subject it was necessary to develop an own procedure for the NMR analysis of paramagnetic compounds. This method is based on factor analysis and as demonstrated in the second part of this work, is clearly superior to all previous procedures. (orig.).
This poster presentation covered a number of issues related to the new regulations concerning information on new substances derived from the Canadian Environmental Protection Act (CEPA). The authors described the background, and the objectives of the research project. A brief overview of the Acid Mine Drainage (AMD) process was provided, as well as the sulphate reduction process. The general methodology was explained, and the results of the bioactivation presented. The process followed for the bioaugmentation and the results obtained were presented. The regulations concerning information on new substances derived from the CEPA were described. The authors then presented their conclusions and perspectives. 26 figs.
A series of [60]fullerene-substituted phenylalanine (Baa) and lysine derivatives have been prepared by the condensation of 1,2-(4prime-oxocyclohexano)fullerene with the appropriately protected (4-amino)phenylalanine and lysine, respectively. Conversion of the imine to the corresponding amine is achieved by di-acid catalyzed hydroboration. The reduction of the imine is not accompanied by hydroboration of the fullerene cage. The [70]fullerene phenylalanine derivative has also been prepared as have the di-amino acid derivatives. The compounds were characterized by MALDI-TOF mass spectrometry, UV/Vis spectroscopy, and cyclic voltammetry. 1H and 13C NMR spectroscopy allowed the observation of diastereomers. Fullerene-substituted peptides may be synthesized on relatively large scale by solid-pha...
We provide a first-principles, perturbative derivation of the AdS5/CFT4 Y-system that has been proposed to solve the spectrum problem of N=4 SYM. The proof relies on the computation of quantum effects in the fusion of some loop operators, namely the transfer matrices. More precisely we show that the leading quantum corrections in the fusion of transfer matrices induce the correct shifts of the spectral parameter in the T-system. As intermediate steps we study UV divergences in line operators up to first order and compute the fusion of line operators up to second order for the pure spinor string in AdS5xS5. We also argue that the derivation can be easily extended to other integrable models, some of which describe string theory on AdS4, AdS3 and AdS2 spacetimes.
Molecular dynamics simulations have been carried out of the radial distribution function of the hard sphere fluid for a range of densities in the equilibrium fluid and just into the metastable region. The first derivative of the hard-sphere radial distribution function at contact was computed and its density dependence fitted to a simple analytic form. Comparisons were made with semi-empirical formulae from the literature, and of these the formula proposed by Tao et al (1992 Phys. Rev. A 46 8007) was found to be in best agreement with the simulation data, although it slightly underestimates the derivative at the higher packing fractions in excess of about 0.45. Close to contact, within a few per cent of the particle diameter, the radial distribution function can be represented well by a second order polynomial. An exponential function, which has some useful analytic features, can also be applied in this region.
Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo(a)pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors. 2 tabs.
A spectrophotometric study has been made of the complex formation of vanadium (3) with arsenazo(1), arsenazo(3) and some monosubstituted derivatives of chromotropic acid and sulphanylamides. In acid medium vanadium (3) reacts with each of these reagents to produce a 1:1 complex. Optimum conditions of the complex formation was found. The effect of H"+ on the complex formation of vanadium (3) with chromotropic acid derivatives was established. It was found by the graphical method that the formation of the complex is accompanied by the elimination of one proton. Patterns were found of the influence of the nature of substituents in the organic compound on the ionization constants of acid groups and stability of complexes. Molar extinction coefficients, equilibrium constants of the formation reactions and instability constants for the complexes were calculated. The structure of complexes was suggested. Similar behaviour of all the reagents was ...
Digital topographic models are the foundation of more advanced modeling applications and ultimately inform planning and decision making in many fields. Despite this, the error associated with these models and derived attributes is commonly overlooked. Little attention has been given in the scientific literature to the benefits gained from having less error in a model or to the corresponding cost associated with reducing model error by choosing one product over another. To address these gaps in knowledge we evaluated the error associated with five digital elevation models (DEMs) and derived attributes of slope and aspect relative to the same attributes derived from LiDAR data. We also estimated the acquisition and processing costs per square kilometer of the five test models and the LiDAR m...
An oxidative method for enriching the content of humic acids in a mined lignite from Umbria (central Italy) is described. A mild oxidation using H{sub 2}O{sub 2} in an alkaline medium was successful in increasing the percentage of lignite-derived humidifed carbon from 5.77% to 33.67%. The newly formed humic acids showed a higher number of oxygen-bearing functional groups, a lower carbon/oxygen ratio and a higher absorbance ratio at 465 and 665 nm (E{sub 4}/E{sub 6}) in diluted solution compared to the native lignite-derived humic acids. A high E{sub 4}/E{sub 6} ratio indicated less condensation of the aromatic nucleus and a lower molecular weight in comparison to the lignite-derived native humic acids.
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 ...
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 ...
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.
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 ...
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 ...
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 ...
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, ...
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 ...
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...
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 ...
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 ...
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 ...
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' ...
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...
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...
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.
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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 ...
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.
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.
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 ...
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...
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.
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 ...
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.
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.
Determination of the specific surface of uranium oxides: UO_2 and U_3O_8 using a simplified equation derived from the Brunauer, Emmett and Teller theory. The method is suitable for samples having a surface between 6 to 50 m"2.
Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects...Full Text Available
Background.The air bubbles and foam that develop during the preparation of platelet units have traditionally been considered to interact with the platelets, causing activation and...Full Text Available
Spectral line intensity data are presented for ionized hydrogen regions in the giant spiral galaxy M101. The influence of interstellar extinction is assessed and electron temperatures of the gas clouds are derived.
We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these...Full Text Available
A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO−)]...Full Text Available
The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor...Full Text Available
The phylogeny and taxonomy of mammalian species were originally based upon shared or derived morphological characteristics. However, genetic analyses have more recently played an increasingly important...Full Text Available
Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apolipoprotein that is genetically linked to and similar in structure to apoA-I, the major apolipoprotein in high density lipoproteins...Full Text Available
A new strategy is presented for the synthesis of graft copolymers using only the ring-opening metathesis polymerization (ROMP). From a ROMP-derived main chain, pendant maleimide functional groups...Full Text Available
The ubiquitin–proteasome pathway is the principal system for extralysosomal protein degradation in eukaryotic cells, and is essential for the regulation and maintenance of basic cellular processes,...Full Text Available
A substantial proportion of lymph node-negative patients who receive adjuvant chemotherapy do not derive any benefit from this aggressive and potentially toxic treatment. However, standard histopathological...Full Text Available
Auxin-induced pea (Pisum sativum) stem section elongation is enhanced at levels of 3 to 40 micromolar by six new classes of alkane derivatives additional to those described earlier,...Full Text Available
Phosphoramidite reagents can phosphitylate guanine bases at the O6-position during solid phase synthesis and serious chain cleavage occurs if the base phosphitylation is not eliminated before the iodine/water...Full Text Available
Benzidine (4,4'-diaminobiphenyl) is a known human carcinogen; exposure to this substance resulted in an epidemic of bladder cancer among workers in the dye industry in Europe and North America. The...Full Text Available
A theoretical derivation of the intershell mass--core mass relation of Paczynski is attempted. Formulae developed by Sugimoto and Fujimoto are extended to less massive (m/sub c/< or approx. =1) cores.
A double-blind, placebo-controlled clinical trial of a homeopathic treatment of neonatal calf diarrhoea was performed using 44 calves in 12 dairy herds. Calves with spontaneously derived diarrhoea were...Full Text Available
MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences....Full Text Available
Using the Klein-Gordon equation with a box potential, a mass formula describing the family of nonflavored meson states with I = 1 is derived. The energy levels calculated agree with those observed within an accuracy of approx. 5%. In the model discussed quarks behave like tachyons.
The National Survey and Cadastre - Denmark (KMS) has for several years produced gravity anomaly maps over the oceans derived from satellite altimetry. During the last four years, KMS has also conducted airborne gravity surveys along the coast of Greenland dedicated to complement the existing onshore gravity coverage and fill in new data in the very-near coastal area, where altimetry data may contain gross errors. The airborne surveys extend from the coastline to approximately 100 km offshore, along 6000 km of coastline. An adequate merging of these different data sources is important for the use of gravity data especially, when computing geoid models in coastal regions. The presence of reliable marine gravity data for independent control offers an opportunity to study procedures for the merging of airborne and satellite data around Greenland. Two different merging techniques, both based on collocation, are investigated in this paper. Collocation offers a way of ...
Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug...Full Text Available
A light-sensitive vitamin B12 derivative has been extracted from the adult cestode, Spirometra mansonoides. This corrinoid was identified as the cobamide coenzyme, adenosylcobalamin, by its chromatographic, chemical, and spectral properties. PMID:1003284
The authors shortly describe some basic aspects relating to probabilistic reliability calculation and to the derivation of component reliability data. (GL)
Thermodynamic parameters for prediction of RNA duplex stability are reported. One parameter for duplex initiation and 10 parameters for helix propagation are derived from enthalpy and free-energy changes...Full Text Available
A nodulation plasmid, pRtr-514a, of molecular size 180 megadaltons (Mdal) was identified in Rhizobium trifolii strain NZP514. This plasmid was absent in both spontaneous and heat-cured Nod- derivatives...Full Text Available
The methods of statistical dynamics are applied to a fluid with 5 conserved fields (the mass, the energy, and the three components of momentum) moving in a given external potential. When the potential is zero, we recover a previously derived system of parabolic differential equations, called "corrections to fluid dynamics".
From the gross conservation laws of thermodynamics in a convecting material we derive a bound on the ratio of the rate of production of mechanical or magnetic energy to the rate of internal radioactive...Full Text Available
The thiadiazinon derivative EMD 57033 has been found previously in cardiac muscle to increase isometric force generation without a proportional increase in fiber ATPase, thus causing a reduction in...Full Text Available
Alkyl halides react rapidly with purines and pyrimidines in the presence of fluoride ion. Alkylation of thymidine leads to novel dimeric nucleoside derivatives bridged through N3. Alkylation of thymidine...Full Text Available
Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived...Full Text Available
Bacteriophage M13 mp10 DNA were irradiated with near-UV light in the presence of tetracycline derivatives and primed with synthetic oligonucleotide to be used for DNA synthesis using Escherichia coli DNA polymerase. Chain terminations were observed by denaturing polyacrylamide gel electrophoresis and mapped precisely. All the synthesis stops occurred before or at the level of guanine residues, showing that the photoreaction mediated by tetracycline derivatives led to a preferential alteration of guanine residues. These lesions were demonstrated to be induced in DNA through a pathway involving singlet oxygen. Tetracycline derivatives also photoinduced the breakage of the DNA sugar-phosphate backbone monitored by the conversion of supercoiled phi X174 DNA to a relaxed form. This lesion was shown to be initiated by hydroxyl radicals. The production of this free radical has been confirmed by electron paramagnetic resonance ...
The report gives a comprehensive summary of the experience gained and the problems encountered during the Cat-Ox demonstration program. The report outlines the process design and construction, as well as operating experience and problems. Test results and conclusions derived from...
BackgroundPolyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene...Full Text Available
Three areas have been investigated: coal liquefaction with supercritical fluids, liquefaction by extraction with high boiling liquid solvents, and the production of resins from coal-derived hydrocarbons. The processes are described.
This cross-sectional study evaluated the association between radiographic evidence of alveolar bone loss and the concentration of host-derived bone resorptive factors (interleukin-1 beta, tumor...Full Text Available
BackgroundThe occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived...Full Text Available
Two nitrate reductase (NR) mutants were selected for low nitrate reductase (LNR) activity by in vivo NR microassays of M2 seedlings derived from nitrosomethylurea-mutagenized...Full Text Available
Evaluating the systolic function of the left ventricle (LV) is important in the hemodynamic management of the critically ill patients with circulatory failure. Echocardiography is considered the standard...Full Text Available
Effective connectivity in brain networks can be studied using Granger causality analysis which is based on temporal precedence, while functional connectivity is usually derived using zero-lag...Full Text Available
Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate...Full Text Available
A common approach used to fuse simultaneously recorded EEG and fMRI is to correlate trial-by-trial variability in the EEG, or variability of components derived therefrom, with the blood oxygenation...Full Text Available
Derivations are made for the mass and the mass-turnover time scale of an accretion disk as a function of the accretion rate, the observed disk radius, the non-viscous disk radius, and two parameters. These parameters depend on the effectiveness of viscosity and tidal angular momentum loss. Application is made to DQ Herculis.
A method is presented to derive the absolute dimensions of early-type detached binaries by combining the observed parameters with results of evolutionary computations. The method is used to obtain the absolute dimensions of nine close binaries. We find that most systems have an initial masss ratio near 1.
The national standards and state derivatives must be reinforced by models of curricular reform. In this paper, ARISE presents one model based on a set of principles--coherence, integration of the sciences, movement from concrete ideas to abstract ones, inquiry, connection and application, sequencing that is responsive to how people learn.
Thiamin(e), also known as vitamin B1, is now known to play a fundamental role in energy metabolism. Its discovery followed from the original early research on the ‘anti-beriberi factor’...Full Text Available
May 31, 2011 ... Synthesis and Structural Characterization of a Novel Indium Mercapto Derivative [Clln(SCH2(CO)O)2]2-[(4-MepyH)2]2+. 284. System Mass ...