WorldWideScience

Sample records for additive mutational effects

  1. Additive dominant effect of a SOX10 mutation underlies a complex phenotype of PCWH.

    Ito, Yukiko; Inoue, Naoko; Inoue, Yukiko U; Nakamura, Shoko; Matsuda, Yoshiki; Inagaki, Masumi; Ohkubo, Takahiro; Asami, Junko; Terakawa, Youhei W; Kohsaka, Shinichi; Goto, Yu-ichi; Akazawa, Chihiro; Inoue, Takayoshi; Inoue, Ken

    2015-08-01

    Distinct classes of SOX10 mutations result in peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease, collectively known as PCWH. Meanwhile, SOX10 haploinsufficiency caused by allelic loss-of-function mutations leads to a milder non-neurological disorder, Waardenburg-Hirschsprung disease. The cellular pathogenesis of more complex PCWH phenotypes in vivo has not been thoroughly understood. To determine the pathogenesis of PCWH, we have established a transgenic mouse model. A known PCWH-causing SOX10 mutation, c.1400del12, was introduced into mouse Sox10-expressing cells by means of bacterial artificial chromosome (BAC) transgenesis. By crossing the multiple transgenic lines, we examined the effects produced by various copy numbers of the mutant transgene. Within the nervous systems, transgenic mice revealed a delay in the incorporation of Schwann cells in the sciatic nerve and the terminal differentiation of oligodendrocytes in the spinal cord. Transgenic mice also showed defects in melanocytes presenting as neurosensory deafness and abnormal skin pigmentation, and a loss of the enteric nervous system. Phenotypes in each lineage were more severe in mice carrying higher copy numbers, suggesting a gene dosage effect for mutant SOX10. By uncoupling the effects of gain-of-function and haploinsufficiency in vivo, we have demonstrated that the effect of a PCWH-causing SOX10 mutation is solely pathogenic in each SOX10-expressing cellular lineage in a dosage-dependent manner. In both the peripheral and central nervous systems, the primary consequence of SOX10 mutations is hypomyelination. The complex neurological phenotypes in PCWH patients likely result from a combination of haploinsufficiency and additive dominant effect. PMID:25959061

  2. Effective Temperature of Mutations

    Derényi, Imre; Szöllősi, Gergely J.

    2015-02-01

    Biological macromolecules experience two seemingly very different types of noise acting on different time scales: (i) point mutations corresponding to changes in molecular sequence and (ii) thermal fluctuations. Examining the secondary structures of a large number of microRNA precursor sequences and model lattice proteins, we show that the effects of single point mutations are statistically indistinguishable from those of an increase in temperature by a few tens of kelvins. The existence of such an effective mutational temperature establishes a quantitative connection between robustness to genetic (mutational) and environmental (thermal) perturbations.

  3. Simultaneous Estimation of Additive and Mutational Genetic Variance in an Outbred Population of Drosophila serrata.

    McGuigan, Katrina; Aguirre, J David; Blows, Mark W

    2015-11-01

    How new mutations contribute to genetic variation is a key question in biology. Although the evolutionary fate of an allele is largely determined by its heterozygous effect, most estimates of mutational variance and mutational effects derive from highly inbred lines, where new mutations are present in homozygous form. In an attempt to overcome this limitation, middle-class neighborhood (MCN) experiments have been used to assess the fitness effect of new mutations in heterozygous form. However, because MCN populations harbor substantial standing genetic variance, estimates of mutational variance have not typically been available from such experiments. Here we employ a modification of the animal model to analyze data from 22 generations of Drosophila serrata bred in an MCN design. Mutational heritability, measured for eight cuticular hydrocarbons, 10 wing-shape traits, and wing size in this outbred genetic background, ranged from 0.0006 to 0.006 (with one exception), a similar range to that reported from studies employing inbred lines. Simultaneously partitioning the additive and mutational variance in the same outbred population allowed us to quantitatively test the ability of mutation-selection balance models to explain the observed levels of additive and mutational genetic variance. The Gaussian allelic approximation and house-of-cards models, which assume real stabilizing selection on single traits, both overestimated the genetic variance maintained at equilibrium, but the house-of-cards model was a closer fit to the data. This analytical approach has the potential to be broadly applied, expanding our understanding of the dynamics of genetic variance in natural populations. PMID:26384357

  4. MTHFR homozygous mutation and additional risk factors for cerebral infarction in a large Italian family.

    Del Balzo, Francesca; Spalice, Alberto; Perla, Massimo; Properzi, Enrico; Iannetti, Paola

    2009-01-01

    Several cases with cerebral infarctions associated with the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) have been reported. Given the large number of asymptomatic individuals with the MTHFR mutation, additional risk factors for cerebral infarction should be considered. This study describes a large family with the MTHFR mutation and a combination of heterozygous factor V Leiden mutations and different additional exogenous and endogenous thrombogenic risk factors. Psychomotor retardation and a left fronto-insular infarct associated with the MTHFR mutation together with diminished factor VII and low level of protein C was documented in the first patient. In the second patient, generalized epilepsy and a malacic area in the right nucleus lenticularis was associated with the MTHFR mutation and a low level of protein C. In the third patient, right hemiparesis and a left fronto-temporal porencephalic cyst were documented, together with the MTHFR mutation and hyperhomocysteinemia. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of infants with cerebral infarctions associated with the MTHFR mutation and of their related family members. PMID:19068258

  5. Identification of additional IDH mutations associated with oncometabolite R(-)-2-hydroxyglutarate production

    Ward, Patrick S.; Cross, Justin R.; Lu, Chao; Weigert, Oliver; Abel-Wahab, Omar; Levine, Ross L.; Weinstock, David M.; SHARP, KIM A.; Thompson, Craig B.

    2011-01-01

    Mutationsin cytosolic isocitrate dehydrogenase 1 (IDH1) or its mitochondrial homolog IDH2 can lead to R(-)-2-hydroxyglutarate (2HG) production. To date, mutations in three active site arginine residues IDH1 R132, IDH2 R172, and IDH2 R140 have been shown to result in the neomorphic production of 2HG. Here we report three additional 2HG-producing IDH1 mutations: IDH1 R100 which is affected in adult glioma, IDH1 G97 which is mutated in colon cancer cell lines and pediatric glioblastoma, and IDH1...

  6. Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations.

    Liat Rockah-Shmuel

    2015-08-01

    Full Text Available Systematic mappings of the effects of protein mutations are becoming increasingly popular. Unexpectedly, these experiments often find that proteins are tolerant to most amino acid substitutions, including substitutions in positions that are highly conserved in nature. To obtain a more realistic distribution of the effects of protein mutations, we applied a laboratory drift comprising 17 rounds of random mutagenesis and selection of M.HaeIII, a DNA methyltransferase. During this drift, multiple mutations gradually accumulated. Deep sequencing of the drifted gene ensembles allowed determination of the relative effects of all possible single nucleotide mutations. Despite being averaged across many different genetic backgrounds, about 67% of all nonsynonymous, missense mutations were evidently deleterious, and an additional 16% were likely to be deleterious. In the early generations, the frequency of most deleterious mutations remained high. However, by the 17th generation, their frequency was consistently reduced, and those remaining were accepted alongside compensatory mutations. The tolerance to mutations measured in this laboratory drift correlated with sequence exchanges seen in M.HaeIII's natural orthologs. The biophysical constraints dictating purging in nature and in this laboratory drift also seemed to overlap. Our experiment therefore provides an improved method for measuring the effects of protein mutations that more closely replicates the natural evolutionary forces, and thereby a more realistic view of the mutational space of proteins.

  7. Cellular effects of LRRK2 mutations

    Cookson, Mark R.

    2012-01-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a relatively common cause of inherited Parkinson's disease (PD) but the mechanism(s) by which mutations lead to disease are poorly understood. Here, I will discuss what is known about LRRK2 in cellular models, focusing on specifically on assays that have been used to tease apart the effects of LRRK2 mutations on cellular phenotypes. LRRK2 expression has been suggested to cause loss of neuronal viability, although because it also has a stro...

  8. Additive decompositions with interaction effects

    Biewen, Martin

    2012-01-01

    This paper proposes a comprehensive, path-independent decomposition formula of changes into ceteris paribus effects and interaction effects. The formula implies a reassessment of sequential decomposition methods that are widely used in the literature and that are restrictive in how they treat interaction effects. If counterfactual outcomes are correctly specified, it may also be viewed as a description of certain aspects of causality in the situation where more than one causal influence is pr...

  9. BRAF mutation in papillary thyroid microcarcinoma – additional marker of risk stratification

    Dmitriy Yuriyevich Semyonov

    2014-11-01

    Full Text Available BackgroundPapillary thyroid microcarcinoma (PTMC is heterogeneous group of tumor less than 1 cm in the diameter. The volume of surgical treatment stay unstable because unclear biological potential of PTMC.AimThe aim of our study was to assess the utility of BRAF gene mutation as preoperative additional marker of risk stratification.Materials and methodsWe include 44 patient who were operated in general surgery department Pavlov State Medical University from 2001 to 2013. In all 44 cases BRAF gene mutation was detected and compared with clinic-morphological features (multifocality, invasive growth, lymph node metastasis, recurrence retrospectivelyResultsIn our study the frequency of BRAF gene mutation was 68.2%. On multivariate regression analysis the presence of bilateral tumoural foci, lymph node metastasis and the presence of capsular invasion were significantly related to BRAF positive gene status.ConclusionsThus, appropriate volume for the BRAF positive PTMC is thyroidectomy with central compartment lymph node dissection.

  10. Beyond Mutations: Additional Mechanisms and Implications of SWI/SNF Complex Inactivation

    Stefanie eMarquez

    2015-02-01

    Full Text Available SWI/SNF is a major regulator of gene expression. Its role is to facilitate the shifting and exposure of DNA segments within the promoter and other key domains to transcription factors and other essential cellular proteins. This complex interacts with a wide range of proteins and does not function within a single, specific pathway; thus, it is involved in a multitude of cellular processes, including DNA repair, differentiation, development, cell adhesion, and growth control. Given SWI/SNF’s prominent role in these processes, many of which are important for blocking cancer development, it is not surprising that the SWI/SNF complex is targeted during cancer initiation and progression both by mutations and by nonmutational mechanisms. Currently, the understanding of the types of alterations, their frequency, and their impact on the SWI/SNF subunits is an area of intense research that has been bolstered by a recent cadre of NextGen sequencing studies. These studies have revealed mutations in SWI/SNF subunits, indicating that this complex is thus important for cancer development. The purpose of this review is to put into perspective the role of mutations versus other mechanisms in the silencing of SWI/SNF subunits, in particular, BRG1 and BRM. In addition, this review explores the recent development of synthetic lethality and how it applies to this complex, as well as how BRM polymorphisms are becoming recognized as potential clinical biomarkers for cancer risk.

  11. Islet-intrinsic effects of CFTR mutation.

    Koivula, Fiona N Manderson; McClenaghan, Neville H; Harper, Alan G S; Kelly, Catriona

    2016-07-01

    Cystic fibrosis-related diabetes (CFRD) is the most significant extra-pulmonary comorbidity in cystic fibrosis (CF) patients, and accelerates lung decline. In addition to the traditional view that CFRD is a consequence of fibrotic destruction of the pancreas as a whole, emerging evidence may implicate a role for cystic fibrosis transmembrane-conductance regulator (CFTR) in the regulation of insulin secretion from the pancreatic islet. Impaired first-phase insulin responses and glucose homeostasis have also been reported in CF patients. CFTR expression in both human and mouse beta cells has been confirmed, and recent studies have shown differences in endocrine pancreatic morphology from birth in CF. Recent experimental evidence suggests that functional CFTR channels are required for insulin exocytosis and the regulation of membrane potential in the pancreatic beta cell, which may account for the impairments in insulin secretion observed in many CF patients. These novel insights suggest that the pathogenesis of CFRD is more complicated than originally thought, with implications for diabetes treatment and screening in the CF population. This review summarises recent emerging evidence in support of a primary role for endocrine pancreatic dysfunction in the development of CFRD. Summary • CF is an autosomal recessive disorder caused by mutations in the CFTR gene • The vast majority of morbidity and mortality in CF results from lung disease. However CFRD is the largest extra-pulmonary co-morbidity and rapidly accelerates lung decline • Recent experimental evidence shows that functional CFTR channels are required for normal patterns of first phase insulin secretion from the pancreatic beta cell • Current clinical recommendations suggest that insulin is more effective than oral glucose-lowering drugs for the treatment of CFRD. However, the emergence of CFTR corrector and potentiator drugs may offer a personalised approach to treating diabetes in the CF population

  12. Studies on biological effects of ion beams on lethality, molecular nature of mutation, mutation rate, and spectrum of mutation phenotype for mutation breeding in higher plants

    Recently, heavy ions or ion beams have been used to generate new mutants or varieties, especially in higher plants. It has been found that ion beams show high relative biological effectiveness (RBE) of growth inhibition, lethality, and so on, but the characteristics of ion beams on mutation have not been clearly elucidated. To understand the effect of ion beams on mutation induction, mutation rates were investigated using visible known Arabidopsis mutant phenotypes, indicating that mutation frequencies induced by carbon ions were 20-fold higher than by electrons. In chrysanthemum and carnation, flower-color and flower-form mutants, which are hardly produced by gamma rays or X rays, were induced by ion beams. Novel mutants and their responsible genes, such as UV-B resistant, serrated petals and sepals, anthocyaninless, etc. were induced by ion beams. These results indicated that the characteristics of ion beams for mutation induction are high mutation frequency and broad mutation spectrum and therefore, efficient induction of novel mutants. On the other hand, PCR and sequencing analyses showed that half of all mutants induced by ion beams possessed large DNA alterations, while the rest had point-like mutations. Both mutations induced by ion beams had a common feature that deletion of several bases were predominantly induced. It is plausible that ion beams induce a limited amount of large and irreparable DNA damage, resulting in production of a null mutation that shows a new mutant phenotype. (author)

  13. The Oenothera plastome mutator: effect of UV irradiation and nitroso-methyl urea on mutation frequencies

    Oenothera plants homozygous for a recessive plastome mutator allele (pm) showed spontaneous mutation frequencies for plastome genes that are 200-fold higher than spontaneous levels. Mutations occurred at high frequencies in plants grown in the field, in a glasshouse, or as leaf tip cultures under fluorescent light, indicating that the plastome mutator activity is UV-independent. However, the chlorotic sectors became visible at an earlier stage of development when seedlings were irradiated, compared to seedlings that were not exposed to UV. These results imply that the rate of sorting-out was increased by the irradiation treatment, possibly due to a decrease in the effective number of multiplication-competent plastids, or a reduction in the extent of cytoplasmic mixing. Nitroso-methyl urea treatment of seeds had a dramatic effect on mutation frequency in both wild-type and plastome mutator samples. When the background mutation rates were low, the combination of the plastome mutator nucleus and the chemical mutagenesis treatment resulted in a synergistic effect, suggesting that the plastome mutator may involve a cpDNA repair pathway. (author)

  14. A DSPP Mutation Causing Dentinogenesis Imperfecta and Characterization of the Mutational Effect

    Sook-Kyung Lee

    2013-01-01

    Full Text Available Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER. In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.

  15. Environmental stresses can alleviate the average deleterious effect of mutations

    Leibler Stanislas

    2003-05-01

    Full Text Available Abstract Background Fundamental questions in evolutionary genetics, including the possible advantage of sexual reproduction, depend critically on the effects of deleterious mutations on fitness. Limited existing experimental evidence suggests that, on average, such effects tend to be aggravated under environmental stresses, consistent with the perception that stress diminishes the organism's ability to tolerate deleterious mutations. Here, we ask whether there are also stresses with the opposite influence, under which the organism becomes more tolerant to mutations. Results We developed a technique, based on bioluminescence, which allows accurate automated measurements of bacterial growth rates at very low cell densities. Using this system, we measured growth rates of Escherichia coli mutants under a diverse set of environmental stresses. In contrast to the perception that stress always reduces the organism's ability to tolerate mutations, our measurements identified stresses that do the opposite – that is, despite decreasing wild-type growth, they alleviate, on average, the effect of deleterious mutations. Conclusions Our results show a qualitative difference between various environmental stresses ranging from alleviation to aggravation of the average effect of mutations. We further show how the existence of stresses that are biased towards alleviation of the effects of mutations may imply the existence of average epistatic interactions between mutations. The results thus offer a connection between the two main factors controlling the effects of deleterious mutations: environmental conditions and epistatic interactions.

  16. Effective Structural Health Monitoring with Additive Manufacturing

    De Baere, Dieter; Strantza, Maria; Hinderdael, Michaël; Devesse, Wim; Guillaume, Patrick

    2014-01-01

    The current remaining challenges for structural health monitoring (SHM) systems prevented the introduction of SHM systems on a large scale within industrial applications. An effective SHM system is required for the reduction of the direct operation costs, improvement of the life-safety and the introduction of additive manufactured components for critical structures. In this paper, a new structural health monitoring methodology will be presented for components that can be processed by additive...

  17. EGFR mutation frequency and effectiveness of erlotinib

    Weber, Britta; Hager, Henrik; Sorensen, Boe S;

    2014-01-01

    OBJECTIVES: In 2008, we initiated a prospective study to explore the frequency and predictive value of epidermal growth factor receptor (EGFR) mutations in an unselected population of Danish patients with non-small cell lung cancer offered treatment with erlotinib, mainly in second-line. MATERIAL...

  18. Sintering of magnesia: effect of additives

    Satyananda Behera; Ritwik Sarkar

    2015-10-01

    Effect of different additives, namely Cr2O3, Fe2O3 and TiO2, up to 2 wt% was studied on the sintering and microstructural developments of the chemically pure magnesia using the pressureless sintering technique between 1500 and 1600° C. Sintering was evaluated by per cent densification and microstructural developments were studied by electron microscopy and elemental distribution of the additives in the sintered products was also investigated for their distribution in the matrix. Cr2O3 and TiO2 were found to deteriorate the densification associated with grain growth. Fe2O3 was found to improve the densification and well-compacted grain distribution was observed in the microstructure.

  19. Effect of space mutation of photosynthetic characteristics of soybean varieties

    In order to elucidate the response of the photosynthetic traits of soybean to space mutation, three soybean varieties (lines) of Heinong 48, Heinong 44 and Ha 2291-Y were carried by artificial satellite in 2006 and the net photo synthetic rate (Pn), stomatal conductance (Cond), intercellular CO2 concentration (Ci) and stomatal resistance (Rs) from SP1 to SP4 generation were determined. The results showed that space mutation affected photosynthesis traits of soy bean. The photosynthetic rate of soybean varieties by space mutation occurred different levels of genetic variation and the positive mutation rate were higher. Coefficient of variation among generations were SP2 >SP3 >SP4 >CK. Results suggest that space mutation can effectively create soybean materials with higher photosynthetic rate. (authors)

  20. Addition agents effects on hydrocarbon fuels burning

    Larionov, V. M.; Mitrofanov, G. A.; Sakhovskii, A. V.

    2016-01-01

    Literature review on addition agents effects on hydrocarbon fuels burning has been conducted. The impact results in flame pattern and burning velocity change, energy efficiency increase, environmentally harmful NOx and CO emission reduction and damping of self-oscillations in flow. An assumption about water molecules dissociation phenomenon existing in a number of practical applications and being neglected in most explanations for physical- chemical processes taking place in case of injection of water/steam into combustion zone has been noted. The hypothesis about necessity of water dissociation account has been proposed. It can be useful for low temperature combustion process control and NOx emission reduction.

  1. Chlorambucil effectively induces deletion mutations in mouse germ cells.

    Russell, L B; Hunsicker, P R; Cacheiro, N L; Bangham, J W; Russell, W. L.; Shelby, M D

    1989-01-01

    The chemotherapeutic agent chlorambucil was found to be more effective than x-rays or any chemical investigated to date in inducing high yields of mouse germ-line mutations that appear to be deletions or other structural changes. Induction of mutations involving seven specific loci was studied after exposures of various male germ-cell stages to chlorambucil at 10-25 mg/kg. A total of 60,750 offspring was scored. Mutation rates in spermatogonial stem cells were not significantly increased over...

  2. New approaches for effective mutation induction in gamma field

    The purpose of the report is to clarify the effects of chronic irradiation using in vitro culture on inducing the mutation of two model plants. Culture technique combined with irradiation can overcome the problem of chimera formation and provided 10 times greater mutation efficiency than conventional method. Proper mutagenic treatment using cultured materials is indispensable to effective mutation induction. The chronic culture method showed the widest color spectrum in chrysanthemum and extended toward not only the negative but positive direction. However, the acute culture methods indicated a relatively low mutation rate and a very limited flower color spectrum. Flower color mutation of the regenerations could be induced more from petals and buds than from leaves. These facts is supposed that the gene loci fully expressed on floral organs may be unstable for mutation by mutagenesis or culture. It may be likely to control a direction of desired mutation. One possible reason why the chronic culture methods showed higher frequencies is that most of the cells composing the tissue and organs continually irradiated into a cell division which was highly sensitive and more mutable to irradiation. Under these conditions, many mutated sectors may accumulate in the cells of the growing organs. Regenerated mutant lines show remarkable decrease of chromosome numbers by irradiation. It is a proper indicator to monitor radiation damage. In this study, the six flower color mutant varieties registered were derived from chronic irradiation. The combined method of chronic irradiation with floral organ cultures proved to be of particularly great practical use in mutation breeding for not only flower species but any other species. (author)

  3. New approaches for effective mutation induction in gamma field

    Nagatomi, Shigeki [National Institute of Agrobiological Resources, Institute of Radiation Breeding, Omiya, Ibaraki (Japan)

    2001-03-01

    The purpose of the report is to clarify the effects of chronic irradiation using in vitro culture on inducing the mutation of two model plants. Culture technique combined with irradiation can overcome the problem of chimera formation and provided 10 times greater mutation efficiency than conventional method. Proper mutagenic treatment using cultured materials is indispensable to effective mutation induction. The chronic culture method showed the widest color spectrum in chrysanthemum and extended toward not only the negative but positive direction. However, the acute culture methods indicated a relatively low mutation rate and a very limited flower color spectrum. Flower color mutation of the regenerations could be induced more from petals and buds than from leaves. These facts is supposed that the gene loci fully expressed on floral organs may be unstable for mutation by mutagenesis or culture. It may be likely to control a direction of desired mutation. One possible reason why the chronic culture methods showed higher frequencies is that most of the cells composing the tissue and organs continually irradiated into a cell division which was highly sensitive and more mutable to irradiation. Under these conditions, many mutated sectors may accumulate in the cells of the growing organs. Regenerated mutant lines show remarkable decrease of chromosome numbers by irradiation. It is a proper indicator to monitor radiation damage. In this study, the six flower color mutant varieties registered were derived from chronic irradiation. The combined method of chronic irradiation with floral organ cultures proved to be of particularly great practical use in mutation breeding for not only flower species but any other species. (author)

  4. Effects of intronic mutations in the LDLR gene on pre-mRNA splicing: Comparison of wet-lab and bioinformatics analyses

    O.L. Holla; S. Nakken; M. Mattingsdal; T. Ranheim; K.E. Berge; J.C. Defesche; T.P. Leren

    2009-01-01

    Screening for mutations in the low density lipoprotein receptor (LDLR) gene has identified more than 1000 mutations as the cause of familial hypercholesterolemia (FH). In addition, numerous intronic mutations with uncertain effects on pre-mRNA splicing have also been identified. In this study, we ha

  5. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations

    Pomp, Elisabeth R.; Cessie, le Saskia; Rosendaal, Frits R.; Doggen, Carine J.M.

    2007-01-01

    In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), body weight, height and body mass index (BMI) were evaluated as risk factors. Additionally, the joint effect of obesity together with oral contraceptive use and prothrombotic mutations on the ris

  6. Food Additives and Effects to Human Health

    Ayper Boga; Secil Binokay

    2010-01-01

    Food purchasing patterns have changed dramatically over the past fifty years. Packaged and processed foods get many a family through the day. They’re convenient, portable, and they stay fresh for a long time. There are over fourteen thousand man-made chemicals added to American food supply today. Food additives are not natural nutrition for humans or their pets. Children are suffering the most from food additives because they are exposed to food chemicals from infancy, and human bodies w...

  7. Nurse Scheduling by Cooperative GA with Effective Mutation Operator

    Ohki, Makoto

    In this paper, we propose an effective mutation operators for Cooperative Genetic Algorithm (CGA) to be applied to a practical Nurse Scheduling Problem (NSP). The nurse scheduling is a very difficult task, because NSP is a complex combinatorial optimizing problem for which many requirements must be considered. In real hospitals, the schedule changes frequently. The changes of the shift schedule yields various problems, for example, a fall in the nursing level. We describe a technique of the reoptimization of the nurse schedule in response to a change. The conventional CGA is superior in ability for local search by means of its crossover operator, but often stagnates at the unfavorable situation because it is inferior to ability for global search. When the optimization stagnates for long generation cycle, a searching point, population in this case, would be caught in a wide local minimum area. To escape such local minimum area, small change in a population should be required. Based on such consideration, we propose a mutation operator activated depending on the optimization speed. When the optimization stagnates, in other words, when the optimization speed decreases, the mutation yields small changes in the population. Then the population is able to escape from a local minimum area by means of the mutation. However, this mutation operator requires two well-defined parameters. This means that user have to consider the value of these parameters carefully. To solve this problem, we propose a periodic mutation operator which has only one parameter to define itself. This simplified mutation operator is effective over a wide range of the parameter value.

  8. Dominance effects of deleterious and beneficial mutations in a single gene of the RNA virus ϕ6.

    Sarah B Joseph

    Full Text Available Most of our knowledge of dominance stems from studies of deleterious mutations. From these studies we know that most deleterious mutations are recessive, and that this recessivity arises from a hyperbolic relationship between protein function (i.e., protein concentration or activity and fitness. Here we investigate whether this knowledge can be used to make predictions about the dominance of beneficial and deleterious mutations in a single gene. We employed a model system--the bacteriophage φ6--that allowed us to generate a collection of mutations in haploid conditions so that it was not biased toward either dominant beneficial or recessive deleterious mutations. Screening for the ability to infect a bacterial host that does not permit infection by the wildtype φ6, we generated a collection of mutations in P3, a gene involved in attachment to the host and in phage particle assembly. The resulting collection contained mutations with both deleterious and beneficial effects on fitness. The deleterious mutations in our collection had additive effects on fitness and the beneficial mutations were recessive. Neither of these observations were predicted from previous studies of dominance. This pattern is not consistent with the hyperbolic (diminishing returns relationship between protein function and fitness that is characteristic of enzymatic genes, but could have resulted from a curve of increasing returns.

  9. Rosiglitazone and Fenofibrate Additive Effects on Lipids

    Ahmad Slim

    2011-01-01

    Full Text Available Background. To evaluate the effect of rosiglitazone, fenofibrate, or their combined use on plasma lipids in normoglycemic healthy adults. Methods and Results. Subjects were randomized in a double-blind fashion to rosiglitazone + placebo, fenofibrate + placebo, rosiglitazone + fenofibrate, or matching double placebo. The between-group difference in the change in fasting TG, high-density lipoprotein cholesterol (HDL-C, LDL-C, and plasma apolipoproteins A-I, A-II, and C-III level were compared after 12 weeks of treatment. A total of 548 subjects were screened and 41 met the inclusion criteria. After 12 weeks of therapy, the median change in the triglyceride levels showed a significant reduction ranging from 47 to 55 mg per deciliter in the fenofibrate only and rosiglitazone/fenofibrate groups compared with placebo (=0.0496. However, the rosiglitazone only group did not show significant change in triglyceride level. The change in the Apo AII showed increase in all the treatment groups compared with placebo (=0.009. There was also significant change in the Apo CIII that showed reduction of its level in the fenofibrate only and rosiglitazone/fenofibrate groups (=0.0003. Conclusion. Rosiglitazone does not appear to modulate hypertriglyceridemia in patients with elevated triglycerides independent of glucose metabolism.

  10. Somatic mutations in Tradescantia as a model system for studying the effects of the environmental agents

    The application of the plant model system for studying the biological effects of ionizing radiation and chemical mutagens is presented. The model system is based on the somatic mutation frequency in stamen hair cells of Tradescantia clones heterosygous for flower color. The interaction of chemical mutagens with radiation in the induction of somatic mutations was investigated. The results demonstrate the synergistic interaction between radiation and chemical mutagens like ethyl methanesulfonate and di-bromoethane. The synergistic effect is clearly manifested after combined treatment with radiation and chemicals. In the low dose region the effect depends on the radiation dose and chemical exposure. Other results show the influence of the fluoride treatment on the radiation effect. The fluoride treatment is likely to alter the DNA double strand breaks repair processes. Additionally the usefulness of the model system for studying the mutagenic effectiveness of the pollution in the ambient air is presented. 148 refs. (author)

  11. Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis.

    Jawhar, M; Schwaab, J; Schnittger, S; Meggendorfer, M; Pfirrmann, M; Sotlar, K; Horny, H-P; Metzgeroth, G; Kluger, S; Naumann, N; Haferlach, C; Haferlach, T; Valent, P; Hofmann, W-K; Fabarius, A; Cross, N C P; Reiter, A

    2016-01-01

    Most patients with KIT D816V(+) advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V(+) advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03), but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, the presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V(+) SM. On the basis of these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM. PMID:26464169

  12. Mutational Effects on the Folding Dynamics of a Minimized Hairpin‡

    Scian, Michele; Shu, Irene; Olsen, Katherine A.; Hassam, Khalil; Andersen, Niels H.

    2013-01-01

    The fold stabilities and folding dynamics of a series of mutants of a model hairpin, KTW-NPATGK-WTE (HP7), are reported. The parent system and the corresponding DPATGK loop species display sub-μs folding time constants. The mutational studies revealed that ultrafast folding requires both some pre-structuring of the loop and a favorable interaction between the chain termini at the transition state. In the case of YY-DPETGT-WY, another sub-μs folding species [Davis, C. M.; Xiao, S.; Raleigh, D. P.; Dyer, R. B. (2012) J. Am. Chem. Soc. 134, 14476–14482], a hydrophobic cluster provides the latter. In the case of HP7, the Coulombic interaction between the terminal NH3+ and CO2− units provides this; a C-terminal Glu to amidated Ala mutation results in a 5-fold folding rate retardation. The effects of mutations within the reversing loop indicate the balance between loop flexibility (favoring fast conformational searching) and turn-formation in the unfolded state is a major factor in determining the folding dynamics. The –NAAAKX- loops examined display no detectable turn formation propensity in other hairpin constructs, but do result in stable analogs of HP7. Peptide KTW-NAAAKK-WTE displays the same fold stability as HP7 but both the folding and unfolding time constants are greater by a factor of 20. PMID:23521619

  13. Mutational effects on the folding dynamics of a minimized hairpin.

    Scian, Michele; Shu, Irene; Olsen, Katherine A; Hassam, Khalil; Andersen, Niels H

    2013-04-16

    The fold stabilities and folding dynamics of a series of mutants of a model hairpin, KTW-NPATGK-WTE (HP7), are reported. The parent system and the corresponding DPATGK loop species display submicrosecond folding time constants. The mutational studies revealed that ultrafast folding requires both some prestructuring of the loop and a favorable interaction between the chain termini in the transition state. In the case of YY-DPETGT-WY, another submicrosecond folding species [Davis, C. M., Xiao, S., Raleigh, D. P., and Dyer, R. B. (2012) J. Am. Chem. Soc. 134, 14476-14482], a hydrophobic cluster provides the latter. In the case of HP7, the Coulombic interaction between the terminal NH3(+) and CO2(-) units provides this; a C-terminal Glu to amidated Ala mutation results in a 5-fold retardation of the folding rate. The effects of mutations within the reversing loop indicate the balance between loop flexibility (favoring fast conformational searching) and turn formation in the unfolded state is a major factor in determining the folding dynamics. The -NAAAKX- loops examined display no detectable turn formation propensity in other hairpin constructs but do result in stable analogues of HP7. Peptide KTW-NAAAKK-WTE displays the same fold stability as HP7, but both the folding and unfolding time constants are greater by a factor of 20. PMID:23521619

  14. Point Mutations Effects on Charge Transport Properties of the Tumor-Suppressor Gene p53

    Shih, Chi-Tin; Roche, Stephan; Römer, Rudolf A.

    2007-01-01

    We report on a theoretical study of point mutations effects on charge transfer properties in the DNA sequence of the tumor-suppressor p53 gene. On the basis of effective single-strand or double-strand tight-binding models which simulate hole propagation along the DNA, a statistical analysis of charge transmission modulations associated with all possible point mutations is performed. We find that in contrast to non-cancerous mutations, mutation hotspots tend to result in significantly weaker {...

  15. Computing Stability Effects of Mutations in Human Superoxide Dismutase 1

    Kepp, Kasper Planeta

    2014-01-01

    physiological importance. In this work, stability changes of SOD1 mutations were computed with five methods, CUPSAT, I-Mutant2.0, I-Mutant3.0, PoPMuSiC, and SDM, with emphasis on structural sensitivity as a potential issue in structure-based protein calculation. The large correlation between experimental...... interest, but had little impact on overall batch estimates. Protein-interaction effects (as a mimic of crystal packing) were small for the more accurate methods. Thus, batch computations, relevant to, e.g., comparisons of disease/nondisease mutant sets or different clades in phylogenetic trees, are much...

  16. Assessment of computational methods for predicting the effects of missense mutations in human cancers

    Gnad, Florian; Baucom, Albion; Mukhyala, Kiran; Manning, Gerard; Zhang, Zemin

    2013-01-01

    Background Recent advances in sequencing technologies have greatly increased the identification of mutations in cancer genomes. However, it remains a significant challenge to identify cancer-driving mutations, since most observed missense changes are neutral passenger mutations. Various computational methods have been developed to predict the effects of amino acid substitutions on protein function and classify mutations as deleterious or benign. These include approaches that rely on evolution...

  17. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes

    An increasing number of studies show that genetic markers can aid in refining prognostic information and predicting the benefit from systemic therapy. Our goal was to develop a high throughput, cost-effective and simple methodology for the detection of clinically relevant hot spot mutations in colon cancer. The Maldi-Tof mass spectrometry platform and OncoCarta panel from Sequenom were used to profile 239 colon cancers and 39 metastatic lymph nodes from NSABP clinical trial C-07 utilizing routinely processed FFPET (formalin-fixed paraffin-embedded tissue). Among the 238 common hot-spot cancer mutations in 19 genes interrogated by the OncoCarta panel, mutations were detected in 7 different genes at 26 different nucleotide positions in our colon cancer samples. Twenty-four assays that detected mutations in more than 1% of the samples were reconfigured into a new multiplexed panel, termed here as ColoCarta. Mutation profiling was repeated on 32 mutant samples using ColoCarta and the results were identical to results with OncoCarta, demonstrating that this methodology was reproducible. Further evidence demonstrating the validity of the data was the fact that the mutation frequencies of the most common colon cancer mutations were similar to the COSMIC (Catalog of Somatic Mutations in Cancer) database. The frequencies were 43.5% for KRAS, 20.1% for PIK3CA, and 12.1% for BRAF. In addition, infrequent mutations in NRAS, AKT1, ABL1, and MET were detected. Mutation profiling of metastatic lymph nodes and their corresponding primary tumors showed that they were 89.7% concordant. All mutations found in the lymph nodes were also found in the corresponding primary tumors, but in 4 cases a mutation was present in the primary tumor only. This study describes a high throughput technology that can be used to interrogate DNAs isolated from routinely processed FFPET and identifies the specific mutations that are common to colon cancer. The development of this technology and the Colo

  18. Use of amplification refractory mutation system PCR assay as a simple and effective tool to detect HIV-1 drug resistance mutations.

    Nanfack, Aubin J; Agyingi, Lucy; Noubiap, Jean Jacques N; Ngai, Johnson N; Colizzi, Vittorio; Nyambi, Phillipe N

    2015-05-01

    Access to genotyping assays to determine successful antiretroviral treatment (ART) is limited in resource-constrained settings by high cost, suggesting the need for a cost-effective and simplified method to identify HIV-1 drug resistance (HIVDR) mutations. In this study, an amplification refractory mutation system (ARMS)-PCR assay was developed and used to investigate the most frequent HIVDR mutations affecting first-line ART in settings where WHO ART guidelines are applied. Seventy-five HIV-positive (HIV(+)) samples from Cameroon were used to assess the performance of this assay. Sequencing of HIV-1 reverse transcriptase was simultaneously performed for comparison, and discordant samples were tested with a Trugene HIV-1 genotyping kit. The ARMS-PCR assay was able to detect M184V, T215Y/F, K103N, and Y181C mutations with sensitivities of 96.8%, 85.7%, 91.3%, and 70%, respectively, and specificities of 90.6%, 95%, 100%, 96.9%, respectively, compared with data on sequencing. The results indicated the highest positive predictive value for K103N (100%) and the highest negative predictive value for M184V (97.5%). ARMS-PCR's limits of detection for mutations M184V, T215Y/F, K103N, and Y181C were HIV-1 clades (CRF02_AG and non-CRF02_AG). In addition, this approach was more cost-effective than other genotyping assays. The high throughput, the cost-effectiveness, and the simplicity of the ARMS-PCR assay make it a suitable tool to monitor HIVDR patterns in resource-constrained settings with broad HIV-1 genetic diversity. PMID:25788547

  19. Downstream effects of plectin mutations in epidermolysis bullosa simplex with muscular dystrophy.

    Winter, Lilli; Türk, Matthias; Harter, Patrick N; Mittelbronn, Michel; Kornblum, Cornelia; Norwood, Fiona; Jungbluth, Heinz; Thiel, Christian T; Schlötzer-Schrehardt, Ursula; Schröder, Rolf

    2016-01-01

    Mutations of the human plectin gene (PLEC) on chromosome 8q24 cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). In the present study we analyzed the downstream effects of PLEC mutations on plectin protein expression and localization, the structure of the extrasarcomeric desmin cytoskeleton, protein aggregate formation and mitochondrial distribution in skeletal muscle tissue from three EBS-MD patients. PLEC gene analysis in a not previously reported 35-year-old EBS-MD patient with additional disease features of cardiomyopathy and malignant arrhythmias revealed novel compound heterozygous (p.(Phe755del) and p.(Lys1040Argfs*139)) mutations resulting in complete abolition of plectin protein expression. In contrast, the other two patients with different homozygous PLEC mutations showed preserved plectin protein expression with one only expressing rodless plectin variants, and the other markedly reduced protein levels. Analysis of skeletal muscle tissue from all three patients revealed severe disruption of the extrasarcomeric intermediate filament cytoskeleton, protein aggregates positive for desmin, syncoilin, and synemin, degenerative myofibrillar changes, and mitochondrial abnormalities comprising respiratory chain dysfunction and an altered organelle distribution and amount.Our study demonstrates that EBS-MD causing PLEC mutations universally result in a desmin protein aggregate myopathy phenotype despite marked differences in individual plectin protein expression patterns. Since plectin is the key cytolinker protein that regulates the structural and functional organization of desmin filaments, the defective anchorage and spacing of assembled desmin filaments is the key pathogenetic event that triggers the formation of desmin protein aggregates as well as secondary mitochondrial pathology. PMID:27121971

  20. Biological effects of space-induced mutation on robinia pseudoacacia

    Dry seeds of Robinia pseudoacacia were carried by Shijian No.8 breeding satellite for mutagenesis and the biological effect of space-induced mutation was studied. The parameters of Robinia pseudoacacia such as plant height, stem base, branch number, knot spacing, length of thorn and chlorophyll content were analyzed, and, at the same time, the genetic diversity was tested by SSR marker. The results showed that the plant height and stem base of 2-year-old seedlings which derived from space mutagenesis were 22.0% and 24.1% lower than those of control, and 3-year-old seedlings were 13.1% and 22.4% lower than those of control, respectively. While the inhibiting effect of plant height became undermined in the following growth years. However, the inhibiting effect in stem base existed all the time,the length of thorn of branch and stem were 15.6% and 28.6% shorter than the control,respectively. Compared with the control,the variation of the length of thorn from stem was extremely significant. The variation of chlorophyll a content from space mutagenesis compared with control was not remarkable, while the total chlorophyll and chlorophyll b contents were 18.7% and 9.7% lower than those of control, respectively, and the difference between space mutagenesis and control was significant. While the chlorophyll a/b was 25.6% higher than that of control, but the difference was not significant. The coefficient of variation of the relative traits was increased by the space mutagenesis. The extensively population genome mutation after space-induction were not detected by SSR (Simple Sequence Repeats). (authors)

  1. Effect of additives on the purification of urease

    Yu, X.; Wang, J.; Ulrich, J.

    2015-12-01

    The effect of additives on the purification of proteins was investigated. The target protein studied here is the enzyme urease. Studies on the purification of urease from jack bean meal were carried out. 32% (v/v) acetone was utilized to extract urease from the jack bean meal. Further purification by crystallization with the addition of 2-mercaptoethanol and EDTA disodium salt dehydrate was carried out. It was found out that the presence of additives can affect the selectivity of the crystallization. Increases in both purity and yield of the urease after crystallization were observed in the presence of additives, which were proven using both SDS-PAGE and activity. Urease crystals with a yield of 69.9% and a purity of 85.1% were obtained in one crystallization step in the presence of additives. Furthermore, the effect of additives on the thermodynamics and kinetics of urease crystallization was studied.

  2. Mutations Closer to the Active Site Improve the Promiscuous Aldolase Activity of 4-Oxalocrotonate Tautomerase More Effectively than Distant Mutations.

    Rahimi, Mehran; van der Meer, Jan-Ytzen; Geertsema, Edzard M; Poddar, Harshwardhan; Baas, Bert-Jan; Poelarends, Gerrit J

    2016-07-01

    The enzyme 4-oxalocrotonate tautomerase (4-OT), which catalyzes enol-keto tautomerization as part of a degradative pathway for aromatic hydrocarbons, promiscuously catalyzes various carbon-carbon bond-forming reactions. These include the aldol condensation of acetaldehyde with benzaldehyde to yield cinnamaldehyde. Here, we demonstrate that 4-OT can be engineered into a more efficient aldolase for this condensation reaction, with a >5000-fold improvement in catalytic efficiency (kcat /Km ) and a >10(7) -fold change in reaction specificity, by exploring small libraries in which only "hotspots" are varied. The hotspots were identified by systematic mutagenesis (covering each residue), followed by a screen for single mutations that give a strong improvement in the desired aldolase activity. All beneficial mutations were near the active site of 4-OT, thus underpinning the notion that new catalytic activities of a promiscuous enzyme are more effectively enhanced by mutations close to the active site. PMID:27238293

  3. Integrated genetic and epigenetic analysis of bladder cancer reveals an additive diagnostic value of FGFR3 mutations and hypermethylation events

    Serizawa, Reza R; Ralfkiaer, Ulrik; Steven, Kenneth;

    2011-01-01

    screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We...

  4. Pairwise-additive hydrophobic effect for alkanes in water

    Wu, Jianzhong; Prausnitz, John M.

    2008-01-01

    Pairwise additivity of the hydrophobic effect is indicated by reliable experimental Henry's constants for a large number of linear and branched low-molecular-weight alkanes in water. Pairwise additivity suggests that the hydrophobic effect is primarily a local phenomenon and that the hydrophobic interaction may be represented by a semiempirical force field. By representing the hydrophobic potential between two methane molecules as a linear function of the overlap volume of the hydration layer...

  5. Platelet hexosaminidase a enzyme assay effectively detects carriers missed by targeted DNA mutation analysis.

    Nakagawa, Sachiko; Zhan, Jie; Sun, Wei; Ferreira, Jose Carlos; Keiles, Steven; Hambuch, Tina; Kammesheidt, Anja; Mark, Brian L; Schneider, Adele; Gross, Susan; Schreiber-Agus, Nicole

    2012-01-01

    Biochemical testing of hexosaminidase A (HexA) enzyme activity has been available for decades and has the ability to detect almost all Tay-Sachs disease (TSD) carriers, irrespective of ethnic background. This is increasingly important, as the gene pool of those who identify as Ashkenazi Jewish is diversifying. Here we describe the analysis of a cohort of 4,325 individuals arising from large carrier screening programs and tested by the serum and/or platelet HexA enzyme assays and by targeted DNA mutation analysis. Our results continue to support the platelet assay as a highly effective method for TSD carrier screening, with a low inconclusive rate and the ability to detect possible disease-causing mutation carriers that would have been missed by targeted DNA mutation analysis. Sequence analysis performed on one such platelet assay carrier, who had one non-Ashkenazi Jewish parent, identified the amino acid change Thr259Ala (A775G). Based on crystallographic modeling, this change is predicted to be deleterious, as threonine 259 is positioned proximal to the HexA alpha subunit active site and helps to stabilize key residues therein. Accordingly, if individuals are screened for TSD in broad-based programs by targeted molecular testing alone, they must be made aware that there is a more sensitive and inexpensive test available that can identify additional carriers. Alternatively, the enzyme assays can be offered as a first tier test, especially when screening individuals of mixed or non-Jewish ancestry. PMID:23430931

  6. Pleiotropic Effect of tatC Mutation on Metabolism of Pathogen Yesinia enterocolitica

    2007-01-01

    Objective To analyze the impact of depletion of the twin arginine translocation (TAT) system on virulence and physiology of Yersinia enterocolitica for a better understanding of its pathogenicity. Methods We constructed a △tatC::SpRmutant of Yersinia enterocolitica by P1 phage mediated transduction using Escherichia coli K-12 △tatC::SpR strain as a donor. Results A P1-mediated genetic material transfer was found between the two species of enterobacteria, indicating a great potential of acquisition of antibiotic resistance in emergency of a new threatening pathogen by genetic material exchanges.Periplasmic trimethylamine N-oxidase reductase activity was detected in the wild type Y. enterocolitica strain and translocation of this enzyme was completely abolished by the △tatC::SpR mutation. In addition, the △tatC::SpR mutation showed a pleiotropic effect on the metabolism of Y. enterocolitica. However, the tat mutation did not seem to affect the mobility and virulence of Y.enterocolitica under the conditions used. Conclusion Unlike other pathogenic bacteria studied, the TAT system of Y.enterocolitica might play an important role in the pathogenic process, which is distinct from other pathogens, such as Pseudomonas aeruginosa and enterohemorrhagic E. coli O157:H7.

  7. The A431E mutation in PSEN1 causing Familial Alzheimer’s Disease originating in Jalisco State, Mexico: an additional fifteen families

    Murrell, Jill; Ghetti, Bernardino; Cochran, Elizabeth; Macias-Islas, Miguel Angel; Medina, Luis; Varpetian, Arousiak; Cummings, Jeffrey L.; Mendez, Mario F.; KAWAS, CLAUDIA; Chui, Helena; Ringman, John M.

    2006-01-01

    Nine families with autosomal dominant Alzheimer’s disease (AD), all of whom had the Ala431Glu substitution in the PSEN1 gene and came from Jalisco State in Mexico, have been previously reported. As they shared highly polymorphic flanking dinucleotide marker alleles, this strongly suggests that this mutation arose from a common founder. In the current letter, we expand this observation by describing an additional 15 independent families with the Ala431Glu substitution in the PSEN1 gene and con...

  8. MICO: A meta-tool for prediction of the effects of non-synonymous mutations

    Lee, Gilliean; Chen, Chin-Fu

    2014-01-01

    The Next Generation Sequencing (NGS) is a state-of-the-art technology that produces high throughput data with high resolution mutation information in the genome. Numerous methods with different efficiencies have been developed to predict mutational effects in the genome. The challenge is to present the results in a balanced manner for better biological insights and interpretation. Hence, we describe a meta-tool named Mutation Information Collector (MICO) for automatically querying and collect...

  9. Disparate Effects of Different Mutations in Plakoglobin on Cell Mechanical Behavior

    Huang, Hayden; Asimaki, Angeliki; Lo, Denise; McKenna, William; Saffitz, Jeffrey

    2008-01-01

    Mutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of heart and skin diseases. This has led to the hypothesis that defective cell-cell adhesion is the underlying cause of injury in tissues that repeatedly bear high mechanical loads. In this study, we examined the effects of two different mutations in plakoglobin on cell migration, stiffness, and adhesion. One is a C-terminal mutation causing Naxos disease, a recessive syndrome of arrhythmogenic right vent...

  10. Study on thermal effects & sulfurized additives, in lubricating greases

    Shah, Ami Atul

    Lithium Base grease constitutes about 50% of market. The greases are developed to be able to work in multiple working conditions and have longer working life. Greases with extreme pressure additives and anti-wear additives have been developed as a solution to many of the applications. These developed greases are tested under ASTM D2266 testing conditions to meet the requirements. The actual working conditions, although, differ than the real testing conditions. The loading, speed and temperature conditions can be more harsh, or fluctuating in nature. The cyclic nature of the parameters cannot be directly related to the test performance. For this purpose studies on the performance under spectrum loading, variable speed and fluctuating temperature must be performed. This study includes tests to understand the effect of thermal variation on some of the most commonly used grease additives that perform well under ASTM D2266 testing conditions. The studied additives include most widely used industrial extreme pressure additive MoS2. Performance of ZDDP which is trying to replace MoS2 in its industrial applications has also been studied. The tests cover study of extreme pressure, anti-wear and friction modifier additives to get a general idea on the effects of thermal variation in three areas. Sulphur is the most common extreme pressure additive. Sulphur based MoS 2 is extensively used grease additive. Study to understand the tribological performance of this additive through wear testing and SEM/EDX studies has been done. This performance is also studied for other metallic sulfides like WS2 and sulphur based organic compound. The aim is to study the importance of the type of bond that sulphur shares in its additive's structure on its performance. The MoS2 film formation is found to be on the basis of the FeS formation on the substrate and protection through sacrificial monolayer deposition of the MoS2 sheared structure. The free Mo then tends to oxidise. An attempt to

  11. Mutational effects of space flight on Zea mays seeds

    Mei, M.; Qiu, Y.; He, Y.; Bucker, H.; Yang, C. H.

    1994-01-01

    The growth and development of more than 500 Zea mays seeds flown on Long Duration Exposure Facility (LDEF) were studied. Somatic mutations, including white-yellow stripes on leaves, dwarfing, change of leaf sheath color or seedling color were observed in plants developed from these seeds. When the frequency of white-yellow formation was used as the endpoint and compared with data from ground based studies, the dose to which maize seeds might be exposed during the flight was estimated to be equivalent to 635 cGy of gamma rays. Seeds from one particular holder gave a high mutation frequency and a wide mutation spectrum. White-yellow stripes on leaves were also found in some of the inbred progenies from plants displayed somatic mutation. Electron microscopy studies showed that the damage of chloroplast development in the white-yellow stripe on leaves was similar between seeds flown on LDEF and that irradiated by accelerated heavy ions on ground.

  12. Effects of additives on glyphosate activity in purple nutsedge

    Effects of additives on 14 C-glyphosate penetration into purple nutsedge leaves were examined in the laboratory and efficacy of glyphosate for purple nutsedge control was studied in the greenhouse and field. The addition of (NH4)2 SO4 at 1.0% (v/v) + diesel oil at 1,0% (v/v) + Tendal at 1.0% (v/v) increased 14C-glyphosate penetration into nutsedge leaves more than the addition of either one alone. (NH4)2SO4 at 1.0% + diesel oil at 1.0% + Tendal at 0.12 or 0.25% increased the phytotoxicity of glyphosate at 0.5 and 0.75 kg, a.e./ha on nutsedge plants in the greenhouse but not in the field. Additives did not enhance glyphosate activity by reducing the number of nutsedae tubers. (author)

  13. Ethnic differentials in health: the additional effect of ethnic density

    Feng, Zhixin; Vlachantoni, Athina; Falkingham, Jane; Evandrou, Maria

    2016-01-01

    It is well established that there are differentials in health among individuals of different Black and Minority Ethnic (BME) heritage. BME communities are unevenly concentrated across England and Wales. This paper examines the effect of residential density of one’s own ethnic group on physical health outcomes in England and Wales. In addition, it explores whether the effects of ethnic density on physical health outcomes are concealed by area deprivation, and whether individual economic depriv...

  14. Insights into enzyme point mutation effect by molecular simulation: phenylethylamine oxidation catalyzed by monoamine oxidase A.

    Oanca, Gabriel; Purg, Miha; Mavri, Janez; Shih, Jean C; Stare, Jernej

    2016-05-21

    The I335Y point mutation effect on the kinetics of phenylethylamine decomposition catalyzed by monoamine oxidase A was elucidated by means of molecular simulation. The established empirical valence bond methodology was used in conjunction with the free energy perturbation sampling technique and a classical force field representing the state of reactants and products. The methodology allows for the simulation of chemical reactions, in the present case the breaking of the α-C-H bond in a phenylethylamine substrate and the subsequent hydrogen transfer to the flavin cofactor, resulting in the formation of the N-H bond on flavin. The empirical parameters were calibrated against the experimental data for the simulated reaction in a wild type protein and then used for the calculation of the reaction free energy profile in the I335Y mutant. In very good agreement with the measured kinetic data, mutation increases the free energy barrier for the rate limiting step by slightly more than 1 kcal mol(-1) and consequently decreases the rate constant by about an order of magnitude. The magnitude of the computed effect slightly varies with simulation settings, but always remains in reasonable agreement with the experiment. Analysis of trajectories reveals a major change in the interaction between phenyl rings of the substrate and the neighboring Phe352 residue upon the I335Y mutation due to the increased local polarity, leading to an attenuated quadrupole interaction between the rings and destabilization of the transition state. Additionally, the increased local polarity in the mutant allows for a larger number of water molecules to be present near the active site, effectively shielding the catalytic effect of the enzyme and contributing to the increased barrier. PMID:27121693

  15. Effect of mutation and polyploidy breeding methods in tree cotton (Gossypium arboreum)

    An experiment was conducted during 1988 to understand the effect of mutation and ploy ploidy breeding methods in improving economically important characters of tree or desi cotton (Gossypium arboreum L.). It was determined by evaluating derivatives of M5 and C5 generation by the 2 methods. Polyploidy method proved more effective in improving halo length and seed index, whereas mutation breeding method in improving seed-cotton yield. No method proved effective in improving ginning out turn however, mutation method was slightly superior to polyploidy method. Adoption of polyploidy rather than mutation breeding method proved more effective for improving negatively correlation characters, i.e. ginning out turn with halo length and seed index. Magnitude of genetic variability was higher in the population derived by mutation breeding method, indicating better scope for further improvement. (author). 6 refs., 2 tabs

  16. Mutational effects of γ-rays and carbon ion beams on Arabidopsis seedlings

    Yoshihara, Ryouhei; Nozawa, Shigeki; Hase, Yoshihiro; Narumi, Issay; Hidema, Jun; Sakamoto, Ayako N

    2013-01-01

    To assess the mutational effects of radiation on vigorously proliferating plant tissue, the mutation spectrum was analyzed with Arabidopsis seedlings using the plasmid-rescue method. Transgenic plants containing the Escherichia coli rpsL gene were irradiated with γ-rays and carbon ion beams (320-MeV 12C6+), and mutations in the rpsL gene were analyzed. Mutant frequency increased significantly following irradiation by γ-rays, but not by 320-MeV 12C6+. Mutation spectra showed that both radiatio...

  17. Contamination effects of drilling fluid additives on cement slurry

    Youzhi Zheng

    2015-10-01

    Full Text Available During the cementation of deep wells, contamination at the contact surface between cement slurry and drilling fluid will present a technical challenge, which may threaten operation safety. To deal with the problem, lab tests and analysis were performed specifically on the compatibility of fluids during cementation in Sichuan and Chongqing gas fields. Impacts of commonly used additives for drilling fluids were determined on fluidity and thickening time of conventional cement slurry. Through the infrared spectrum analysis, SEM and XRD, infrared spectrum data of kalium polyacrylamide (KPAM and bio-viscosifier were obtained, together with infrared spectrum, SEM and XRD data of cement slurry with additives. Contamination mechanisms of the cement slurry by conventional additives for drilling fluid were reviewed. Test results show that both KPAM and bio-viscosifier are such high-molecular materials that the long chains in these materials may easily absorb cement particles in the slurry to form mixed network structures; as a result, cement particles were prone to agglomeration and eventually lost their pumpability. Finally, assessment of and testing methods for the contamination effects of drilling fluid additives on cement slurry were further improved to form standards and codes that may help solve the said problems. This study will provide technological supports for the preparation of drilling fluids with desirable properties prior to cementation, the selection of optimal drilling fluids additives, and the development of innovative drilling fluids additives.

  18. Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium.

    Agashe, Deepa; Sane, Mrudula; Phalnikar, Kruttika; Diwan, Gaurav D; Habibullah, Alefiyah; Martinez-Gomez, Norma Cecilia; Sahasrabuddhe, Vinaya; Polachek, William; Wang, Jue; Chubiz, Lon M; Marx, Christopher J

    2016-06-01

    Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context. PMID:26908584

  19. Tin nanoparticles as an effective conductive additive in silicon anodes

    Zhong, L.; Beaudette, C.; Guo, J.; Bozhilov, K.; Mangolini, L.

    2016-01-01

    We have found that the addition of tin nanoparticles to a silicon-based anode provides dramatic improvements in performance in terms of both charge capacity and cycling stability. Using a simple procedure and off-the-shelf additives and precursors, we developed a structure in which the tin nanoparticles are segregated at the interface between the silicon-containing active layer and the solid electrolyte interface. Even a minor addition of tin, as small as ∼2% by weight, results in a significant decrease in the anode resistance, as confirmed by electrochemical impedance spectroscopy. This leads to a decrease in charge transfer resistance, which prevents the formation of electrically inactive “dead spots” in the anode structure and enables the effective participation of silicon in the lithiation reaction. PMID:27484849

  20. Tin nanoparticles as an effective conductive additive in silicon anodes.

    Zhong, L; Beaudette, C; Guo, J; Bozhilov, K; Mangolini, L

    2016-01-01

    We have found that the addition of tin nanoparticles to a silicon-based anode provides dramatic improvements in performance in terms of both charge capacity and cycling stability. Using a simple procedure and off-the-shelf additives and precursors, we developed a structure in which the tin nanoparticles are segregated at the interface between the silicon-containing active layer and the solid electrolyte interface. Even a minor addition of tin, as small as ∼2% by weight, results in a significant decrease in the anode resistance, as confirmed by electrochemical impedance spectroscopy. This leads to a decrease in charge transfer resistance, which prevents the formation of electrically inactive "dead spots" in the anode structure and enables the effective participation of silicon in the lithiation reaction. PMID:27484849

  1. Sentinel and other mutational effects in offspring of cancer survivors

    To date, no agent has been documented to cause germ cell mutation in human beings, with the possible exception of radiation causing abnormal meiotic chromosomes in testes. For studies in humans, mutation epidemiologists prefer the cohort approach, starting with an exposed population and looking for mutations that may be expressed in offspring as variants in health, chromosomes, proteins, or nucleic acids. Currently patients with cancer are the cohort exposed to the largest doses of potential mutagens, i.e., radiotherapy and drugs. In 12 large studies with over 825 patients and 1573 pregnancies, 46 (4%) of 1240 liveborns had a major birth defect, a rate comparable to that in the general population. One of these was a classic sentinel phenotype, i.e., a new sporadic case of a dominant mendelian syndrome. In collaboration with 5 U.S. cancer registries, we interviewed a retrospective cohort of 2383 patients diagnosed with cancer under age 20 years, from 1945 through 1975. Records were sought to verify major genetic disease, defined as a cytogenetic or single gene disorder or 1 of 15 isolated birth defects. In 2308 offspring of survivors, 5 had a chromosomal syndrome, 11 had a single gene disorder, and 62 had at least one major malformation. Among 4722 offspring of sibling controls, the respective numbers were 7, 12, and 127, nonsignificant differences. 7% of the parents of the offspring with possibly new mutations received potentially mutagenic therapy, compared with 12% of parents of normal children. Since pregnancy in or by cancer survivors is still a rare event, future efforts to document germ cell mutation may be best studied through international cooperation coupled with diverse laboratory measures of mutation

  2. Effects of small ionic amphiphilic additives on reverse microemulsion morphology

    Hopkins Hatzopoulos, Marios T; James, Craig; Rogers, Sarah E.; Grillo, Isabelle; Dowding, Peter J; Eastoe, Julian

    2014-01-01

    HypothesisInitial studies (Hopkins Hatzopoulos et al. (2013)) have shown that ionic hydrotropic additives can drive a sphere-to-cylinder (ellipsoid) transition in water-in-oil (w/o) microemulsions stabilized by the anionic surfactant Aerosol-OT; however the origins of this behaviour remained unclear. Here systematic effects of chemical structure are explored with a new set of hydrotropes, in terms of an aromatic versus a saturated cyclic hydrophobic group, and linear chain length of alkyl car...

  3. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis.

    Di Fede, Giuseppe; Catania, Marcella; Morbin, Michela; Rossi, Giacomina; Suardi, Silvia; Mazzoleni, Giulia; Merlin, Marco; Giovagnoli, Anna Rita; Prioni, Sara; Erbetta, Alessandra; Falcone, Chiara; Gobbi, Marco; Colombo, Laura; Bastone, Antonio; Beeg, Marten; Manzoni, Claudia; Francescucci, Bruna; Spagnoli, Alberto; Cantù, Laura; Del Favero, Elena; Levy, Efrat; Salmona, Mario; Tagliavini, Fabrizio

    2009-03-13

    beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673-->valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced beta-amyloid (Abeta) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Abeta aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimer's disease. PMID:19286555

  4. Effect of additives on physicochemical properties in amorphous starch matrices.

    Liang, Jun; Wang, Simon; Ludescher, Richard D

    2015-03-15

    The effect of the addition of non-reducing sugars or methylcellulose on the matrix physical properties and rate of non-enzymatic browning (NBR) between exogenous glucose+lysine in a starch-based glassy matrix were studied, using the methods of luminescence and FTIR. Amorphous starch-based matrices were formulated by rapidly dehydrating potato starch gel mixed with additives at weight ratios of 7:93 (additive:starch). Data on the phosphorescence emission energy and lifetime from erythrosin B dispersed in the matrices indicated that sugars decreased starch matrix mobility in a Tg-dependent manner, except for trehalose that interacted with starch in a unique mode, while methylcellulose, the additive with the highest Tg, increased the molecular mobility. Using FTIR, we found that methylcellulose decreased the strength of hydrogen bond network and sugars enhanced the hydrogen bond strength in the order: trehalose>maltitol>sucrose. Comparing those changes with the rate of NBR between exogenous glucose+lysine, we suggest that NBR rates are primarily influenced by matrix mobility, which is modulated by the hydrogen bond network, and interactions among components. PMID:25308673

  5. A study on photoreceptor by using the effect of additives

    We have been studied photosensitization mechanism's additive effect, of perylene 3,4,9,10-tetracarboxyl-diimide and X-phthalocyanine (charge generation materials), using the photochemical and photoelectrochemical approach. It was found that the photoreceptor on the excited state reacts with metal oxide, which creates the charge transfer on the interface of SnO2/electrolyte. In the electrode (X5P1) made of five X-phthalocyanine and single perylene 3,4,9,10-tetracarboxyldiimide layers, the cathodic photocurrent of X-phthalocyanine in the 400-600 nm region was increased by the addition of perylene 3,4,9,10-tetracarboxyldiimide. The maximum wavelength of fluorescence of perylene 3,4,9,10-tetracarboxyldiimide showed no dependence on the temperature. The addition of 4-dibenzylamino-2-methylbenzaldehyde diphenylhydrazone known as charge transport material was represented as decreasing photocurrent for X-phthalocyanine and perylene 3,4,9,10-tetracarboxyldiimide, respectively. In the electrode (X1P1) made of single X-phthalocyanine and single perylene 3,4,9,10-tetracarboxyldiimide layers, an anodic photocurrent of about 10.5 nA was generated by addition of hydroquinone at 550 nm. And the characteristic of photoinduced discharge was shown to decrease by a factor 5 and the speed of dark decay was increased by a factor of 1.2

  6. Effect of radiation resistance additives for insulation materials

    For the electric wires and cables used in radiation environment such as nuclear power stations and fuel reprocessing facilities, the properties of excellent radiation resistance are required. For these insulators and sheath materials, ethylene propylene rubber, polyethylene and other polymers have been used, but it cannot be said that they always have good radiation resistance. However, it has been well known that radiation resistance can be improved with small amount of additives, and heat resistance and burning retarding property as well as radiation resistance are given to the insulators of wires and cables for nuclear facilities by mixing various additives. In this research, the measuring method for quantitatively determining the effect of Anti-rad (radiation resistant additive) was examined. Through the measurement of gel fraction, radical formation and decomposed gas generation, the effect of Anti-rad protecting polymers from radiation deterioration was examined from the viewpoint of chemical reaction. The experimental method and the results are reported. The radiation energy for cutting C-H coupling is polymers is dispersed by Anti-rad, and the probability of cutting is lowered. Anti-rad catches and extinguishes radicals that start oxidation reaction. (K.I.)

  7. Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin

    Doud, Michael B.; Bloom, Jesse D.

    2016-01-01

    Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin—including the stalk epitopes targeted by broadly neutralizing antibodies—have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution. PMID:27271655

  8. Evaluating the Effects of Additives on Drilling Fluid Characteristics

    Uche OSOKOGWU*

    2014-06-01

    Full Text Available Drilling fluid plays a vital role in hole cleaning, suspension of cuttings, prevent caving, and ensure the tightness of the well wall. Moreover, they also help in cooling and lubricating the drilling tool, transfer the hydraulic power and carry information about the nature of the drilled formation by raising the cuttings from the bottom to the surface, using a simple mixture of water and clays, to complex mixtures of various specific organic and inorganic products as additives. These additives improve fluid rheological properties and filtration capability, allowing bits to penetrate heterogeneous geological formations. Two potassium Chloride polymers were formulated to test the effect of varying concentration of additives on the drilling fluid characteristic for water base mud. From the experimental results of formulation 1and 2, rheological properties shows that the plastic viscosities are 18 and 8Cp and yield point are 32 and 8 lb/100ft2 respectively. Also the mud weights are 8.4 and 8.3ppg, fluid loss, 11and 13 mls, and pH are 12.7and 12.5 respectively. Two oil base muds were also formulated to test the effect of additives on drilling fluid characteristic at varying concentration. From the experimental results, the rheological properties show that the plastic viscosities are 19and 13Cp and yield point are 21 and 10lb/100ft2 respectively. Also the mud weights are 9.5 and 9.0 ppg, fluid loss, 6 and 10 mls, and pH are 10.5and 9.7 respectively. Electrical stability which is the increase in voltage across a probe until the emulsion breaks and a current is established were also obtained as 400 and 340v in the oil base mud. It will vary with the amount of water - the more water generally the lower the stability; as the emulsion stabilizes the electrical stability increases..

  9. Effect of Residue Mutation on the Electrostatic Potential in EcCIC

    ZOU Xianwu; DONG Shuxiang; WANG Xiaoqing; HUANG Shengyou

    2007-01-01

    The effect of mutation of strongly conserved porelining residues in the chloride channel EcClC on the electrostatic potential and binding free energy of the chloride ion was studied using explicit protein-membrane structures. Electrostatic potential distribution and binding free energy of the chloride ion at different binding sites in the wild-type and mutated EcClC were calculated with APBS. The potential data reveal that the electrostatic potential around the selectivity filter, especially around the site Sext and Scen becomes more negative as the residue R147 was mutated to C147. The electrostatic binding free energy shows that the binding free energy of the chloride ion at all binding sites becomes more positive as R147 was mutated. It follows that mutation of R147 decreases ion stabilization at binding sites and affects channel's gating.

  10. Microsatellite instability and BRAF mutation in colorectal cancer: clinicopathological characteristics and effects on survival

    Sebnem Batur

    2016-04-01

    Full Text Available Prognostic significance of microsatellite instability (MSI status and B-type Raf proto-oncogene (BRAF mutation in colorectal cancer is controversial. The aim of this study was to examine the clinical and pathological characteristics associated with microsatellite stability and the effect of MSI and BRAF mutation on the survival of patients with colorectal cancer. The study included 145 colorectal cancer cases. All the patients were examined for DNA mismatch repair (MMR proteins with an immunohistochemical method. Molecular assessment of microsatellite instability was available in a subset of 41 patients. In addition, BRAF mutation analysis was performed in 30 cases. Immunohistochemically, MMR deficiency was present in 28 (19.3% patients. Female gender (p=0.001, lesion size ≥ 5 cm (p=0.013, Crohn like response (p=0.035, and right-sided localization (p<0.001 were significantly more frequent among MMR deficient patients. The overall survival was 44.1±5.1 months (95% CI, 33.7-54.4. Multivariate analyses identified only high tumor grade as an independent predictor of poor overall survival: OR, 6.7 (95% CI 2.1-21.7, p=0.002. In the subset of patients with available BRAF assessment (n=30, a negative BRAF status was associated with better survival when compared to a positive BRAF status (36.7±2.1 vs. 34.1±7.2 months, p=0.048. The sensitivity and specificity of the immunohistochemical method in predicting positive MSI status, with the molecular method as a reference, were 85.7% (95% CI: 56.2%-97.5% and 88.9% (95% CI: 69.7%-97.1%, respectively. BRAF appears to be a significant predictor of a worse outcome in patients with colorectal cancer. Further studies with a large spectrum of clinical and biological variables are warranted.

  11. Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking.

    Tiulpakov, Anatoly; White, Carl W; Abhayawardana, Rekhati S; See, Heng B; Chan, Audrey S; Seeber, Ruth M; Heng, Julian I; Dedov, Ivan; Pavlos, Nathan J; Pfleger, Kevin D G

    2016-08-01

    Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a genetic disease first described in 2 unrelated male infants with severe symptomatic hyponatremia. Despite undetectable arginine vasopressin levels, patients have inappropriately concentrated urine resulting in hyponatremia, hypoosmolality, and natriuresis. Here, we describe and functionally characterize a novel vasopressin type 2 receptor (V2R) gain-of-function mutation. An L312S substitution in the seventh transmembrane domain was identified in a boy presenting with water-induced hyponatremic seizures at the age of 5.8 years. We show that, compared with wild-type V2R, the L312S mutation results in the constitutive production of cAMP, indicative of the gain-of-function NSIAD profile. Interestingly, like the previously described F229V and I130N NSIAD-causing mutants, this appears to both occur in the absence of notable constitutive β-arrestin2 recruitment and can be reduced by the inverse agonist Tolvaptan. In addition, to understand the effect of various V2R substitutions on the full receptor "life-cycle," we have used and further developed a bioluminescence resonance energy transfer intracellular localization assay using multiple localization markers validated with confocal microscopy. This allowed us to characterize differences in the constitutive and ligand-induced localization and trafficking profiles of the novel L312S mutation as well as for previously described V2R gain-of-function mutants (NSIAD; R137C and R137L), loss-of-function mutants (nephrogenic diabetes insipidus; R137H, R181C, and M311V), and a putative silent V266A V2R polymorphism. In doing so, we describe differences in trafficking between unique V2R substitutions, even at the same amino acid position, therefore highlighting the value of full and thorough characterization of receptor function beyond simple signaling pathway analysis. PMID:27355191

  12. The effects of extremely low frequency magnetic fields on mutation induction in mice

    Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F1 hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible

  13. The effects of extremely low frequency magnetic fields on mutation induction in mice

    Wilson, James W. [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom); Haines, Jackie; Sienkiewicz, Zenon [Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom)

    2015-03-15

    Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F{sub 1} hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible.

  14. EFFECT OF THE ANTIMUTAGENS VANILLIN AND CINNAMALDEHYDE ON THE SPONTANEOUS MUTATION SPECTRA OF SALMONELLA TA104

    Effect of the Antimutagens Vanillin and Cinnamaldehyde on the / Spontaneous Mutation Spectra of Salmonella TAlO4 Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that, when added to assay plates, reduced the spontaneous mutant frequency in Salmonella typhi...

  15. Additive effects of acetic acid upon hydrothermal reaction of amylopectin

    It is well known that over 0.8 kg kg−1 of starch is consisted of amylopectin (AP). In this study, production of glucose for raw material of ethanol by hydrothermal reaction of AP as one of the model compound of food is discussed. Further, additive effects of acetic acid upon hydrothermal reactions of AP are also investigated. During hydrothermal reaction of AP, production of glucose occurred above 453 K, and the glucose yield increased to 0.48 kg kg−1 at 473 K. Upon hydrothermal reaction of AP at 473 K, prolongation of the holding time was not effective for the increase of the glucose yield. Upon hydrothermal reaction of AP at 473 K for 0 s, the glucose yield increased significantly by addition between 0.26 mol L−1 and 0.52 mol L−1 of acetic acid. However, the glucose yield decreased and the yield of the other constituents increased with the increases of concentration of acetic acid from 0.65 mol L−1 to 3.33 mol L−1. It was considered that hydrolysis of AP to yield glucose was enhanced due to the increase of the amount of proton derived from acetic acid during hydrothermal reaction with 0.52 mol L−1 of acetic acid. -- Highlights: ► Glucose production by hydrothermal reaction of amylopectin (AP) at 473 K. ► Glucose yield increased to 0.48 kg kg-1 at 473 K. ► Prolongation of holding time was not effective for glucose yield. ► Glucose yield increased significantly by acetic acid (0.26–0.52 mol L-1) addition. ► Hydrolysis of AP to glucose was enhanced due to increase of proton from acetic acid.

  16. Effect of the G375C and G346E achondroplasia mutations on FGFR3 activation.

    Lijuan He

    Full Text Available Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia mutants in these experiments, a finding which supports a direct link between the severity of dwarfism phenotypes and the level and mechanism of FGFR3 over-activation. The mutations do not increase the cross-linking propensity of FGFR3, contrary to previous expectations that the achondroplasia mutations stabilize the FGFR3 dimers. Instead, the phosphorylation efficiency within un-liganded FGFR3 dimers is increased, and this increase is likely the underlying cause for pathogenesis in achondroplasia. We further investigate the G346E mutation, which has been reported to cause achondroplasia in one case. We find that this mutation does not increase FGFR3 phosphorylation and decreases FGFR3 cross-linking propensity, a finding which raises questions whether this mutation is indeed a genetic cause for human dwarfism.

  17. Priming effects in Haplic Luvisol after different substrate additions

    Bogomolova, I.; Blagodatskaya, E.; Blagodatsky, S.; Kuzyakov, Y.

    2009-04-01

    Although soils contain considerable amounts of soil organic carbon (SOC), most of it is not easily available for microorganisms. Addition of various substrates to soil (for example, plant residues, root exudates) may affect SOC mineralization. The addition of mineral nutrients, especially N, may also affect C turnover and so change the mineralization rate of SOC. Such short-term changes in mineralization of organic substance of soil were termed as "priming-effects" (Bingemann et al., 1953). Priming effect leads to additional mineralization of SOC (van Elsas and van Overbeek, 1993). It has been shown that not only plant residues induce priming effects (Sauerbeck, 1966; Stemmer et al., 1999; Bell et al., 2003), but also easily available substrates such as sugars or amino acids, which are present in soil solutions and root exudates (Vasconcellos, 1994; Shen and Bartha, 1997; Hamer and Marschner, 2002). Since easily available substrates may not only accelerate SOC mineralization, but also may retard it, Kuzyakov et al. (2000) differentiated between positive and negative priming effects. It is not clear until now, how long priming effects persists in soil after substrate addition, and if they are induced every time when a substrate becomes available in soil. So, the aim of this study was to evaluate effects of glucose and plant residues on SOM decomposition, and influence of glucose on plant residues decomposition in soil. The experimental layout was designed as two factor experiment: 1) plant residues and 2) available substrate amendment. Maize shoot residues (50 mg added to 5 g soil) were 14C labeled (9•104 DPM per 5 g soil). Soil without of any plant residues served as a control for this treatment. Two levels of D (+) glucose as easily available substrates were added after three months of pre-incubation of soil samples with maize residues: 0.009 mg glucose C g-1 soil and 0.225 mg glucose C g-1 soil. The glucose was uniformly labelled with 14C (2.37•104 DPM per 5

  18. Parental source effect of inherited mutations in the dystrophin gene of mice and men

    Kress, W.; Grimm, T.; Mueller, C.R. [Institute of Human Genetics, Wuerburg (Germany); Bittner, R. [Institute of Anatomy, Wein (Australia)

    1994-09-01

    Skewed X-inactivation has been suspected the genetic cause for some manifesting female carriers of BMD and DMD. To test whether a parental source effect on the protein expression of the dystrophin gene exists, we have set up backcrosses of mdx mice to wild type strains, enabling us to study the effect of the well-defined origin of the mutation on the dystrophin expression. In skeletal muscle sections the immunohistological staining patterns of dystrophin antibodies were showing a significant difference in the proportion of dystrophin positive versus negative fibers, suggesting a lower expression of paternally inherited mdx mutations. These data are in concordance with the pyruvate kinase (PK) levels in the serum: PK levels were much higher when the mutation was of maternal origin as compared to PK levels in paternally derived mutations. In order to test this {open_quotes}paternal source effect{close_quotes} in humans, we checked obligatory carriers of Becker muscular dystrophy (BMD) for the origin of their mutations. Creatin kinase (CK) levels in 21 carriers with maternally derived mutations were compared to CK values from 8 heterozygotes with mutations of paternal origin: CK (mat) = 140.3 IU/1 versus CK (pat) = 48.6 IU/I. The difference is statistically significant at the 5% level. These observations suggest either a differential X-inactivation or an imprinting of the dystrophin gene in mice and men.

  19. MITF mutations associated with pigment deficiency syndromes and melanoma have different effects on protein function.

    Grill, Christine; Bergsteinsdóttir, Kristín; Ogmundsdóttir, Margrét H; Pogenberg, Vivian; Schepsky, Alexander; Wilmanns, Matthias; Pingault, Veronique; Steingrímsson, Eiríkur

    2013-11-01

    The basic-helix-loop-helix-leucine zipper (bHLHZip) protein MITF (microphthalmia-associated transcription factor) is a master regulator of melanocyte development. Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS). Additionally, both somatic and germline mutations have been found in MITF in melanoma patients. Here, we characterize the DNA-binding and transcription activation properties of 24 MITF mutations found in WS2A, TS and melanoma patients. We show that most of the WS2A and TS mutations fail to bind DNA and activate expression from melanocyte-specific promoters. Some of the mutations, especially R203K and S298P, exhibit normal activity and may represent neutral variants. Mutations found in melanomas showed normal DNA-binding and minor variations in transcription activation properties; some showed increased potential to form colonies. Our results provide molecular insights into how mutations in a single gene can lead to such different phenotypes. PMID:23787126

  20. The influence of oil additives on the effectiveness of herbicides

    Andrzej Chwedoruk

    2013-12-01

    Full Text Available The possibility to decrease herbicide doses without reducing their weed controlling effectiveness was investigated in two microplots and one field experiment. The following herbicides were used: atrazine, mixture of atrazine with terbutrine, MCPA + MCPP, MCPA + dikamba, desmedipham and phenmedipham (Betanal 31, 32 or 37. They were combined with one or several of the following adjuvants: parafinic oil, refuse product of rape oil rafination, oil mixture from the Institute of Organic Chemistry Industry (IPO-Warsaw, surfactant Rokafenol N-1O, mineral oil Nr 8 (Aviol. It was shown that the doses of herbicides could be lowered by 30-50% without loosing their phytotoxic effect on weeds due to addition of adjuvants. The mineral oil 8 was very active in a mixture with Betanal 37 and was completly non toxic toward sugar beets. The oil mixture from IPO and Rokafenol N-10 were very active in mixtures with atrazine or atraizine with terbutrine.

  1. Differential effects of CSF-1R D802V and KIT D816V homologous mutations on receptor tertiary structure and allosteric communication.

    Priscila Da Silva Figueiredo Celestino Gomes

    Full Text Available The colony stimulating factor-1 receptor (CSF-1R and the stem cell factor receptor KIT, type III receptor tyrosine kinases (RTKs, are important mediators of signal transduction. The normal functions of these receptors can be compromised by gain-of-function mutations associated with different physiopatological impacts. Whereas KIT D816V/H mutation is a well-characterized oncogenic event and principal cause of systemic mastocytosis, the homologous CSF-1R D802V has not been identified in human cancers. The KIT D816V oncogenic mutation triggers resistance to the RTK inhibitor Imatinib used as first line treatment against chronic myeloid leukemia and gastrointestinal tumors. CSF-1R is also sensitive to Imatinib and this sensitivity is altered by mutation D802V. Previous in silico characterization of the D816V mutation in KIT evidenced that the mutation caused a structure reorganization of the juxtamembrane region (JMR and facilitated its departure from the kinase domain (KD. In this study, we showed that the equivalent CSF-1R D802V mutation does not promote such structural effects on the JMR despite of a reduction on some key H-bonds interactions controlling the JMR binding to the KD. In addition, this mutation disrupts the allosteric communication between two essential regulatory fragments of the receptors, the JMR and the A-loop. Nevertheless, the mutation-induced shift towards an active conformation observed in KIT D816V is not observed in CSF-1R D802V. The distinct impact of equivalent mutation in two homologous RTKs could be associated with the sequence difference between both receptors in the native form, particularly in the JMR region. A local mutation-induced perturbation on the A-loop structure observed in both receptors indicates the stabilization of an inactive non-inhibited form, which Imatinib cannot bind.

  2. Eddy damping effect of additional conductors in superconducting levitation systems

    Jiang, Zhao-Fei; Gou, Xiao-Fan

    2015-12-01

    Passive superconducting levitation systems consisting of a high temperature superconductor (HTSC) and a permanent magnet (PM) have demonstrated several fascinating applications such as the maglev system, flywheel energy storage. Generally, for the HTSC-PM levitation system, the HTSC with higher critical current density Jc can obtain larger magnetic force to make the PM levitate over the HTSC (or suspended below the HTSC), however, the process of the vibration of the levitated PM, provides very limited inherent damping (essentially hysteresis). To improve the dynamic stability of the levitated PM, eddy damping of additional conductors can be considered as the most simple and effective approach. In this article, for the HTSC-PM levitation system with an additional copper damper attached to the HTSC, we numerically and comprehensively investigated the damping coefficient c, damping ratio, Joule heating of the copper damper, and the vibration frequency of the PM as well. Furthermore, we comparatively studied four different arrangements of the copper damper, on the comprehensive analyzed the damping effect, efficiency (defined by c/VCu, in which VCu is the volume of the damper) and Joule heating, and finally presented the most advisable arrangement.

  3. Probing the "additive effect" in the proline and proline hydroxamic acid catalyzed asymmetric addition of nitroalkanes to cyclic enones.

    Hanessian, Stephen; Govindan, Subramaniyan; Warrier, Jayakumar S

    2005-11-01

    The effect of chirality and steric bulk of 2,5-disubstituted piperazines as additives in the conjugate addition of 2-nitropropane to cyclohexenone, catalyzed by l-proline, was investigated. Neither chirality nor steric bulk affects the enantioselectivity of addition, which gives 86-93% ee in the presence of achiral and chiral nonracemic 2,5-disubstituted piperazines. Proline hydroxamic acid is shown for the first time to be an effective organocatalyst in the same Michael reaction. PMID:16189834

  4. Thermal processing of EVA encapsulants and effects of formulation additives

    Pern, F.J.; Glick, S.H. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    The authors investigated the in-situ processing temperatures and effects of various formulation additives on the formation of ultraviolet (UV) excitable chromophores, in the thermal lamination and curing of ethylene-vinyl acetate (EVA) encapsulants. A programmable, microprocessor-controlled, double-bag vacuum laminator was used to study two commercial as formulated EVA films, A9918P and 15295P, and solution-cast films of Elvaxrm (EVX) impregnated with various curing agents and antioxidants. The results show that the actual measured temperatures of EVA lagged significantly behind the programmed profiles for the heating elements and were affected by the total thermal mass loaded inside the laminator chamber. The antioxidant Naugard P{trademark}, used in the two commercial EVA formulations, greatly enhances the formation of UV-excitable, short chromophores upon curing, whereas other tested antioxidants show little effect. A new curing agent chosen specifically for the EVA formulation modification produces little or no effect on chromophore formation, no bubbling problems in the glass/EVX/glass laminates, and a gel content of {approximately}80% when cured at programmed 155{degrees}C for 4 min. Also demonstrated is the greater discoloring effect with higher concentrations of curing-generated chromophores.

  5. Effect of the G375C and G346E Achondroplasia Mutations on FGFR3 Activation

    He, Lijuan; Serrano, Christopher; Niphadkar, Nitish; Shobnam, Nadia; Hristova, Kalina

    2012-01-01

    Two mutations in FGFR3, G380R and G375C are known to cause achondroplasia, the most common form of human dwarfism. The G380R mutation accounts for 98% of the achondroplasia cases, and thus has been studied extensively. Here we study the effect of the G375C mutation on the phosphorylation and the cross-linking propensity of full-length FGFR3 in HEK 293 cells, and we compare the results to previously published results for the G380R mutant. We observe identical behavior of the two achondroplasia...

  6. Mortar cohesión. The effect of additives

    Castro, J. H.

    1975-12-01

    Full Text Available This study was concerned with the hydration of clinker compounds in the presence of different additives; it appeared that accelerating additives, such as calcium chloride and silicic acid, produce longer fibers of tobermorite, whereas inhibitors, such as sugar, produce shorter fibers of tobermorite. This same effect was observed in the hydration of anhydrite, in which large crystals of gypsum were produced in the presence of sodium sulphate. So the cohesion in mortars of cement and anhydrite is explained in terms of the role of fibers.Se estudia la hidratación del clínker en presencia de diferentes aditivos encontrándose que los aceleradores, como el cloruro cálcico y el ácido salicílico, producen tobermorita de fibra larga y los inhibidores, como el azúcar, tobermorita de fibra corta. Este mismo efecto se encuentra en la anhidrita, produciéndose cristales de yeso largo, en presencia del sulfato de sodio, y cristales cortos en ausencia del catalizador. La cohesión de un mortero depende luego del largo de sus fibras. Así la cohesión de los morteros de cemento y anhidrita se explican en función del rol de la fibra.

  7. Effect of chemical additives on flow characteristics of coal slurries

    E.S. Mosa; A.-H. M. Saleh; T.A. Taha; A.M. El-Molla [Al-Azhar University, Cairo (Egypt). Mining & Petroleum Engineering Department

    2008-07-01

    In the present paper, the effect of chemical additives or reagents on rheological characteristics of coal water slurry (CWS) was investigated. The power-law model was applied to determine the non-Newtonian properties of coal slurries. Three types of dispersants namely, sulphonic acid, sodium tripolyphosphate and sodium carbonate were studied and tested at different concentrations ranging from 0.5 to 1.5% by weight from total solids. Sodium salt of carboxymethyl cellulose (Na-CMC) and xanthan gum were tested as stabilizers at concentrations in the range of 0.05 to 0.25% by weight from total solids. It was found that apparent viscosity and flow properties of CWS are sensitive to the use of chemical additives (dispersants and stabilizers). Among studied dispersing agents, sulphonic acid recorded the best performance in modification and reducing CWS viscosity. The best dosage of all tested dispersants was found to be 0.75% by wt of solids. With regard to studied stabilizers, Na-CMC recorded better performance than xanthan gum. The best dosage of investigated stabilizers was found to be as 0.1 % by wt. from total solids. 13 refs., 9 figs., 1 tab.

  8. Effect of different additives on the properties of lithium alanate

    2008-01-01

    LiAlH4 doped with Ni and Ce(SO4)2 additives and the effect of doping on temperature and hydrogen release were studied by pressure-content-temperature (PCT) experiment and X-ray diffraction (XRD) analysis.It is indicated that doping with Ni induces a significant decrease in temperature in the first step and LiAlH4 doped with 1mol% Ni presents the most absorption of hydrogen.Doping with Ce(SO4)2 also causes a marked decrease,while the amount of hydrogen release changes only slightly.The results from X-ray diffraction analysis show that doping does not cause any structural change; Ni and Ce-containing phases are not observed at room temperature or even at 250℃.

  9. Dolomite addition effects on the thermal expansion of ceramic tiles

    The thermal expansion of ceramic tiles is of greater importance in engineering applications because the ceramics are relatively brittle and cannot tolerate large internal strain imposed by thermal expansion. When ceramic bodies are produced for glazed ties the compatibility of this property of the components should be considered to avoid damage in the final products. Carbonates are an important constituent of ceramic wall-title bodies and its presence in formulations and the reactions that occur between them and other components modify body properties. The influence in expansivity by additions of calcium magnesium carbonate in a composition of wall tile bodies has been investigated. The relative content of mineralogical components was determined by X-ray diffraction and thermal expansion by dilatometric measurements. The results was indicated that with the effect of calcium-magnesium phases and porosity on thermal expansion of wall tile bodies. (author)

  10. Understanding the distribution of fitness effects of mutations by a biophysical-organismal approach

    Bershtein, Shimon

    2011-03-01

    The distribution of fitness effects of mutations is central to many questions in evolutionary biology. However, it remains poorly understood, primarily due to the fact that a fundamental connection that exists between the fitness of organisms and molecular properties of proteins encoded by their genomes is largely overlooked by traditional research approaches. Past efforts to breach this gap followed the ``evolution first'' paradigm, whereby populations were subjected to selection under certain conditions, and mutations which emerged in adapted populations were analyzed using genomic approaches. The results obtained in the framework of this approach, while often useful, are not easily interpretable because mutations get fixed due to a convolution of multiple causes. We have undertaken a conceptually opposite strategy: Mutations with known biophysical and biochemical effects on E. coli's essential proteins (based on computational analysis and in vitro measurements) were introduced into the organism's chromosome and the resulted fitness effects were monitored. Studying the distribution of fitness effects of such fully controlled replacements revealed a very complex fitness landscape, where impact of the microscopic properties of the mutated proteins (folding, stability, and function) is modulated on a macroscopic, whole genome level. Furthermore, the magnitude of the cellular response to the introduced mutations seems to depend on the thermodynamic status of the mutant.

  11. Mutation induction for domestication of Cuphea: Effects of gamma rays

    Full text: Oils of the so called lauric acid group plants are very interesting for industries commercially because of their relatively high content of saturated medium chain triglycerides (MCT), in particular lauric acid (C12:0). Steep melting point curves and low melting points make these oils particularly suitable as fats for synthetic creams, hard butters and similar products; sodium soaps of MCT's are hard, stable to oxidation, and free lathering. Palm kernel oil from Elaeis guineensis Jacq. and coconut oil from Cocos nucifera L. are the two most important commercial source of MCT's for the chemical industry. However, because of large variation in production and price, industries became interested in a continuous supply of MCT's from other species. The genus Cuphea (Lythraceae) contains a large number of herbaceous annuals adapted to temperate climate whose seed oil contains high levels of MCT's. Unfortunately, a common characteristic of the wild species is seed shattering during ripening. Seed shattering could be due to floral zygomorphy which causes the placenta to rupture the ovary wall during development, exposing the seeds; exposed seeds dry and are quickly shed. Seed dormancy is another major deterrent to the agronomic use of Cuphea. It appears to result from hard seed coats as well as from physiological factors and can be effectively broken only by prolonged after-ripening (up to a year). Natural genetic variation in Cuphea does not appear to be suitable for the development of non-shattering types. Therefore, the potential of broadening genetic variation through mutagenesis (using EMS) was investigated, first in the autogamous species C. aperta and in the allogamous species C. lanceolata, and C. procumbens. Mutants having somewhat improved seed retention were selected from all three species, however, expressivity was complete only in C. aperta. According to HIRSINGER and ROEBBELEN, the autogamous species C. tolucana Peyr. (n=12) and C. wrightii A. Gray

  12. Effect of adsorbent addition on floc formation and clarification.

    Younker, Jessica M; Walsh, Margaret E

    2016-07-01

    Adding adsorbent into the coagulation process is an emerging treatment solution for targeting hard-to-remove dissolved organic compounds from both drinking water and industrial wastewater. The impact of adding powdered activated carbon (PAC) or organoclay (OC) adsorbents with ferric chloride (FeCl3) coagulant was investigated in terms of potential changes to the coagulated flocs formed with respect to size, structure, and breakage and regrowth properties. The ability of dissolved air flotation (DAF) and sedimentation (SED) clarification processes to remove hybrid adsorbent-coagulant flocs was also evaluated through clarified water quality analysis of samples collected in bench-scale jar test experiments. The jar tests were conducted using both a synthetic fresh water and oily wastewater test water spiked with dissolved aromatic compounds phenol and naphthalene. Results of the study demonstrated that addition of adsorbent reduced the median coagulated floc size by up to 50% but did not affect floc strength or regrowth potential after application of high shear. Experimental results in fresh water demonstrated that sedimentation was more effective than DAF for clarification of both FeCl3-PAC and FeCl3-OC floc aggregates. However, experimental tests performed on the synthetic oily wastewater showed that coagulant-adsorbent floc aggregates were effectively removed with both DAF and sedimentation treatment, with lower residual turbidity achieved in clarified water samples than with coagulation treatment alone. Addition of OC or PAC into the coagulation process resulted in removals of over half, or nearly all of the dissolved aromatics, respectively. PMID:27064206

  13. Synergistic and compensatory effects of two point mutations conferring target-site resistance to fipronil in the insect GABA receptor RDL.

    Zhang, Yixi; Meng, Xiangkun; Yang, Yuanxue; Li, Hong; Wang, Xin; Yang, Baojun; Zhang, Jianhua; Li, Chunrui; Millar, Neil S; Liu, Zewen

    2016-01-01

    Insecticide resistance can arise from a variety of mechanisms, including changes to the target site, but is often associated with substantial fitness costs to insects. Here we describe two resistance-associated target-site mutations that have synergistic and compensatory effects that combine to produce high and persistent levels of resistance to fipronil, an insecticide targeting on γ-aminobytyric acid (GABA) receptors. In Nilaparvata lugens, a major pest of rice crops in many parts of Asia, we have identified a single point mutation (A302S) in the GABA receptor RDL that has been identified previously in other species and which confers low levels of resistance to fipronil (23-fold) in N. lugans. In addition, we have identified a second resistance-associated RDL mutation (R300Q) that, in combination with A302S, is associated with much higher levels of resistance (237-fold). The R300Q mutation has not been detected in the absence of A302S in either laboratory-selected or field populations, presumably due to the high fitness cost associated with this mutation. Significantly, it appears that the A302S mutation is able to compensate for deleterious effects of R300Q mutation on fitness cost. These findings identify a novel resistance mechanism and may have important implications for the spread of insecticide resistance. PMID:27557781

  14. Effect of the uvrD mutation on excision repair.

    Kuemmerle, N B; Masker, W E

    1980-01-01

    A pair of related Escherichia coli K-12 strains, one of which contains the uvrD101 mutation, were constructed and compared for ability to perform various steps in the excision repair of deoxyribonucleic acid damage inflicted by ultraviolet radiation. The results of this study indicated: (i) ultraviolet sensitivity in the uvrD101 mutant was greater than that of wild type but less than that measured in an incision-deficient uvrA mutant; (ii) host cell reactivation paralleled the survival data; ...

  15. Mutational Effects on the Folding Dynamics of a Minimized Hairpin‡

    Scian, Michele; Shu, Irene; Olsen, Katherine A.; Hassam, Khalil; Andersen, Niels H.

    2013-01-01

    The fold stabilities and folding dynamics of a series of mutants of a model hairpin, KTW-NPATGK-WTE (HP7), are reported. The parent system and the corresponding DPATGK loop species display sub-μs folding time constants. The mutational studies revealed that ultrafast folding requires both some pre-structuring of the loop and a favorable interaction between the chain termini at the transition state. In the case of YY-DPETGT-WY, another sub-μs folding species [Davis, C. M.; Xiao, S.; Raleigh, D....

  16. AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations

    Yuan, Youzhong; Zhou, Liming; Miyamoto, Toshihiro; Iwasaki, Hiromi; Harakawa, Nari; Hetherington, Christopher J.; Burel, Sebastien A.; Lagasse, Eric; Weissman, Irving L.; Akashi, Koichi; Zhang, Dong-Er

    2001-01-01

    The t(8;21) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). The translocation, which involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8, generates an AML1-ETO fusion transcription factor. To examine the effect of the AML1-ETO fusion protein on leukemogenesis, we made transgenic mice in which expression of AML1-ETO is under the control of the human MRP8 promoter (hMRP8-AML1-ETO). AML1-ETO is specifically expressed in mye...

  17. Effect of the uvrD mutation on excision repair

    A pair of related Escherichia coli K-12 strains, one of which contains the uvrD101 mutation, were constructed and compared for ability to perform various steps in the excision repair of deoxyribonucleic acid damage inflicted by ultraviolet radiation. The results of this study indicated: (i) ultraviolet sensitivity in the uvrD101 mutant was greater than that of wild type but less than that measured in an incision-deficient uvrA mutant; (ii) host cell reactivation paralleled the survival data; (iii) postirradiation deoxyribonucleic acid degradation was virtually identical in the two strains; (iv) incision, presumably at the sites of pyrimidine dimers, proceeded normally in the uvrD101 strain; (v) excision of pyrimidine dimers was markedly reduced in both rate and extent in the uvrD101 mutant; (vi) the amount of repair resynthesis was the same in both strains, and there was no evidence of abnormally long repair patches in the uvrD mutant; and (vii) rejoining of incision breaks was slow and incomplete in the uvrD strain. These data suggest that the ultraviolet sensitivity conferred by the uvrD mutation arises from inefficient removal of pyrimidine dimers or from failure to close incision breaks. The data are compatible with the notion that the uvrD+ gene product affects the conformation of incised deoxyribonucleic acid molecules

  18. Effect of the uvrD mutation on excision repair

    Kuemmerle, N.B.; Masker, W.E.

    1980-05-01

    A pair of related Escherichia coli K-12 strains, one of which contains the uvrD101 mutation, were constructed and compared for ability to perform various steps in the excision repair of deoxyribonucleic acid damage inflicted by ultraviolet radiation. The results of this study indicated: (i) ultraviolet sensitivity in the uvrD101 mutant was greater than that of wild type but less than that measured in an incision-deficient uvrA mutant; (ii) host cell reactivation paralleled the survival data; (iii) postirradiation deoxyribonucleic acid degradation was virtually identical in the two strains; (iv) incision, presumably at the sites of pyrimidine dimers, proceeded normally in the uvrD101 strain; (v) excision of pyrimidine dimers was markedly reduced in both rate and extent in the uvrD101 mutant; (vi) the amount of repair resynthesis was the same in both strains, and there was no evidence of abnormally long repair patches in the uvrD mutant; and (vii) rejoining of incision breaks was slow and incomplete in the uvrD strain. These data suggest that the ultraviolet sensitivity conferred by the uvrD mutation arises from inefficient removal of pyrimidine dimers or from failure to close incision breaks. The data are compatible with the notion that the uvrD+ gene product affects the conformation of incised deoxyribonucleic acid molecules.

  19. Radical effects on mutation spectra in lambda phage

    Mutations in the lambda repressor gene cI (710 bp) were induced by 60Co-gamma radiation in dissolved lambda phage DNA. After in vitro DNA packaging to lambda phage particles (pack phage) and phenotypic expression of the mutants, DNA was sequenced directly. Two-thirds of mutations were located in the amino terminus region of the gene without any signs of hotspots. Changes consisted of (+1) insertions (25%) and base substitutions (75%). Transitions were exclusively G/C to A/T. Transversions were mostly G/C to C/G and few G/C to T/A. A/T to T/A transversions, A/T to G/C transitions, deletions and gross rearrangements were not found. In most of the base substitutions a pre-existing base pair had been replaced by an A/T pair; this might come from 'non- instructional sites' like abasic sites. Several mechanisms for base substitutions are considered. (author)

  20. Age and sex effects on human mutation rates. An old problem with new complexities

    Base substitution mutations are far more common in human males than in females, and the frequency increases with paternal age. Both can be accounted for by the greater number of pre-meiotic cell divisions in males, especially old ones. In contrast, small deletions do not show any important age effect and occur with approximately equal frequency in the two sexes. Mutations in most genes include both types, and the sex and paternal age effect depends on the proportion of the two types. A few traits, of which Apert Syndrome is best understood, are mutation hot spots with all the mutations occurring in one or two codons, usually at one nucleotide. They occur with very high frequency almost exclusively in males and the frequency increases rapidly with paternal age. It has been suggested that the mutant cells have a selective advantage in the male germ-line prior to meiosis. Evidence for this surprising, but important, hypothesis is discussed. A possible mechanism is the conversion of asymmetrical stem-cell divisions into symmetric ones. Some traits with complex etiology show a slight paternal age effect. There is also a short discussion of the high deleterious mutation rate and the role of sexual reproduction in reducing the consequent mutation load. (author)

  1. Differential effects of human L1CAM mutations on complementing guidance and synaptic defects in Drosophila melanogaster.

    Sirisha Kudumala

    Full Text Available A large number of different pathological L1CAM mutations have been identified that result in a broad spectrum of neurological and non-neurological phenotypes. While many of these mutations have been characterized for their effects on homophilic and heterophilic interactions, as well as expression levels in vitro, there are only few studies on their biological consequences in vivo. The single L1-type CAM gene in Drosophila, neuroglian (nrg, has distinct functions during axon guidance and synapse formation and the phenotypes of nrg mutants can be rescued by the expression of human L1CAM. We previously showed that the highly conserved intracellular FIGQY Ankyrin-binding motif is required for L1CAM-mediated synapse formation, but not for neurite outgrowth or axon guidance of the Drosophila giant fiber (GF neuron. Here, we use the GF as a model neuron to characterize the pathogenic L120V, Y1070C, C264Y, H210Q, E309K and R184Q extracellular L1CAM missense mutations and a L1CAM protein with a disrupted ezrin-moesin-radixin (ERM binding site to investigate the signaling requirements for neuronal development. We report that different L1CAM mutations have distinct effects on axon guidance and synapse formation. Furthermore, L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila. In addition, the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation. Thus, the pathological phenotypes observed in humans are likely to be caused by the disruption of signaling required for both, guidance and synaptogenesis.

  2. ISOLATION OF ENDOPHYTIC ACTINOMYCETES FROM MEDICINAL PLANTS AND ITS MUTATIONAL EFFECT IN BIOCONTROL ACTIVITY

    Hema Shenpagam N.*, D. Kanchana Devi ** and Sinduja G.

    2012-11-01

    Full Text Available In the present study, the endophytic actinomycetes were collected from three medicinal plants Azadiracta indica, Ocimum sanctum and Phyllanthus amarus. Endophytic actinomycetes were isolated using different media like Starch casein agar, Starch casein nitrate agar, Actinomycetes isolation agar and Soyabean agar, while it showed more colonies in Starch casein agar. The endophytic actinomycetes were stained and biochemical tests were performed. Antimicrobial compound was purified from the filtrate by ethanol extraction method. Antagonistic activities of endophytic actinomycetes isolates were tested against bacterial pathogens (Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa and the fungi Rhizopus. For the selected isolates antibiotic resistance was checked using various antibiotic discs like Amoxycillin, Penicillin, Rifampicin and Ampicillin. The strains which showed efficient antibacterial activity were selected to study the effect of mutation by physical and chemical method. In this study, UV mutated endophytic actinomycetes increase antibiotic production than non-mutated endophytic Actinomycetes, whereas in chemical mutation it does not increase the antibiotic production.

  3. Human immunodeficiency virus type 1 integrase: effect on viral replication of mutations at highly conserved residues.

    Cannon, P M; Wilson, W; Byles, E; Kingsman, S M; Kingsman, A J

    1994-08-01

    Sequence comparisons of the integrase (IN) proteins from different retroviruses have identified several highly conserved residues. We have introduced mutations at 16 of these sites into the integrase gene of human immunodeficiency virus type 1 and analyzed the phenotypes of the resulting viruses. The viruses were all normal for p24 content and reverse transcriptase activity. In addition, all of the mutants could infect T-cell lines and undergo reverse transcription, as assessed by PCR analysis. Most of the mutant viruses also had normal Western blot (immunoblot) profiles, although three of the mutations resulted in reduced signals for IN relative to the wild type on the immunoblots and mutation of residue W235 completely abolished recognition of the protein by pooled sera from human immunodeficiency virus type 1-positive patients. Mutations that have previously been shown to abolish activity in in vitro studies produced noninfectious viruses. The substitution of W235 was notable in producing a noninfectious virus, despite previous reports of this residue being nonessential for IN activity in vitro (A.D. Leavitt, L. Shiue, and H.E. Varmus, J. Biol. Chem. 268:2113-2119, 1993). In addition, we have identified four highly conserved residues that can be mutated without any affect on viral replication in T-cell lines. PMID:8035478

  4. Effect of solid additives on pyrolysis behaviour of Makerwal coal

    Ahmad, T.; Nisar, J.; Awan, I.A.; Ahmad, I. [University of Peshawar, Peshawar (Pakistan)

    2009-02-15

    The method used in this study provides a quantitative description of the relationship between the chemical structure of coal and the physical and chemical properties of the resultant pyrolysis products (gas, tar, liquid, and char). The purpose of this study is to investigate the effect of inorganic solid additives (Na{sub 2}CO{sub 3}, K{sub 2}CO{sub 3}, CaCO{sub 3}, MgCO{sub 3}, Fe{sub 2}O{sub 3} and CaSO{sub 4},), on flash pyrolysis of high volatile bituminous coal samples from Makerwal coalfields by using open tubular type pyrolyzer coupled with gas chromatography. Two different coal samples were selected for this purpose. The sampling apparatus consisted of two traps in order to separate the products into fractions on the basis of their volatility such as tar, liquid, and gaseous fractions. The product yields released from each sample in their raw, de-mineralized and salt treated form were monitored. The gaseous fractions were directly introduced to GC for identification. The gases were C{sub 1}-C{sub 5}, hydrocarbons. The pyrolysis was carried out at 690{sup o}C. Some evaluations and comparisons, from the results obtained, are presented.

  5. Effects of Several Purple Potato Additions on Bread Quality

    Bădărău Carmen Liliana

    2016-04-01

    Full Text Available Potato cultivars with purple flesh represent an efficient and natural source of antioxidants, this vegetable having high content in polyphenols (especially anthocyanin pigments. The research goal of this work was to evaluate the anthocyanin and polyphenols content of several Romanian potato varieties (Albastru-Violet de Gălănești and Christian and the effects of these potatoes (add to dough in different proportions on several bread quality indicators. The bread quality depends on physical and chemical properties and on several signs like: flavor and taste, external appearance, crumb porosity and texture, bread’s volume. In this research experiment, beside the total polyphenols and anthocyanin content, the analysis performed on bread (prepared using different potatoes addition 5%, 15% and 30% were sensorial and physic chemical analysis (product volume, crumb porosity, height/diameter ratio, moist and acidity. Experimental results indicated that 15% purple potato cultivar added on the dough was the most indicate proportion to be used in bread processing.

  6. I-129 Moessbauer effect of polyacetylene with iodine addition

    The I-129 Moessbauer effect of polyacetylene with iodine addition was measured. The gamma-ray used was emitted from the first excited state of I-129, which is a decay product of Te-129. The Te-129 was produced by neutron irradiation of ZnTe128. The state of iodine in the #betta#-carotene-iodine complex was studied by the Moessbauer method. An obtained Moessbauer spectrum showed the presence of two kinds of iodine. As a result, it can be said that the #betta#-carrotene iodine complex is present in an ionic state of (C40H56)+ I3-. The states of iodine doped into cis- and trans-polyacetylene were also measured by the Moessbauer method. The test samples were made by dipping the polyacetylene into carbon tetrachloride solution of iodine. The obtained Moessbauer spectra were more complex than that of the #betta#-carotene iodine complex. Eight components of iodine were assumed for the analysis of spectra. It is suggested that the iodine states in polyacetylene are I3- and I5-. The I5- ions are linear. The number of I5- increases with increase of the iodine concentration in cis and trans polyacetylene. (Kato, T.)

  7. Mutation accumulation and fitness effects in hybridogenetic populations: a comparison to sexual and asexual systems

    Bagheri Homayoun C

    2007-05-01

    Full Text Available Abstract Background Female only unisexual vertebrates that reproduce by hybridogenesis show an unusual genetic composition. They are of hybrid origin but show no recombination between the genomes of their parental species. Instead, the paternal genome is discarded from the germline prior to meiosis, and gametes (eggs only contain solely unrecombined maternal genomes. Hence hybridogens only transmit maternally inherited mutations. Hybridity is restored each generation by backcrossing with males of the sexual parental species whose genome was eliminated. In contrast, recombining sexual species propagate an intermixed pool of mutations derived from the maternal and paternal parts of the genome. If mutation rates are lower in female gametes than males, it raises the possibility for lower mutation accumulation in a hybridogenetic population, and consequently, higher population fitness than its sexual counterpart. Results We show through Monte-Carlo simulations that at higher male to female mutation ratios, and sufficiently large population sizes, hybridogenetic populations can carry a lower mutation load than sexual species. This effect is more pronounced with synergistic forms of epistasis. Mutations accumulate faster on the sexual part of the genome, and with the purifying effects of epistasis, it makes it more difficult for mutations to be transmitted on the clonal part of the genome. In smaller populations, the same mechanism reduces the speed of Muller's Ratchet and the number of fixed mutations compared to similar asexual species. Conclusion Since mutation accumulation can be less pronounced in hybridogenetic populations, the question arises why hybridogenetic organisms are so scarce compared to sexual species. In considering this, it is likely that comparison of population fitnesses is not sufficient. Despite competition with the sexual parental species, hybrid populations are dependent on the maintenance of – and contact with – their

  8. Electrodeposition of Asphaltenes. 2. Effect of Resins and Additives

    Khvostichenko, Daria S; Andersen, Simon Ivar

    2010-01-01

    Electrodeposition of asphaltenes from oil/heptane, asphaltene/heptane, and asphaltene/heptane/additive mixtures has been investigated. Toluene, native petroleum resins, and a synthetic asphaltene dispersant, p-nonylphenol, were used as additives. The addition of these components led to partial...... preparation of the mixture and the toluene content. Introduction of petroleum resins into asphaltene/heptane mixtures resulted in neutralization of the asphaltene particle charge. The addition of p-nonylphenol to asphaltene suspensions in heptane did not alter the charge of asphaltene particles. Current...

  9. Effect of Additional Structure on Effective Stack Height of Gas Dispersion in Atmosphere

    Takenobu Michioka

    2016-03-01

    Full Text Available Wind-tunnel experiments were conducted to evaluate the effect of additional structure (building, sea wall and banking on the effective stack height, which is usually used in safety analyses of nuclear power facilities in Japan. The effective stack heights were estimated with and without the additional structure in addition to the reactor building while varying several conditions such as the source height, the height of additional structure and the distance between the source position and the additional structure. When the source height is equivalent to the reactor building height, the additional structure enhances both the vertical and horizontal gas dispersion widths and decreases the ground gas concentration, and it means that the additional structure does not decrease the effective stack height. When the source height is larger than the reactor height, the additional structures might affect the effective stack height. As the distance between the source and the additional structure decreases, or as the height of the additional structure increases, the structure has a larger effect on the effective stack height.

  10. Two heterozygous Cav3.2 channel mutations in a pediatric chronic pain patient: recording condition-dependent biophysical effects.

    Souza, Ivana A; Gandini, Maria A; Wan, Miranda M; Zamponi, Gerald W

    2016-04-01

    We report expression system-dependent effects of heterozygous mutations (P769L and A1059S) in the Cav3.2 CACNA1H gene identified in a pediatric patient with chronic pain and absence seizures. The mutations were introduced individually into recombinant channels and then analyzed by means of electrophysiology. When both mutants were co-expressed in tsA-201 cells, we observed a loss of channel function, with significantly smaller current densities across a wide range of voltages (-40 to +20 mV). In addition, when both mutant channels were co-expressed, the channels opened at a more depolarizing potential with a ~5-mV right shift in the half-activation potential, with no changes in half-inactivation potential and the rate of recovery from inactivation. Interestingly, when both mutants were co-expressed in the neuronal-derived CAD cells in a different extracellular milieu, the effect was remarkably different. Although not statistically significant (p replacement of extracellular sodium and potassium with tetraethylammonium chloride. Our results show that experimental conditions can be a confounding factor in the biophysical effects of T-type calcium channel mutations found in certain neurological disorders. PMID:26706850

  11. The effects of in utero irradiation on mutation induction and transgenerational instability in mice

    Barber, Ruth C.; Hardwick, Robert J.; Shanks, Morag E.; Glen, Colin D.; Mughal, Safeer K.; Voutounou, Mariel [Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH (United Kingdom)

    2009-05-12

    Epidemiological evidence suggests that the deleterious effects of prenatal irradiation can manifest during childhood, resulting in an increased risk of leukaemia and solid cancers after birth. However, the mechanisms underlying the long-term effects of foetal irradiation remain poorly understood. This study was designed to analyse the impact of in utero irradiation on mutation rates at expanded simple tandem repeat (ESTR) DNA loci in directly exposed mice and their first-generation (F{sub 1}) offspring. ESTR mutation frequencies in the germline and somatic tissues of male and female mice irradiated at 12 days of gestation remained highly elevated during adulthood, which was mainly attributed to a significant increase in the frequency of singleton mutations. The prevalence of singleton mutations in directly exposed mice suggests that foetal irradiation results in genomic instability manifested both in utero and during adulthood. The frequency of ESTR mutation in the F{sub 1} offspring of prenatally irradiated male mice was equally elevated across all tissues, which suggests that foetal exposure results in transgenerational genomic instability. In contrast, maternal in utero exposure did not affect the F{sub 1} stability. Our data imply that the passive erasure of epigenetic marks in the maternal genome can diminish the transgenerational effects of foetal irradiation and therefore provide important clues to the still unknown mechanisms of radiation-induced genomic instability. The results of this study offer a plausible explanation for the effects of in utero irradiation on the risk of leukaemia and solid cancers after birth.

  12. Ecotoxicological effects of activated carbon addition to sediments.

    Jonker, M.T.O.; Suijkerbuijk, M.P.; Schmitt, H.; Sinnige, T.L.

    2009-01-01

    Activated carbon (AC) addition is a recently developed technique for the remediation of sediments and soils contaminated with hydrophobic organic chemicals. Laboratory and field experiments have demonstrated that the addition of 3-4% of AC can reduce aqueous concentrations and the bioaccumulation po

  13. Chemistry of Food Additives: Direct and Indirect Effects.

    Pauli, George H.

    1984-01-01

    The primary component(s), impurities, and degradation products of polysorbate 80, nitrate and nitrite salts, and diethylpyrocarbonate (DEPC) are discussed. Safety considerations related to these food additives are also noted. The chick-edema factor which results from an additive in poultry feed is also discussed. (JN)

  14. In silico investigation of molecular effects caused by missense mutations in creatine transporter protein

    Zhang, Zhe; Schwatz, Charles; Alexov, Emil

    2011-03-01

    Creatine transporter (CT) protein, which is encoded by SLC6A8 gene, is essential for taking up the creatine in the cell, which in turn plays a key role in the spatial and temporal maintenance of energy in skeletal and cardiac muscle cells. It was shown that some missense mutations in CT cause mental retardation, while others are harmless non-synonymous single nucleoside polymorphism (nsSNP). Currently fifteen missense mutations in CT are known, among which twelve are disease-causing. Sequence analysis reveals that there is no clear trend distinguishing disease-causing from harmless missense mutations. Because of that, we built 3D model of the CT using highly homologous template and use the model to investigate the effects of mutations of CT stability and hydrogen bond network. It is demonstrated that disease-causing mutations affect the folding free energy and ionization states of titratable group in much greater extend as compared with harmless mutations. Supported by grants from NLM, NIH, grant numbers 1R03LM009748 and 1R03LM009748-S1.

  15. Concentration addition, independent action and generalized concentration addition models for mixture effect prediction of sex hormone synthesis in vitro

    Hadrup, Niels; Taxvig, Camilla; Pedersen, Mikael;

    2013-01-01

    of the concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) models. First we measured effects of single chemicals and mixtures thereof on steroid synthesis in H295R cells. Then single chemical data were applied to the models; predictions of mixture effects were calculated...... and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast...

  16. Correlated mutations in protein sequences: Phylogenetic and structural effects

    Lapedes, A.S. [Los Alamos National Lab., NM (United States). Theoretical Div.]|[Santa Fe Inst., NM (United States); Giraud, B.G. [C.E.N. Saclay, Gif/Yvette (France). Service Physique Theorique; Liu, L.C. [Los Alamos National Lab., NM (United States). Theoretical Div.; Stormo, G.D. [Univ. of Colorado, Boulder, CO (United States). Dept. of Molecular, Cellular and Developmental Biology

    1998-12-01

    Covariation analysis of sets of aligned sequences for RNA molecules is relatively successful in elucidating RNA secondary structure, as well as some aspects of tertiary structure. Covariation analysis of sets of aligned sequences for protein molecules is successful in certain instances in elucidating certain structural and functional links, but in general, pairs of sites displaying highly covarying mutations in protein sequences do not necessarily correspond to sites that are spatially close in the protein structure. In this paper the authors identify two reasons why naive use of covariation analysis for protein sequences fails to reliably indicate sequence positions that are spatially proximate. The first reason involves the bias introduced in calculation of covariation measures due to the fact that biological sequences are generally related by a non-trivial phylogenetic tree. The authors present a null-model approach to solve this problem. The second reason involves linked chains of covariation which can result in pairs of sites displaying significant covariation even though they are not spatially proximate. They present a maximum entropy solution to this classic problem of causation versus correlation. The methodologies are validated in simulation.

  17. The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

    Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G., E-mail: yara_yingling@ncsu.edu

    2012-12-01

    Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: Black-Right-Pointing-Pointer All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. Black-Right-Pointing-Pointer Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. Black-Right-Pointing-Pointer Lys and Arg mutations most dramatically destabilize collagen fibril properties. Black-Right-Pointing-Pointer Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

  18. On the effect of thallium additions on cadmium amalgam potentials

    A study has been made of the influence of additives of thallium on potentials of cadmium amalgams with thallium contents of 10, 20, 30, and 40 at.% at 20, 40, 60, and 80 deg C. Additives of thallium have been found to shift the potential of cadmium amalgams towards the range of negative values which indicates an increase in the activity of cadmium. A possibility of calculation of the potential shift for heterogeneous cadmium amalgams on introducing thallium has been shown

  19. Effect of cationic polyelectrolytes addition in cement cohesion

    Edison Albert Zuluaga-Hernández; Bibian A Hoyos

    2014-01-01

    Here is studied the variation in cohesion of cement main phase (C-S-H) as a result of cationic polyelectrolytes addition (quaternary amines spermine and norspermidine). Cohesion study was carried out by molecular simulation techniques (Monte Carlo) using a primitive model in a canonical ensemble (NVT). The proposed model takes into account the influence of ionic size of each particle and the addition of polyelectrolytes with different charge number and separation. The results obtained show th...

  20. Effect of mutated IκBα transfection on multidrug resistance in hilar cholangiocarcinoma cell lines

    Ru-Fu Chen; Zhi-Hua Li; Xian-He Kong; Ji-Sheng Chen

    2005-01-01

    AIM: To explore the expression effect of mutated IκBαtransfection on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells by inhibiting the activity of nuclear transcription factor-κB (NF-κB).METHODS: We used the mutated IκBα plasmid to transfect QBC939HCVC+ cells and QBC939 cells, and electrophoretic gel mobility shift assay (EMSA) to detect the binding activity of NF-κB DNA and the effect of the transfrecting mutated IκBα plasmid on multidrug resistance gene (MDR-1) in hilar cholangiocarcinoma cells and its expression protein (P-GP).RFSULTS: Plasmid DNA was digested by restriction enzymes Xbal and Hand Ⅲ, and its product after electrophoresis showed two bands with a big difference in molecular weight,with a size of 4.9 kb and 1.55 kb respectively, which indicated that the carrier was successfully constructed and digested with enzymes. The radioactivity accumulation of QBC939HCVC+and QBC939 cells transfected with mutated IκBα plasmid was significantly lower than that of the control group not transfected with mutated IκBα plasmid. Double densimeter scanning showed that the relative signal density between the tansfection group and non-transfection group was significantly different, which proved that the mutated IκBα plasmid could inhibit the binding activity of NF-κB DNA in hilar cholangiocarcinoma cells. Compared to control group not transfected with m IκBα plasmid, the expression level of MDR-1mRNA in the QBC939 and QBC939HCVC+ cells transfected with mutated IκBα plasmid was lower. The expression intensity of P-GP protein in QBC939 and QBC939HCVC+ cells transfected with mutated IκBα was significantly lower than that of the control group not transfected with mutated IκBα plasmid.CONCLUSION: The mutated IκBα plasmid transfection can markedly reverse the multidrug resistance of hilar cholangiocarcinoma cells. Interruption of NF-κB activity may become a new target in gene therapy for hilar cholangiocarcinogenesic carcinoma.

  1. The effect of β2-α2 loop mutation on amyloidogenic properties of the prion protein

    Dutta, Arpana; Chen, Shugui; Surewicz, Witold K.

    2013-01-01

    Recent studies revealed that elk-like S170N/N174T mutation in mouse prion protein (moPrP), which results in an increased rigidity of β2-α2 loop, leads to a prion disease in transgenic mice. Here we characterized the effect of this mutation on biophysical properties of moPrP. Despite similar thermodynamic stabilities of wild type and mutant proteins, the latter was found to have markedly higher propensity to form amyloid fibrils. Importantly, this effect was observed even under fully denaturin...

  2. The Effect Acid Addition on Characteristic Effervescent Tablet of Tamarillo

    Fidela Violalita

    2015-01-01

    Full Text Available The aim of study was to determine the percentage of acid and its influence on characteristic effervescent tablet of tamarillo. The percentages of  acid addition that consist with citric acid and tartaric acid (1:1 were 15%, 20%, 25%, 30% and 35%. Water content, pH solution, vitamin C content, soluble duration, friability of tablet and organoleptic test on colour, aroma and flavour of tamarillo effervescent tablet were determined after addition of acid. The results showed that the difference in percentage of acid addition significantly affected to the water content, pH solution, soluble duration and friability of tablets. Based on organoleptic test, the tablet consist of 25% addition of acid was the best percentage of acid addition. The quality parameters in this percentage were the water content 6.09%, pH solution 4.80,  vitamin C 498.0800 mg/tablet, soluble duration 3.96 minute, friability of tablet 0.11%, while the averages of organoleptic test for colour were 3.40 (ordinary, aroma 3.36 (ordinary, and flavour 3.76 (like.

  3. Effect of space flight mutation on eggplant and analysis of genetic diversity by ssr molecular marker

    Seeds of three eggplant varieties (05 - 7, 05 - 9 and 05 - 18) were carried byShijian 8satellite for space flight treatment. The space flight mutation effects on eggplant were studied and the genetic diversity of mutant lines was analyzed using SSR markers. The results showed that space flight had obvious effects on the seed germination in eggplant SP1 generation and other characters such as plant height, plant type, leaf shape, fruit shape in the second generation. Most of the mutated characters could stably inherit in the third generation. The results also indicated that different eggplant genotypes resporded different to the space flight mutation; the long eggplant 05 - 18 was much more sensitive than other two varieties. Great variation between variant lines and their original varieties were detected by SSR markers, suggesting that space flight could induce molecular variation in eggplant. (authors)

  4. The cosmological constant. A small addition with a great effect

    The consequences of a cosmological constant Λ to cosmological models on the one hand and to Newton's gravitational law in the weak field expansion on the other hand are discussed. In case of a negative Λ with Λ∼10-56 cm-2 the universe is open but does not expand forever. Furthermore, its age is compatible with the age of the oldest globular clusters. On the other hand, Newton's gravitational law is modified by an additional attractive force term linearly increasing woth the distance. This term acts only over very large distances. If one assumes a value Λ∼=-10-56 cm-2 the additional term acts for stars over a characteristic scale of about 120 pc and for galaxies over a characteristic scale of about 0.8 Mpc. A positive cosmological constant Λ∼=-10-56 cm-2 leads to an additional repulsive force which would have prevented the existence of galaxy clusters

  5. Effect of shaddock albedo addition on the properties of frankfurters

    Shan, Bing; Li, Xingmin; Pan, Teng; Zheng, Limin; Zhang, Hao; Guo, Huiyuan; JIANG, LU; Zhen, Shaobo; Ren, Fazheng

    2014-01-01

    To explore the potential as a natural auxiliary emulsifier, shaddock albedo was added into frankfurters at six different levels: 0.0, 2.5, 5.0, 7.5, 10 and 12.5 %. The emulsion capacity (EC) of meat batters and cooking properties of frankfurters were evaluated. EC of meat batters was improved with the addition of shaddock albedo and the maximum value was reached at the 5 % albedo concentration. The addition of shaddock albedo resulted in lower cooking losses of frankfurters, with the lowest v...

  6. Effects of Video Games as Reinforcers for Computerized Addition Performance.

    Axelrod, Saul; And Others

    1987-01-01

    Four 2nd-grade students completed addition problems on a computer, using video games as reinforcers. Two variable ratio schedules of reinforcement failed to increase student accuracy or the rate of correct responses. In a no-games reinforcement condition, students had more opportunities to respond and had a greater number of correct answers.…

  7. EFFECTS OF PROPERTIES POLYMERIC ADDITIVES IN RHEOLOGIC AND DRILLING FLUIDS

    Danielly Vieira de Lucena

    2014-03-01

    Full Text Available The influence of carboxymethylcellulose, CMC (filtrate reducer and xanthan gum (viscosifier in plastic and apparent viscosity at yield strength and the volume of filtrate in the composition of drilling fluids based on water was investigated based on statistical design. Five formulations consist of a range of concentrations used commercially were utilized in the design of the experiment. The formulations were prepared in accordance with company standards Petrobras. Regression models were calculated and correlated with the properties of the compositions. The relevance and validation of the models were confirmed by statistical analysis. The design can be applied to statistically optimize the mud properties considering the addition of CMC and xanthan gum, and to provide a better understanding of the influence of additives on the properties of polymer-based fluid system water. From the study it was observed that the values of the rheological properties vary with the concentration of additives, increasing with increasing concentration of the same, and that the concentration of the additives caused a decline of parameter values filtration.

  8. The effect of chemical additives on the synthesis of ethanol

    Chuang, S.S.C.

    1992-03-06

    The objective of this research was to investigate the reaction mechanism of higher alcohol and aldehyde synthesis from syngas and the role of additives in the synthesis. An in situ IR reaction system and probe molecule technique were developed to study adsorbed species, active sites, and reaction pathway during reaction. The catalysts used for this study included silica-supported Rh, Ru, and Ni. (VC)

  9. Effect of Calcium Additive on the Crystallization of Struvite

    Perwitasari Dyah Suci

    2016-01-01

    Full Text Available Crystallization of struvite [MgNH4PO4.6H2O] may lead to the deposition of scale which may create significant problems in the process pipes, pumps and other industrial equipment. However, struvite precipitation can be benefited for phosphate recovery for use of fertilizer. The aim at the present work was to investigate calcium additive on struvite precipitation. The experiment was carried out in a batch mode using a 1-liter Pyrex glass vessel mechanically agitated for 200 rpm. The scale-forming solution was prepared for mixing solutions to MgCl2 and NH4H2PO4 with Mg+2 , NH4+ and PO4-3 in a molar ratio of 1: 1:1. The crystallization temperature of 30 and 40 °C was selected. Ca was added into the crystallizing solution to chloride dihydrate 0.4M (CaCl2•2H2O. Then each solution was pH adjusted to 9 by addition of KOH. The crystals obtained were characterized using SEM for morphology, EDS for elemental analysis as well as XRPD Rietveld analysis for crystaline phases. The induction periods varied from 10 to 90 min, which means that the struvite crystals began forming 10 to 90 min after mixing of the solution. It was observed that the Ca additive may inhibit the struvite crystallization. SEM analysis revealed that the struvite crystals obtained were predominantly of irregular prismatic morphology. Furthermore, the EDS pattern revealed that the elemental composition of the crystals consisted of Ca, Cl, S Mg, N, and P, providing that many crystalline phase found in the crystals such as Gypsum, CaCl2, struvite, struvite-(K and sylvite. It was observed that the Ca additive appeared to inhibit the struvite crystallization.

  10. Effects of additives on thermal stability of Li ion cells

    Doughty, Daniel H.; Roth, E. Peter; Crafts, Chris C.; Nagasubramanian, G.; Henriksen, Gary; Amine, Khalil

    Li ion cells are being developed for high-power applications in hybrid electric vehicles, because these cells offer superior combination of power and energy density over current cell chemistries. Cells using this chemistry are proposed for battery systems in both internal combustion engine and fuel cell-powered hybrid electric vehicles. However, the safety of these cells needs to be understood and improved for eventual widespread commercial applications. The thermal-abuse response of Li ion cells has been improved by the incorporation of more stable anode carbons and electrolyte additives. Electrolyte solutions containing vinyl ethylene carbonate (VEC), triphenyl phosphate (TPP), tris(trifluoroethyl)phosphate (TFP) as well as some proprietary flame-retardant additives were evaluated. Test cells in the 18,650 configuration were built at Sandia National Laboratories using new stable electrode materials and electrolyte additives. A special test fixture was designed to allow determination of self-generated cell heating during a thermal ramp profile. The flammability of vented gas and expelled electrolyte was studied using a novel arrangement of a spark generator placed near the cell to ignite vent gas if a flammable gas mixture was present. Flammability of vent gas was somewhat reduced by the presence of certain additives. Accelerating rate calorimetry (ARC) was also used to characterize 18,650-size test cell heat and gas generation. Gas composition was analyzed by gas chromatography (GC) and was found to consist of CO 2, H 2, CO, methane, ethane, ethylene and small amounts of C1-C4 organic molecules.

  11. Effect of shaddock albedo addition on the properties of frankfurters.

    Shan, Bing; Li, Xingmin; Pan, Teng; Zheng, Limin; Zhang, Hao; Guo, Huiyuan; Jiang, Lu; Zhen, Shaobo; Ren, Fazheng

    2015-07-01

    To explore the potential as a natural auxiliary emulsifier, shaddock albedo was added into frankfurters at six different levels: 0.0, 2.5, 5.0, 7.5, 10 and 12.5 %. The emulsion capacity (EC) of meat batters and cooking properties of frankfurters were evaluated. EC of meat batters was improved with the addition of shaddock albedo and the maximum value was reached at the 5 % albedo concentration. The addition of shaddock albedo resulted in lower cooking losses of frankfurters, with the lowest value obtained at the 7.5 % level. The presence of shaddock albedo decreased the total expressible fluid (TEF) and the proportion of fat in total expressible fluid (PF) which indicated the emulsion stability of frankfurters and the lowest values both occurred at the concentration of 7.5 %. Shaddock albedo inclusion increased the lightness and yellowness of frankfurters and decreased redness. Texture profile analysis showed increased hardness and decreased chewiness of frankfurters with the addition of shaddock albedo. Consequently, shaddock albedo could be a potential source of auxiliary emulsifier filler for emulsion-type meat products. PMID:26139927

  12. Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

    Colombo Elisa A

    2012-01-01

    Full Text Available Abstract Background Poikiloderma with Neutropenia (PN is a rare autosomal recessive genodermatosis caused by C16orf57 mutations. To date 17 mutations have been identified in 31 PN patients. Results We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel C16orf57 mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain. Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase. According to bioinformatic prediction, all known C16orf57 mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding. Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect. Conclusions In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance. The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the

  13. Founder effect of a prevalent phenylketonuria mutation in the Oriental population

    A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro413 for Arg413 in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations

  14. EFFECTS OF MUTATIONS IN THE POLYMERASE GENE OF HEPATITIS B VIRUS GENOME ON LAMIVUDINE THERAPY

    韩永年; 张欣欣; 陆志檬; 张东华

    2001-01-01

    Objective To explore the effects of mutations in tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif of the polymerase in the hepatitis B virus ( HBV) genome on lamivudine antiviral therapy. Methods Partial HBV DNA segment containing the YMDD motif in the P gene was obtained through amplification by polymerase chain reaction ( PCR ) from 19 chronic hepatitis B patients with serum HBV DNA positive at the 48th week treatment with lamivudine and subjected to automatic sequencing. Influences of variants with YMDD mutations on lamivudine therapy were seen by observing the dynamic changes of serum HBV DNA and ALT levels. Results Serum HBV DNA breakthrough was found in 3 out of 10 individuals with detection of the YMDD mutations at the 48th week and in 5 at the 52th week, 2 of the 5 patients accompanied by serum ALT re-elevation, whereas of 9 subjects without YMDD mutations, 2 experienced an HBV DNA breakthrough at the 48th week and 1 of them had a conversion from HBV DNA positive to negative at the 52th week. Patients with detectable HBV DNA level had a fluctuating level of serum ALT all time during the treatment. Conclusion Detection of mutations in the YMDD motif of polyrnerase gene in HBV genome during the lamivudine therapy will be helpful to monitoring its therapeutic outcomes.

  15. Cognitive Effects of Greek Affiliation in College: Additional Evidence

    Pascarella, Ernest T.; Flowers, Lamont; Whitt, Elizabeth J.

    2009-01-01

    Previous research published in this journal found broad-based negative effects of Greek affiliation on standardized measures of cognitive development after 1 year of college. Following the same sample, and employing essentially the same research design and analytic model, the present study found that the negative effects of Greek affiliation were…

  16. Mutation Testing for Effective Verification of Digital Components of Physical Systems

    Kushik, N. G.; Evtushenko, N. V.; Torgaev, S. N.

    2015-12-01

    Digital components of modern physical systems are often designed applying circuitry solutions based on the field programmable gate array technology (FPGA). Such (embedded) digital components should be carefully tested. In this paper, an approach for the verification of digital physical system components based on mutation testing is proposed. The reference description of the behavior of a digital component in the hardware description language (HDL) is mutated by introducing into it the most probable errors and, unlike mutants in high-level programming languages, the corresponding test case is effectively derived based on a comparison of special scalable representations of the specification and the constructed mutant using various logic synthesis and verification systems.

  17. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect

    Tiemann-Boege, Irene; Navidi, William; Grewal, Raji; Cohn, Dan; Eskenazi, Brenda; Wyrobek, Andrew J.; Arnheim, Norman

    2002-01-01

    The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g., achondroplasia) increase in incidence with the age of the father is consistent with this idea. Although it is assumed that the paternal age effect is the result of an increasing frequency of mutant sperm as a man grows older, no direct molecular measurement of the germ-line mutation ...

  18. The effects of maternal irradiation during adulthood on mutation induction and transgenerational instability in mice

    Abouzeid Ali, Hamdy E. [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Radiobiological Applications Department, Nuclear Research Centre, Atomic Energy Authority, Cairo (Egypt); Barber, Ruth C. [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom)

    2012-04-01

    The long-term genetic effects of maternal irradiation remain poorly understood. To establish the effects of radiation exposure on mutation induction in the germline of directly exposed females and the possibility of transgenerational effects in their non-exposed offspring, adult female BALB/c and CBA/Ca mice were given 1 Gy of acute X-rays and mated with control males. The frequency of mutation at expanded simple tandem repeat (ESTR) loci in the germline of directly exposed females did not differ from that of controls. Using a single-molecule PCR approach, ESTR mutation frequency was also established for both germline and somatic tissues in the first-generation offspring of irradiated parents. While the frequency of ESTR mutation in the offspring of irradiated males was significantly elevated, maternal irradiation did not affect stability in their F{sub 1} offspring. Considering these data and the results of our previous study, we propose that, in sharp contrast to paternal exposure to ionising radiation, the transgenerational effects of maternal high-dose acute irradiation are likely to be negligible.

  19. Additive effect of propofol and fentanyl precipitating cardiogenic shock

    AC Jesudoss Prabhakaran

    2013-01-01

    Full Text Available The intravenous administration of propofol and fentanyl has become a common practice in a variety of clinical settings including outpatient dermatologic, cosmetic and oral surgery. The combination provides both systematic sedation and analgesia with low incidence of unwanted side effects. The cardiogenic shock is very uncommon in healthy individuals. The cardiovascular depressive effect of propofol and fentanyl has been well established, but the development of cardiogenic shock is very rare when these drugs are used together. Hence the awareness of this effect is advantageous to the patients undergoing such surgeries

  20. Effects of an additional dimension in the Young experiment

    Barros, Allan Kardec

    2015-01-01

    The results of the Young experiment can be analyzed either by classical or Quantum Physics. The later one though leads to a more complete interpretation, based on two different patterns that appear when one works either with single or double slits. Here we show that the two patterns can be derived from a single principle, in the context of General Relativity, if one assumes an additional spatial dimension to the four known today. The found equations yield the same results as those in Quantum Mechanics.

  1. Effects of an additional dimension in the Young experiment

    Barros, Allan Kardec, E-mail: allan@elo.com.br

    2015-09-15

    The results of the Young experiment can be analyzed either by classical or Quantum Physics. The later one though leads to a more complete interpretation, based on two different patterns that appear when one works either with single or double slits. Here we show that the two patterns can be derived from a single principle, in the context of General Relativity, if one assumes an additional spatial dimension to the four known today. The found equations yield the same results as those in Quantum Mechanics.

  2. Effects of an additional dimension in the Young experiment

    The results of the Young experiment can be analyzed either by classical or Quantum Physics. The later one though leads to a more complete interpretation, based on two different patterns that appear when one works either with single or double slits. Here we show that the two patterns can be derived from a single principle, in the context of General Relativity, if one assumes an additional spatial dimension to the four known today. The found equations yield the same results as those in Quantum Mechanics

  3. Assessing the effects of Aedes aegypti kdr mutations on pyrethroid resistance and its fitness cost.

    Luiz Paulo Brito

    Full Text Available Pyrethroids are the most used insecticide class worldwide. They target the voltage gated sodium channel (NaV, inducing the knockdown effect. In Aedes aegypti, the main dengue vector, the AaNaV substitutions Val1016Ile and Phe1534Cys are the most important knockdown resistance (kdr mutations. We evaluated the fitness cost of these kdr mutations related to distinct aspects of development and reproduction, in the absence of any other major resistance mechanism. To accomplish this, we initially set up 68 crosses with mosquitoes from a natural population. Allele-specific PCR revealed that one couple, the one originating the CIT-32 strain, had both parents homozygous for both kdr mutations. However, this pyrethroid resistant strain also presented high levels of detoxifying enzymes, which synergistically account for resistance, as revealed by biological and biochemical assays. Therefore, we carried out backcrosses between CIT-32 and Rockefeller (an insecticide susceptible strain for eight generations in order to bring the kdr mutation into a susceptible genetic background. This new strain, named Rock-kdr, was highly resistant to pyrethroid and presented reduced alteration of detoxifying activity. Fitness of the Rock-kdr was then evaluated in comparison with Rockefeller. In this strain, larval development took longer, adults had an increased locomotor activity, fewer females laid eggs, and produced a lower number of eggs. Under an inter-strain competition scenario, the Rock-kdr larvae developed even slower. Moreover, when Rockefeller and Rock-kdr were reared together in population cage experiments during 15 generations in absence of insecticide, the mutant allele decreased in frequency. These results strongly suggest that the Ae. aegypti kdr mutations have a high fitness cost. Therefore, enhanced surveillance for resistance should be priority in localities where the kdr mutation is found before new adaptive alleles can be selected for diminishing the

  4. Additive effect of propofol and fentanyl precipitating cardiogenic shock

    AC Jesudoss Prabhakaran

    2013-01-01

    The intravenous administration of propofol and fentanyl has become a common practice in a variety of clinical settings including outpatient dermatologic, cosmetic and oral surgery. The combination provides both systematic sedation and analgesia with low incidence of unwanted side effects. The cardiogenic shock is very uncommon in healthy individuals. The cardiovascular depressive effect of propofol and fentanyl has been well established, but the development of cardiogenic shock is very rare w...

  5. Human immunodeficiency virus type 1 integrase: effect on viral replication of mutations at highly conserved residues.

    Cannon, P M; Wilson, W; Byles, E; Kingsman, S M; Kingsman, A J

    1994-01-01

    Sequence comparisons of the integrase (IN) proteins from different retroviruses have identified several highly conserved residues. We have introduced mutations at 16 of these sites into the integrase gene of human immunodeficiency virus type 1 and analyzed the phenotypes of the resulting viruses. The viruses were all normal for p24 content and reverse transcriptase activity. In addition, all of the mutants could infect T-cell lines and undergo reverse transcription, as assessed by PCR analysi...

  6. Effect of hydrogen addition on autoignited methane lifted flames

    Choin, Byung Chul

    2012-01-01

    Autoignited lifted flames in laminar jets with hydrogen-enriched methane fuels have been investigated experimentally in heated coflow air. The results showed that the autoignited lifted flame of the methane/hydrogen mixture, which had an initial temperature over 920 K, the threshold temperature for autoignition in methane jets, exhibited features typical of either a tribrachial edge or mild combustion depending on fuel mole fraction and the liftoff height increased with jet velocity. The liftoff height in the hydrogen-assisted autoignition regime was dependent on the square of the adiabatic ignition delay time for the addition of small amounts of hydrogen, as was the case for pure methane jets. When the initial temperature was below 920 K, where the methane fuel did not show autoignition behavior, the flame was autoignited by the addition of hydrogen, which is an ignition improver. The liftoff height demonstrated a unique feature in that it decreased nonlinearly as the jet velocity increased. The differential diffusion of hydrogen is expected to play a crucial role in the decrease in the liftoff height with increasing jet velocity.

  7. Inverse dose-rate effect for mutation induction by γ-rays in human lymphoblasts

    In order to define further the effects of differences in recombinational proficiency on cell survival and mutation by ionizing radiation, we exposed the syngenic cell lines TK6 and WTK1 to continuous low dose-rate γ-irradiation. We previously demonstrated that acute X-ray exposure results in lower survival and lower mutation induction at both the thymidine kinase (tk) and the hypoxanthine-guanine phosphoribosyltransferase (hprt) loci in TK6 cells compared with WTK1 cells. These differences were attributed in part to reduced levels of recombination in the TK6 line relative to WTK1. Using a low dose rate 137Cs irradiator, we exposed asynchronous growing populations of these cells to γ-rays at 14.3, 6.7 and 2.7 cGy/h. Both cell lines exhibited a dose-rate effect on survival. Compared with acute doses, the low dose-rates also protected against mutation induction at the hrpt locus in WTK1, but protection was inversely related to dose-rate. There was also a slight inverse dose-rate effect in TK6, with mutation induction at the lowest dose-rate exceeding that at acute exposures. (Author)

  8. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

    Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients) appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436), has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Our experiments demonstrated an effective action of Dabrafenib (GSK2118436) and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment

  9. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

    Gentilcore Giusy

    2013-01-01

    Full Text Available Abstract Background Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436, has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Methods Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Results Our experiments demonstrated an effective action of Dabrafenib (GSK2118436 and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. Conclusion These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.

  10. The biological effects and clinical implications of BRCA mutations: where do we go from here?

    Stoppa-Lyonnet, Dominique

    2016-09-01

    BRCA1 and BRCA2 are tumour-suppressor genes encoding proteins that are essential for the repair of DNA double-strand breaks by homologous recombination (HR). Cells that lack either BRCA1 or BRCA2 repair these lesions by alternative, more error-prone mechanisms. Individuals carrying germline pathogenic mutations in BRCA1 or BRCA2 are at highly elevated risk of developing breast and/or ovarian cancer. Genetic testing for germline pathogenic mutations in BRCA1 and BRCA2 has proved to be a valuable tool for determining eligibility for cancer screening and prevention programmes. In view of increasing evidence that the HR DNA repair pathway can also be disrupted by sequence variants in other genes, screening for other BRCA-like defects has potential implications for patient care. Additionally, there is a growing argument for directly testing tumours for pathogenic mutations in BRCA1, BRCA2 and other genes involved in HR-DNA repair as inactivation of these genes may be strictly somatic. Tumours in which HR-DNA repair is altered are most likely to respond to emerging targeted therapies, such as inhibitors of poly-ADP ribose polymerase. This review highlights the biological role of pathogenic BRCA mutations and other associated defects in DNA damage repair mechanisms in breast and ovarian cancer, with particular focus on implications for patient management strategies. PMID:27514841

  11. Effective face recognition using bag of features with additive kernels

    Yang, Shicai; Bebis, George; Chu, Yongjie; Zhao, Lindu

    2016-01-01

    In past decades, many techniques have been used to improve face recognition performance. The most common and well-studied ways are to use the whole face image to build a subspace based on the reduction of dimensionality. Differing from methods above, we consider face recognition as an image classification problem. The face images of the same person are considered to fall into the same category. Each category and each face image could be both represented by a simple pyramid histogram. Spatial dense scale-invariant feature transform features and bag of features method are used to build categories and face representations. In an effort to make the method more efficient, a linear support vector machine solver, Pegasos, is used for the classification in the kernel space with additive kernels instead of nonlinear SVMs. Our experimental results demonstrate that the proposed method can achieve very high recognition accuracy on the ORL, YALE, and FERET databases.

  12. Effect of B addition to hypereutectic Ti-based alloys

    Louzguina-Luzgina, Larissa V. [Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba-Ku, Sendai 980-8577 (Japan); Louzguine-Luzgin, Dmitri V. [WPI Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba-Ku, Sendai 980-8577 (Japan)], E-mail: dml@imr.tohoku.ac.jp; Inoue, Akihisa [WPI Advanced Institute for Materials Research, Tohoku University, Katahira 2-1-1, Aoba-Ku, Sendai 980-8577 (Japan)

    2009-04-17

    The structure and mechanical properties of Ti-Fe-B and Ti-Fe-Co-B alloys produced in the shape of the arc-melted ingots of about 25 mm diameter and 10 mm height are studied. The hypereutectic alloys showed excellent compressive mechanical properties. The structures of the high-strength and ductile hypereutectic alloys studied by X-ray diffractometry and scanning electron microscopy were found to consist of the primary cubic cP2 intermetallic compound (TiFe-phase or a solid solution on its base) and a dispersed eutectic consisting of this cP2 intermetallic compound + BCC cI2 {beta}-Ti supersaturated solid solution phase. The addition of B increased mechanical strength. Si causes embrittlement owing to the formation of alternative intermetallic compounds. The structure and deformation behaviour were studied.

  13. Effect of ethanol fuel additive on diesel emissions.; TOPICAL

    Engine-out emissions from a Volkswagen model TDI engine were measured for three different fuels: neat diesel fuel, a blend of diesel fuel and additives containing 10% ethanol, and a blend of diesel fuel and additives containing 15% ethanol. The test matrix covered five speeds from 1,320 to 3,000 rpm, five torques from 15 Nm to maximum plus the 900-rpm idle condition, and most of the points in the FTP-75 and US-06 vehicle tests. Emissions of particulate matter (PM), nitrogen oxides (NO(sub x)), unburned hydrocarbons (HCs), and carbon monoxide (CO) were measured at each point, as were fuel consumption, exhaust oxygen, and carbon dioxide output. PM emissions were reduced up to 75% when ethanol-diesel blends were used instead of neat diesel fuel. Significant reductions in PM emissions occurred over one-half to two-thirds of the test matrix. NO(sub x) emissions were reduced by up to 84%. Although the regions of reduced NO(sub x) emissions were much smaller than the regions of reduced PM emissions, there was considerable overlap between the two regions where PM emissions were reduced by up to 75% and NO(sub x) emissions were reduced by up to 84%. Such simultaneous reduction of both PM and NO(sub x) emissions would be difficult to achieve by any other means. HC and CO emissions were also reduced in the regions of reduced PM and NO(sub x) emissions that overlapped. Because the ethanol-diesel blends contain less energy on both a per-unit-mass basis and a per-unit-volume basis, there was a reduction in maximum torque of up to 10% and an increase in brake-specific fuel consumption of up to 7% when these blends were used

  14. Joint effects of heavy metal binary mixtures on seed germination, root and shoot growth, bacterial bioluminescence, and gene mutation

    In Chul Kong

    2013-01-01

    This investigation was to assess the joint effects of metal binary mixtures on seed germination,root and shoot growth,bacterial bioluminescence,and gene mutation based on the one toxic unit (1 TU) approach.Different sensitivities and orders of toxicity of metal mixtures were observed among the bioassays.In general,mostly additive or antagonistic effects were observed,while almost no synergistic effects by the binary metal mixtures in all bioassays.Therefore,the combined effects of heavy metals in the different bioassays were difficult to generalize since they were dependent on both chemical type and the organism used in each bioassay.However,these results indicate that a battery of bioassays with mixture chemicals as opposed to just a single assay with single metal is a better strategy for the bioassessment of environmental pollutants.

  15. Proceedings of the 8th workshop on plant mutation breeding. Effective use of physical/chemical mutagens

    The Workshop on Plant Mutation Breeding of FNCA (Forum for Nuclear Cooperation in Asia), was held on 9-13 October 2000 in Hanoi, Vietnam. The Workshop was co-sponsored by the Science and Technology Agency (STA), the Ministry of Science, Technology and Environment (MOSTE of Vietnam) and the Ministry of Agriculture and Rural Development (MARD of Vietnam) in cooperation with the Ministry of Agriculture, Forestry and Fisheries (MAFF), National Institute of Agrobiological Resources (NIAR of Vietnam), the Japan Atomic Industrial Forum (JAIF) and Japan Atomic Energy Research Institute (JAERI). Two Scientists, a Project Leader and an expert on methodology for plant/crop mutation breeding, participated from each of the member countries, i.e. China, Indonesia, Malaysia, the Philippines, Thailand, Vietnam and Japan. Also attending the Workshop were, one participant from Korea, seven participants from both Japan and Vietnam. The number of the participants in the Workshop totalled about sixty people including guests and observers. Sixteen papers including eight invited papers on the current status of methodology for plant/crop mutation breeding in the participating countries were presented. Discussions were focused on the subject concerning 'Effective Use of Physical/Chemical Mutagens', as well as a detailed report on the current status of research in each participating country. In addition, the topics of developing a mutant breeding database, an information exchange for plant/crop mutation breeding, and more tightly bound international co-operative research in the near future were also high on the agenda. This proceeding compiles the invited and contributed papers that were submitted from the speakers. (author)

  16. Proceedings of the 8th workshop on plant mutation breeding. Effective use of physical/chemical mutagens

    Kume, Tamikazu; Watanabe, Kazuo; Tano, Shigemitsu (eds.) [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    The Workshop on Plant Mutation Breeding of FNCA (Forum for Nuclear Cooperation in Asia), was held on 9-13 October 2000 in Hanoi, Vietnam. The Workshop was co-sponsored by the Science and Technology Agency (STA), the Ministry of Science, Technology and Environment (MOSTE of Vietnam) and the Ministry of Agriculture and Rural Development (MARD of Vietnam) in cooperation with the Ministry of Agriculture, Forestry and Fisheries (MAFF), National Institute of Agrobiological Resources (NIAR of Vietnam), the Japan Atomic Industrial Forum (JAIF) and Japan Atomic Energy Research Institute (JAERI). Two Scientists, a Project Leader and an expert on methodology for plant/crop mutation breeding, participated from each of the member countries, i.e. China, Indonesia, Malaysia, the Philippines, Thailand, Vietnam and Japan. Also attending the Workshop were, one participant from Korea, seven participants from both Japan and Vietnam. The number of the participants in the Workshop totalled about sixty people including guests and observers. Sixteen papers including eight invited papers on the current status of methodology for plant/crop mutation breeding in the participating countries were presented. Discussions were focused on the subject concerning 'Effective Use of Physical/Chemical Mutagens', as well as a detailed report on the current status of research in each participating country. In addition, the topics of developing a mutant breeding database, an information exchange for plant/crop mutation breeding, and more tightly bound international co-operative research in the near future were also high on the agenda. This proceeding compiles the invited and contributed papers that were submitted from the speakers. (author)

  17. Measuring epistasis in fitness landscapes: The correlation of fitness effects of mutations.

    Ferretti, Luca; Schmiegelt, Benjamin; Weinreich, Daniel; Yamauchi, Atsushi; Kobayashi, Yutaka; Tajima, Fumio; Achaz, Guillaume

    2016-05-01

    Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness landscapes are high-dimensional, simple measures of their structure are used as statistics in empirical applications. Epistasis is one of the most relevant features of fitness landscapes. Here we propose a new natural measure of the amount of epistasis based on the correlation of fitness effects of mutations. This measure has a natural interpretation, captures well the interaction between mutations and can be obtained analytically for most landscape models. We discuss how this measure is related to previous measures of epistasis (number of peaks, roughness/slope, fraction of sign epistasis, Fourier-Walsh spectrum) and how it can be easily extended to landscapes with missing data or with fitness ranks only. Furthermore, the dependence of the correlation of fitness effects on mutational distance contains interesting information about the patterns of epistasis. This dependence can be used to uncover the amount and nature of epistatic interactions in a landscape or to discriminate between different landscape models. PMID:26854875

  18. The Mutation Breeding and Mutagenic Effect of Air Plasma on Penicillium Chrysogenum

    桂芳; 王辉; 王鹏; 刘会; 蔡晓春; 胡以华; 袁成凌; 郑之明

    2012-01-01

    Low temperature air plasma was used as the mutation tool for penicillin-producing strain Penicillium chrysogenum. The discharge conditions were RF power of 360 W, temperature of 40℃ in a sealed chamber, and pressure of 10 Pa to 30 Pa. The result showed that the kinetics of the survival rate followed a typical saddle-shaped curve. Based on a statistic analysis, at the treating duration of 10 min, the positive mutation rate was as high as 37.5% while the negative mutation rate was low. The colonial morphology changed obviously when the plasma treating duration reached or exceeded 45 min. After both primary and secondary screening, a mutant designated as aPc051310 with high productivity of penicillin was obtained, and a strong mutagenic effect on P. chrysogenurn was observed in the process. It was proved that after five generations, the mutant aPc051310 still exhibits a high productivity. All the results prove that the plasma mutation method could be developed as a convenient and effective tool to breed high-yield strains in the fermentation industry, while expanding the plasm application at the same time.

  19. Effect of extracellular calcium on the additive effect of theophylline on the cardiac response to catecholamine

    Shamkuwar Prashant

    2008-01-01

    Full Text Available At different extracellular calcium concentrations, the positive inotropic effect of isoproterenol and isoproterenol in combination with theophylline, a phosphodiesterase inhibitor have been evaluated in the isolated frog heart and the isolated guinea pig left atria to investigate whether extracellular calcium produces any effect on the additive effect of the theophylline on the cardiac response to catecholamine. Cumulative dose response study of isoproterenol and isoproterenol in presence of theophylline at different extracellular calcium concentration was performed. The study revealed an increase in additive effect of theophylline on the cardiac response to catecholamine with increase in extracellular calcium concentration, but increase in extracellular calcium concentration decreased the myocardial responsiveness to additive effect of theophylline and isoproterenol combination. The mechanism of positive inotropic effect of isoproterenol and in combination with theophylline involves increase in intracellular cAMP by different pathways and extracellular calcium produces positive inotropic effect by initiating the interaction between the contractile proteins actin and myosin. The study revealed that an increase in the concentration of extracellular calcium increased the additive effect of theophylline and isoproterenol combination, but a decrease in the myocardial responsiveness was observed.

  20. IMMUNOMODULATORY EFFECT OF PHYTO-ADDITIVES IN BROILER CHICKENS

    LAVINIA ŞTEF

    2013-12-01

    Full Text Available The experiment was been performed in the sector of Nutrition and Animal Feeding discipline from Timisoara Didactic Station, on a 6 week period, beginning with hatching and finishing with 42 days of age, on 120 broilers divided into four experimental variants, each of them with 30 individuals. In LEU group was incorporated essential oils of Satureja hortensis, Mentha piperita and Hyperici herba 250 mg in 1 kg combined fodder, in LEP group was included in combined fodder structure a plants premix in 2%, in LEUP group was incorporated plants premix 2% +250 mg essential oil of Satureja hortensis, Mentha piperita, Hyperici herba in 1 kg combined fodder. After seric lizozime quntification was observed an increase with 303.46% in LEPU group, followed by LEU with 200.14%, results who demonstrated the presence of an immunological stimulation in broiler chickens. Increased values of seric properdine were observed in LEPU group, with 210.45% more increased in comparison with LM group, followed by LEU group, demonstrating that the changing of unspecific immune effectors values took place like a result of a exogenous substance with immunomodulator effect. Was also observed an easy increase of limfocytes in LPU group, but not so important like in first two determinations, if the experiment will continue, these values maybe will be significant increased, taking into consideration that these increases become more evident after a period of time after stimulation.

  1. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity.

    Joyce, Peter I; Mcgoldrick, Philip; Saccon, Rachele A; Weber, William; Fratta, Pietro; West, Steven J; Zhu, Ning; Carter, Sarah; Phatak, Vinaya; Stewart, Michelle; Simon, Michelle; Kumar, Saumya; Heise, Ines; Bros-Facer, Virginie; Dick, James; Corrochano, Silvia; Stanford, Macdonnell J; Luong, Tu Vinh; Nolan, Patrick M; Meyer, Timothy; Brandner, Sebastian; Bennett, David L H; Ozdinler, P Hande; Greensmith, Linda; Fisher, Elizabeth M C; Acevedo-Arozena, Abraham

    2015-04-01

    Transgenic mouse models expressing mutant superoxide dismutase 1 (SOD1) have been critical in furthering our understanding of amyotrophic lateral sclerosis (ALS). However, such models generally overexpress the mutant protein, which may give rise to phenotypes not directly relevant to the disorder. Here, we have analysed a novel mouse model that has a point mutation in the endogenous mouse Sod1 gene; this mutation is identical to a pathological change in human familial ALS (fALS) which results in a D83G change in SOD1 protein. Homozgous Sod1(D83G/D83G) mice develop progressive degeneration of lower (LMN) and upper motor neurons, likely due to the same unknown toxic gain of function as occurs in human fALS cases, but intriguingly LMN cell death appears to stop in early adulthood and the mice do not become paralyzed. The D83 residue coordinates zinc binding, and the D83G mutation results in loss of dismutase activity and SOD1 protein instability. As a result, Sod1(D83G/D83G) mice also phenocopy the distal axonopathy and hepatocellular carcinoma found in Sod1 null mice (Sod1(-/-)). These unique mice allow us to further our understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels. PMID:25468678

  2. The Potential Negative Effects of Interleukin 1 B in Multiple Sclerosis Patients with MEFV Mutation

    Mahmut Alpayci

    2013-10-01

    Full Text Available Multiple sclerosis patients, who are carriers of MEditerranean FeVer (MEFV gene mutation, have faster progression than the non-carriers. However, its underlying mechanism is not well understood. This article proposes the potential role of interleukin-1β (IL-1β that may be responsible for this rapid progression. Mutations in MEFV, the gene encoding for protein pyrin, cause familial Mediterranean fever, lead to gain of pyrin function, resulting in inappropriate IL-1β release. Interleukin-1β is a major mediator of systemic inflammation and fever, and also it contributes to permeability of the blood-brain barrier in active lesions of multiple sclerosis. Moreover, IL-1β promotes apoptosis of neurons and oligodendrocytes that produce the myelin sheath, which insulates axons. Thus, inflammatory damage, the blood-brain barrier disfunction, effects of fever on the central nervous system (or Uhthoff’s phenomenon, and apoptosis of neurons and oligodendrocytes, which play an important role in the pathogenesis and clinical course of multiple sclerosis, can be induced by increased activation and release of IL-1β in the presence of MEFV gene mutations. Therefore, screening for MEFV mutations in patients with multiple sclerosis and treatment planning with IL-1β targeting drugs for the carriers, may be a logical idea that will be a source of inspiration for scientific studies.

  3. Distinctive effects of nicotinic receptor intracellular-loop mutations associated with nocturnal frontal lobe epilepsy.

    Weltzin, Maegan M; Lindstrom, Jon M; Lukas, Ronald J; Whiteaker, Paul

    2016-03-01

    Previously characterized nicotinic acetylcholine receptor (nAChR) autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)-associated mutations are found in α2, α4 and β2 subunit transmembrane (TM) domains. They predominantly increase ACh potency and, for β2-subunit mutants, increase macroscopic currents. Two recently-identified mutations, α4(R336H) and β2(V337G), located in the intracellular cytoplasmic loop (C2) have been associated with non-familial NFLE. Effects of these mutations on α4β2-nAChR function and expression were studied for the first time, using two-electrode voltage clamp recordings in Xenopus laevis oocytes. Biased-ratio preparations elucidated the mutations' effects at alternate isoforms: high-sensitivity [HS; (α4)2(β2)3] or low-sensitivity [LS; (α4)3(β2)2] via 1:10 or 30:1 [α4:β2] cRNA injection ratios, respectively. An unbiased (1:1 [α4:β2] cRNA) injection ratio was also used to study potential shifts in isoform expression. α4(R336H)-containing receptors showed significant increases in maximal ACh-induced currents (Imax) in all preparations (140% increase compared to wild type control). β2(V337G)-containing receptors significantly increased Imax in the LS-favoring preparation (20% increase compared to control). Expression of either mutation consistently produced enrichment of HS-isoform expression in all preparations. α4β2-nAChR harboring either NFLE mutant subunit showed unchanged ACh, sazetidine-A, nicotine, cytisine and mecamylamine potency. However, both mutant subunits enhanced partial agonist efficacies in the LS-biased preparation. Using β2-subunit-specific [(125)I]mAb 295 immunolabeling, nAChR cell-surface expression was determined. Antibody binding studies revealed that the β2(V337G) mutation tended to reduce cell-surface expression, and function per receptor was significantly increased by either NFLE mutant subunit in HS-favoring preparations. These findings identify both common and differing features between

  4. Effects of mutations on the structure and function of silkworm type 1 acetylcholinesterase.

    Wang, B B; Li, F C; Xu, K Z; Ni, M; Hu, J S; Tian, J H; Li, Y Y; Shen, W D; Li, B

    2016-05-01

    AChE is the target of organophosphate (OP) and carbamate (CB) pesticides, and mutations in the gene can significantly reduce insects' sensitivity to these pesticides. Bombyx mori is highly sensitive to pesticides. To investigate the effects of mutations on AChE1 structure and function, we used a prokaryotic system to express B.mori wild type AChE1 (wAChE1) and mutant AChE1 (mAChE1) in this study. Active AChE1 proteins were obtained after refolding and purification, and wAChE1 and mAChE1 had similar activities. After incubation with 10(-6)M physostigmine and 10(-3)mg/mL phoxim, the remaining enzyme activity of mAChE1 was 4.42% and 8.86% higher than that of wAChE1's, respectively. Three-dimensional analysis of mutation AChE1 (mAChE1) revealed that the Ser and Ala side chains extended toward the central part of S285 with distances of just 2.80Å and 3.68Å, respectively, which changed the spatial structure of the active center and reduced its sensitivity to pesticides. These results indicated that the mutations altered the 3D structure of AChE1, which may affect the binding of physostigmine and phoxim to the serine residue at the active center, leading to reduced sensitivity. Our study helps understand the relationship between AChE1 mutations and pesticide resistance and provides a new direction for the cultivation of new pesticide-resistant varieties of B.mori. PMID:27017875

  5. The effect of antagonistic pleiotropy on the estimation of the average coefficient of dominance of deleterious mutations.

    Fernández, B; García-Dorado, A; Caballero, A

    2005-12-01

    We investigate the impact of antagonistic pleiotropy on the most widely used methods of estimation of the average coefficient of dominance of deleterious mutations from segregating populations. A proportion of the deleterious mutations affecting a given studied fitness component are assumed to have an advantageous effect on another one, generating overdominance on global fitness. Using diffusion approximations and transition matrix methods, we obtain the distribution of gene frequencies for nonpleiotropic and pleiotropic mutations in populations at the mutation-selection-drift balance. From these distributions we build homozygous and heterozygous chromosomes and assess the behavior of the estimators of dominance. A very small number of deleterious mutations with antagonistic pleiotropy produces substantial increases on the estimate of the average degree of dominance of mutations affecting the fitness component under study. For example, estimates are increased three- to fivefold when 2% of segregating loci are over-dominant for fitness. In contrast, strengthening pleiotropy, where pleiotropic effects are assumed to be also deleterious, has little effect on the estimates of the average degree of dominance, supporting previous results. The antagonistic pleiotropy model considered, applied under mutational parameters described in the literature, produces patterns for the distribution of chromosomal viabilities, levels of genetic variance, and homozygous mutation load generally consistent with those observed empirically for viability in Drosophila melanogaster. PMID:16118193

  6. The Effect of Mutation and Selection on Codon Adaptation in Escherichia coli Bacteriophage

    Chithambaram, Shivapriya; Prabhakaran, Ramanandan; Xia, Xuhua

    2014-01-01

    Studying phage codon adaptation is important not only for understanding the process of translation elongation, but also for reengineering phages for medical and industrial purposes. To evaluate the effect of mutation and selection on phage codon usage, we developed an index to measure selection imposed by host translation machinery, based on the difference in codon usage between all host genes and highly expressed host genes. We developed linear and nonlinear models to estimate the C→T mutati...

  7. Cochlear implantation effect on deaf children with gap junction protein beta 2 gene mutation

    KONG Ying; LIU Sha; WANG Su-ju; Li Shu-jing; LIANG Shuang

    2013-01-01

    Background The popularization and promotion of gene diagnosis technology makes it possible to detect deafness genes for children with congenital hearing impairment,and the proportion of gap junction protein beta 2 (GJB2) gene mutations in cochlear implant patients is 26.5% We did follow-up evaluation on auditory rehabilitation effect for all 31 deaf children with GJB2 gene mutation after cochlear implantation to provide a reference for such patients.Methods Application of “the genetic deafness gene chip detection kit” and “gene complete sequence analysis” were applied to conduct detection on common genetic deafness gene mutation hotspots of the hearing impaired children with cochlear implantation.To conduct auditory rehabilitation effect evaluation on all 31 cases of patients with GJB2 genetic deafness after 3,6 and 12 months of the operation respectively.The single factor repeated measure analysis of variance (ANOVA) was applied to analysis whether there were significant difference among the results of initial consonant of a Chinese syllable recognition at 3 different stages after the operation,the results of vowel of a Chinese syllable recognition at 3 different stages after the operation,and the results of two-syllable recognition at 3 different stages after the operation.Results The 235delC is the high-incidence mutational site in 31 cases of patients with GJB2 genetic deafness,and the total detection rate is up to 90.3% (28/31).There were significant differences in the initial consonant and the vowel of a Chinese syllable recognition rate,and the two-syllable recognition rates at 3,6,and 12 months after the operation (P<0.01).Conclusion Cochlear implantation is a safe and effective measure for auditory reconstruction,enabling patients with GJB2 hereditary severe sensorineural deafness to achieve auditory speech recognition effectively.

  8. The Effect of Post-Reproductive Lifespan on the Fixation Probability of Beneficial Mutations.

    Stefano Giaimo

    Full Text Available Post-reproductive lifespan is a common trait among mammals and is usually considered to be neutral; i.e. with no influence on population dynamics. Here, we explore the role of post-reproductive lifespan in the fixation probability of beneficial genetic variation. We compare two separate, stationary populations living in a constant environment that are equivalent except for the average time their respective members spend in the post-reproductive stage of life. Using a recently derived approximation, we show that fixation of a beneficial mutation is more likely in the population with greater post-reproductive longevity. This finding is surprising, as the population with more prolonged post-reproductive lifespan has smaller effective size and the classic population-genetic model would suggest that decreasing effective size reduces fixation chances of beneficial mutations. Yet, as we explain, in the age-structured case, when effective size gets smaller because of longer post-reproductive lifespan but census size is kept equal, a beneficial mutation has a higher likelihood to get fixed because it finds itself at higher initial frequency.

  9. Differential effects of radical scavengers on X-ray-induced mutation and cytotoxicity in human cells

    The cytotoxic and mutagenic effects of X irradiation on a human lymphoblast cell line were examined in the presence of two radioprotective agents which modulate damage to DNA. The cells were treated with X rays alone or in the presence of either dimethyl sulfoxide or cysteamine. Surviving fraction and mutation to trifluorothymidine resistance (tk locus) and to 6-thioguanine resistance (hgprt locus) were measured. Survival was enhanced when the cells were irradiated in the presence of dimethyl sulfoxide; the D0 rose from 58 to 107 rad. However, at both genetic loci the induced mutant fractions were identical in the presence or absence of dimethyl sulfoxide. Survival was enhanced to a greater degree when the cells were irradiated in the presence of cysteamine; the D0 rose from 58 to 200 rad. Cysteamine also protected the cells from X-ray-induced mutation; the frequencies of X-ray-induced mutation at both the tk and hgprt loci were reduced by 50-75%. No protective effects were observed unless dimethyl sulfoxide or cysteamine was present during irradiation. These findings are discussed in terms of the hypothesis that, unlike for cell killing, radiation-induced mutagenesis in human lymphoblast cells is not mediated by the actions of aqueous free radicals, but rather by the direct effects of ionizing radiation

  10. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA.

    Burnett, Alan K; Hills, Robert K; Green, Claire; Jenkinson, Sarah; Koo, Kenneth; Patel, Yashma; Guy, Carol; Gilkes, Amanda; Milligan, Donald W; Goldstone, Anthony H; Prentice, Archibald G; Wheatley, Keith; Linch, David C; Gale, Rosemary E

    2010-02-01

    We investigated the benefit of adding all-trans retinoic acid (ATRA) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome, and considered interactions between treatment and molecular markers. Overall, 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose. There were data on FLT3 internal tandem duplications and NPM1 mutations (n = 592), CEBPA mutations (n = 423), and MN1 expression (n = 195). The complete remission rate was 68% with complete remission with incomplete count recovery in an additional 16%; 8-year overall survival was 32%. There was no significant treatment effect for any outcome, with no significant interactions between treatment and demographics, or cytarabine randomization. Importantly, there were no interactions by FLT3/internal tandem duplications, NPM1, or CEBPA mutation. There was a suggestion that ATRA reduced relapse in patients with lower MN1 levels, but no significant effect on overall survival. Results were consistent when restricted to patients with normal karyotype. ATRA has no overall effect on treatment outcomes in this group of patients. The study did not identify any subgroup of patients likely to derive a significant survival benefit from the addition of ATRA to chemotherapy. PMID:19965647

  11. Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma

    Jian-Wei Zhang; Hong-Yuan Zhao; Yu-Xiang Ma; Zhi-Huang Hu; Pei-Yu Huang; Li Zhang; Tao Qin; Shao-Dong Hong; Jing Zhang; Wen-Feng Fang; Yuan-Yuan Zhao; Yun-Peng Yang; Cong Xue; Yan Huang

    2015-01-01

    Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC. Methods:By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed. Results:Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes:7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis. Conclusions:Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.

  12. Direct Estimate of the Spontaneous Mutation Rate Uncovers the Effects of Drift and Recombination in the Chlamydomonas reinhardtii Plastid Genome.

    Ness, Rob W; Kraemer, Susanne A; Colegrave, Nick; Keightley, Peter D

    2016-03-01

    Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input of de novo mutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation in Chlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic data set of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies in C. reinhardtii and demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome. PMID:26615203

  13. Effects of short-term spontaneous mutation accumulation for life history traits in grape phylloxera, Daktulosphaira vitifoliae.

    Downie, D A

    2003-11-01

    Mutation is the source of all genetic variation, but rate of input and effects of new mutations for phenotypic traits related to fitness and the role they play in the maintenance of genetic variation are still subject to controversy. These parameters are important in models of the evolution of sex and recombination, the persistence of asexual populations, and the extinction of small populations. Most estimates have come from a few model organisms. Here, mutation accumulation experiments were conducted with three clones of grape phylloxera, Daktulosphaira vitifoliae Fitch, a gall forming herbivore and pest of grapes, to estimate the rate of input and effects of spontaneous mutation on life history traits. This is perhaps the first such experiment using a non-model organism of economic importance. Significant heritable genetic variation accrued in one of three sets of lines for one of four traits measured, and deleterious effects of mutation were found for two of four traits in two of the three sets of lines. Estimates of the parameters by the Bateman-Mukai (BM) method were within the range found in previous studies but at the lower end for genomic mutation rate, U approximately 0.023 and mutational variance, V(M) approximately 0.0003, the upper end for average heterozygous effect, alpha, of approximately -0.11, and on the order of previous estimates for mutational heritability, hM approximately 0.007. Under a model of equal effects of mutations, maximum likelihood (ML) estimates of U were slightly higher, and of alpha lower, than the BM estimates. Support limits were too large to provide much confidence in the ML estimates, however, and models of mutational effects assuming a gamma distribution of effects under different values of the shape parameter, beta, could not be distinguished though likelihoods tended to be lower at lower values of beta (more leptokurtic). Rapid accumulation of deleterious mutations suggest that for many pest species, adaptive response under

  14. Aromatase inhibiting and combined estrogenic effects of parabens and estrogenic effects of other additives in cosmetics

    There is concern widely on the increase in human exposure to exogenous (anti)estrogenic compounds. Typical are certain ingredients in cosmetic consumer products such as musks, phthalates and parabens. Monitoring a variety of human samples revealed that these ingredients, including the ones that generally are considered to undergo rapid metabolism, are present at low levels. In this in vitro research individual compounds and combinations of parabens and endogenous estradiol (E2) were investigated in the MCF-7 cell proliferation assay. The experimental design applied a concentration addition model (CA). Data were analyzed with the estrogen equivalency (EEQ) and method of isoboles approach. In addition, the catalytic inhibitory properties of parabens on an enzyme involved in a rate limiting step in steroid genesis (aromatase) were studied in human placental microsomes. Our results point to an additive estrogenic effect in a CA model for parabens. In addition, it was found that parabens inhibit aromatase. Noticeably, the effective levels in both our in vitro systems were far higher than the levels detected in human samples. However, estrogenic compounds may contribute in a cumulative way to the circulating estrogen burden. Our calculation for the extra estrogen burden due to exposure to parabens, phthalates and polycyclic musks indicates an insignificant estrogenic load relative to the endogenous or therapeutic estrogen burden

  15. Effects of track structure and cell inactivation on the calculation of heavy ion mutation rates in mammalian cells

    Cucinotta, F. A.; Wilson, J. W.; Shavers, M. R.; Katz, R.

    1996-01-01

    It has long been suggested that inactivation severely effects the probability of mutation by heavy ions in mammalian cells. Heavy ions have observed cross sections of inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. In the track structure model of Katz the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated using the dose-response of the system to gamma-rays and the radial dose of the ions and may be equal to unity at small impact parameters for some ions. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT mutations in Chinese hamster cells and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability of mutation by relativistic heavy ions due to the radial extension of ions track from delta-rays in agreement with the microlesion concept. The effects of inactivation on mutations rates make it very unlikely that a single parameter such as LET or Z*2/beta(2) can be used to specify radiation quality for heavy ion bombardment.

  16. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    Aquino, B.; Stefanello, A.A.; Oliveira, M.A.S.; Pedrosa, F.O.; Souza, E.M.; Monteiro, R.A.; Chubatsu, L.S. [Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR (Brazil)

    2015-07-10

    NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain.

  17. Effect of point mutations on Herbaspirillum seropedicae NifA activity

    NifA is the transcriptional activator of the nif genes in Proteobacteria. It is usually regulated by nitrogen and oxygen, allowing biological nitrogen fixation to occur under appropriate conditions. NifA proteins have a typical three-domain structure, including a regulatory N-terminal GAF domain, which is involved in control by fixed nitrogen and not strictly required for activity, a catalytic AAA+ central domain, which catalyzes open complex formation, and a C-terminal domain involved in DNA-binding. In Herbaspirillum seropedicae, a β-proteobacterium capable of colonizing Graminae of agricultural importance, NifA regulation by ammonium involves its N-terminal GAF domain and the signal transduction protein GlnK. When the GAF domain is removed, the protein can still activate nif genes transcription; however, ammonium regulation is lost. In this work, we generated eight constructs resulting in point mutations in H. seropedicae NifA and analyzed their effect on nifH transcription in Escherichia coli and H. seropedicae. Mutations K22V, T160E, M161V, L172R, and A215D resulted in inactive proteins. Mutations Q216I and S220I produced partially active proteins with activity control similar to wild-type NifA. However, mutation G25E, located in the GAF domain, resulted in an active protein that did not require GlnK for activity and was partially sensitive to ammonium. This suggested that G25E may affect the negative interaction between the N-terminal GAF domain and the catalytic central domain under high ammonium concentrations, thus rendering the protein constitutively active, or that G25E could lead to a conformational change comparable with that when GlnK interacts with the GAF domain

  18. The use of Citrus tissue culture for mutation breeding. Effects of plant growth substances and gamma irradiation on embryogenesis

    An embryogenic callus subcultured from unfertilized ovules of the 'Shamouti' orange (Citrus sinensis) was established and is used for mutation-breeding. The callus is habituated and lines of differing embryogenic potential were established. The effect of growth substances and of gamma-irradiation on embryogenesis were studied. Auxins and cytokinins inhibited embryogenesis while inhibitors of auxin synthesis and a cytokinin antagonist significantly stimulate embryogenesis in an embryogenic line. A non-embryogenic callus line did not respond to these treatments. Stimulation of embryogenesis was observed when callus but not when the medium was irradiated. Age of callus prior to subculture and irradiation intensities modify irradiation induced embryogenesis by changing optimal dose range and radiosensitivity of the callus. Addition of IAA to unirradiated medium resulted in increased embryogenesis and greatly stimulated plantlet development in certain combinations of irradiation dose and IAA concentration. (author)

  19. The effects of lexA101, recB21, recF143 and uvrD3 mutations on liquid-holding recovery in ultraviolet-irradiated Escherichia coli K12 recA56

    Using an Escherichia coli K12 recA strain, we have tested the effects of incorporating additional mutations affecting deoxyribonucleic acid (DNA) repair on ultraviolet-radiation sensitivity and in the expression of liquid-holding recovery (LHR). (This laboratory had previously shown that a mutation at uvrA, uvrB or uvrC blocked LHR in a recA strain). In the recA56 background, an additional lexA101 mutation had no effect on UV-radiation sensitivity or LHR. The addition of a recB21 mutation to recA56 did not alter UV-radiation sensitivity, but greatly increased the rate of LHR. The recB gene product (exonuclease V) appears to act as a competitive inhibitor both of excision repair and of photoreactivation under liquid-holding (LH) conditions. The uvrD3 mutation increased the radiation sensitivity of a recA strain, and almost completely blocked LHR. The recA uvrD strain showed more DNA degradation and DNA double-strand breaks during LH than did the recA strain. Rhe recF143 mutation increased both UV-radiation sensitivity and LHR in a recA strain, suggesting that the recF gene product may also function in recA-independent pathways of DNA repair. (orig.)

  20. Effects of some natural extracts on tradescantia somatic cell pink mutation frequencies induced by gamma-ray

    This study deals with the effect of some natural extracts on the pink mutations induced by radiation in Tradescantia 4430 stamen hair cells. Inflorescence cuttings, with or without pretreatments of natural extracts for 3 hours, were exposed to 1 Gy of gamma ray. Comparisons were made on the basis of pooled data during the peak interval between the mean pink mutation frequencies of the two experimental groups. Pretreatments of FB or FB-I resulted in two-fold increases of the pink mutation frequencies, compared to those of control group. Synergism between certain fractions and radiation was a possible cause of increased DNA damage. On the other hand, the extract PG in proper concentrations significantly reduced the pink mutation frequencies (p<0.05). The result meant that PG had a protective effect on radiation-induced cell damage. Tradescantia proved to be an excellent biological model system for assessing the radiomodification effects of natural materials

  1. Effects of partial hepatectomy on induction of mutation frequency by gamma-rays in new HITEC mice

    Mutations induced in vivo by radiation were studied with a transgenic mouse strain, called New HITEC (Hypersensitive In vitro Test of Carcinogenecity), carrying the rpsL gene as a reporter for mutation detection. The wild-type rpsL gene and a gene inducing a kanamycin-resistant phenotype were placed on a pSSW plasmid shuttle vector, and were transfected into E. coli by electroporation after extraction from mouse genomic DNA. Transfected cells were plated on LB plates containing Kanamycine (Km) or Km plus Streptomycine (Sm). The ratio of the colony number on Km and Sm plates to that on Km plates is defined as the rpsL mutation frequency. We had previously investigated differences in mutation frequencies in the testis, spleen, liver, brain, and thymus using rpsL transgenic mice. However, there were some problems in the analysis with a high background mutation frequency. To solve this problem, a partial hepatectomy was tried to increase the mutation frequency detection. The mice were exposed to 3 Gy of gamma rays at 24, 40, 48, or 72 hours after the hepatectomy. Then, the liver was resected on day 7-10 after irradiation, and the mutation frequencies were analyzed. In the mice exposed 24 hours after hepatectomy, the mutation frequency increased approximately four times compared with that of the control mice. In the mice exposed 40, 48, or 72 hours after hepatectomy, the increase in mutation frequency was 2-3 times greater than that of the control mice. These results indicate that hepatectomy is effective in raising the mutation frequency along with the appropriate timing of irradiation

  2. The novel R347g pathogenic mutation of aromatic amino acid decarboxylase provides additional molecular insights into enzyme catalysis and deficiency.

    Montioli, Riccardo; Paiardini, Alessandro; Kurian, Manju A; Dindo, Mirco; Rossignoli, Giada; Heales, Simon J R; Pope, Simon; Voltattorni, Carla Borri; Bertoldi, Mariarita

    2016-06-01

    We report here a clinical case of a patient with a novel mutation (Arg347→Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475-fold drop of kcat compared to the wild-type enzyme. In attempting to unravel the reason(s) for this catalytic defect, we have carried out bioinformatics analyses of the crystal structure of AADC-carbidopa complex with the modelled catalytic loop (residues 328-339). Arg347 appears to interact with Phe103, as well as with both Leu333 and Asp345. We have then prepared and characterized the artificial F103L, R347K and D345A mutants. F103L, D345A and R347K exhibit about 13-, 97-, and 345-fold kcat decrease compared to the wild-type AADC, respectively. However, unlike F103L, the R347G, R347K and R347Q mutants as well as the D345A variant appear to be more defective in catalysis than in protein folding. Moreover, the latter mutants, unlike the wild-type protein and the F103L variant, share a peculiar binding mode of dopa methyl ester consisting of formation of a quinonoid intermediate. This finding strongly suggests that their catalytic defects are mainly due to a misplacement of the substrate at the active site. Taken together, our results highlight the importance of the Arg347-Leu333-Asp345 hydrogen-bonds network in the catalysis of AADC and reveal the molecular basis for the pathogenicity of the variants R347. Following the above results, a therapeutic treatment for patients bearing the mutation R347G is proposed. PMID:26994895

  3. The Effect of Antagonistic Pleiotropy on the Estimation of the Average Coefficient of Dominance of Deleterious Mutations

    Fernández, B.; García-Dorado, A; Caballero, A.

    2005-01-01

    We investigate the impact of antagonistic pleiotropy on the most widely used methods of estimation of the average coefficient of dominance of deleterious mutations from segregating populations. A proportion of the deleterious mutations affecting a given studied fitness component are assumed to have an advantageous effect on another one, generating overdominance on global fitness. Using diffusion approximations and transition matrix methods, we obtain the distribution of gene frequencies for n...

  4. The additive and interactive effects of parenting and children's personality on externalizing behaviour

    Prinzie, P; Onghena, P; Hellinckx, W; Grietens, H; Ghesquiere, P; Colpin, H

    2003-01-01

    Parenting practices have been previously linked to childhood externalizing behaviour However little attention has been given to the potential effect of individual personality differences among children on this relation. The current study assesses the additive effects of children's personality charac

  5. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases

    Lenz, Tobias L.; Deutsch, Aaron J.; Han, Buhm; Hu, Xinli; Okada, Yukinori; Eyre, Stephen; Knapp, Michael; Zhernakova, Alexandra; Huizinga, Tom W. J.; Abecasis, Gonçalo; Becker, Jessica; Boeckxstaens, Guy; Chen, Wei-Min; Franke, Andre; Gladman, Dafna D

    2015-01-01

    Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (ncases = 5,337), type 1 diabetes (T1D; ncases...

  6. Ultaviolet-induced frameshift mutagenesis in Salmonella typhimurium: absence of an effect of mutation frequency decline

    Enhanced yields of UV-induced back mutants to prototrophy are observed when irradiated cells of the Salmonella typhimurium frameshift strain LT2 hisC3076(R46) are plated on defined medium containing broth (2.5%, v/v) rather than a trace (0.02 μg/ml) of the required nutrient (histidine). This broth effect is not abolished, and is in fact augmented, in an excision-deficient derivative of hisC3076(R46) carrying the uvr-302 mutation. Since similar broth effects on UV-induced base-pair substitution mutagenesis have usually been attributed to inhibition of mutation frequency decline (MFD), and since MFD is in turn thought to reflect the activity of an intact excision-repair system, we sought to determine whether or not UV-induced premutational lesions leading to the production of frameshifts are susceptible to MFD. Results with the doubly auxotrophic strain LT2 hisC3076 leuA150 (pKM101) showed that in a population of cells actually undergoing MFD (as judged by a rapid loss of UV-induced reversions of the base-pair substitution marker (leuA150)), no concomitant loss of UV-induced reversions of the frameshift hisC3076 marker could be detected. (orig.)

  7. Modulation of Additive and Interactive Effects in Lexical Decision by Trial History

    Masson, Michael E. J.; Kliegl, Reinhold

    2013-01-01

    Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model…

  8. Effect of small additions of vanadium and niobium on structure and mechanical properties of ductile iron

    Fraś E.; Górny M.; Kawalec M.

    2007-01-01

    Results of investigations of influence of small additions of vanadium (up to 0,15 % V) and niobium (up to 0,04% Nb) on structure of ductile iron is presented in this work. Effect of these additions on distribution of graphite nodule diameter, nodule count, fraction and carbide count have been determined. Investigations of effect of small additions of vanadium and niobium on mechanical properties taking into account tensile strength, yield strength and elongation have also been made.

  9. The Effect of Additional Funds for Low-Ability Pupils - A Nonparametric Bounds Analysis

    de Haan, Monique

    2012-01-01

    This paper investigates the effect of a policy measure that gives secondary schools additional resources for low-ability pupils. Schools are free in deciding how to spend the additional money. I use a nonparametric bounds analysis to estimate upper and lower bounds on the effect of additional funds on exam results of pupils. First I investigate what can be concluded without imposing assumptions; next I layer weak nonparametric assumptions to tighten the bounds. The tightest bounds show that t...

  10. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  11. Site-specific mutations of FtsZ - effects on GTPase and in vitro assembly

    Stricker Jesse

    2001-05-01

    Full Text Available Abstract Background FtsZ, the major cytoskeletal protein in bacterial cytokinesis, assembles in vitro into protofilaments, which can further associate into sheets, bundles or tubes. We have constructed 16 site-directed mutants of E. coli ftsZ, and tested them for GTP hydrolysis and assembly in vitro, and for their ability to complement the temperature sensitive ftsZ84 mutation in E. coli. Results The mutants were grouped into three classes. Benign mutants, which mapped mostly to the front and back surface of the protofilament, were able to complement ftsZ84 in vivo and showed normal assembly in vitro. GTP contact mutations had less than 10% of wild type GTPase activity. They could all assemble in vitro, and several of these mutants could complement ftsZ84. A third, and newly discovered, class of mutations mapped to the sides of the protofilaments. These lateral mutants had mostly normal GTPase and assembly in vitro, but none of them complemented ftsZ84. The non-complementing mutants showed greatly reduced expression from the pBS58 vector, suggesting possible dominant negative effects. Conclusions Several mutants with greatly reduced GTPase could still complement ftsZ84, suggesting that the high level of GTPase observed in vitro is not essential for in vivo function. All of the lateral mutants failed to complement ftsZ84, which suggests that these surfaces of the protofilaments are important for function in cell division. These lateral surfaces may mediate association of FtsZ protofilaments into pairs or small sheets, although their structure is apparently different from the sheets assembled in DEAE dextran or calcium.

  12. Combined Effects of Thermal Neutrons and Diethyl Sulphate on Mutation Frequency and Spectrum in Rice

    Treatment of rice seeds of variety Ptb-10 with 0.076 molar solution of diethyl sulphate drastically reduced the germination of seeds to 21% and the survival of plants to 13%. When seeds irradiated with thermal neutron doses of 5 x 1011 nth/cm2, 1 x 1012 nth/cm2, 5 x 1012 nth/cm2 and 1 x 1013 nth/cm2 were treated with 0.076 M solution of diethyl sulphate, there was an increase of germination and survival with increase in thermal neutron dose. There was a synergistic effect on mutation frequency in combined treatments of 5 x 1011 nth/cm2 and 1 x 1012 nth/cm2 and diethyl sulphate. The mutation frequency, however, decreased with higher doses of neutron and chemical treatments corresponding to survival. Better germination with combined treatments was obtained only when the seeds were treated with the chemical within 24 to 36 h after irradiation. When irradiated seeds were stored for a week or more, no difference could be noted between chemical and combined treatments. Furthermore, low concentration (0.0456 M) and prolonged treatment (4 h) also failed to show appreciable increase in germination. The better germination and survival with some combined treatments can possibly be due to physiological stimulation often noticed with neutron irradiation or due to the acceleration of hydrolysis and loss of efficiency of the chemical. The decrease in mutation frequency with better survival suggests loss of efficiency of the chemical due to rapid hydrolysis. (author)

  13. Effects on human transcriptome of mutated BRCA1 BRCT domain: A microarray study

    BRCA1 (breast cancer 1, early onset) missense mutations have been detected in familial breast and ovarian cancers, but the role of these variants in cancer predisposition is often difficult to ascertain. In this work, the molecular mechanisms affected in human cells by two BRCA1 missense variants, M1775R and A1789T, both located in the second BRCT (BRCA1 C Terminus) domain, have been investigated. Both these variants were isolated from familial breast cancer patients and the study of their effect on yeast cell transcriptome has previously provided interesting clues to their possible role in the pathogenesis of breast cancer. We compared by Human Whole Genome Microarrays the expression profiles of HeLa cells transfected with one or the other variant and HeLa cells transfected with BRCA1 wild-type. Microarray data analysis was performed by three comparisons: M1775R versus wild-type (M1775RvsWT-contrast), A1789T versus wild-type (A1789TvsWT-contrast) and the mutated BRCT domain versus wild-type (MutvsWT-contrast), considering the two variants as a single mutation of BRCT domain. 201 differentially expressed genes were found in M1775RvsWT-contrast, 313 in A1789TvsWT-contrast and 173 in MutvsWT-contrast. Most of these genes mapped in pathways deregulated in cancer, such as cell cycle progression and DNA damage response and repair. Our results represent the first molecular evidence of the pathogenetic role of M1775R, already proposed by functional studies, and give support to a similar role for A1789T that we first hypothesized based on the yeast cell experiments. This is in line with the very recently suggested role of BRCT domain as the main effector of BRCA1 tumor suppressor activity

  14. The combined effect of two mutations that alter serially homologous color pattern elements on the fore and hindwings of a butterfly

    Vedder Lindsey

    2007-05-01

    differentiation of the signaling centers of a subset of the serial homologous eyespots present on both the fore and the hindwing in a dose-dependent fashion. The effect of Missing on the forewing, however, is only observed when the mutation Spotty introduces additional eyespots on this wing. Spotty, on the other hand, controls the differentiation of eyespot centers only on the forewing. Spotty, unlike Missing, may be under Ubx gene regulation, since it affects a subset of eyespots on only one of the serially homologous wings.

  15. Effect of Particle Addition on Degradation Rate of Methylene Blue in an Ultrasonic Field

    Honma, Chiemi; Kobayashi, Daisuke; Matsumoto, Hideyuki; Takahashi, Tomoki; Kuroda, Chiaki; Otake, Katsuto; Shono, Atsushi

    2013-07-01

    Ultrasound has been found to be an attractive advanced technology for the degradation of hazardous organic compounds in water. In addition, the sonochemical reaction is enhanced by particle addition. However, the enhancement mechanism of particle addition has not been investigated well, because ultrasound enhances not only chemical reactions but also mass transfer. In this study, the ultrasonic degradation of methylene blue was carried out, and the effects of the ultrasonic irradiation condition on the degradation rate were investigated. The effect of ultrasonic frequency on the improvement of degradation by particle addition was also investigated. The order of degradation rate with frequency was the same as the tendency of sonochemical efficiency value obtained using KI oxidation dosimetry method (SEKI). The degradation process of methylene blue was intensified by particle addition, and the degradation rate increased with increasing amount of particle addition. The enhancement of degradation rate by particle addition was influenced by both ultrasonic frequency and type or diameter of particles.

  16. Study on mutation induced effect of gamma ray and DES on black bean phaseolus vulgaris

    The study on mutation induced effect of gamma ray and DES on black bean Phaseolus vulgaris was carried out at Radiobiology Department, Nuclear Research Institute of Dalat. Dry seeds of variety No.1847 - Bonita - Cuba in set of 13 black bean varieties were irradiated with gamma ray from 60Co source at dose range from 150 Gy to 350 Gy and treated with DES at concentration from 0.1% to 0.3% in 2 hours for experiments in laboratory. The doses of 200, 250, 300 Gy and concentration of 0.2% DES in 2 hours were selected to treat dry seeds for experiments on the field. In populations of M1 generation, the height, number of branches and fruits per plant, number of seeds per fruit were decreased with increasing of irradiation doses. In populations of M2 generation, individual variants in leaf shape, chlorophyll, short stem, dwarf, early maturity, flowering in very short time were obtained and selected in all treatment cases. Mutation frequency at dose of 300 Gy was higher than that in other treatment cases, but ratio of sterility is also largest. The mutant lines of early maturity and short stem with flowering in very short time are promised materials for further studies. (author)

  17. Mutation effects of C2+ ion irradiation on the greasy Nitzschia sp

    Highlights: • The optimal conditions of C2+ ion irradiation on Nitzschia sp. were discussed. • Get the “saddle type” survival curve. • One mutant whose lipid content improved significantly was selected. • The C2+ ion irradiation didn’t change the algae's morphology and growth rate. - Abstract: Screening and nurturing algae with high productivity, high lipid content and strong stress resistance are very important in algae industry. In order to increase the lipid content, the Nitzschia sp. was irradiated with a 3 MeV C2+ beam. The sample pretreatment method was optimized to obtain the best mutagenic condition and the survival ratio curve. The positive mutants with a significant improvement in lipid content were screened and their C2+ mutagenic effects were analyzed by comparing the greasiness and growth characteristics with the wild type algae. Results showed that when the Nitzschia sp. was cultivated in nutritious medium containing 10% glycerol solution, and dried on the filter for 5 min after centrifugation, the realization of the microalgae heavy ion mutagenesis could be done. The survival ratio curve caused by C2+ irradiation was proved to be “saddle-shaped”. A positive mutant was screened among 20 survivals after irradiation, the average lipid content of the mutation increased by 9.8% than the wild type after 4 generations. But the growth rate of the screened mutation didn’t change after the heavy ion implantation compared to the wild type algae

  18. Site-directed mutation of a laccase from Thermus thermophilus: Effect on the activity profile

    Liu Xin

    2012-01-01

    Full Text Available A site-directed mutant R453T of a laccase from Thermus thermophilus HB27 (Tth-laccase was constructed in order to investigate the effect on laccase catalytic properties. The mutated gene was cloned and overexpressed in Escherichia coli. Nickel-affinity purification was achieved and followed by copper ion incorporation. The mature mutated enzyme was quantitatively equal to the wild type. A photometric assay based on the oxidation of the substrate 2,2-azino-bis-(3- ethylbenzthiazoline-6-sulfonate (ABTS was employed in comparison with the wild-type Tth-laccase on catalytic properties. The R453T mutant exhibited improvement in substrate affinity and specific activity at room temperature, whereas those parameters were not significantly influenced when the temperature increased up to 65°C or higher. The mutant had better catalytic activity than that of the wild type at acidic pH. Investigated by circular dichroism spectroscopy, the mutant Tth-laccase displayed similar profiles at low and high temperatures.

  19. Effect of mutations in the uthetarD cistron of Escherichia coli on repair resynthesis

    Kuemmerle, N.B.; Ley, R.D.; Masker, W.E. (Oak Ridge National Lab., TN (USA). Biology Div.)

    1982-01-01

    The resynthesis step of the excision repair pathway has been examined in Escherichia coli K12 strains isogenic except for mutations in the uvrD cistron. Strains mutant at the uvrD3, uvrD101, uvrE156, and recLl52 loci exhibited slight but distinct differences in their response to ultraviolet radiation. The repair capacity of the uvrD101 mutant was given special attention. Repair resynthesis in this mutant was saturated at fluences greater than about 20 J/m/sup 2/. Isopycnic analysis of repaired deoxyribonucleic acid from this strain revealed a two-fold increase over its wild-type counterpart in the amount of repair replication performed after a dose of 15 J/m/sup 2/. Sedimentation velocity analysis of DNA after selective photolysis of bromouracil-containing repaired regions showed that the uvrD101 mutation exerted its primary effect on the long-patch component of excision repair. The uvrD101 mutant performed long-patch repair at a larger number of sites than the number repaired by this mode in the wild-type strain; these patches were more extensive in length than the long-patch component in wild-type.

  20. The effect of mutations in the uthetarD cistron of Escherichia coli on repair resynthesis

    The resynthesis step of the excision repair pathway has been examined in Escherichia coli K12 strains isogenic except for mutations in the uvrD cistron. Strains mutant at the uvrD3, uvrD101, uvrE156, and recLl52 loci exhibited slight but distinct differences in their response to ultraviolet radiation. The repair capacity of the uvrD101 mutant was given special attention. Repair resynthesis in this mutant was saturated at fluences greater than about 20 J/m2. Isopycnic analysis of repaired deoxyribonucleic acid from this strain revealed a two-fold increase over its wild-type counterpart in the amount of repair replication performed after a dose of 15 J/m2. Sedimentation velocity analysis of DNA after selective photolysis of bromouracil-containing repaired regions showed that the uvrD101 mutation exerted its primary effect on the long-patch component of excision repair. The uvrD101 mutant performed long-patch repair at a larger number of sites than the number repaired by this mode in the wild-type strain; these patches were more extensive in length than the long-patch component in wild-type. (orig.)

  1. The state of the art on zinc addition effect in the nuclear reactor coolant system

    Zinc addition to the primary coolant appears promising with regard to reducing radiation dose rate, and is being used in several plants. Zinc acts to inhibit the corrosion of stainless steel by forming a thin protective film. This oxide film, with no associated increase in cobalt concentration within the film, thereby lowers the dose rate. This report on the state of art presents an overview of the zinc addition to the reactor coolant to reduce the primary system dose rate. This report discusses the effect of zinc addition for BWRs and PWRs, the thermodynamic of zinc chemistry, and the effect of zinc addition on material corrosion. (author)

  2. The state of the art on zinc addition effect in the nuclear reactor coolant system

    Kim, U. C.; Sung, K. W.; Kim, K. R.; Paek, S.; Maeng, W. Y

    1999-12-01

    Zinc addition to the primary coolant appears promising with regard to reducing radiation dose rate, and is being used in several plants. Zinc acts to inhibit the corrosion of stainless steel by forming a thin protective film. This oxide film, with no associated increase in cobalt concentration within the film, thereby lowers the dose rate. This report on the state of art presents an overview of the zinc addition to the reactor coolant to reduce the primary system dose rate. This report discusses the effect of zinc addition for BWRs and PWRs, the thermodynamic of zinc chemistry, and the effect of zinc addition on material corrosion. (author)

  3. The Ups and Downs of Mutation Frequencies during Aging Can Account for the Apert Syndrome Paternal Age Effect

    Song-Ro Yoon; Jian Qin; Rivka L Glaser; Ethylin Wang Jabs; Wexler, Nancy S; Rebecca Sokol; Norman Arnheim; Peter Calabrese

    2009-01-01

    Author Summary Epidemiological studies show that the incidence of some genetic diseases increases with the age of the father. This “paternal age effect” is traditionally explained by the fact that, as men age, the male germ-line cells continue to divide, and each division presents an additional chance for mutation. Apert syndrome is an example of such a disease; virtually all cases are caused by spontaneous base substitution mutations of paternal origin at either one of just two sites. In thi...

  4. Biphenyl compounds are hydroxyl radical scavengers: their effective inhibition for UV-induced mutation in Salmonella typhimurium TA102.

    Fujita, S; Taira, J

    1994-09-01

    In our previous study, we found several hydroxylated biphenyl compounds have a great scavenging effect for hydroxyl radicals (.OH). In this study, to elucidate the relationship between generation of the .OH and photo-mutagenesis, six biphenyl compounds such as dehydrodieugenol, dehydrodivanillyl alcohol, dehydrodidihydroeugenol, dehydrodicreosol, magnolol and honokiol, respectively, were examined for their ability to inhibit UV-induced mutation in Salmonella typhimurium TA102. The relative mutagenic activities (RMA, %) indicated the mutation frequency of treated cells divided by the mutation frequency of control cells times 100%. The RMA (%) are as follows: 28 +/- 1, 31 +/- 1, 33 +/- 1, 41 +/- 2, 62 +/- 1, and 62 +/- 4 at concentrations of 5 micrograms per plate for dehydrodieugenol, dehydrodivanillyl alcohol, dehydrodidihydroeugenol, dehydrodicreosol, magnolol, and honokiol, respectively. These values indicate that low concentrations of these biphenyl compounds effectively suppress UV-induced mutagenesis. Also, these compounds acted as effective antimutagens in a dose-dependent manner (0.00005-5 micrograms per plate). These compounds are effective .OH scavengers. Consequently, the results obtained above suggest that these compounds could inhibit against UV-induced mutations by scavenging of .OH generated by UV irradiation. The results also suggest that .OH are associated with UV-induced mutation in Salmonella typhimurium TA102. PMID:7982632

  5. Non-additive genetic effects for fertility traits in Canadian Holstein cattle (Open Access publication

    Miglior Filippo

    2007-02-01

    Full Text Available Abstract The effects of additive, dominance, additive by dominance, additive by additive and dominance by dominance genetic effects on age at first service, non-return rates and interval from calving to first service were estimated. Practical considerations of computing additive and dominance relationships using the genomic relationship matrix are discussed. The final strategy utilized several groups of 1000 animals (heifers or cows in which all animals had a non-zero dominance relationship with at least one other animal in the group. Direct inversion of relationship matrices was possible within the 1000 animal subsets. Estimates of variances were obtained using Bayesian methodology via Gibbs sampling. Estimated non-additive genetic variances were generally as large as or larger than the additive genetic variance in most cases, except for non-return rates and interval from calving to first service for cows. Non-additive genetic effects appear to be of sizeable magnitude for fertility traits and should be included in models intended for estimating additive genetic merit. However, computing additive and dominance relationships for all possible pairs of individuals is very time consuming in populations of more than 200 000 animals.

  6. The Inhibitory Effects of Aqueous Extract from Guava Twigs, Psidium guajava L., on Mutation and Oxidative Damage

    Zhi-Chyang Kang

    2013-01-01

    Full Text Available This study examines the inhibitory effects of the aqueous extract from guava twigs (GTE, Psidium guajava L., on mutation and oxidative damage. The results show that GTE inhibits the mutagenicity of 4-nitroquinoline-N-oxide (4-NQO, a direct mutagen, and 2-aminoanthracene (2-AA, an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. In addition, GTE shows radical scavenging, reducing activities, tyrosinase inhibition, and liposome protection effects. Meanwhile, GTE in the range of 0.1–0.4 mg/mL protects liver cells from tert-butyl-hydroperoxide-(t-BHP- induced cytotoxicity. Furthermore, the cytotoxicity inhibition of GTE in the t-BHP-treated cells was demonstrated in a dose-dependent manner. High-performance liquid chromatography analysis suggests that the major phenolic constituents in GTE are gallic acid, ferulic acid, and myricetin. These active phenolic components may contribute to the biological protective effects of GTE in different models. The data suggest that GTE exhibiting biological activities can be applied to antimutation, antityrosinase, and antioxidative damage.

  7. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice.

    Edgar, D.; Shabalina, I.; Camara, Y.; Wredenberg, A.; Calvaruso, M.A.; Nijtmans, L.G.J.; Nedergaard, J.; Cannon, B.; Larsson, N.G.; Trifunovic, A.

    2009-01-01

    The mtDNA mutator mice have high levels of point mutations and linear deletions of mtDNA causing a progressive respiratory chain dysfunction and a premature aging phenotype. We have now performed molecular analyses to determine the mechanism whereby these mtDNA mutations impair respiratory chain fun

  8. Effects of the jimpy mutation on mouse retinal structure and function.

    Hovhannisyan, Anahit; Benkner, Boris; Biesemeier, Antje; Schraermeyer, Ulrich; Kukley, Maria; Münch, Thomas A

    2015-12-15

    The Jimpy mutant mouse has a point mutation in the proteolipid protein gene (plp1). The resulting misfolding of the protein leads to oligodendrocyte death, myelin destruction, and failure to produce adequately myelinated axons in the central nervous system (CNS). It is not known how the absence of normal myelination during development influences neural function. We characterized the Jimpy mouse retina to find out whether lack of myelination in the optic nerve during development has an effect on normal functioning and morphology of the retina. Optokinetic reflex measurements showed that Jimpy mice had, in general, a functional visual system. Both PLP1 antibody staining and reverse transcriptase-polymerase chain reaction for plp1 mRNA showed that plp1 is not expressed in the wild-type retina. However, in the optic nerve, plp1 is normally expressed, and consequently, in Jimpy mutant mice, myelination of axons in the optic nerve was mostly absent. Nevertheless, neither axon count nor axon ultrastructure in the optic nerve was affected. Physiological recordings of ganglion cell activity using microelectrode arrays revealed a decrease of stimulus-evoked activity at mesopic light levels. Morphological analysis of the retina did not show any significant differences in the gross morphology, such as thickness of retinal layers or cell number in the inner and outer nuclear layer. The cell bodies in the inner nuclear layer, however, were larger in the peripheral retina of Jimpy mutant mice. Antibody labeling against cell type-specific markers showed that the number of rod bipolar and horizontal cells was increased in Jimpy mice. In conclusion, whereas the Jimpy mutation has dramatic effects on the myelination of retinal ganglion cell axons, it has moderate effects on retinal morphology and function. PMID:26011242

  9. Additivity of Feature-Based and Symmetry-Based Grouping Effects in Multiple Object Tracking.

    Wang, Chundi; Zhang, Xuemin; Li, Yongna; Lyu, Chuang

    2016-01-01

    Multiple object tracking (MOT) is an attentional process wherein people track several moving targets among several distractors. Symmetry, an important indicator of regularity, is a general spatial pattern observed in natural and artificial scenes. According to the "laws of perceptual organization" proposed by Gestalt psychologists, regularity is a principle of perceptual grouping, such as similarity and closure. A great deal of research reported that feature-based similarity grouping (e.g., grouping based on color, size, or shape) among targets in MOT tasks can improve tracking performance. However, no additive feature-based grouping effects have been reported where the tracking objects had two or more features. "Additive effect" refers to a greater grouping effect produced by grouping based on multiple cues instead of one cue. Can spatial symmetry produce a similar grouping effect similar to that of feature similarity in MOT tasks? Are the grouping effects based on symmetry and feature similarity additive? This study includes four experiments to address these questions. The results of Experiments 1 and 2 demonstrated the automatic symmetry-based grouping effects. More importantly, an additive grouping effect of symmetry and feature similarity was observed in Experiments 3 and 4. Our findings indicate that symmetry can produce an enhanced grouping effect in MOT and facilitate the grouping effect based on color or shape similarity. The "where" and "what" pathways might have played an important role in the additive grouping effect. PMID:27199875

  10. Non–lineage/stage-restricted effects of a gain-of-function mutation in tyrosine phosphatase Ptpn11 (Shp2) on malignant transformation of hematopoietic cells

    Xu, Dan; Liu, Xia; Yu, Wen-Mei; Meyerson, Howard J.; Guo, Caiying; Gerson, Stanton L.; Qu, Cheng-Kui

    2011-01-01

    Activating mutations in protein tyrosine phosphatase 11 (Ptpn11) have been identified in childhood acute leukemias, in addition to juvenile myelomonocytic leukemia (JMML), which is a myeloproliferative disorder (MPD). It is not clear whether activating mutations of this phosphatase play a causal role in the pathogenesis of acute leukemias. If so, the cell origin of leukemia-initiating stem cells (LSCs) remains to be determined. Ptpn11E76K mutation is the most common and most active Ptpn11 mut...

  11. Mutagenic effects of gamma rays and EMS on frequency and spectrum of chlorophyll mutations in urdbean (Vigna mungo (L.) Hepper)

    Chlorophyll mutations act as a significant index in the judgment of induced genetic variations in mutagen treated populations. Different types of chlorophyll mutation have been observed in various crop plants. In the current study, the effect of different concentrations (40 kR, 50 kR and 60 kR) of gamma rays, Ethyl Methane Sulphonate (50 mM, 60 mM and 70 mM) in single and combination dose/concentration on the frequency and spectrum of chlorophyll mutation and the effect of VBN 4 urdbean variety to such irradiation dose was observed. Results showed induction of broad spectrum of chlorophyll mutations which included albina, xantha, chlorina and viridis. Among these chlorina type was predominant in all the mutagenic treatments. The albina type of chlorophyll mutants occurred very rarely and was found only at 60 mM of EMS treatment and at 40 kR + 50 mM, 60 kR + 70 mM of combination treatments. Based on the chlorophyll mutation frequency, gamma rays were most effective followed by EMS and combination of treatments. (author)

  12. Effect of Additives on Wood Pellet Physical and Thermal Characteristics: A Review

    Dmitry Tarasov; Chander Shahi; Mathew Leitch

    2013-01-01

    Additives play a major role in wood pellet characteristics and are a subject of major interest as they act as binding agents for the biomass raw material. Past research has reported the use of lignosulphonate, dolomite, starches, potato flour and peel, and some motor and vegetable oils as additives for wood pellet production. This paper reviews the available research on the effect of different additives on wood pellets' physical and thermal characteristics. It was found that lignosulphonate a...

  13. Effects of Food Additives on Susceptibility of Gram Negative Bacteria Derived from Dry-Fermented Sausage

    DORJ, Serjmyadag; SHIMADA, Kenichiro; SEKIKAWA, Mitsuo; 島田, 謙一郎; 関川, 三男

    2009-01-01

    This study examined the effects of food additives on gram-negative bacteria. The food additives used included synthetic antioxidants (butylated hydroxyanisole, BHA, and butylated hydroxytoluene, BHT), a curing agent and lactic acid with or without a cell-free supernatant (CFS) containing antimicrobial compounds of Lactobacillus sakei D-1001. The gram-negative bacteria were selected from dry-fermented sausages and cultured with different food additives for 18 h in nutrient broth, and then anot...

  14. The Effects of Different Silage Additives on the Quality of Sugar Beet Pulp Silage

    ŞAHİN, Kâzım; ÇERÇİ, İ. Halil; GÜLER, Talat

    1999-01-01

    In this study, the effect of different silage additive added during ensiling period was investigated on the silages quality and determination of storage characters of sugar beet pulp. Treatment groups consisted of silage additives. These groups were K group no additives, F group with %5 formic acid, P group with %8 whole crop barley after wilting silage, M group with %8 corn silage and S group with whole crop barley added straw with treated HCI silage. The changes in nutrients contents, fe...

  15. Synergistic effect of additives including multifunctional acrylates in wood plastic composites

    Wood Plastic Composite (WPC) was prepared with simul (soft wood, density = 0.4g/cc) and butylmethacrylate (BMA) monomer using 10% methanol as the swelling agent. Effect of additives including multifunctional acrylates such as tripropylene glycol diacrylate (TPGDA), trimethylol propane triacrylate (TMPTA), oligomer acrylates like the urethane (UA), epoxy (EA) and polyester (PEA) acrylates and N-vinyl pyrrolidone (NVP) was investigated using 1 to 3 Mrad dose at 0.8 Mrad/h. Synergistic increases in polymer loading yields was achieved in presence of the additives, particularly with the trifunctional acrylate (TMPTA). In addition, acid as well as urea were also used as co-additives and synergistic enhancement in yields of polymer loading were obtained. The synergistic polymer loading by acid addition causes substantial decrease in tensile strength of the composite; but other additives and co-additives increase both the polymer loading and the tensile strength in these systems. (author)

  16. Cardiac effects of the c.1583 C→G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy.

    Zhang, Li; Shen, Hongrui; Zhao, Zhe; Bing, Qi; Hu, Jing

    2015-10-01

    The present study aimed to examine and analyze cardiac involvement in two Emery‑Dreifuss muscular dystrophy (EDMD) pedigrees caused by the c.1583 C→G mutation of the lamin A/C gene (LMNA). The clinical and genetic characteristics of members of two families with EDMD were evaluated by performing neurological examinations, skeletal muscle biopsies, cardiac evaluations, including electrocardiography, 24 h Holter, ultrasound cardiography and 99TcM‑MIBI‑gated myocardiac perfusion imaging, and genomic DNA sequencing. Family history investigations revealed an autosomal dominant transmission pattern of the disease in Family 1 and a sporadic case in Family 2. The three affected patients exhibited typical clinical features of EDMD, including joint contractures, muscle weakness and cardiac involvement. Muscle histopathological investigation revealed dystrophic features. In addition, each affected individual exhibited either cardiac arrhythmia, which was evident as sinus tachycardia, atrial flutter or complete atrioventricular inhibition. Cardiac imaging revealed dilated cardiomyopathy in two of the individuals, one of whom was presented with heart failure. The second patient presented with no significant abnormalities in cardiac structure or function. The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein. In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure. As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis. PMID:26165385

  17. Effects of biological pit additives on microbial ecology of stored pig manure

    The effects of biological pit additives on microbial ecology in stored pig manure were investigated using a dynamic manure storage system, which allowed for continual addition of swine feces and urine. After 13 weeks of manure collection and storage, four treatments were added to tanks (900 L capaci...

  18. Trends in lignin modification: a comprehensive analysis of the effects of genetic manipulations/mutations on lignification and vascular integrity

    Anterola, Aldwin M.; Lewis, Norman G.

    2002-01-01

    activities. Such enzymes thus fulfill subsidiary processing roles, with all (except CCOMT) apparently being bifunctional for both H and G substrates. Their severe downregulation does, however, predictably result in impaired monolignol biosynthesis, reduced lignin deposition/vascular integrity, (upstream) metabolite build-up and/or shunt pathway metabolism. There was no evidence for an alternative acid/ester O-methyltransferase (AEOMT) being involved in lignin biosynthesis.The G/S lignin pathway networks are operative in specific cell types in angiosperms and employ two additional biosynthetic steps to afford the corresponding S components, i.e. through introduction of an hydroxyl group at C-5 and its subsequent O-methylation. [These enzymes were originally classified as ferulate-5-hydroxylase (F5H) and caffeate O-methyltransferase (COMT), respectively.] As before, neither step has apparently any role in carbon allocation to the pathway; hence their individual downregulation/manipulation, respectively, gives either a G enriched lignin or formation of the well-known S-deficient bm3 "lignin" mutant, with cell walls of impaired vascular integrity. In the latter case, COMT downregulation/mutation apparently results in utilization of the isoelectronic 5-hydroxyconiferyl alcohol species albeit in an unsuccessful attempt to form G-S lignin proper. However, there is apparently no effect on overall G content, thereby indicating that deposition of both G and S moieties in the G/S lignin forming cells are kept spatially, and presumably temporally, fully separate. Downregulation/mutation of further downstream steps in the G/S network [i.e. utilizing 4CL, CCR and CAD isoforms] gives predictable effects in terms of their subsidiary processing roles: while severe downregulation of 4CL gave phenotypes with impaired vascular integrity due to reduced monolignol supply, there was no evidence in support of increased growth and/or enhanced cellulose biosynthesis. CCR and CAD downregulation/mutations

  19. Effect of cold atmospheric pressure He-plasma jet on DNA change and mutation

    Yaopromsiri, C.; Yu, L. D.; Sarapirom, S.; Thopan, P.; Boonyawan, D.

    2015-12-01

    Cold atmospheric pressure plasma jet (CAPPJ) effect on DNA change was studied for assessment of its safety. The experiment utilized a home-developed CAPPJ using 100% helium to directly treat naked DNA plasmid pGFP (plasmid green fluorescent protein). A traversal electric field was applied to separate the plasma components and both dry and wet sample conditions were adopted to investigate various factor roles in changing DNA. Plasma species were measured by using optical emission spectroscopy. DNA topological form change was analyzed by gel electrophoresis. The plasma jet treated DNA was transferred into bacterial Escherichia coli cells for observing mutation. The results show that the He-CAPPJ could break DNA strands due to actions from charge, radicals and neutrals and potentially cause genetic modification of living cells.

  20. Polyelectrolyte addition effect on the properties of setting hydraulic cements based on calcium phosphate

    In the present work the effects of the addition of some poly electrolytes (sodium alginate and poly acrylic acid) on the solubility, crystalline phases, pH and mechanical strength under compression of three calcium phosphate cements were studied. (author)

  1. 75 FR 66752 - ILP Effectiveness Evaluation 2010; Additional Notice of Multi-Stakeholder Technical Conference on...

    2010-10-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission ILP Effectiveness Evaluation 2010; Additional Notice of Multi- Stakeholder..., ``Notice of Interviews, Teleconferences, Regional Workshops And Multi-Stakeholder Technical Conference...

  2. Effects of 16S rRNA gene mutations on tetracycline resistance in Helicobacter pylori

    Gerrits, Monique; Berning, M.; Vliet, Arnoud; Kuipers, Ernst; Kusters, Johannes

    2003-01-01

    textabstractThe triple-base-pair 16S rDNA mutation AGA(926-928)-->TTC mediates high-level tetracycline resistance in Helicobacter pylori. In contrast, single- and double-base-pair mutations mediated only low-level tetracycline resistance and decreased growth rates in the presence of tetracycline, explaining the preference for the TTC mutation in tetracycline-resistant H. pylori isolates.

  3. Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase activity of SAMHD1 can not explain the retroviral restriction defect.

    Bhattacharya, Akash; Wang, Zhonghua; White, Tommy; Buffone, Cindy; Nguyen, Laura A; Shepard, Caitlin N; Kim, Baek; Demeler, Borries; Diaz-Griffero, Felipe; Ivanov, Dmitri N

    2016-01-01

    SAMHD1, a dNTP triphosphohydrolase, contributes to interferon signaling and restriction of retroviral replication. SAMHD1-mediated retroviral restriction is thought to result from the depletion of cellular dNTP pools, but it remains controversial whether the dNTPase activity of SAMHD1 is sufficient for restriction. The restriction ability of SAMHD1 is regulated in cells by phosphorylation on T592. Phosphomimetic mutations of T592 are not restriction competent, but appear intact in their ability to deplete cellular dNTPs. Here we use analytical ultracentrifugation, fluorescence polarization and NMR-based enzymatic assays to investigate the impact of phosphomimetic mutations on SAMHD1 tetramerization and dNTPase activity in vitro. We find that phosphomimetic mutations affect kinetics of tetramer assembly and disassembly, but their effects on tetramerization equilibrium and dNTPase activity are insignificant. In contrast, the Y146S/Y154S dimerization-defective mutant displays a severe dNTPase defect in vitro, but is indistinguishable from WT in its ability to deplete cellular dNTP pools and to restrict HIV replication. Our data suggest that the effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain the retroviral restriction defect, and we hypothesize that enzymatic activity of SAMHD1 is subject to additional cellular regulatory mechanisms that have not yet been recapitulated in vitro. PMID:27511536

  4. Combined-modality radioimmunotherapy: synergistic effect of paclitaxel and additive effect of bevacizumab

    Introduction: This study was undertaken to investigate the effect of paclitaxel and bevacizumab on the therapeutic efficacy of 90Y-labeled B3 monoclonal antibody, directed against Ley antigen, for the treatment of Ley-positive A431 tumors implanted subcutaneously in the right hind flank of nude mice. Methods: When the tumor size reached ∼200 mm3, the mice received a single dose of intravenous (iv) 90Y-labeled B3 (60 μCi/150 μg or 100 μCi/150 μg B3), intraperitoneal paclitaxel (40 mg/kg) or iv bevacizumab (5 mg/kg) for monotherapy. To investigate the effect of combined therapies on survival, the mice were treated with two or three agents in the following combinations: 90Y-B3 on day 0 and paclitaxel on day 1; bevacizumab on −1 day and 90Y-B3 on day 0; bevacizumab on −1 day and paclitaxel on day 1; bevacizumab, 90Y-B3 and paclitaxel each at 1-day intervals. The mice with no treatment were used as a control. The tumor volume at 1000 mm3 was used as a surrogate end point of survival. Results: Compared to control animals, paclitaxel delayed tumor growth with a significantly longer median survival time (P90Y-B3 increased the median survival time in a dose-dependent manner (P90Y-B3 showed a statistically insignificant increase in the median survival time compared to 90Y-B3 alone (P=.25). The tumor sizes of all animals in these groups reached the surrogate end point of survival by day 35. In contrast, the combined therapy involving 90Y-B3 with paclitaxel showed a striking synergistic effect in shrinking tumors and prolonging the survival time (P90Y-B3 and 100 μCi 90Y-B3, respectively. The addition of bevacizumab treatment 1 day before the combined therapy of 60 μCi 90Y-B3 with paclitaxel did not produce a statistically significant increase in survival when compared to the 90Y-B3 with paclitaxel (P>.10). Fluorescence microscopy analysis indicated that paclitaxel increased, whereas bevacizumab decreased, the accumulation and penetration of Alexa Fluor 647-B3 into

  5. Categorical and continuous - disentangling the neural correlates of the carry effect in multi-digit addition

    Dressel Katharina; Willmes Klaus; Klein Elise; Domahs Frank; Wood Guilherme; Nuerk Hans-Christoph; Moeller Korbinian

    2010-01-01

    Abstract Background Recently it was suggested that the carry effect observed in addition involves both categorical and continuous processing characteristics. Methods In the present study, we aimed at identifying the specific neural correlates associated with processing either categorical or continuous aspects of the carry effect in an fMRI study on multi-digit addition. Results In line with our expectations, we observed two distinct parts of the fronto-parietal network subserving numerical co...

  6. Effects of BRCA1 and BRCA2 mutations on female fertility

    Smith, Ken R.; Hanson, Heidi A.; Mineau, Geraldine P; Buys, Saundra S.

    2011-01-01

    Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into m...

  7. A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis

    Di Fede, G; Catania, M; Morbin, M; Rossi, G; S. Suardi; Mazzoleni, G; Merlin, M.; A.R. Giovagnoli; Prioni, S.; A. Erbetta; C. Falcone; Gobbi, M.; L. Colombo; A. Bastone; M. Beeg

    2009-01-01

    β-Amyloid precursor protein (APP) mutations cause familial Alzheimer’s disease with nearly complete penetrance. We found an APP mutation [alanine-673→valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced β-amyloid (Aβ) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-t...

  8. Effects of Roundup formulations, nutrient addition, and Western mosquitofish (Gambusia affinis) on aquatic communities.

    Geyer, Rebecca L; Smith, Geoffrey R; Rettig, Jessica E

    2016-06-01

    Aquatic communities can be affected by herbicides, nutrient addition, and non-native fish species. We conducted a mesocosm experiment to examine the direct and interactive effects of three stressors: (1) Roundup formulations (Roundup Weed and Grass Killer(®) and Roundup Poison Ivy and Tough Brush Killer Plus(®)), (2) nutrient addition, and (3) the presence of the non-native Western mosquitofish (Gambusia affinis), on experimental pond communities. Roundup formulations had the most widespread effects on the zooplankton community, but effects varied between formulations and among taxa. The only significant effect of nutrient addition was a lowering of Daphnia abundance in the nutrient addition treatments. The abundances of Daphnia, mid-sized cladocerans, and total zooplankton were lowered by mosquitofish, but no other taxa showed significant mosquitofish effects. We found several two-way and three-way interactions among the stressors, but these varied among zooplankton taxa. Chlorophyll a levels were higher with nutrient addition but were not significantly affected by Roundup formulation or mosquitofish. Our results suggest toxicity of Roundup formulations varies among taxa, and Roundup formulations differ in their toxicity to zooplankton, but with no cascading effects on primary producers. In addition, interactions among stressors affected the zooplankton community. PMID:26944427

  9. Effect of Nano Oil Additive Proportions on Friction and Wear Performance of Automotive Materials

    A. Vadiraj

    2012-03-01

    Full Text Available The effect of nano boric acid and nano copper based engine and transmission oil additives in different volume ratios (1:10, 2:10, and 3:10 on friction and wear performance of cast iron and case carburized gear steel has been investigated. The results show that coefficient of friction increases with increase in volume ratio of engine oil additives and decreases with increasing in volume ratio of transmission oil additives. Cast iron substrate shows higher wear damage than case carburized gear steel. Nano copper additive with crystalline atomic structure shows more severe three body wear compared to boric acid with layered lattice structure.

  10. The Effects of Non—Metal Additives on Hydration Reisitance of MgO—C Bricks

    OUYAGNG; WANGRuikun; 等

    2000-01-01

    The general method of solving the problem of hydration of MgO-C brick is by adding with metal Si,Mg or compround metal additives,but metal additives have bad effect on the MgO-C brick,The test tried adding non-metal additives to matrix material.The results showed that a suitable amount of this kind of additives not only inhibits hydration of MgO-C brick and does not affect corrosion resistance and avoids thermal expansion,but also can improve oxidation resistance.

  11. Dlx5 Homeodomain:DNA Complex: Structure, Binding and Effect of Mutations Related to Split Hand and Foot Malformation Syndrome.

    Proudfoot, Andrew; Axelrod, Herbert L; Geralt, Michael; Fletterick, Robert J; Yumoto, Fumiaki; Deacon, Ashley M; Elsliger, Marc-André; Wilson, Ian A; Wüthrich, Kurt; Serrano, Pedro

    2016-03-27

    The Dlx5 homeodomain is a transcription factor related to the Drosophila distal-less gene that is associated with breast and lung cancer, lymphoma, Rett syndrome and osteoporosis in humans. Mutations in the DLX5 gene have been linked to deficiencies in craniofacial and limb development in higher eukaryotes, including split hand and foot malformation 1 in humans. Our characterization of a Dlx5 homeodomain:(CGACTAATTAGTCG)2 complex by NMR spectroscopy paved the way for determination of its crystal structure at 1.85Å resolution that enabled rationalization of the effects of disease-related mutations on the protein function. A Q186H mutation linked to split hand and foot malformation 1 likely affects affinity of DNA binding by disrupting water-mediated interactions with the DNA major groove. A more subtle effect is implicated for the Q178P mutation, which is not in direct contact with the DNA. Our data indicate that these mutations diminish the ability of the Dlx5 homeodomain to recognize and bind target DNAs, and they likely destabilize the formation of functional complexes. PMID:26829219

  12. Effects of additives in α- and θ-alumina: an ab initio study

    It is of high fundamental and practical importance to be able to control the formation and stability of the different crystalline phases of alumina (Al2O3). In this study, we have used density functional theory methods to investigate the changes induced in the thermodynamically stable α phase and the metastable θ phase as one eighth of the Al atoms are substituted for different additives (Sc, W, Mo, Cr, Cu, Si, and B). The calculations predict that the additives strongly affect the relative stability between the two phases. Most tested additives are shown to shift the relative stability towards, and in some cases completely stabilize, the θ phase, while Cu doping is predicted to increase the relative stability of the α phase. The reasons for these effects are discussed, as are possible implications on the growth and use of doped aluminas in practical applications. In addition, the effects of the additives on bulk moduli and densities of states have been investigated

  13. Effects of phosphate additives on the stability of positive electrolytes for vanadium flow batteries

    Highlights: • A series of phosphates is investigated as additives for vanadium flow battery. • Superior V(V) thermal stability and improved electrochemical performance. • Enhanced battery efficiency and slower capacity fading. • Mechanism for the stabilization and performance improvement is put forward. • NH4H2PO4 indicates a promising candidate for additive of the positive electrolyte. - Abstract: A series of phosphates is investigated as additives to improve the stability of the electrolyte for vanadium flow battery (VFB). Two selected additives show positive effect on the stability of electrolytes under ex-situ stability tests and in situ flow cell experiments. The effects of additives on electrolyte are studied by Nuclear magnetic resonance (NMR), X-ray diffraction (XRD), Raman spectroscopy, Cyclic voltammetry (CV), Electrochemical impedance spectroscopy (EIS) and charge–discharge test. The results show that a VFB using the electrolyte with NH4H2PO4additive demonstrates significantly improved redox reaction reversibility and activity, and higher energy efficiency. In addition, the cell employing the electrolyte with NH4H2PO4 exhibits a charge capacity fading rate much slower than the cell without additives during the cycling at high temperature. These results indicate that the phosphate additives are highly beneficial to improving the stability and reliability of VFB

  14. Deletion mutations of bacteriophage

    Resolution of mutation mechanism with structural changes of DNA was discussed through the studies using bacteriophage lambda. One of deletion mutations inductions of phage lambda is the irradiation of ultraviolet ray. It is not clear if the inductions are caused by errors in reparation of ultraviolet-induced damage or by the activation of int gene. Because the effective site of int gene lies within the regions unnecessary for existing, it is considered that int gene is connected to deletion mutations induction. A certain system using prophage complementarity enables to detect deletion mutations at essential hereditary sites and to solve the relations of deletion mutations with other recombination system, DNA reproduction and repairment system. Duplication and multiplication of hereditary elements were discussed. If lambda deletion mutations of the system, which can control recombination, reproduction and repairment of added DNA, are constructed, mutations mechanism with great changes of DNA structure can be solved by phage lambda. (Ichikawa, K.)

  15. Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

    Swayne, Breanne G.; Kawata, Alice [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Behan, Nathalie A. [Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Williams, Andrew; Wade, Mike G. [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); MacFarlane, Amanda J. [Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada); Yauk, Carole L., E-mail: carole.yauk@hc-sc.ga.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9 (Canada)

    2012-09-01

    To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0 mg/kg), control (2 mg/kg) and supplemented (6 mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity.

  16. Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

    To date, fewer than 50 mutagens have been studied for their ability to cause heritable mutations. The majority of those studied are classical mutagens like radiation and anti-cancer drugs. Very little is known about the dietary variables influencing germline mutation rates. Folate is essential for DNA synthesis and methylation and can impact chromatin structure. We therefore determined the effects of folic acid-deficient (0 mg/kg), control (2 mg/kg) and supplemented (6 mg/kg) diets in early development and during lactation or post-weaning on mutation rates and chromatin quality in sperm of adult male Balb/c mice. The sperm chromatin structure assay and mutation frequencies at expanded simple tandem repeats (ESTRs) were used to evaluate germline DNA integrity. Treatment of a subset of mice fed the control diet with the mutagen ethylnitrosourea (ENU) at 8 weeks of age was included as a positive control. ENU treated mice exhibited decreased cauda sperm counts, increased DNA fragmentation and increased ESTR mutation frequencies relative to non-ENU treated mice fed the control diet. Male mice weaned to the folic acid deficient diet had decreased cauda sperm numbers, increased DNA fragmentation index, and increased ESTR mutation frequency. Folic acid deficiency in early development did not lead to changes in sperm counts or chromatin integrity in adult mice. Folic acid supplementation in early development or post-weaning did not affect germ cell measures. Therefore, adequate folic acid intake in adulthood is important for preventing chromatin damage and mutation in the male germline. Folic acid supplementation at the level achieved in this study does not improve nor is it detrimental to male germline chromatin integrity.

  17. Effect of dedifferentiation on time to mutation acquisition in stem cell-driven cancers.

    Alexandra Jilkine

    2014-03-01

    Full Text Available Accumulating evidence suggests that many tumors have a hierarchical organization, with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells. It is unclear, however, whether cancer stem cells originate from normal stem cells or from dedifferentiated progenitor cells. To address this, we mathematically modeled the effect of dedifferentiation on carcinogenesis. We considered a hybrid stochastic-deterministic model of mutation accumulation in both stem cells and progenitors, including dedifferentiation of progenitor cells to a stem cell-like state. We performed exact computer simulations of the emergence of tumor subpopulations with two mutations, and we derived semi-analytical estimates for the waiting time distribution to fixation. Our results suggest that dedifferentiation may play an important role in carcinogenesis, depending on how stem cell homeostasis is maintained. If the stem cell population size is held strictly constant (due to all divisions being asymmetric, we found that dedifferentiation acts like a positive selective force in the stem cell population and thus speeds carcinogenesis. If the stem cell population size is allowed to vary stochastically with density-dependent reproduction rates (allowing both symmetric and asymmetric divisions, we found that dedifferentiation beyond a critical threshold leads to exponential growth of the stem cell population. Thus, dedifferentiation may play a crucial role, the common modeling assumption of constant stem cell population size may not be adequate, and further progress in understanding carcinogenesis demands a more detailed mechanistic understanding of stem cell homeostasis.

  18. Effects of gamma-irradiation-induced mutation on upland cotton pollen grains

    Despite the demonstrated value of gamma ray as a tool in plant mutation research, in the genetic plant species upland cotton (Gossypium hirsutum L.), such mutations have not been extensively studied. To investigate these questions, the upland cotton cultivar 'Sumian 22' pollen grains were irradiated by gamma rays (20Gy). The irradiation effects on pollen grains were tested considering the ultrastructure changes in the exine and interior walls of pollen grains, their germination rate, DNA polymorphism in the pollen grains, the actin filament in pollen tube, fertilization, and boll development after the pistils were pollinated by the pollen grains which were irradiation with γ-rays. As compared with the control, although the cell structures inside the pollen grain were destroyed, its exine and interior walls of the pollen grain were not etched. The amount and the density of pollen grain inclusions decreased and the size of the lacuna and starch granules increased. Pollen grain germination rate decreased by 37%. The number of pollen tubes in the style declined by 38%, but the growth speed of the tubes did not change. All of the pollen tubes reached the end of the style at 13-h after pollination. This result was consistent with that of the control. Also, the weight and the diameter of the ovary decreased and shortened. No evident change of the fecundation time of ovule was observed. The significant difference on DNA polymorphism was found between irradiation pollen grain and control after pollination by Simple sequence repeats (SSR) molecular marker. The actin filament of the apical domain in pollen tube was destabilized, and in the approximately apical domain, the actin cytoskeleton component disappeared. Various mutants were appeared in the M1 progenies. These results indicate that gamma rays can cause a series of biological changes in irradiated-pollen grains and their progenies of upland cotton. (author)

  19. EF-hand Ca 2+-binding bioluminescent proteins: effects of mutations and alternative divalent cations

    Rowe, Laura; Ensor, Mark; Daunert, Sylvia

    2007-02-01

    Bioluminescent photoproteins, such as aequorin and obelin, are proteins that emit light upon binding calcium. Aequorin and obelin contain four EF-hand domains arranged into a globular structure. The loop region of these EF-hand domains binds calcium by coordinating it in a pentagonal bipyramidal structure with oxygen atoms. The binding of calcium to these EF-hands causes a slight conformational change in the protein, which leads to the oxidation of the internally sequestered chromophore, coelenterazine, producing coelenteramide and CO II. The excited coelenteramide then relaxes radiatively, emitting bioluminescence at 471 nm in aequorin or 491 nm in obelin. Although calcium is the traditional, and generally the most powerful, triggering ligand in this bioluminescence reaction, alternative di- and trivalent cations can also bind to the EF-hand loops and stimulate luminescence. Species capable of this cross-reactivity include: Cd 2+, Ba 2+, Mn 2+, Sr 2+, Mg 2+, and several lanthanides. Magnesium is also known to modulate the bioluminescence of wild-type aequorin, increase its stability, and decrease its aggregation tendency. Both wild-type aequorin and wild-type obelin contain several cysteine residues, aequorin has three and obelin has five. It is believed that these cysteine residues play an important, but as of yet unknown, role in the bioluminescence of these proteins, since mutating most of these residues causes significant loss in bioluminescent activity. In order to explore whether or not these cysteine residues contributed to the specificity of the EF-hand domains for cations we generated four aequorin and obelin mutants and observed their luminescent intensity and decay kinetics by stimulation with calcium, barium, and magnesium. It was found that the cysteine mutations do appear to alter the effects that alternative divalent cations have on the bioluminescence of both aequorin and obelin.

  20. Mutation effects of C{sup 2+} ion irradiation on the greasy Nitzschia sp

    Yang, Y.N., E-mail: ynyangbuaa@gmail.com [School of Chemistry and Environment, Beihang University, 37th Xueyuan Road, Haidian District, P.O. Box 106, 100191 Beijing (China); Liu, C.L.; Wang, Y.K. [School of Chemistry and Environment, Beihang University, 37th Xueyuan Road, Haidian District, P.O. Box 106, 100191 Beijing (China); Xue, J.M. [State Key Lab of Nuclear Physics and Nuclear Technology, Peking University, 100084 Beijing (China)

    2013-11-15

    Highlights: • The optimal conditions of C{sup 2+} ion irradiation on Nitzschia sp. were discussed. • Get the “saddle type” survival curve. • One mutant whose lipid content improved significantly was selected. • The C{sup 2+} ion irradiation didn’t change the algae's morphology and growth rate. - Abstract: Screening and nurturing algae with high productivity, high lipid content and strong stress resistance are very important in algae industry. In order to increase the lipid content, the Nitzschia sp. was irradiated with a 3 MeV C{sup 2+} beam. The sample pretreatment method was optimized to obtain the best mutagenic condition and the survival ratio curve. The positive mutants with a significant improvement in lipid content were screened and their C{sup 2+} mutagenic effects were analyzed by comparing the greasiness and growth characteristics with the wild type algae. Results showed that when the Nitzschia sp. was cultivated in nutritious medium containing 10% glycerol solution, and dried on the filter for 5 min after centrifugation, the realization of the microalgae heavy ion mutagenesis could be done. The survival ratio curve caused by C{sup 2+} irradiation was proved to be “saddle-shaped”. A positive mutant was screened among 20 survivals after irradiation, the average lipid content of the mutation increased by 9.8% than the wild type after 4 generations. But the growth rate of the screened mutation didn’t change after the heavy ion implantation compared to the wild type algae.

  1. The effective use of physical and chemical mutagen in the induction of mutation for crop improvement in Malaysia

    Abdul Rahim Harun [Malaysian Institute for Nuclear Technology Research, Bangi, Selangor (Malaysia)

    2001-03-01

    The earliest work of induced mutations breeding program in Malaysia was reported in 1967. The project was carried out by Rubber Research Institute of Malaysia using x-radiation in an attempt to improve rubber trees for dwarfism and disease resistance. Subsequently, more efforts were taken up by the universities to promote the technology for genetic changes and creation of new genetic resources, particularly in crops that are not easily achievable through conventional techniques. Gamma radiation is always been used as physical mutagen, while ethyl methane sulfonate (EMS) was a popular chemical mutagen used in induced mutation breeding in the country. Gamma rays is an effective mutagen to which more than 30 potential mutants were produced up to now through mutagenesis of several important food crops and ornamental plants. Although chemical mutagen such as EMS were reported being used, the result is not so convincing as compared to gamma radiation. Malaysian Institute for Nuclear Technology Research (MINT) has initiated and promoted nuclear technique in mutation breeding for the improvement of importance food crops such as rice, legume and other potential crops for export, like fruit trees and ornamentals. Gamma radiation is the main source of mutagen used in mutation-breeding programme at MINT. The effectiveness of these two mutagens were verified with mutants derived through induced mutation breeding in the country which some mutant has shown outstanding improvement and released as new varieties and cultivars. This paper summarises and discuss the effects as well as achievement attained through the use of ionizing radiation and chemical mutagen in plant mutation breeding in Malaysia. (author)

  2. The effective use of physical and chemical mutagen in the induction of mutation for crop improvement in Malaysia

    The earliest work of induced mutations breeding program in Malaysia was reported in 1967. The project was carried out by Rubber Research Institute of Malaysia using x-radiation in an attempt to improve rubber trees for dwarfism and disease resistance. Subsequently, more efforts were taken up by the universities to promote the technology for genetic changes and creation of new genetic resources, particularly in crops that are not easily achievable through conventional techniques. Gamma radiation is always been used as physical mutagen, while ethyl methane sulfonate (EMS) was a popular chemical mutagen used in induced mutation breeding in the country. Gamma rays is an effective mutagen to which more than 30 potential mutants were produced up to now through mutagenesis of several important food crops and ornamental plants. Although chemical mutagen such as EMS were reported being used, the result is not so convincing as compared to gamma radiation. Malaysian Institute for Nuclear Technology Research (MINT) has initiated and promoted nuclear technique in mutation breeding for the improvement of importance food crops such as rice, legume and other potential crops for export, like fruit trees and ornamentals. Gamma radiation is the main source of mutagen used in mutation-breeding programme at MINT. The effectiveness of these two mutagens were verified with mutants derived through induced mutation breeding in the country which some mutant has shown outstanding improvement and released as new varieties and cultivars. This paper summarises and discuss the effects as well as achievement attained through the use of ionizing radiation and chemical mutagen in plant mutation breeding in Malaysia. (author)

  3. A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

    Escámez María-José

    2010-09-01

    Full Text Available Abstract Background Recessive Dystrophic Epidermolysis Bullosa (RDEB is a genodermatosis caused by more than 500 different mutations in the COL7A1 gene and characterized by blistering of the skin following a minimal friction or mechanical trauma. The identification of a cluster of RDEB pedigrees carrying the c.6527insC mutation in a specific area raises the question of the origin of this mutation from a common ancestor or as a result of a hotspot mutation. The aim of this study was to investigate the origin of the c.6527insC mutation. Methods Haplotypes were constructed by genotyping nine single nucleotides polymorphisms (SNPs throughout the COL7A1 gene. Haplotypes were determined in RDEB patients and control samples, both of Spanish origin. Results Sixteen different haplotypes were identified in our study. A single haplotype cosegregated with the c.6527insC mutation. Conclusion Haplotype analysis showed that all alleles carrying the c.6527insC mutation shared the same haplotype cosegregating with this mutation (CCGCTCAAA_6527insC, thus suggesting the presence of a common ancestor.

  4. Induced mutations in chickpea (Cicer arietinum L.) I. comparative mutagenic effectiveness and efficiency of physical & chemical mutagens

    Mutagenic effectiveness usually means the rate of mutation as related to dose. Mutagenic efficiency refers to the mutation rate in relation to damage. Studies on comparative mutagenic effectiveness and efficiency of two physical (gamma rays and fast neutrons) and two chemical mutagens (NMU and EMS) on two desi (G 130 & H 214), one kabuli (C 104) and one green seeded (L 345) chickpea (Cicer arietinum L.) have been reported. The treatments included three doses each of gamma rays (400, 500 and 600 Gy) and fast neutrons (5, 10 and 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU 0.01% 20h and 0.02% 8h) and EMS (0.1% 20h and 0.2% 8h). Results indicated that chemical mutagens, particularly NMU are not only more effective but also efficient than physical mutagens in inducing mutations in chickpea. Mutagenic effectiveness and efficiency showed differential behaviour depending upon mutagen and varietal type. Chemical mutagens were more efficient than physical in inducing cholorophyll as well as viable and total number of mutations. Among the mutagens NMU was the most potent, while in the physical, gamma rays were more effective. Out of four mutagens, NMU was the most effective and efficient in inducing a high frequency and wide spectrum of chlorophyll mutations in the M2 followed by fast neutrons. While gamma rays showed least effectiveness, EMS was least efficient mutagens. Major differences in the mutagenic response of the four cultivars were observed. The varieties of desi type were more resistant towards mutagenic treatment than kabuli and green seeded type

  5. Nitrogen Addition Altered the Effect of Belowground C Allocation on Soil Respiration in a Subtropical Forest.

    He, Tongxin; Wang, Qingkui; Wang, Silong; Zhang, Fangyue

    2016-01-01

    The availabilities of carbon (C) and nitrogen (N) in soil play an important role in soil carbon dioxide (CO2) emission. However, the variation in the soil respiration (Rs) and response of microbial community to the combined changes in belowground C and N inputs in forest ecosystems are not yet fully understood. Stem girdling and N addition were performed in this study to evaluate the effects of C supply and N availability on Rs and soil microbial community in a subtropical forest. The trees were girdled on 1 July 2012. Rs was monitored from July 2012 to November 2013, and soil microbial community composition was also examined by phospholipid fatty acids (PLFAs) 1 year after girdling. Results showed that Rs decreased by 40.5% with girdling alone, but N addition only did not change Rs. Interestingly, Rs decreased by 62.7% under the girdling with N addition treatment. The reducing effect of girdling and N addition on Rs differed between dormant and growing seasons. Girdling alone reduced Rs by 33.9% in the dormant season and 54.8% in the growing season compared with the control. By contrast, girdling with N addition decreased Rs by 59.5% in the dormant season and 65.4% in the growing season. Girdling and N addition significantly decreased the total and bacterial PLFAs. Moreover, the effect of N addition was greater than girdling. Both girdling and N addition treatments separated the microbial groups on the basis of the first principal component through principal component analysis compared with control. This indicated that girdling and N addition changed the soil microbial community composition. However, the effect of girdling with N addition treatment separated the microbial groups on the basis of the second principal component compared to N addition treatment, which suggested N addition altered the effect of girdling on soil microbial community composition. These results suggest that the increase in soil N availability by N deposition alters the effect of

  6. Effects of minor alloying additions on the strength and swelling behavior of an austenitic stainless steel

    A set of 32 alloys consisting of various additions of the elements Mo, W, Al, Ti, Nb, C and Si to an Fe-7.5 Cr-20 Ni alloy were made in order to investigate the effects of these solute additions on alloy swelling and strength. Both single and multiple additions were examined. The influence of various solute elements on the swelling behavior in the range 500 to 7300C was investigated using 4 MeV Ni ion bombardment to a dose 170 dpa. It was found that on an atomic percent basis, the elements may be arranged in order of decreasing effectiveness in reducing peak temperature swelling as follows: Ti, C, Nb, Si, and Mo. Small amounts of aluminum enhance swelling. Additions of Si, Ti, or Nb truncate the high temperature swelling regime of the ternary alloy. Mo, W, and C do not have a strong effect on the temperature dependence of swelling. The results may be interpreted in terms of the effect of point defect trapping on void growth rates, and it is suggested that the changes in peak temperature are the result of small changes in the free vacancy formation energy. A method for treating certain multiple additions is proposed. The effect of these alloying additions on short time high temperature strength properties was estimated using hot hardness measurements over the temperature range 22 to 8500C. On an atom percent basis Nb and Ti were most effective in conferring solid solution strengthening and Si the least effective. In the regime 22 to approximately 6500C, the hardness data was found to fit an equation of the form: H = H0 + b/T; where H is the hardness, T is the temperature, and H0 and b are constants for a given alloy. An empirical method was devised to estimate the hot hardness of alloys containing more than one solute addition

  7. A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect.

    McEntagart, Meriel; Williamson, Kathleen A; Rainger, Jacqueline K; Wheeler, Ann; Seawright, Anne; De Baere, Elfride; Verdin, Hannah; Bergendahl, L Therese; Quigley, Alan; Rainger, Joe; Dixit, Abhijit; Sarkar, Ajoy; López Laso, Eduardo; Sanchez-Carpintero, Rocio; Barrio, Jesus; Bitoun, Pierre; Prescott, Trine; Riise, Ruth; McKee, Shane; Cook, Jackie; McKie, Lisa; Ceulemans, Berten; Meire, Françoise; Temple, I Karen; Prieur, Fabienne; Williams, Jonathan; Clouston, Penny; Németh, Andrea H; Banka, Siddharth; Bengani, Hemant; Handley, Mark; Freyer, Elisabeth; Ross, Allyson; van Heyningen, Veronica; Marsh, Joseph A; Elmslie, Frances; FitzPatrick, David R

    2016-05-01

    Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions. PMID:27108798

  8. Estimation of direct effects for survival data by using the Aalen additive hazards model

    Martinussen, T.; Vansteelandt, S.; Gerster, M.;

    2011-01-01

    We extend the definition of the controlled direct effect of a point exposure on a survival outcome, other than through some given, time-fixed intermediate variable, to the additive hazard scale. We propose two-stage estimators for this effect when the exposure is dichotomous and randomly assigned...

  9. Effect of rhenium addition on tungsten fuzz formation in helium plasmas

    Khan, A.; De Temmerman, G.; Morgan, T. W.; M. B. Ward,

    2016-01-01

    The effect of the addition of rhenium to tungsten on the formation of a nanostructure referred to as ‘fuzz’ when exposed to helium plasmas at fusion relevant ion fluxes was investigated in the Magnum and Pilot PSI devices at the FOM Institute DIFFER. The effect rhenium had on fuzz growth was seen to

  10. SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition.

    Kim, Eunhee; Ilagan, Janine O; Liang, Yang; Daubner, Gerrit M; Lee, Stanley C-W; Ramakrishnan, Aravind; Li, Yue; Chung, Young Rock; Micol, Jean-Baptiste; Murphy, Michele E; Cho, Hana; Kim, Min-Kyung; Zebari, Ahmad S; Aumann, Shlomzion; Park, Christopher Y; Buonamici, Silvia; Smith, Peter G; Deeg, H Joachim; Lobry, Camille; Aifantis, Iannis; Modis, Yorgo; Allain, Frederic H-T; Halene, Stephanie; Bradley, Robert K; Abdel-Wahab, Omar

    2015-05-11

    Mutations affecting spliceosomal proteins are the most common mutations in patients with myelodysplastic syndromes (MDS), but their role in MDS pathogenesis has not been delineated. Here we report that mutations affecting the splicing factor SRSF2 directly impair hematopoietic differentiation in vivo, which is not due to SRSF2 loss of function. By contrast, SRSF2 mutations alter SRSF2's normal sequence-specific RNA binding activity, thereby altering the recognition of specific exonic splicing enhancer motifs to drive recurrent mis-splicing of key hematopoietic regulators. This includes SRSF2 mutation-dependent splicing of EZH2, which triggers nonsense-mediated decay, which, in turn, results in impaired hematopoietic differentiation. These data provide a mechanistic link between a mutant spliceosomal protein, alterations in the splicing of key regulators, and impaired hematopoiesis. PMID:25965569