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Sample records for promoting mutation induction

  1. Mutation induction by heavy ions

    Science.gov (United States)

    Kiefer, J.; Stoll, U.; Schneider, E.

    1994-10-01

    Mutation induction by heavy ions is compared in yeast and mammalian cells. Since mutants can only be recovered in survivors the influence of inactivation cross sections has to be taken into account. It is shown that both the size of the sensitive cellular site as well as track structure play an important role. Another parameter which influences the probability of mutation induction is repair: Contrary to naive assumptions primary radiation damage does not directly lead to mutations but requires modification to reconstitute the genetic machinery so that mutants can survive. The molecular structure of mutations was analyzed after exposure to deuterons by amplification with the aid of polymerase chain reaction. The results-although preliminary-demonstrate that even with densely ionizing particles a large fraction does not carry big deletions which suggests that point mutations may also be induced by heavy ions.

  2. Mutation induction by ion beams in plants

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    The effect of ion beams such as C, He, and Ne ions was investigated on the mutation induction in plants with the expectation that ion beams of high linear energy transfer (LET) can frequently produce large DNA alternation such as inversion, translocation and large deletion rather than point mutation. Mutation frequency was investigated using Arabidopsis visible phenotype loci and was 8 to 33 fold higher for 220 MeV carbon ions than for electrons. Mutation spectrum was investigated on the flower color of chrysanthemum cv to find that flower mutants induced by ion beams show complex and stripe types rather than single color. Polymerase chain reaction analysis was performed to investigate DNA alteration of mutations. In conclusion, the characteristics of ion beams for the mutation induction are 1) high frequency, 2) broad mutation spectrum, and 3) novel mutants. (S. Ohno)

  3. Mutation induction by ion beams in plants

    International Nuclear Information System (INIS)

    Tanaka, Atsushi

    2001-01-01

    The effect of ion beams such as C, He, and Ne ions was investigated on the mutation induction in plants with the expectation that ion beams of high linear energy transfer (LET) can frequently produce large DNA alternation such as inversion, translocation and large deletion rather than point mutation. Mutation frequency was investigated using Arabidopsis visible phenotype loci and was 8 to 33 fold higher for 220 MeV carbon ions than for electrons. Mutation spectrum was investigated on the flower color of chrysanthemum cv to find that flower mutants induced by ion beams show complex and stripe types rather than single color. Polymerase chain reaction analysis was performed to investigate DNA alteration of mutations. In conclusion, the characteristics of ion beams for the mutation induction are 1) high frequency, 2) broad mutation spectrum, and 3) novel mutants. (S. Ohno)

  4. Mutation induction in plants by ionizing radiation

    International Nuclear Information System (INIS)

    1985-01-01

    This training film deals with the use of x-rays, gamma rays and fast neutrons for mutation induction in plants. Specific features of different types of ionizing radiation and of biological materials are outlined and methods demonstrated which control modifying factors and warrant an efficient physical mutagenesis. The first step of mutation breeding aims at an enhanced level of genetic variation which forms the basis for mutant selection and use in plant breeding

  5. Mutation induction of orchids by ion beams

    International Nuclear Information System (INIS)

    Affrida Abu Hassan; Zaiton Ahmad; Sakinah Ariffin; Oono, Yutaka; Hase, Yoshihiro; Shikazono; Naoya; Narumi, Issay; Tanaka, Atsushi

    2010-01-01

    Mutation induction using ionizing radiation provides an effective alternative means for improvement of orchids. In this study, ion beams were used because they have much higher linear energy transfer (LET) than X-rays or gamma rays, and subsequently lead to higher mutation frequency and broad mutation spectrum. The proto corm-like bodies (PLBs) of three orchid species (Dendrobium crumenatum, Dendrobium mirbellianum) were irradiated at various doses with 320 MeV 12 C 6+ ions accelerated by Azimuthally Varying Field (AVF) cyclotron at JAEAs Takasaki Ion Accelerators for Advanced Radiation Application (TIARA). The optimum irradiation condition and the effect of irradiation on each species were studied, particularly on flower colour and morphology, flowering habit and insect resistance. Dose effects on plantlet regeneration for each species were also obtained. Some morphological changes were observed in flowers of Dendrobium crumenatum, whilst one insect resistant mutant was obtained in Dendrobium mirbellianum. (author)

  6. Mutation induction by ion beams in arabidopsis

    International Nuclear Information System (INIS)

    Tanaka, Atsushi

    1999-01-01

    An investigation was made on characteristics of ion beams for the biological effects and the induction of mutation using Arabidopsis plant as a model plant for the molecular genetics. Here, the characteristics of mutation at the molecular level as well as new mutants induced by ion beams were described. The ast and sep1 were obtained from the offspring of 1488 carbon ion-irradiated seeds respectively. The uvi1-uvi4 mutants were also induced from 1280 M 1 lines. Thus, ion beams can induce not only known mutants such as tt, gl and hy but also novel mutants with high frequency. Even in the tt phenotype, two new mutant loci other than known loci were found. In chrysanthemum, several kinds of single, complex or stripped flower-color mutants that have been never induced by γirradiation, indicating that ion beams could produce a variety of mutants with the same phenotype. In conclusion, ion beams for the mutation induction are characterized by 1) to induce mutants with high frequency, 2) to show broad mutation spectrum and 3) to produce novel mutants. For these reasons, chemical mutagens such as EMS and low LET ionizing radiation such as X-rays and γ-rays will predominantly induce many but small modifications or DNA damages on the DNA strands. As the result, several point mutations will be produced on the genome. On the contrary, ion beams as a high LET ionizing radiation will not cause so many but large and irreparable DNA damage locally, resulting in production of limited number of null mutation. (M.N.)

  7. Mutation induction by ion beams in arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    1999-07-01

    An investigation was made on characteristics of ion beams for the biological effects and the induction of mutation using Arabidopsis plant as a model plant for the molecular genetics. Here, the characteristics of mutation at the molecular level as well as new mutants induced by ion beams were described. The ast and sep1 were obtained from the offspring of 1488 carbon ion-irradiated seeds respectively. The uvi1-uvi4 mutants were also induced from 1280 M{sub 1} lines. Thus, ion beams can induce not only known mutants such as tt, gl and hy but also novel mutants with high frequency. Even in the tt phenotype, two new mutant loci other than known loci were found. In chrysanthemum, several kinds of single, complex or stripped flower-color mutants that have been never induced by {gamma}irradiation, indicating that ion beams could produce a variety of mutants with the same phenotype. In conclusion, ion beams for the mutation induction are characterized by 1) to induce mutants with high frequency, 2) to show broad mutation spectrum and 3) to produce novel mutants. For these reasons, chemical mutagens such as EMS and low LET ionizing radiation such as X-rays and {gamma}-rays will predominantly induce many but small modifications or DNA damages on the DNA strands. As the result, several point mutations will be produced on the genome. On the contrary, ion beams as a high LET ionizing radiation will not cause so many but large and irreparable DNA damage locally, resulting in production of limited number of null mutation. (M.N.)

  8. Mutation induction in grasspea (Lathyrus sativus L.)

    International Nuclear Information System (INIS)

    Ali, M.S.; Shaikh, M.A.Q.; Islam, M.S.; Saha, C.S.

    1989-01-01

    Full text: Grasspea is a widely grown food legume in Bangladesh, suited particularly for marginal conditions. Its yields are low, its main drawback, however, is that the seeds contain a neurotoxin BOAA, which requires heat degradation before consumption. The genetic base of local varieties is rather narrow. Introduced varieties are even lower yielding than the local ones or fail to flower and produce seeds. Thus, mutation induction of local cultivars should be regarded as a means for creating useful genetic variation. Seeds of the grasspea cultivar 'BINA Acc. No.1' collected from Jessore were treated with 2-5 mM solutions of sodium azide. A wide range of genetic variation was obtained regarding plant height, number of pods per plant, days to maturity. (author)

  9. p53 mutations promote proteasomal activity.

    Science.gov (United States)

    Oren, Moshe; Kotler, Eran

    2016-07-27

    p53 mutations occur very frequently in human cancer. Besides abrogating the tumour suppressive functions of wild-type p53, many of those mutations also acquire oncogenic gain-of-function activities. Augmentation of proteasome activity is now reported as a common gain-of-function mechanism shared by different p53 mutants, which promotes cancer resistance to proteasome inhibitors.

  10. Induction and isolation of somatic mutations in vegetatively propagated plants

    International Nuclear Information System (INIS)

    Donini, B.

    1975-01-01

    Research carried out since 1963 concentrated on techniques of mutagenic treatment: problems of exposure, type of radiation (acute irradiation by x- and γ-rays, and chronic exposure in the gamma field), conditions during and after irradiation, mechanisms of mutation induction, and methodology of isolation of somatic mutations. Analyses of somatic mutations included studies on apple, pear, olive, peach, grape and cherry plants. Young trees, dormant and rooted scions, summer and floral buds or seeds were used

  11. Mutation induction in Lathyrus sativus L

    International Nuclear Information System (INIS)

    Singh, M.; Chaturvedi, S.N.

    1989-01-01

    Full text: Seeds of the grass pea varieties 'LSD 6' and 'S 220' were treated with 10-25 kR gamma rays, 0.1-0.4% EMS or 0.01-0.04% NMH. DMSO in 1% solution applied together with 10 kR gamma rays, 0.1% EMS or 0.01% NMH increased the effects of the mutagens. M 2 progenies were checked for morphological and leaf color mutations. From data obtained the following treatments appear appropriate: 15kR gamma rays; 10 kR gamma rays + DMSO; 0.1% EMS; 0.01% NMH. (author)

  12. Influence of mutation induction on the chemical composition of ...

    African Journals Online (AJOL)

    Cowpea is one of the major sources of plant protein in Nigeria. The nutritional value of cowpea has long been recognized in Africa. This study was conducted to examine the influence of mutation induction on nutritional quality of cowpea. Dry sample of cowpea 'IT84S 2246 D' mutants and the non irradiated parent were ...

  13. Mutation induction in yeast by very heavy ions

    Science.gov (United States)

    Kiefer, J.

    1994-10-01

    Resistance to canavanine was studied in haploid yeast after exposure to heavy ions (argon to uranium) of energies between 1 and 10 MeV/u covering a LET-range up to about 10000 keV/μm. Mutations were found in all instances but the induction cross sections increased with ion energy. This is taken to mean that the contribution of penumbra electrons plays an important role. The probability to recover surviving mutants is highest if the cell is not directly hit by the particle. The experiments demonstrate that the geometrical dimensions of the target cell nucleus as well as its sensitivity in terms of survival have a critical influence on mutation induction with very heavy ions.

  14. New approaches for effective mutation induction in gamma field

    Energy Technology Data Exchange (ETDEWEB)

    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)

  15. New approaches for effective mutation induction in gamma field

    International Nuclear Information System (INIS)

    Nagatomi, Shigeki

    2001-01-01

    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)

  16. Mutation induction by ion beams in higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Atsushi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2003-04-01

    This review mainly describes study results obtained in the Takasaki ion-beam (IB) irradiation facility (TIARA) on the mutation induction in higher plants. Biological effects like lethality and on budding of IBs (carbon, Ne and Ar) are discussed in relation with their linear energy transfer (LET), relative biological effectiveness and the developmental states in shepherd's-purse and tobacco. Induced mutation by IB are characterized by those findings that the mutation rate by C beam is 1.9 x 10{sup -6}, being 17 times higher than the electron beam, in the shepherd's-purse, that C beam induces larger structural changes than electron beam when examined by molecular mechanism of tt and gl gene mutations, and that mutation spectrum of IB is different from that of {gamma}-ray and is wider. Novel mutants are described on shepherd's-purse (pigment mutants, ultraviolet (UV)-resistant and sensitive ones, and flowering ones), disease-resistant rice, barley and tobacco plants, and flowering plants. IB mutation is possibly useful for solving the problems of environment and foods in future. (N.I.)

  17. Mutation induction for improving of tangerine in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Majd, F.; Jahangirzadeh, E.; Vedadi, S.; Tafti, M. Naseri; Rastegari, J. [Nuclear Research Center for Agriculture and Medicine, Karaj (Iran, Islamic Republic of)

    2009-05-15

    Genetic variation is an essential component of crop breeding. Induced mutations are highly effective in enhancing natural variability of genetic resources, and have been instrumental in developing improved cultivars of crops including fruits crops. Recent advances in biotechnological techniques have shown a great potential as efficient methodologies for vegetative micropropagation, screening techniques and genetic characterization including mutation induction. On this basis, a local, well- adapted and widely-consumed Clementine cultivar was selected for introduction into a mutation induction programme in order to reduce the excessive seeds in the fruits. A physical mutagen (γ-ray) was applied at doses of 35, 40 and 45 Gy on selected seedling apical buds. Irradiated buds were grafted onto sour orange root stocks (M{sub 1}V{sub 1}) and chimeras disassociated by further vegetative propagation. Finally M{sub 1}V{sub 3} plants were transferred to the field and after the production of fruits, selection for the desired fruit types was undertaken. The results showed that the radiation treatment was able to produce mutant genotypes with seedless fruits, early and late ripening and cold tolerance. (author)

  18. Induction of recessive mutations in potato using tissue culture techniques

    International Nuclear Information System (INIS)

    Enckevort, L.J.G. van; Hoogkamp, T.J.H.; Bergervoet, J.E.M.; Visser, R.G.F.; Jacobsen, E.; Stiekma, W.J.; Pereira, A.

    2001-01-01

    In potato, two different in vitro approaches were used to generate recessive mutants. In the first method, monoploid plant material was irradiated to isolate and identify amylose-free (amf) mutants in potato. For isolating secondary mutants in the amf background new monoploids of the amf type were developed. A few selected amf monoploids showed excellent vigour in vitro, large leave; and microtuber formation. A diploid and a monoploid were tested for in vitro mutation induction and irradiated with 0 to 16 Gy X rays. The optimal dose for survival and mutation induction was between 4 and 8 Gy and plants were regenerated from irradiated leaf explants. In the second approach, mutants were induced by insertion of transposable elements in the diploids. This method was used to mutate R genes for resistance to Phytophthora infestans. Diploid heterozygous Rr plants with the immobilised Ds element, closely linked to one of the R genes, were selected. Mobilisation of Ds using Ac element transposase resulted in the selection of plants with active somatic Ds excision frequency of about 10%. In vitro protoplast isolation and plant regeneration from such plants enabled the selection of regenerants with new independent Ds insertions. Hygromycin selection (Ds excision marker on the T-DNA) during protoplast regeneration increased the frequency of Ds excision regenerants to 56%. A total of 582 hygromycin resistant plants were regenerated and selected in vitro. Preliminary analysis of the regenerants showed re-insertions of Ds in the predicted coding sequences of genes. (author)

  19. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

    NARCIS (Netherlands)

    M. Remke (Marc); E.A. Ramaswamy; M. Peacock (Munro); D.J.H. Shih (David J.); C. Koelsche (Christian); P.A. Northcott (Paul A.); N. Hill (Nadia); S. Cavalli (Silvia); M. Kool (Marcel); X. Wang (Xin); S. Mack (Stephen); M. Barszczyk (Mark); A.S. Morrissy (A. Sorana); X. Wu (Xiaochong); S. Agnihotri (Sameer); P. Luu (Phan); D. Jones (David); L. Garzia (Livia); A.M. Dubuc (Adrian); N. Zhukova (Nataliya); R. Vanner (Robert); J.M. Kros (Johan); P.J. French (Pim); E.G. van Meir (Erwin); R. Vibhakar (Rajeev); K. Zitterbart (Karel); J.A. Chan (Jennifer); L. Bognár (László); A. Klekner (Almos); B. Lach (Boleslaw); S. Jung (Shin); F. Saad (Fred); L.M. Liau (Linda); S. Albrecht (Steffen); M. Zollo (Maurizio); M.K. Cooper (Michael); R.C. Thompson (Reid); O. Delattre (Olivier); F. Bourdeaut (Franck); F.F. Doz (François); M. Garami (Miklós); P. Hauser (Peter); C.G. Carlotti (Carlos); T.E. Van Meter (Timothy); L. Massimi (Luca); D. Fults (Daniel); L.W. Pomeroy (Laura); T. Kumabe (Toshiro); Y.S. Ra (Young Shin); J.R. Leonard (Jeffrey); S.K. Elbabaa (Samer); J. Mora (Jaume); J.B. Rubin (Joshua); Y.-J. Cho (Yoon-Jae); R.E. McLendon (Roger); D.D. Bigner (Darell); C.G. Eberhart (Charles); M. Fouladi (Maryam); R.J. Wechsler-Reya (Robert); R. Faria (Rui); S.E. Croul (Sidney); A. Huang (Anding); E. Bouffet (Eric); C.E. Hawkins (Cynthia); M. Dirks (Maaike); W.A. Weiss (William); U. Schüller (Ulrich); A. Pollack (Aaron); P. Rutkowski (Piotr); D. Meyronet (David); A. Jouvet (Anne); M. Fèvre-Montange (Michelle); N. Jabado (Nada); M. Perek-Polnik (Marta); W.A. Grajkowska (Wieslawa); S.-K. Kim (Seung-Ki); J.T. Rutka (James); E. Malkin (Elissa); U. Tabori (Uri); S.M. Pfister (Stefan); A. Korshunov (Andrey); A. von Deimling (Andreas); M.D. Taylor (Michael)

    2013-01-01

    textabstractTelomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought

  20. Mutation induction of roses through in vitro propagation

    International Nuclear Information System (INIS)

    Amran Abd Halim; Azhar Mohamad; Rusli Ibrahim

    2002-01-01

    The genus Rosa has been exploited for a variety used extensively in commercial production for many cultivars. Mutation induction is an alternative way of creating more variations in a single variety. Radiosensitivity test was carried out to identify optimum doses in mutation induction. Shoot tips of excises from in vitro plantlets were irradiated with doses of 0, 20, 40, 60, 80 and 100 Gy using a gamma cell with a 60 Co source at dose rate of 0.25 Gy s -1 . Irradiated shoot tips were cultured on semi solid modified Murashige and Skoog (MS) containing cytokinin (BAP) hormone and incubated at 24 with a photoperiod of 16 hours (3500 lux). Radiosensitivity was assessed by the rate of shoot proliferation four weeks after treatment. Increasing gamma ray doses caused a reduction of survival rate as well as the average shoots produced per plantlet. Through linear estimation of buds and shoots proliferation, radiation dose that reduced the growth to 50% of the control treatment (LD 50 ) was 53 Gy for miniature roses and 60 Gy for cut roses. Based on the radiosensitivity test 20 and 40 Gy were selected for irradiation to get new mutant varieties of roses. Changes in flower characters were found in three treated plants after three months in the green house. (Author)

  1. Mutation induction in spores of Bacillus subtilis by accelerated very heavy ions

    International Nuclear Information System (INIS)

    Baltschukat, K.; Horneck, G.; Buecker, H.; Facius, R.; Schaefer, M.

    1986-01-01

    Mutation induction (resistance to sodium azide) in spores of Bacillus subtilis was investigated after irradiation with heavy ions from Neon to Uranium with specific particle energies between 0.17 and 18.6 MeV/u. A strong dependence of the mutation induction cross section on particle charge and energy was observed. From the results it was concluded that mutation induction in bacterial spores by very heavy ions is mainly caused by secondary electrons. (orig.)

  2. Mutation induction and evaluation of high yield rice mutants

    International Nuclear Information System (INIS)

    Abdul Rahim Harun; Sobri Husein; Rusli Ibrahim

    2006-01-01

    The successful use of plant breeding for improving crops requires the existence of genetic variation of useful traits. Unfortunately, the desired variation is often lacking. However, radiation has been used to induce mutations and thereby generate genetic variation from which desired mutants may be selected. Mutation induction has become a proven way of creating variation within a crop variety. It offers the possibility of inducing desired attributes that either cannot be expressed in nature or have been lost during evolution. Rice is security food crop in Malaysia. Efforts were undertaken to enhance rice yield from 4.0 tones per hectare in 1995 to 5.5 tones per hectare in 2010. Proper management and good varieties are two factors that require for enhancing yield of rice. In this research, purified seeds of MR211 and MR219 were gamma irradiated at 100 to 400 Gray and sown for planting as M1 generation at MARDI experimental plot. The M2 population was sown in bulk with population size around 15,000 to 20,000 plants. Individual plant selection was carried out at maturity and each selected plant became a mutant line of M3 generation. Agronomic trial of M3 mutants lines were conducted in Mardi, Tanjung Karang, Selangor. About 115 of selected mutant lines were evaluated. Each row of those mutant lines were planted in two rows at planting distance of 25cm within and between rows. These mutant lines were visually observed and data were recorded in each of every mutant line. (Author)

  3. Studies on the effective methods for induction of mutations of vegetatively propagated plants by the use of the gamma field

    International Nuclear Information System (INIS)

    Nakajima, Kenji

    1977-01-01

    In the gamma field for the whole plant irradiation of vegetatively propagated plants, artificial induction of mutations in rose, tea, mulberry and chrysanthemum has been studied since 1962. The studies include induction of wholly mutated shoots (sports), irradiation techniques for mutation induction, usage of cultivars in mutation breeding and re-treatment of induced mutations with gamma ray. The results so far attained are described as follows: effects of the cutting back treatment on the induction of sports; induction of radiation injuries and mutations by whole plant irradiation; and re-treatment of induced mutants with gamma ray. (Mori, K.)

  4. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

    Energy Technology Data Exchange (ETDEWEB)

    Somers, Christopher M. [University of Regina, Department of Biology, 3737 Wascana Parkway, Regina, SK, S4S 0A2 (Canada)]. E-mail: chris.somers@uregina.ca

    2006-06-25

    Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species.

  5. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: Lessons learned from lab mice

    International Nuclear Information System (INIS)

    Somers, Christopher M.

    2006-01-01

    Expanded simple tandem repeat (ESTR) DNA loci that are unstable in the germline have provided the most sensitive tool ever developed for investigating low-dose heritable mutation induction in laboratory mice. Ionizing radiation exposures have shown that ESTR mutations occur mainly in pre-meiotic spermatogonia and stem cells. The average spermatogonial doubling dose is 0.62-0.69 Gy for low LET, and 0.18-0.34 Gy for high LET radiation. Chemical alkylating agents also cause significant ESTR mutation induction in pre-meiotic spermatogonia and stem cells, but are much less effective per unit dose than radiation. ESTR mutation induction efficiency is maximal at low doses of radiation or chemical mutagens, and may decrease at higher dose ranges. DNA repair deficient mice (SCID and PARP-1) with elevated levels of single and double-strand DNA breaks have spontaneously elevated ESTR mutation frequencies, and surprisingly do not show additional ESTR mutation induction following irradiation. In contrast, ESTR mutation induction in p53 knock-outs is indistinguishable from that of wild-type mice. Studies of sentinel mice exposed in situ to ambient air pollution showed elevated ESTR mutation frequencies in males exposed to high levels of particulate matter. These studies highlight the application of the ESTR assay for assessing environmental hazards under real-world conditions. All ESTR studies to date have shown untargeted mutations that occur at much higher frequencies than predicted. The mechanism of this untargeted mutation induction is unknown, and must be elucidated before we can fully understand the biological significance of ESTR mutations, or use these markers for formal risk assessment. Future studies should focus on the mechanism of ESTR mutation induction, refining dose responses, and developing ESTR markers for other animal species

  6. Complexity of the ultraviolet mutation frequency response curve in Escherichia coli B/r: SOS induction, one-lesion and two-lesion mutagenesis

    International Nuclear Information System (INIS)

    Doudney, C.O.

    1976-01-01

    Three distinct sections of the ultraviolet mutation frequency response (MFR) curve toward tryptophan prototrophy have been demonstrated in Escherichia coli B/r WP2 trp thy and its uvrA derivative in log-phase growth in minimal medium. The initial section, which appears fluence-squared, may reflect the necessity, if mutation is to result, for induction of two lesions, one located within the potentially mutated genetic locus and the other damaging deoxyribonucleic acid replication and resulting in induction of the error-prone SOS repair function. A second linear section is ascribed to the continued induction, after exposure above that sufficient for complete SOS expression, of isolated lesions which lead to mutation in potentially mutated loci. The third section demonstrates an increased rate of mutagenesis and suggests the induction of two lesions in proximity which result in additional mutations. Split-exposure studies support the inducible nature of the SOS function and suggest that mutation frequency decline (MFD) is due to excision resulting from or related to the prevention of SOS induction by inhibition of protein synthesis. Preirradiation tryptophan starvation of the uvr + strain for 30 min decreases MFR in the first and second sections of the curve. Reduction of MFR in the third section requires more prestarvation time and is blocked by nalidixic acid. The decreased MFR of the first and second sections is ascribed to promotion of postirradiation MFD based on excision and that of the third section to completion of the chromosome during the prestarvation period

  7. Telomerase reverse transcriptase promoter mutations in bladder cancer

    DEFF Research Database (Denmark)

    Allory, Yves; Beukers, Willemien; Sagrera, Ana

    2014-01-01

    for detection of recurrences in urine in patients with urothelial bladder cancer (UBC). DESIGN, SETTING, AND PARTICIPANTS: A set of 111 UBCs of different stages was used to assess TERT promoter mutations by Sanger sequencing and TERT messenger RNA (mRNA) expression by reverse transcription...... surveillance after diagnosis of non-muscle-invasive UBC (n=194), was tested using a SNaPshot assay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association of mutation status with age, sex, tobacco, stage, grade, fibroblast growth factor receptor 3 (FGFR3) mutation, progression-free survival, disease...... frequent among FGFR3 mutant tumors (p=0.0002). There was no association between TERT mutations and mRNA expression (p=0.3). Mutations were not associated with clinical outcome. In urine, TERT mutations had 90% specificity in subjects with hematuria but no bladder tumor, and 73% in recurrence-free UBC...

  8. RGE of fission neutrons under the recessive mutation induction in Drosophila Melanogaster

    International Nuclear Information System (INIS)

    Aleksandrov, I.D.; Aleksandrova, M.V.; Lapidus, I.L.; Korablinova, S.V.; )

    2001-01-01

    The RCR-analysis of 81 γ- and neutron-induced vg recessive mutations in ripe sperm of Drosophila melanogaster males of combined with complementation assay with the vg[nw83b27] deletion mutation is used to detect precisely the RGE values of neutrons (0.85 MeV) under the chromosome and point mutation induction. The results obtained show that all genetic end-points increase linearly with γ-ray and neutron dose. Thereby, the efficacy of neutrons is found to be twice (and more) as large as that of γ-rays under the all macro- and micro-aberration mutation induction. Unlike that, the RGE of neutrons are more than twice as low as that of γ-rays under the gene/point mutation induction [ru

  9. Germline TERT promoter mutations are rare in familial melanoma

    DEFF Research Database (Denmark)

    Harland, Mark; Petljak, Mia; Robles-Espinoza, Carla Daniela

    2016-01-01

    Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57...... T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers....... The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte...

  10. Mutation induction in Haemophilus influenzae by ICR-191. Pt. 1

    International Nuclear Information System (INIS)

    Perdue, S.W.; Kimball, R.F.; McGray, P.C.; Tennessee Univ., Oak Ridge

    1981-01-01

    The investigation of mutagenic mechanisms in Haemophilus influenzae has been confined until now to mutagens that normally produce mainly base pair substitutions. This paper describes the development of a system suitable for detecting frameshift mutations induced by ICR-191. The system involves reversions from thymidine dependence to thymidine independence. Evidence is presented from a comparison of the responses to ICR-191 and to N-methyl-N'-nitro-N-nitrosoguanidine that the system is specific for frameshift mutations. The genetic recombination involved in transformation leads to a marked increase in spontaneous reversion of the frameshift mutations but not of the base substitution mutations. Presumably, this is a consequence of mispairing, with consequent change in the number of bases, during the recombination. (orig.)

  11. The experience of induction of mutation on barley in Peru

    International Nuclear Information System (INIS)

    Romero Loli, M.; Pozo Cardenas, M.; Gomez Pando, L.

    1984-01-01

    Work on induced mutation of barley was started in 1978 under the Programme of Cereal Improvement. Barley was irradiated with gamma radiation at doses of 12, 15, 18, 21, and 24 Krad. Radiation doses of 18 and 21 Krad gave the highest frequency of albino and cloroticos mutants. Induced mutation is being carried out in different parts of the country to develop mutants having early germination property. These mutants will play an important role in the late cultivation in the mountain areas of Peru

  12. In vitro methods for mutation induction in potato ( Solanum ...

    African Journals Online (AJOL)

    Potato (Solanum tuberosum L.) is an important vegetable and staple crop worldwide and mainly propagated vegetatively. Breeding of potato is problematic and therefore induced mutation is an attractive means of improving the crop. In vitro culture systems, and especially the production of microtubers, are ideal for such ...

  13. Mutation induction by and mutational interaction between monochromatic wavelength radiations in the near-ultraviolet and visible ranges

    International Nuclear Information System (INIS)

    Tyrrell, R.M.

    1980-01-01

    The induction of mutations (reversion to tryptophan independence) by various UV (254, 313, 334 and 365 nm) and visible (405 and 434 nm) wavelengths was measured in exponential phase populations of Escherichia coli B/r thy trp and B/r thy trp uvr A by assay of irradiated populations on semi-enriched media. No mutations were induced in the repair proficient strain at wavelengths longer than 313 nm. Mutations were induced to the excisionless strain at wavelengths as long as 405 nm but less than expected from the known amount of DNA damage induced. Irradiation at the long wavelenths (434, 405, 365 and 334 nm) suppressed the appearance of 254- or 313 nm-induced mutations in the repair competent strain but not in the excision deficient strain. The relative dose-requirement for mutation suppression was related to the relative efficiency of these wavelengths in inducing growth delay. These results suggest that the growth delay induced by near-UV and visible wavelenghts allows more time for the 'error-free' excision repair process to act on the potentially mutagenic lesions induced by 254- and 313-nm radiations, thereby reducing the mutation frequency observed in the repair-proficient strain. The level of near-UV mutation induced in the excision deficient strain is lower than expected from the DNA damage known to be induced. It is possible that near-UV radiation induces a class of lethal lesions that are not susceptible to error-prone repair. (author)

  14. Induction of spontaneous and UV-induced mutations during commitment to meiosis in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Machida, I.; Nakai, S.

    1980-01-01

    Inductions of reversions of nonsense, missense and frameshift-type mutations were investigated in a diploid cell population of Saccharomyces cerevisiae during commitment to meiosis, by using the medium-transfer technique from sporulation medium to vegetative medium. The yields of spontaneous reverse mutations obtained from the cells that were committed to different stages during meiosis were rather constant irrespective of the alleles tested, although the yields of both intergenic and intragenic recombinations markedly increased. The susceptibilities to UV-induced reverse mutations examined during commitment to meiosis were not changed appreciably. It is concluded that induction of base-change-type mutations in meiosis is not essentially different from that in mitosis. (orig.)

  15. Induction of somatic mutations in ornamental plants by ionizing radiations and chemical mutagens

    International Nuclear Information System (INIS)

    Desai, B.M.; Abraham, V.

    1980-01-01

    Improvement in some ornamental plants through induction of somatic mutations by ionizing radiations and chemical mutagens viz. colchicine, EMS and DS has been attempted. Mutants of high ornamental value have been evolved, isolated and multiplied in canna, perennial portulaca, tuberose, bougainvillea, hibiscus, daisy, lilies. These pertain to changes in colour, shape and size of flower and foliage. Procedural details on induction, isolation, stabilisation of the mutants and description of the new characteristics are presented. (author)

  16. Mutation induction in haploid yeast after split-dose radiation-exposure. Pt. 1

    International Nuclear Information System (INIS)

    Schenk, K.; Zoelzer, F.; Kiefer, J.

    1989-01-01

    Mutation induction was investigated in wild-type haploid yeast Saccharomyces cerevisiae after split-dose UV-irradiation. Cells were exposed to fractionated 254 nm-UV-doses separated by intervals from 0 to 6 h with incubation either on non-nutrient or nutrient agar between. The test parameter was resistance to canavanine. If modifications of sensitivity due to incubation are appropriately taken into account there is no change of mutation frequency. (orig.)

  17. Induction of mutations in tomato variety Solar Set

    International Nuclear Information System (INIS)

    Peiris, R.

    1995-01-01

    The production of tomatoes in Sri Lanka is hampered by many problems. Tomato is an economic crop which is nutritious and has export potential. The major constraint for tomato production is Bacterial Wilt caused by Pseudomonas Solanacearum. A study was initiated with the obnjective of finding tomato genotype having resistance to bacterial wilt. The seeds of the varity, Solar Set which is highly susceptible to bacterial wilt was exposed to irradiation from Co 60 source after adjusting moisture content to 14%. The dosese given were 0, 25, 30, 35, 40, 45, 50 krad. The seeds were sown in plastic trays and germination count was taken after 3 days. The LD50 value for the induction of mutants in tomato variety Solar Set is observed to be 35.6 Kr and it is the best dose value for the induction of beneficial mutants in tomato variety, Solar Set by irradiation

  18. Mutation induction in oil palm cultures using gamma irradiation

    International Nuclear Information System (INIS)

    Rohani Othman; Rajinder Singh; Mohd Nazir Basiran

    2002-01-01

    Induced mutations have played an important role in the improvement of wide range of food crops, ornamental plants and oil crops such as sesame and sunflower. Based on these successes an attempt was made to employ the mutagenesis techniques to broaden the genetic variation in breeding materials of oil palm. Traits of interest are high yield, dwarfness and disease resistance. Embryogenic callus initiated from several high yielding clones were exposed to gamma irradiation for optimum dose determination. (Author)

  19. Mutation induction in repair-deficient strains of Drosophila

    International Nuclear Information System (INIS)

    Wuergler, F.E.; Graf, U.

    1980-01-01

    Experimental evidence indicates a polygenic control of mutagenesis in Drosophila melanogaster. In oocytes chromosome aberrations detected as half-translocations or dominant lethals depend on a repair system which in a number of genetically nonrelated strains shows different repair capacities. Sister chromatid exchanges are easily studied as ring chromosome losses. They develop through a genotype controlled mechanism from, premutational lesions. Stocks with particular pairs of third chromosomes were discovered in which increased sensitivity of larvae to the toxic effects of a monofunctional alkylating agent correlates with high frequencies of x-ray induced SCE's. Sex-linked mutagen-sensitive mutants could be shown to control mutation fixation: pronounced maternal effects were found when sperm carrying particular types of premutational lesions were introduced into different types of mutant oocytes. The mutant mus(1)101D1 was found to be unable to process lesions induced by the crosslinking agent nitrogen mustard into point mutations. Alkylation damage leads to increased point mutation frequencies in the excision repair deficient mutant mei-9L1, but to reduced frequencies in the post-replication repair deficient mutant mei-41D5. It became clear that the study of maternal effects on mutagenized sperm represents an efficient tool to analyze the gentic control of mutagenesis in the eukaryotic genome of Drosophila melanogaster

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Wilson, James W.; Haines, Jackie; Sienkiewicz, Zenon; Dubrova, Yuri E.

    2015-01-01

    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 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

  2. Genetic improvement of sweet potato through somatic embyrogenesis and in vitro induction of mutations

    Energy Technology Data Exchange (ETDEWEB)

    Sonnino, A; Thinh, N T; Santangelo, E; Mini, P [Centro Ricerche Energia, ENEA, Rome (Italy)

    1997-07-01

    Mutation breeding is a promising option for the genetic improvement of sweet potato. Callus induction, somatic embryogenesis and plant regeneration was investigated in twenty-two sweet potato varieties of different origin. Plant regeneration was found to depend on the genotype and composition of the induction medium. The regeneration through somatic embryogenesis induced morphological and physiological changes among the regenerated plants. The irradiation with 30 to 50 Gy of meristems before culture on induction medium inhibited somatic embryogenesis. A number of accessions were evaluated in field trials and showed wide differences in yield. (author). 6 refs, 6 tabs.

  3. Genetic improvement of sweet potato through somatic embyrogenesis and in vitro induction of mutations

    International Nuclear Information System (INIS)

    Sonnino, A.; Thinh, N.T.; Santangelo, E.; Mini, P.

    1997-01-01

    Mutation breeding is a promising option for the genetic improvement of sweet potato. Callus induction, somatic embryogenesis and plant regeneration was investigated in twenty-two sweet potato varieties of different origin. Plant regeneration was found to depend on the genotype and composition of the induction medium. The regeneration through somatic embryogenesis induced morphological and physiological changes among the regenerated plants. The irradiation with 30 to 50 Gy of meristems before culture on induction medium inhibited somatic embryogenesis. A number of accessions were evaluated in field trials and showed wide differences in yield. (author). 6 refs, 6 tabs

  4. Research for structure and function of protein promoting mutation induction

    International Nuclear Information System (INIS)

    Nohmi, Takehiko; Gruz, P.; Shimizu, M.

    2004-01-01

    The nature of Y family DNA polymerase, which takes a damaged deoxynucleotide 3 phosphate (dNTP) into the template, was discussed in detail. Bacterial endoenzyme DNA pol Y1 took in the oxidized dNTP uniquely. The pol Y1 showed following singularity: (1) taking 2-OH-dGTP in opposite side of template A, (2) taking 2-OH-dATP in opposite side of template G and T, (3) not only taking in both of the oxidized dNTP, but also carrying out an elongation reaction of the dNTP, (4) after taking in the oxidized nucleotide continuously, the elongation reaction stopped. Human Y family DNA polymerase, hpol η showed the same nature of the preceding item (1) and (2), also. Above mentioned natures indicated possibility of common nature of Y family polymerase. (M. Suetake)

  5. Induction and evaluation of beneficial mutations in asexually propagated crops

    International Nuclear Information System (INIS)

    Asencion, A.B.; Dy, V.A.; Casyao, J.M.; Gutierrez-Lapade, A.B.; Grafia, A.O.

    1976-03-01

    BNAS camote variety was selected as starting material for mutation breeding research. Single-cell approach through leaf propagation was tried and success was obtained in making the peticle or leaf fragment develop roots. The leaf blade, however, dried up before any shoot could arise. Observations are being made on the agronomic character of twenty collections of gabi (Calocasia), 4 collections of San Fernando (x anthosoma), one collection of galiang and three collections of palawan. The shoot bud at the base of the pineapple leaf turned out to be a useful means of propagating the pineappled. In mutation breeding, this has the advantage over the crown because only few cells are involved in the former. Results indicated that proliferation of the shoot apex is an effect of gamma irradiation at levels varying from 0.5 to 4.0 kr. A 3-krad dose appeared to produce the highest level of proliferation as indicated by the average number of shoot per leaf which was 2.3

  6. Induction of rice mutations by high hydrostatic pressure.

    Science.gov (United States)

    Zhang, Wei; Liu, Xuncheng; Zheng, Feng; Zeng, Songjun; Wu, Kunlin; da Silva, Jaime A Teixeira; Duan, Jun

    2013-09-01

    High hydrostatic pressure (HHP) is an extreme thermo-physical factor that affects the synthesis of DNA, RNA and proteins and induces mutagenesis in microorganisms. Our previous studies showed that exposure to 25-100 MPa HHP for 12 h retarded the germination and affected the viability of rice (Oryza sativa L.) seeds, increased the tolerance of rice plants to cold stress and altered gene expression patterns in germinating rice seeds. However, the mutagenic effect of HHP on rice remains unknown. In this study, exposure to 25, 50, 75 or 100 MPa for 12 h HHP could efficiently induce variation in rice plants. Furthermore, presoaking time and HHP strength during HHP treatment affected the efficiency of mutation. In addition, the Comet assay revealed that exposure to 25-100 MPa HHP for 12 h induced DNA strand breakage in germinating seeds and may have been the source of mutations. Our results suggest that HHP is a promising physical mutagen in rice breeding. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. ''In vivo'' methodology for mutation induction in banana, cultivar ''Maca''

    International Nuclear Information System (INIS)

    Tulmann Neto, A.; Domingues, E.T.; Alvarez, A.L.F.; Mendez, B.M.J.; Ando, A.

    1990-01-01

    Full text: The ''Maca'' cultivar is a banana of high acceptability in the south west of Brazil. However, it is very susceptible to several diseases. Due to the difficulties in the application of the traditional plant breeding methods, the Radiation Genetics Section of CENA is utilising the ''in vivo'', and the ''in vitro'' mutation breeding approach. The ''in vivo'' methodology is based on the work of HAMILTON. This method is being utilised in Brazil for rapid banana propagation. Rhizomes (20 cm diameter) were obtained from young field grown plants before flower differentiation. In these rhizomes, only 5-6 leaf sheaths were retained, the others being removed. The rhizomes were maintained in a greenhouse in boxes with vermiculite, covered with plastic. After one week, all leaf sheaths were removed, until the exposure of the meristematic apex with about 2 mm size. This apex was cut off with a scalpel and a cross shaped cut (2,5 cm) was made. This stimulates the development of lateral buds. After four months, the meristematic apices of these new buds were cut off in the same way and immediately the rhizomes were irradiated with gamma rays. Around the eliminated lateral buds callus developed and new lateral buds were formed. The LD 50 in relation to the number of these new buds produced was around 30 Gy. According to the author of the original method, from the callus one can obtain axillary or adventitious buds. In the early stages it is possible, based on the shape, to distinguish both types. The advantage of utilising adventitious buds originating from only one cell to avoid chimerism is well known in mutation breeding. However, it is not certain whether this is the case in the present method. After detachment from rhizomes and rooting in soil, plants with 15-20 cm height were inoculated with Fusarium oxysporum f.sp. cubense. After 3 weeks the plants showed symptoms of the Panama disease and screening could be done at this stage. The total time between the removal of

  8. ''In vivo'' methodology for mutation induction in banana, cultivar ''Maca''

    Energy Technology Data Exchange (ETDEWEB)

    Tulmann Neto, A; Domingues, E T; Alvarez, A L.F.; Mendez, B M.J.; Ando, A [Centre for Nuclear Energy in Agriculture (CENA), University of Sao Paulo, Piracicaba, SP. (Brazil)

    1990-07-01

    Full text: The ''Maca'' cultivar is a banana of high acceptability in the south west of Brazil. However, it is very susceptible to several diseases. Due to the difficulties in the application of the traditional plant breeding methods, the Radiation Genetics Section of CENA is utilising the ''in vivo'', and the ''in vitro'' mutation breeding approach. The ''in vivo'' methodology is based on the work of HAMILTON. This method is being utilised in Brazil for rapid banana propagation. Rhizomes (20 cm diameter) were obtained from young field grown plants before flower differentiation. In these rhizomes, only 5-6 leaf sheaths were retained, the others being removed. The rhizomes were maintained in a greenhouse in boxes with vermiculite, covered with plastic. After one week, all leaf sheaths were removed, until the exposure of the meristematic apex with about 2 mm size. This apex was cut off with a scalpel and a cross shaped cut (2,5 cm) was made. This stimulates the development of lateral buds. After four months, the meristematic apices of these new buds were cut off in the same way and immediately the rhizomes were irradiated with gamma rays. Around the eliminated lateral buds callus developed and new lateral buds were formed. The LD{sub 50} in relation to the number of these new buds produced was around 30 Gy. According to the author of the original method, from the callus one can obtain axillary or adventitious buds. In the early stages it is possible, based on the shape, to distinguish both types. The advantage of utilising adventitious buds originating from only one cell to avoid chimerism is well known in mutation breeding. However, it is not certain whether this is the case in the present method. After detachment from rhizomes and rooting in soil, plants with 15-20 cm height were inoculated with Fusarium oxysporum f.sp. cubense. After 3 weeks the plants showed symptoms of the Panama disease and screening could be done at this stage. The total time between the

  9. Induction of mutations for nematode resistance in tomato

    International Nuclear Information System (INIS)

    Alameddine, A.

    1976-01-01

    The objective of this work is to develop resistance to root-knot nematodes in tomato by induction, selection and utilization of the newly created resistant strains. Seeds of two varieties of tomato Lycopersicon esculentum L., namely Amcopack and Supermarmande, were subjected to various doses of gamma rays ranging from 10 Krads to 40 Krads in an effort to gain resistance to Meloidogyne incognita Chitwood, the prevalent species of nematodes in Lebanon. The variety Supermarmande seemed not to be affected by irradiation while Amcopack gained some resistance with a corresponding increase in the dose of radiation. The data suggest that in a variety like Amcopack, irradiation may stimulate resistance while in others like Supermarmande, susceptibility is not reduced with a corresponding increase of dosage. Those alterations in reaction within varieties may be due to genetic differences which allow some varieties to acquire resistance to nematodes when exposed to certain dosages, while others to suffer seriously due to sensitivity. (author)

  10. Induction of somatic mutation in chrysanthemum cultivar 'Anupam'

    International Nuclear Information System (INIS)

    Banerji, B.K.; Datta, S.K.

    1990-01-01

    Rooted cuttings of chrysanthemum cv. 'Anupam' were irradiated with 1.5, 2.0 and 2.5 Krad of gamma rays. Significant reduction in survival, plant height, branch, leaf and flower head number and leaf size were recorded after irradiation. Radio sensitivity was determined on the basis of different cytomorphological parameters. Different types of morphological abnormalities in leaves and flower and chromosomal abnormalities during root tip mitosis were observed and the total abnormalities increased with increase in exposure to gamma rays. Significant delay in flower bud initiation, first colour showing and full bloom were recorded in the treated population. Somatic mutations in flower colour could be induced in vM 1 as chimera and a total of three flower colour mutant, i.e., lighter, white and striped were isolated and established in pure form as new cultivars which are of direct use for floriculture industry. (author). 17 refs., 6 figs. , 2 tabs

  11. The induction of somatic mutations by high-LET radiation observed using the Drosophila assay system

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Hoshi, Masaharu; Takada, Jun; Endo, Satoru

    1999-01-01

    To evaluate the mutagenic potential of high-LET radiation, an analysis was made on the production of somatic mutations by 252 Cf fission neutron s and heavy particle ions accelerated by a synchrotron. A Drosophila strain that allows simultaneous detection of two types of mutations in an identical fly was constructed. One was a wing-hair mutation and the other was an eye-color mosaic spot mutation. Measurements were made using a combined assay system of both mutation assays. Larvae were exposed to radiation at the age of post-ovipositional day-3. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots was very high, the relative biological effectiveness (RBE) = 8.5, but the efficiency for eye-color mosaic spot was nearly equal (RBE = 1.2) to that of 137 Cs γ-rays. The RBE of carbon ions for inducing wing-hair mosaic spots increased as an increase in LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damages such as non-rejoinable strand break or clustered double strand break, which increase with LET may be responsible for the induction of wing-hair mutation, while simpler forms of molecular damage may induce a reversion in the white-ivory allele. (M.N.)

  12. Prospects for the development of disease-resistant temperate fruit plants by mutation induction

    International Nuclear Information System (INIS)

    Campbell, A.I.; Wilson, D.

    1977-01-01

    In most of the present conventional fruit breeding programmes disease resistance has become an important objective. Progress is slow because of the long generation time and the genetic complexity of most tree fruit species. The complexity is such that cultivars can only be maintained as clones and it is unlikely that identical genotypes could ever be sexually produced. Hence, the prospect of changing a few characters in an otherwise unchanged genetic background, as might be done by somatic mutation, is attractive. The occurence of natural mutations in some fruit cultivars and the induction of mutations in others demonstrates that such an approach is possible for some characters at least and these may include disease resistance. The yet limited success of mutation breeding in fruit crops may be due in part to the innate difficulties with this group of plants but may also be a consequence of the faulty methods that have been used in the past. New techniques of inducing and selecting mutants in fruit trees are reported, with particular reference to disease resistance and some basic guidelines for success are suggested. The type of disease resistance required will undoubtedly affect the approach used. In theory, monogenic resistance seems more likely to respond to change by mutation induction than polygenic resistance. However, the multiple effects seen in the natural spur-type apple mutants and in the preliminary results with induced apple mutations at Long Ashton suggest that field resistance to some major diseases may not be an unreasonable target

  13. Induction and evaluation of beneficial mutations in mungbean (Phaseolus aureus)

    International Nuclear Information System (INIS)

    Grafia, A.O.; Elec, J.V.

    1976-03-01

    About 500 gamma-irradiated M 1 lines or 500 M 2 plants of MG50-10A were sceened for resistance to powdery mildew. None turned out to be resistant to the disease. Putative increased height mutants in MG50-10A were selected and tested. The results obtained so far are still ambiguous. At least one more retesting for the height character is needed. A non-scattering and long-podded multifoliata mungbean has been developed. It has very attractive and medium-size yellow seeds. The plants matured 2 to 14 days later than MG50-10A. These materials are the sixth generation of the cross between the EMS-induced multifoliata mungbean (parent plant was native yellow) and the green or original MG50-10A. It is however recommended to produce more M 2 seeds using gamma irradiation and post-irradiation heat treatment of the seeds at 80 0 C for at least three hours, produce more M 2 seeds using the ethyl methane sulfonate, provide a final evaluation for the increased-height mutants of MG50-10A, increase the seeds of the new multifoliata mungbean variety while producing breeders seed, obtain the trifoliata version of this new multifoliata variety, work on other mungbean varieties such as the glabrous MGY17 or MGY18, work on induction of resistance to cercospora leaf spot

  14. Induction and evaluation of beneficial mutations in rice

    International Nuclear Information System (INIS)

    Asencion, A.B.; Elec, J.V.

    1976-03-01

    Mutation breeding work in rice at the Agricultural Research Division, PARC, PAEC is a continuing endeavor to improve further the varieties developed by the International Rice Research Institute and the U.P. College of Agriculture. The major objectives are: to improve the yield; to reduce maturity and height; to improve tillering capacity; to improve disease resistance; and to increase protein content. None of the 16 improved-plant-type mutants from fast-neutron-irradiation of IR20 outyielded the original variety. Preliminary test of mutants from thermal-neutron irradiation of C4-630 showed two lines yielding at least as well as original variety in spite of the reduction of maturity by 12 and 13 days, respectively. Gamma irradiation of Intan and Bengawan resulted in the selection of 19 lines for Intan and 9 lines for Bengawan in the M6 generation. The Intan mutants have desirably reduced plant heights and longer grains than the original variety but the desired elimination photo-period sensitivity was not obtained. The Bengawan mutants, likewise were still photoperiod sensitive despite reduced heights. Unfortunately culm diameter was also reduced. The Azmil mutants have reduced plant height and slightly improved tillering capacity. A putative mutant for increased protein content has been identified in the advanced generation of irradiated IR20. A tungro-resistant version of the Philippines-Seed-Board recommended PARC-2 has been developed through selection and screening

  15. Improvement of west Sumatra black rice cultivar through mutation induction

    International Nuclear Information System (INIS)

    Benny Warman; Sobrizal; Irfan Suliansyah; Etti Swasti; Auzar Syarif

    2015-01-01

    Black rice cultivar is a local rice cultivar originating from East Pasaman, West Sumatera which has black endosperm, long growth duration and high plant height. The research was conducted from March 2012 until March 2013 with the objective of improvement the genetic of this black rice cultivar, especially related to the growth duration through mutation breeding. To get the optimum dose, the seeds of this cultivar were irradiated by gamma ray with doses of 0, 100, 200, 300, 400 and 500 Gy, respectively at Center of the Application of Isotopes and Radiation, National Nuclear Energy Agency (PAIR - BATAN), Jakarta. Base don the data of percentage of germination, plant height and root length in the seedling stage, and the percentage of grain sterility in M1 plants, it was obtained that the dose of 200-300 Gy is an effective dose in generating genetic diversity. It was agree with result of variability observations in M2 population derived from 200 Gy irradiated seeds, in which the extensive genetic diversities were observed in the variable of plant height, number of productive tillers and growth duration. From the selection in M2 population it was obtained 81 early maturing plants, with mutant frequency of 0.08 %. These selected early maturing mutants are very useful as initial plant materials in developing black rice leading mutant variety(s) in the future. (author)

  16. The potential for induction of autoimmune disease by a randomly-mutated self-antigen

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm

    2007-01-01

    -antigens can be immunogenic and lead to autoimmunity against wildtype self-antigens. In theory, modified self-antigens can arise by random errors and mutations during protein synthesis and would be recognized as foreign antigens by naïve B and T lymphocytes. Here, it is postulated that the initial auto......, a relation to an infectious disease is described, and it is thought that microbes can play a direct role in induction of autoimmunity, for instance by molecular mimicry or bystander activation of autoreactive T cells. In contrast, less attention has been given to the possibility that modified self......-antigen is not a germline self-antigen, but rather a mutated self-antigen. This mutated self-antigen might interfere with peripheral tolerance if presented to the immune system during an infection. The infection lead to bystander activation of naïve T and B cells with specificity for mutated self-antigen and this can lead...

  17. Ionophoren - a new method of mutation induction in plants

    Energy Technology Data Exchange (ETDEWEB)

    Starzycki, Stanislaw [Plant Breeding and Acclimatisation Institute, Radzikow, Blonie (Poland)

    1990-07-01

    Full text: For many years the work on mutagenesis focussed on using ionizing radiation or chemical compounds. The treatments and doses inducing optimal effect were studied extensively. Many studies concerned mutation spectra observed after the action of different mutagens. Here we describe a new method for obtaining mutants and the first experiences of its application. The new method consists of exposing plants (germinated seeds) to the action of electromagnetic field, which is formed between the anode and cathode of direct current with a voltage of 12 and 24 V. The cathode is a graphite electrode permanently immersed in distilled water. The other electrode (made from silver) is inserted between the germinating seeds. The seeds are in contact with water, though they are not immersed. Therefore, the current flows between the electrodes through the seedlings. In order not to destroy the meristems of young roots the roots were placed above the water. The distance between the electrodes did not exceed 15 cm. After placing the electrodes and seeds the current is switched on. The current did not exceed several Amperes in all the variants of the experiment. The exposure was 2, 5 and 10 minutes. During the exposition the current decreased; differences were distinct - from some tenths to some Amperes. Germinating seeds of maize (pure lines from Exp. Station Smolice), barley, wheat and soybean were exposed in this way to the action of an electromagnetic field. A comparatively low voltage and current caused necrosis of most plants. Few plants produced seeds. In the M{sub 2} generation they were singly sown in pots. Distinct mutants were detected in the M{sub 3} though the scale of their variation was not large. Barley and wheat had a different response than soybean. Certain sectors of spikes were sterile. Plants grown out of these sectors developed seeds again showing sterile sectors. In soybean morphological and physiological differences observed exceeded the variation

  18. Ionophoren - a new method of mutation induction in plants

    International Nuclear Information System (INIS)

    Starzycki, Stanislaw

    1990-01-01

    Full text: For many years the work on mutagenesis focussed on using ionizing radiation or chemical compounds. The treatments and doses inducing optimal effect were studied extensively. Many studies concerned mutation spectra observed after the action of different mutagens. Here we describe a new method for obtaining mutants and the first experiences of its application. The new method consists of exposing plants (germinated seeds) to the action of electromagnetic field, which is formed between the anode and cathode of direct current with a voltage of 12 and 24 V. The cathode is a graphite electrode permanently immersed in distilled water. The other electrode (made from silver) is inserted between the germinating seeds. The seeds are in contact with water, though they are not immersed. Therefore, the current flows between the electrodes through the seedlings. In order not to destroy the meristems of young roots the roots were placed above the water. The distance between the electrodes did not exceed 15 cm. After placing the electrodes and seeds the current is switched on. The current did not exceed several Amperes in all the variants of the experiment. The exposure was 2, 5 and 10 minutes. During the exposition the current decreased; differences were distinct - from some tenths to some Amperes. Germinating seeds of maize (pure lines from Exp. Station Smolice), barley, wheat and soybean were exposed in this way to the action of an electromagnetic field. A comparatively low voltage and current caused necrosis of most plants. Few plants produced seeds. In the M 2 generation they were singly sown in pots. Distinct mutants were detected in the M 3 though the scale of their variation was not large. Barley and wheat had a different response than soybean. Certain sectors of spikes were sterile. Plants grown out of these sectors developed seeds again showing sterile sectors. In soybean morphological and physiological differences observed exceeded the variation encountered in

  19. Kinetics of mutation induction by ultraviolet light in excision-deficient yeast.

    Science.gov (United States)

    Eckardt, F; Haynes, R H

    1977-02-01

    We have measured the frequency of UV-induced reversions (locus plus suppressor) for the ochre alleles ade2-1 and lys2-1 and forward mutations (ade2 adex double auxotrophs) in an excision-deficient strain of Saccharomyces cerevisiae (rad2-20). For very low UV doses, both mutational systems exhibit linear induction kinetics. However, as the dose increases, a strikingly different response is observed: in the selective reversion system a transition to higher order induction kinetics occurs near 9 ergs/mm2 (25% survival), whereas in the nonselective forward system the mutation frequency passes through a maximum near 14 ergs/mm2 (4.4% survival) and then declines. This contrast in kinetics cannot be explained in any straightforward way by current models of induced mutagenesis, which have been developed primarily on the basis of bacterial data. The bacterial models are designed to accommodate the quadratic induction kinetics that are frequently observed in these systems. We have derived a mathematical expression for mutation frequency that enables us to fit both the forward and reversion data on the assumptions that mutagenesis is basically a "single event" Poisson process, and that mutation and killing are not necessarily independent of one another. In particular, the dose-response relations are consistent with the idea that the sensitivity of the revertants is about 25% less than that of the original cell population, whereas the sensitivity of the forward mutants is about 29% greater than the population average. We argue that this relatively small differential sensitivity of mutant and nonmutant cells is associated with events that take place during mutation expression and clonal growth.

  20. Kinetics of mutation induction by ultraviolet light in excision-deficient yeast

    International Nuclear Information System (INIS)

    Eckardt, F.; Haynes, R.H.

    1977-01-01

    We have measured the frequency of uv-induced reversions (locus plus suppressor) for the ochre alleles ade 2-1 and lys 2-1 and forward mutations (ade2 adex double auxotrophs) in an excision-deficient strain of Saccharomyces cerevisiae (rad 2-20). For very low uv doses, both mutational systems exhibit linear induction kinetics. However, as the dose increases, a strikingly different response is observed: in the selective reversion system a transition to higher order induction kinetics occurs near 9 ergs/mm 2 (25 percent survival), whereas in the nonselective forward system the mutation frequency passes through a maximum near 14 ergs/mm 2 (4.4 percent survival) and then declines. This contrast in kinetics cannot be explained in any straightforward way by current models of induced mutagenesis, which have been developed primarily on the basis of bacterial data. The bacterial models are designed to accommodate the quadratic induction kinetics that are frequently observed in these systems. We have derived a mathematical expression for mutation frequency that enables us to fit both the forward and reversion data on the assumptions that mutagenesis is basically a ''single event'' Poisson process, and that mutation and killing are not necessarily independent of one another. In particular, the dose-response relations are consistent with the idea that the sensitivity of the revertants is about 25 percent less than that of the original cell population, whereas the sensitivity of the forward mutants is about 29 percent greater than the population average. We argue that this relatively small differential sensitivity of mutant and nonmutant cells is associated with events that take place during mutation expression and clonal growth

  1. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions

    International Nuclear Information System (INIS)

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami

    2006-01-01

    We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/μm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to 137 Cs γ-rays. The mutation frequency increased up to 105 keV/μm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/μm showed all or partial deletions of exons, while among γ-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not

  2. Induction of mutations in blue-green alga Anacystis nidulans by consolidated and split UV irradiation

    International Nuclear Information System (INIS)

    Amla, D.V.

    1979-01-01

    Ultraviolet mutability of consolidated and split dose treatment in A. nidulans was investigated with reference to induction of phage- and streptomycin-resistant markers. The consolidated UV treatment induced both the markers about 100-150-fold, whereas under photoreactivating conditions the survival of alga was enhanced and mutation frequency was decreased. The split UV treatment with 6 hr dark incubation between two UV exposures enhanced the survival and mutation frequencies to 500-700 fold above the back-ground level. The data give indirect evidence for the presence of error-prone dark repair system in this organism. (auth.)

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

    International Nuclear Information System (INIS)

    Campbell, T.A.

    1989-01-01

    (n=22) would be more promising candidates than C. aperta for domestication: Both are characterized by erect growth, a high number of fruits which are generally borne on the upper portion of the plant, surplus space in the fruits (enhancing the chances of developing a non-shattering type), and lauric acid yields (as a percentage of total seed fatty acids) of 63.3 and 53.9%, respectively. C. tolucana is a diploid whereas C. wrightii may be an allopolyploid. Therefore, in a new series of experiments, dry seeds (2% moisture) of Cuphea tolucana and C. wrightii were exposed to 0 to 30 kR of gamma radiation. After irradiation the seeds were hydrated in oxygenated water. Responses of both species were curvilinear but C. tolucana was considerably more sensitive to gamma radiation than C. wrightii. The range of exposure causing 40 to 60% plant height reduction was approximately 5 to 8 kR in C. tolucana and 9 to 17 kR in C. wrightii. In a second experiment under the same conditions, C. tolucana was exposed to levels of 0 to 12.8 kR and C. wrightii to levels of 0 to 60 kR. A 50% plant height reduction was caused by 10-12 kR in C. tolucana, and between 11 to 18 kR in C. wrightii. Results of both experiments are consistent with the experience that chromosome number and tolerance to radiation are positively correlated. For large scale mutation breeding work, the appropriate gamma ray doses should be 8-12 kR for C. tolucana, and between 11 to 18 kR for C. wrightii. (author)

  4. Cellular transformation by radiation: induction, promotion, and inhibition

    International Nuclear Information System (INIS)

    Borek, C.

    1981-01-01

    Radiation oncogenesis induced in utero in hamsters is expressed at a lower frequency than that induced in vitro. Quantitative studies carried out on hamster embryo cells indicate that neutrons are more effective in their carcinogenic potential than x-rays but also more toxic, that splitting the dose of x-rays at low doses leads to enhanced transformation, but that at high doses protracted radiation has a sparing effect. At all dose ranges survival was increased by protracting the radiation dose, thus suggesting that different repair processes must be involved for survival and transformation. In our qualitative studies, once cells are transformed by radiation, they exhibit a wide range of structural and functional phenotypic changes, some of which are membrane-associated and are expressed within days after induction. Our current studies on nutritional and hormonal influences on radiation transformation indicate the following: Pyrolysate products from broiled protein foods act in synergism with radiation to produce transformation, whereas vitamin A analogs are powerful, preventive agents. Retinoids inhibit both x-ray-induced transformation and its promotion by TPA; these modifications (enhancement by TPA, inhibition by retinoids) are not reflected in sister chromatid exchanges, but are reflected in the level of membrane associated enzymes Na/K ATPase. Whereas retinoids modify late events (expression, promotion), we find that thyroid hormone plays a crucial role in the early phases of radiation and chemically induced transformation. Our recent success in transforming human skin fibroblasts will enable quantitative and qualitative studies of radiation carcinogenesis in a system relevant to man

  5. Interpretation of Mutation Induction by Accelerated Very Heavy Ions in Bacteria

    International Nuclear Information System (INIS)

    Kozubek, S.; Ryznar, L.; Krasavin, E.A.

    1994-01-01

    We propose a simple approach for the calculation of the frequency of mutation induction in bacteria. The approach is based on the calculation of the fraction of energy deposited by accelerated particles in indirect hits, e.i. events in which the particle does not pass through the cell, however, the cell is hit by δ-electrons. This descriptor of the radiation field has been evaluated for different values of the particle energy and different radii of sensitive structure. Four models of the track structure have been used for calculations. The results have been compared with experimental data on mutation induction in bacteria. Two different modes of particle mutagenic action can be distinguished. Available experimental data agree reasonably well with the results of the presented theory if appropriate track structure is taken. Very good results have been obtained with the track structure models of Kudryashov, 1973 and Chatterjee and Magee, 1973. 23 refs., 6 figs., 1 tab

  6. Theory of mutation induction by accelerated very heavy ions in cells

    International Nuclear Information System (INIS)

    Kozubek, S.; Ryznar, L.

    1995-01-01

    Stochastic effects of ionising radiation in humans are related to mutation induction in cells. Therefore experimental data on mutation induction represents one of the endpoints used for the estimation of risk in radiation protection. Only very rough estimates can be made owing to the fact that a suitable theoretical approach does not exist. A simple method is proposed for the evaluation of the efficiency of mutation induction by accelerated very heavy ions in mammalian cells. The approach is based on the calculation of the fraction of energy deposited by accelerated particles in indirect collisions (hits) in the cells. Two different modes of particle mutagenic action can be distinguished. δ ray mutagenesis is related to those particles that preferentially kill the cells in direct hits. Track-core mutagenesis arises from direct hits and is observed for lighter ions or ions with very high energy (LET ≤ 500 keV.μm -1 ). Available experimental data agree reasonably well with the results based on theory. (author)

  7. Inactivation and mutation induction in Saccharomyces cerevisiae exposed to simulated sunlight: evaluation of action spectra.

    Science.gov (United States)

    Schenk-Meuser, K; Pawlowsky, K; Kiefer, J

    1992-07-15

    The effectiveness of polychromatic light irradiation was investigated for haploid yeast cells. Inactivation and mutation induction were measured in both a RAD-wildtype strain and an excision-repair defective strain. The behaviour of vegetative "wet" cells was compared to that of dehydrated cells. The aim of the study was to assess the interaction of UVC with other wavelengths in cells of different states of humidity. The irradiation procedure was therefore carried out using a solar simulator either with full spectrum or with a UVC-blocking filter (modified sunlight) added. The results were analysed on the basis of separately determined action spectra. The summation of the efficiency of individual wavelengths was compared to the values obtained from polychromatic irradiation. It is shown that the effects caused by the whole-spectrum irradiation in wet cells can be predicted sufficiently from the calculation, while dried wildtype cells exhibit higher mutation rates. Thus it can be assumed that drying-specific damage leads to lethal and mutagenic lesions which are processed in different ways, causing a synergistic behaviour in mutation induction. Irradiation of vegetative cells with modified sunlight (UVC-) results in less inactivation and lower mutation rates than were calculated. From these results it can be concluded that this antagonistic behaviour is caused by the interaction of near-UV photoproducts.

  8. The induction of somatic mutations by high-LET radiations using the drosophila assay system

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Takatsuji, Toshihiro

    2004-01-01

    Two types of somatic mutation in Drosophila melanogaster were examined to evaluate the relative biological effectiveness (RBE) of 252 Cf neutrons and heavy ions (carbon ions and neon ions) accelerated with a synchrotron for inducing mutations as a function of linear energy transfer (LET). One is the loss of heterozygosity for wing-hair mutations and the other the reversion of the mutant white-ivory. The measurements were made using a combined mutation assay system; so that induced mutant wing-hair clones as well as revertant eye-color clones could be detected simultaneously in the same fly. Larvae were irradiated at the age of 3 days post-oviposition. The efficiency of 252 Cf neutrons for inducing wing-hair mosaic spots is very high, RBE=8.5, but that for eye-color mosaic spot is almost equal (RBE=1.2) to that of 137 Cs γ-rays. RBE-LET relationships were obtained for the induction of wing-hair and eye-color mosaic spots. The RBE of carbon and neon ions for producing wing-hair mosaic spots increased with increasing LET values. The RBE for the induction of eye-color mutants did not change with LET. These relationships suggest that more complex types of DNA damage such as non-rejoinable strand breaks or clustered double strand breaks that increase with LET may be responsible for inducing the wing-hair mutation, while simpler forms of molecular damage may induce reversion in the white-ivory allele. (author)

  9. Repair capability and the cellular age response for killing and mutation induction after UV

    International Nuclear Information System (INIS)

    Wood, R.D.; Burki, H.J.; California Univ., Berkeley

    1982-01-01

    The cell-cycle response for killing and mutation induction by ultraviolet irradiation was measured in synchronous Chinese hamster ovary cells (CHO wild-type) and in a UV-hypersensitive mutant (43-3B) derived from this line. The CHO 43-3B line shows a greatly enhanced sensitivity to killing (D 0 of 0.3 as compared to 3.2 J/m 2 for the wild-type), is hypermutable, and deficient in DNA repair. For the wild-type, a characteristic age response is seen for killing by UV, with maximum sensitivity in early-S and resistance increasing through the S-phase. There is also a life-cycle specificity for induction of diphtheria-toxin resistance in late-G 1 and early-S. Relatively little variation is seen through the cell cycle for induced 6-thioguanine and ouabain resistance. In contrast, the 43-3B cell line shows a relatively 'flat' response to UV throughout the cell cycle, for both killing and mutation induction. Therefore it appears that the characteristic age responses seen in the wild-type CHO are associated with the function of an essentially error-free repair process. (orig./AJ)

  10. Combining zygotic embryo culture and mutation induction to improve salinity tolerance in avocado (Persea americana Mill)

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes, J. L.; Santiago, L.; Alvarez, A.; Valdés, Y.; Vernhe, M.; Guerra, M.; Altanez, S.; Prieto, E. F. [Centro de Aplicaciones Tecnológicas y Desarrollo Nuclear (CEADEN), Miramar, Playa, C. Habana (Cuba); Rodríguez, N. N.; Arbelo, O. Coto; Velázquez, B.; Rodríguez, J. A.; Sourd, D. G.; Fuentes, V. R. [Instituto de Investigaciones de Fruticultura Tropical (IICF), Miramar, Playa, C. Habana (Cuba); Leal, M. R. [Departamento de Microbiología, Facultad de Biología, Universidad de la Habana, Vedado, C. Habana (Cuba)

    2009-05-15

    Mutation induction and biotechnological techniques are some of the current approaches used in plant breeding. In the present work radiation-induced mutation followed by in vitro culture of zygotic embryos and high osmotic pressure selection methods to improve salt tolerance in avocado are investigated. The in vitro germination, rooting, bud multiplication and plantlet acclimatization of Cuban avocado varieties were recorded. The germination rates of whole embryos in vitro were found to be higher when using mature rather than immature embryos. Almost 80% of the whole embryos derived plantlets produced were successfully acclimatized under greenhouse conditions. An in vitro propagation method for avocado breeding purposes was optimized and documented. However, in vitro multiplication results indicated the need to improve bud multiplication methods in avocado. The survival rates of gamma rays irradiated and salt pressured avocado embryos were also investigated. Both mutagenic (LD{sub 50} = 27-28 Gy) and selective (LD{sub 20} = 157 mM of NaCl) doses were established. A procedure combining zygotic embryo culture and mutation induction was used to obtain. Putative mutant lines derived from salt tolerant rootstocks were developed. Putative M{sub 1}V{sub 3} progenies were planted in the field for segregation analysis. An avocado gene bank was established under the same study. Therefore this methodology appears as an alternative to traditional breeding methods, particularly for improving agronomic characteristics such as salt tolerance in avocado. (author)

  11. Mutation induction by gamma irradiation in a triploid banana Pisang Berangan

    International Nuclear Information System (INIS)

    Mak, C.; Liew, K.W.

    1995-01-01

    Shoot-tip meristems of triploid banana Pisang Berangan (Intan cultivar) were irradiated at 0, 25, 35, 45 and 60 Gy in gamma cell with a Co-60 source. The explants were in-vitro multiplied to produce M sub 1 V sub 4 plants. Increasing gamma doses caused a reduction of survival rates as well as the average number of buds or shoots produced per explant. On the basis of linear estimate of bud/shoot proliferation to gamma doses, the radiation dose that reduced the growth to 50% of the control treatment, i.e. LD sub 50 was about 38 Gy. Many phenotypic variants in growth, leaf deformation and changes in pigmentation and texture were observed in nursery plants. In addition, field-grown plants also produced various forms of bunch and fruit abnormality. Generally, mutagenic treatments resulted in a 4 to 6 fold increase in the frequency of variant plants. For number of weeks to harvest and plant height, the mean values of irradiated plants did not differ significantly from the control plants. However, mutation induction tended not only to increase the variability of these two quantitative traits but also showed a much higher frequency for plants having early fruiting or shorter plant stature. As in-vitro mutation induction could create genetic variability as well as many undesirable variants, it is highly desirable to integrate in-vitro mutation with a selection system that can screen for large mutagen treated populations

  12. Induction of in vivo mutation in chrysanthemum (Dendranthema grandiflora Tzvelev) cv. Pink Repin breeding

    International Nuclear Information System (INIS)

    Neto, Augusto Tulmann; Latado, Rodrigo Rocha

    1997-01-01

    Mutation induction was used with the objective of obtaining mutants for flower colour of chrysanthemum, cv. Repin (pink colour). Rooted cuttings were irradiated with 20 Gy of gamma rays and before the selection the cutting back method was used to advance the generations. The frequency of colour mutants observed was 5.8%. Among the mutants obtainedthe white and dark-pink-coloured ones were evaluated in yield trial and post-harvest. The results indicated that these mutants mantained the same agronomical characteristics showed by the control, with the exception of plant height in the white mutant that was shorter. Due to commercial interest of the producers, these mutants were multiplied and released as new cultivars. The white flower colour mutant was named Cristiane and the dark-pink, Ingrid. This was the first example of cultivars from an ornamental plant released by mutation breeding in Brazil. (author)

  13. Induction of mutation and recombination following UV irradiation during meiosis in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, S.L.; Parry, J.M. (University Coll. of Swansea (UK). Dept. of Genetics)

    1983-03-01

    Irradiation of yeast cultures with ultraviolet light at discrete stages during meiosis produces cyclic variations in sensitivity, i.e. cells are more sensitive to the lethal effects of UV light prior to entry into the meiotic DNA synthesis, and this corresponds to a peak of induction of point mutation. Cells become more resistant to both induced point mutation and lethality as they enter meiotic DNA synthesis, but become more sensitive again during spore formation. The induced level of intragenic recombination rises during the period of commitment ot recombination to a level indistinguishable from the full meiotic level of spontaneous intragenic recombination. Induced reciprocal recombination remains above the spontaneous level up to the point of commitment to sporulation.

  14. The induction of mutation and recombination following UV irradiation during meiosis in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kelly, S.L.; Parry, J.M.

    1983-01-01

    Irradiation of yeast cultures with ultraviolet light at discrete stages during meiosis produces cyclic variations in sensitivity, i.e. cells are more sensitive to the lethal effects of UV light prior to entry into the meiotic DNA synthesis, and this corresponds to a peak of induction of point mutation. Cells become more resistant to both induced point mutation and lethality as they enter meiotic DNA synthesis, but become more sensitive again during spore formation. The induced level of intragenic recombination rises during the period of commitment ot recombination to a level indistinguishable from the full meiotic level of spontaneous intragenic recombination. Induced reciprocal recombination remains above the spontaneous level up to the point of commitment to sporulation. (orig.)

  15. The induction of mutation and recombination following UV irradiation during meiosis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kelly, S L; Parry, J M

    1983-03-01

    Irradiation of yeast cultures with ultraviolet light at discrete stages during meiosis produces cyclic variations in sensitivity, i.e. cells are more sensitive to the lethal effects of UV light prior to entry into the meiotic DNA synthesis, and this corresponds to a peak of induction of point mutation. Cells become more resistant to both induced point mutation and lethality as they enter meiotic DNA synthesis, but become more sensitive again during spore formation. The induced level of intragenic recombination rises during the period of commitment to recombination to a level indistinguishable from the full meiotic level of spontaneous intragenic recombination. Induced reciprocal recombination remains above the spontaneous level up to the point of commitment to sporulation.

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

    International Nuclear Information System (INIS)

    Abouzeid Ali, Hamdy E.; Barber, Ruth C.; Dubrova, Yuri E.

    2012-01-01

    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 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.

  17. Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

    Science.gov (United States)

    Grunseich, Christopher; Wang, Isabel X; Watts, Jason A; Burdick, Joshua T; Guber, Robert D; Zhu, Zhengwei; Bruzel, Alan; Lanman, Tyler; Chen, Kelian; Schindler, Alice B; Edwards, Nancy; Ray-Chaudhury, Abhik; Yao, Jianhua; Lehky, Tanya; Piszczek, Grzegorz; Crain, Barbara; Fischbeck, Kenneth H; Cheung, Vivian G

    2018-02-01

    R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway. We uncovered that genome-wide R-loops influence promoter methylation of over 1,200 human genes. DNA methyl-transferase 1 favors binding to double-stranded DNA over R-loops. Thus, in forming R-loops, nascent RNA blocks DNA methylation and promotes further transcription. Hence, our results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The induction mutation effects of "6"0Co gamma radiation on physiological growth of tomato

    International Nuclear Information System (INIS)

    Gusti Ngurah Sutapa; I Gde Antha Kasmawan

    2016-01-01

    Almost all types of cuisine in Indonesia are using tomatoes as the base material of manufacture. The nutritional value contained in tomatoes is also quite high, because there is a number of vitamin content required by the human body. In addition, the tomatoes in plants featured national horticultural commodity and priority on a number of provinces in Indonesia. So many benefits of tomatoes indicates that the productivity of tomatoes should be improved. One improvement in terms of quality can be done by means of mutation induction with gamma radiation of Co-60. Induction of mutations are genetic changes caused by human effort, one of them is by using radioactive materials. Gamma rays of Co-60 from the IRPASENA facility was exposed to tomato seeds at doses of 50, 100, 150, 200 and 250 Gy. And then measurements were conducted on the physiological growth of leaf width, plant height, number of fruit and wet weight of tomatoes from week 1 until harvest. The results showed a growth curve of tomato is in accordance with sigmoidal plant physiological growth curve. Optimal physiological growth of tomato plants was obtained at dose of gamma radiation of 100 Gy. At this optimal dose physiological growth of tomato plants is the best (superior) than in doses below and above 100 Gy and control. (author)

  19. Induction of mutation in Aspergillus niger for conversion of cellulose into glucose

    Energy Technology Data Exchange (ETDEWEB)

    Helmi, S.; Khalil, A.E.; Tahoun, M.K.; Khairy, A.H. [Univ. of Alexandria Research Centre, Alexandria (Egypt)

    1991-12-31

    Plant wastes are very important part of biomass used and investigated for energy, chemical, and fuel production. Cellulose is the major renewable form of carbohydrate in the world, about 10{sup 11} tons of which is synthesized annually. For general use, it must be hydrolyzed first, either chemically or by cellulases derived from a few specialized microorganisms. Enzymes are acceptable environmentally but expensive to produce. Certainly, induction of mutations and selection of high cellulose microbial strains with significant adaptability to degrade cellulose to glucose is promising solutions. Induction of mutations in other fungi and Aspergillus sp. rather than Aspergillus niger was reported. Aspergillus ustus and Trichoderma harzianum were induced by gamma irradiation indicating mutants that excrete higher cellulose yields, particularly exocellobiohydrolase (Avicelase) than their respective wild types. Mutants from the celluiolytic fungus Penicillium pinophilum were induced by chemical and UV-irradiation. Enhancing the production of endo-1,4-{Beta}-D-glucanase (CMCase) and particularly {Beta}-glucosidase was obtained by gamma irradiation of Altemaria alternate. To overcome the lower activity of {beta}-glucosidase in certain fungi species rather than A. niger, mixed cultures of different species were tried. Thus, Aspergillus phonicis with Trichoderma reesei Rut 30, produced a cellulose complex that improved activity twofold over cellulose from Trichoderma alone.

  20. SOLAR RADIATION AND INDUCTION OF DNA DAMAGE, MUTATIONS AND SKIN CANCERS.

    Energy Technology Data Exchange (ETDEWEB)

    SETLOW,R.B.

    2007-05-10

    An understanding of the effects of sunlight on human skin begins with the effects on DNA and extends to cells, animals and humans. The major DNA photoproducts arising from UVB (280-320 nm) exposures are cyclobutane pyrimidine dimers. If unrepaired, they may kill or mutate cells and result in basal and squamous cell carcinomas. Although UVA (320-400 nm) and visible wavelengths are poorly absorbed by DNA, the existing data indicate clearly that exposures to these wavelengths are responsible, in an animal model, for {approx}95 % of the incidence of cutaneous malignant melanoma (CMM). Six lines of evidence, to be discussed in detail, support the photosensitizing role of melanin in the induction of this cancer. They are: (1) Melanomas induced in backcross hybrids of small tropical fish of the genus Xiphophorus, exposed to wavelengths from 302-547 nm, indicate that {approx}95% of the cancers induced by exposure to sunlight would arise from UVA + visible wavelengths; (2) The action spectrum for inducing melanin-photosensitized oxidant production is very similar to the spectrum for inducing melanoma; (3) Albino whites and blacks, although very sensitive to sunburn and the sunlight induction of non-CMM, have very low incidences of CMM; (4) The incidence of CMM as a function of latitude is very similar to that of UVA, but not UVB; (5) Use of UVA-exposing sun-tanning parlors by the young increases the incidence rate of CMM and (6) Major mutations observed in CMM are not UVB-induced.

  1. Characterization of three Agrobacterium tumefaciens avirulent mutants with chromosomal mutations that affect induction of vir genes.

    Science.gov (United States)

    Metts, J; West, J; Doares, S H; Matthysse, A G

    1991-02-01

    Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum diagremontiana, Nicotiana tabacum, N. debneyi, N. glauca, and Daucus carota but was virulent on Zinnia elegans and Lycopersicon esculentum (tomato). That the mutant phenotype was due to the transposon insertion was determined by cloning the DNA containing the transposon insertion and using the cloned DNA to replace the wild-type DNA in the parent bacterial strain by marker exchange. The transposon insertions in the three mutants mapped at three widely separated locations on the bacterial chromosome. The effects of the mutations on various steps in tumor formation were examined. All three mutants showed no alteration in binding to carrot cells. However, none of the mutants showed any induction of vir genes by acetosyringone under conditions in which the parent strain showed vir gene induction. When the mutant bacteria were examined for changes in surface components, it was found that all three of the mutants showed a similar alteration in lipopolysaccharide (LPS). LPS from the mutants was larger in size and more heavily saccharide substituted than LPS from the parent strain. Two of the mutants showed no detectable alteration in outer membrane and periplasmic space proteins. The third mutant, Ivr-225, was missing a 79-kDa surface peptide. The reason(s) for the failure of vir gene induction in these mutants and its relationship, if any, to the observed alteration in LPS are unknown.

  2. Induction of forward gene mutations in saccharomycetes. Comparison of efficiencies of different mutagens

    International Nuclear Information System (INIS)

    Zakharov, I.A.; Gracheva, L.M.; Ivanov, E.L.; Koval'tsova, S.V.; Kozhina, T.N.; Korolev, V.G.; Fedorova, I.V.; Shanshiashvili, T.A.; Yadgarov, Kh.T.

    1981-01-01

    The data on the induction of forward mutations in locus ade 2 of the wild haploid of Saccharomyces cerevisiae yeasts by three types of mutagens-chamical mutagens, various radiations and defferent isotopes incorporated in the cell - are generalyzed. The ratio of mutation frequency observed at different doses of mutagen to the survival rate logarithm for the same doses is expressed as rectilinear regression M=m(-1 nS). The application of the same mutation system in the case of all studied mutagens allows to consider the inclination value ''m'' to be the characteristic of mutagen efficiency. We propose to call the ratio of the efficiency of a given mutagen to the efficiency of γ-rays (msub(x)/msub(γ)) - the relative mutagenous effifiency (RME). According to the decrease of this index the studied mutagens have stood in the following succession: ethylene imine (EI), nitrosomethylurea (NMU) 89 Sr, UV rays, 35 S, 91 Y, 33 P, 32 P, acridine-yprite, β-radiation ( 32 P), γ-rays, hard X-rays, 3 H, soft X-rays, neutrons, 125 I [ru

  3. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    International Nuclear Information System (INIS)

    Mei, Nan; Arlt, Volker M.; Phillips, David H.; Heflich, Robert H.; Chen, Tao

    2006-01-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32 P-postlabeling and mutant frequency (MF) was determined using the λ Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N 6 -yl]-aristolactam I, 7-[deoxyadenosin-N 6 -yl]-aristolactam II and 7-[deoxyguanosin-N 2 -yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10 8 nucleotides in liver and 95-4598 adducts/10 8 nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10 -6 in liver compared with the MFs of 78-1319 x 10 -6 that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T → T:A transversion was the predominant mutation in AA-treated rats; whereas G:C → A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually

  4. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Nan [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)]. E-mail: nan.mei@fda.hhs.gov; Arlt, Volker M. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Phillips, David H. [Section of Molecular Carcinogenesis, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG (United Kingdom); Heflich, Robert H. [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Chen, Tao [Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States)

    2006-12-01

    Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by {sup 32}P-postlabeling and mutant frequency (MF) was determined using the {lambda} Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N {sup 6}-yl]-aristolactam I, 7-[deoxyadenosin-N {sup 6}-yl]-aristolactam II and 7-[deoxyguanosin-N {sup 2}-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10{sup 8} nucleotides in liver and 95-4598 adducts/10{sup 8} nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10{sup -6} in liver compared with the MFs of 78-1319 x 10{sup -6} that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T {sup {yields}} T:A transversion was the predominant mutation in AA-treated rats; whereas G:C {sup {yields}} A:T transition was the main type of mutation in control

  5. Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions.

    Science.gov (United States)

    Zhang, Feng-Lin; Shen, Guo-Min; Liu, Xiao-Ling; Wang, Fang; Zhao, Ying-Ze; Zhang, Jun-Wu

    2012-08-01

    Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type-specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34(+) haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl(2) induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1-mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  6. Mutation induction in haploid yeast after split-dose radiation-exposure. I. Fractionated UV-irradiation.

    Science.gov (United States)

    Schenk, K; Zölzer, F; Kiefer, J

    1989-01-01

    Mutation induction was investigated in wild-type haploid yeast Saccharomyces cerevisiae after split-dose UV-irradiation. Cells were exposed to fractionated 254 nm-UV-doses separated by intervals from 0 to 6 h with incubation either on non-nutrient or nutrient agar between. The test parameter was resistance to canavanine. If modifications of sensitivity due to incubation are appropriately taken into account there is no change of mutation frequency.

  7. Gender differences in the induction of chromosomal aberrations and gene mutations in rodent germ cells

    International Nuclear Information System (INIS)

    Adler, Ilse-Dore; Carere, Angelo; Eichenlaub-Ritter, Ursula; Pacchierotti, Francesca

    2007-01-01

    Germ cell mutagenicity testing provides experimental data to quantify genetic risk for exposed human populations. The majority of tests are performed with exposure of males, and female data are relatively rare. The reason for this paucity lies in the differences between male and female germ cell biology. Male germ cells are produced throughout reproductive life and all developmental stages can be ascertained by appropriate breeding schemes. In contrast, the female germ cell pool is limited, meiosis begins during embryogenesis and oocytes are arrested over long periods of time until maturation processes start for small numbers of oocytes during the oestrus cycle in mature females. The literature data are reviewed to point out possible gender differences of germ cells to exogenous agents such as chemicals or ionizing radiation. From the limited information, it can be concluded that male germ cells are more sensitive than female germ cells to the induction of chromosomal aberrations and gene mutations. However, exceptions are described which shed doubt on the extrapolation of experimental data from male rodents to the genetic risk of the human population. Furthermore, the female genome may be more sensitive to mutation induction during peri-conceptional stages compared to the male genome of the zygote. With few exceptions, germ cell experiments have been carried out under high acute exposure to optimize the effects and to compensate for the limited sample size in animal experiments. Human exposure to environmental agents, on the other hand, is usually chronic and involves low doses. Under these conditions, gender differences may become apparent that have not been studied so far. Additionally, data are reviewed that suggest a false impression of safety when responses are negative under high acute exposure of male rodents while a mutational response is induced by low chronic exposure. The classical (morphological) germ cell mutation tests are not performed anymore

  8. Improvement of cassava for high dry matter, starch and low cyanogenic glucoside content by mutation induction

    Energy Technology Data Exchange (ETDEWEB)

    Nwachukwu, E C; Mbanaso, E N.A.; Ene, L S.O. [Plant Breeding Div., National Root Crops Research Inst., Umudike, Umuahia (Nigeria)

    1997-07-01

    Cassava (Manihot esculenta Crantz) is an important food in Nigeria. One drawback in its use as a staple food is the presence of cyanogenic glucosides which on hydrolysis produce the very toxic hydrogen cyanide (HCN). To reduce the cyanogenic levels by mutation induction, three locally adopted and high yielding varieties of cassava, TMS 30572, NR 8817 and NR 84111 were irradiated with 20, 25 and 30 Gy gamma rays. There were a wide variation in HCN, dry matter and starch content of irradiated cassava plants, screened in the MV{sub 2} propagation. Fourteen cassavavariant lines were selected for low HCN content, and 22 lines for high dry matter content. These will be further tested for yield in replicated field trials. (author). 7 refs, 3 tabs.

  9. Induction of mutations in antibiotic-producing microorganisms by fast neutrons from the U-120 cyclotron

    International Nuclear Information System (INIS)

    Wolf, J.; Huczkowski, J.; Siejka, D.; Krasnowolski, S.; Brodowicz, M.

    1976-01-01

    The purpose of this study was to investigate the activity of fast neutrons from a U-120 cyclotron in the induction of mutations in streptomycetes, resulting in strains with enhanced antibiotic production. Three streptomycete strains producing the antibiotics: lincomycin, moenomycin, and demethylchlorotetracycline were used. Correlation between the survival rate of spores of the examined strains and neutron dose was determined. Several morphological and physiological features (particularly production of antibiotics for 1543 variants derived from the parent strains) and their distribution within the population were also studied. The survival rate of the streptomycetes spores after irradiation with fast neutrons was found to be an individual strain property. Several variants with considerably increased antibiotic yield were isolated. The results are compared with those obtained after treatment with other mutagens. Several variants of one of the strains with a strongly enhanced antibiotic yield (200-220%) were isolated. No such variants were found after UV irradiation. (author)

  10. Bud irradiation to obtain resistence to citrus canker through induction of mutation

    International Nuclear Information System (INIS)

    Menten, J.O.M.; Pompeu Junior, J.; Dragone, P.; Sobrinho, J.T.; Prada, V.A.; Tulmann Neto, A.; Ando, A.

    1989-01-01

    The radiosensitivity to gamma rays of the bud of the orange cultivar Pera is determined through irradiation of buds with several doses; the irradiated buds were grafted onto rootstocks of lemon cu. Cravo. The grafting percentage and the development of the V 1 stem from the irradiated buds are analysed; it is concluded that the best dose for induction of mutation is 4,0 OK. New buds are irradiated and grafted with this dose. The V 1 stems are Separeted into 3 Groups, according to the position of the buds on the stem. The V 2 stems are analysed according to the morphological alteraTions due to irradiation. (M.A.C.) [pt

  11. Improvement of cassava for high dry matter, starch and low cyanogenic glucoside content by mutation induction

    International Nuclear Information System (INIS)

    Nwachukwu, E.C.; Mbanaso, E.N.A.; Ene, L.S.O.

    1997-01-01

    Cassava (Manihot esculenta Crantz) is an important food in Nigeria. One drawback in its use as a staple food is the presence of cyanogenic glucosides which on hydrolysis produce the very toxic hydrogen cyanide (HCN). To reduce the cyanogenic levels by mutation induction, three locally adopted and high yielding varieties of cassava, TMS 30572, NR 8817 and NR 84111 were irradiated with 20, 25 and 30 Gy gamma rays. There were a wide variation in HCN, dry matter and starch content of irradiated cassava plants, screened in the MV 2 propagation. Fourteen cassavavariant lines were selected for low HCN content, and 22 lines for high dry matter content. These will be further tested for yield in replicated field trials. (author). 7 refs, 3 tabs

  12. Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

    International Nuclear Information System (INIS)

    Kido, H.; Fukusen, N.; Katunuma, N.

    1987-01-01

    In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4β-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17β-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells

  13. Cell killing and mutation induction on Chinese hamster cells by photoradiations

    International Nuclear Information System (INIS)

    Lam, C.K.C.

    1982-01-01

    The subject matter of this investigation concerns the killing and mutagenic effects induced by far-UV radiation and broad spectra of black, white and gold lights. Applying radiation directly on CHO (Chinese hamster ovary) cells, far-UV is more effective than black light, and black light is more effective than white light in inducing proliferative death and in inducing resistance to 6-thioguanine (6TG), ouabain and diptheria toxin (DT). Cells in the G1/early S boundary are the most sensitive to far-UV or unfiltered fluorescent lights. When synchronous cells are irradiated with moderate doses of far-UV or unfiltered broad spectra of black light, mutations to 6-TG and ouabain resistance are slightly higher in early S period than in the remaining parts of the cell cycle. Mutation induction of 6-TG, ouabain or DT resistance is increased in the split-dose samples of the asynchronous and synchronous CHO cells. CHO cells predominantly express an error-prone repair mechanism after photoirradiation

  14. Dose response and mutation induction by ion beam irradiation in buckwheat

    International Nuclear Information System (INIS)

    Morishita, T.; Yamaguchi, H.; Degi, K.; Shikazono, N.; Hase, Y.; Tanaka, A.; Abe, T.

    2003-01-01

    The biological effects of ion beams were investigated to pursue the development of a method for breeding by mutation in buckwheat. Common buckwheat (Botansoba, Bot) and tartary buckwheat (Rotundatiem, Rot) seeds were exposed to various ions in linear energy transfer (LET) at 9-630 keV/μm. The lethal dose 50 (LD 50 ) of ion beams were 10-300 Gy (Bot) and 30-500 Gy (Rot). It was indicated that a penetrating depth in excess of 1.7 mm is necessary to thoroughly saturate the target, and ions with a penetrating depth of less than 2.2 mm were affected by the presence of hulls. The maximum values of the relative biological effectiveness were 17.7 (Rot) and 22.5 (Bot) at 305 keV/μm. The effective cross sections increased with the LET, and the maximum values were 2.7 (Rot) and 3.0 μm 2 (Bot). The mutation induction effects of He and C ions were higher than those of gamma rays

  15. Radiosensitivity of the in vitro cultured young plants for sport mutation induction of stevia rebaudiana bert

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Tai Young; Kim, Ee Youb; Hyun, Kyung Sup; Jo, Han Jig; Lee, Young Il; Ju, Sun Ah; Oh, Seung Cheol [Korea Stevia Research Institute, Jeongeup (Korea, Republic of); Kim, Dong Sub; Kang, Si Yong [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Ko, Jeong Ae [Chonbuk National University, Jeonju (Korea, Republic of)

    2010-12-15

    Due to the increasing incidence of diabetes, obesity and hypertensive, stevia has been placed great attentions as the sweetener to substitute sucrose in the world. Stevia was introduced to Korea in 1970's, but it has not been an attractive crop in that time. However, recently it has more attention for the natural food sweet additives. Because stevia have many problems for cultivation especially cultivar, seed germination, fertility, uniformity and glycoside quality, the sport mutation was attempted to in vitro plants for the improvement of some characteristics. The young in vitro plants was nursed on MS medium supplemented with 1 mg 1{sup -1} GA{sub 3}. Shoots of 10 cm height were irradiated with 0 {approx} 200 Gy of gamma ray and the every node was separated and inoculated on MS basic medium. The lethality, number and length of shoot, numbers of node and branch were investigated for the evaluation of radiosensitivity. The optimum dose of gamma ray seemed to be around 80 Gy for the sport mutation induction in stevia. The lower node was more sensitive than higher node to radiation.

  16. Mutation induction of blechnum gibium a fern species through in vitro propagation

    International Nuclear Information System (INIS)

    Azhar Mohamad; Amran Abd Halim; Rusli Ibrahim

    2002-01-01

    Blechnum gibum is a fern with beutiful symmetry and unique palm-like appearance. Mutation induction is an alternative way to increase its variability in characteristics. Information on the radiosensitivity test is an important factor in deciding the approach to be taken for genetic changes of the fern in mutation breeding. Plantlets of B. gibum were irradiated with doses of 0, 10, 20, 40, 60, 80, 100 and 150 Gy using a gamma cell with a 60 Co source at dose rate of 0.25 Gy s -1 . . Irradiated plantlets were cultured on semi solid modified hormone free Murashige and Skoog (MS) media and incubated at 24 degree C with a photoperiod of 16 hours (3500 lux). Radiosensitivity was assessed by the survival rate 7 weeks after the treatment. Increasing gamma ray doses caused a reduction of survival rate as well as the number of fronds produced per plantlet. LD 50 for B. gibum was 54 Gy as estimated from the dose rate vs survival curve. Regenerated plantlets from treated plantlets showed a stunted and slow recovery growth especially for higher doses as compared to control plantlets. (Author)

  17. Radiosensitivity of the in vitro cultured young plants for sport mutation induction of stevia rebaudiana bert

    International Nuclear Information System (INIS)

    Yoon, Tai Young; Kim, Ee Youb; Hyun, Kyung Sup; Jo, Han Jig; Lee, Young Il; Ju, Sun Ah; Oh, Seung Cheol; Kim, Dong Sub; Kang, Si Yong; Ko, Jeong Ae

    2010-01-01

    Due to the increasing incidence of diabetes, obesity and hypertensive, stevia has been placed great attentions as the sweetener to substitute sucrose in the world. Stevia was introduced to Korea in 1970's, but it has not been an attractive crop in that time. However, recently it has more attention for the natural food sweet additives. Because stevia have many problems for cultivation especially cultivar, seed germination, fertility, uniformity and glycoside quality, the sport mutation was attempted to in vitro plants for the improvement of some characteristics. The young in vitro plants was nursed on MS medium supplemented with 1 mg 1 -1 GA 3 . Shoots of 10 cm height were irradiated with 0 ∼ 200 Gy of gamma ray and the every node was separated and inoculated on MS basic medium. The lethality, number and length of shoot, numbers of node and branch were investigated for the evaluation of radiosensitivity. The optimum dose of gamma ray seemed to be around 80 Gy for the sport mutation induction in stevia. The lower node was more sensitive than higher node to radiation

  18. The influence of calf thymus DNA and deoxyribonucleosides on the induction of different mutation types in Drosophila

    International Nuclear Information System (INIS)

    Ondrej, M.

    1975-01-01

    The influence of an exogenous DNA on the induction of mutations by X rays was compared with the influence of an equimolar mixture of four deoxyribonucleosides. Pre-treatment and post-treatment with the calf thymus DNA did not influence mutation frequency in the specific loci dp, b, cn and bw as well as Minute mutations induced in the Drosophila sperm by X radiation. Pre-treatment with the equimolar mixture of four deoxyribonucleosides increased the frequency of the Minutes but did not affect mutation frequency in the loci dp, b, cn, bw. The equimolar mixture of nucleosides alone induced a low frequency of Minute mutations in the Drosophila sperm. DNA alone induced a low frequency of recessive lethals. These lethals arose as mosaics of small sectors of the gonads of the F 1 females and were revealed as late as in the F 3 generation. (author)

  19. Biological significance of TERT promoter mutation in papillary urothelial neoplasm of low malignant potential.

    Science.gov (United States)

    Wang, Chung-Chieh; Huang, Chao-Yuan; Jhuang, Yu-Lin; Chen, Chih-Chi; Jeng, Yung-Ming

    2018-04-01

    Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been found frequently in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs). TERT promoter mutations were observed in 10 (33%) PUNLMPs and 17 (50%) low-grade NIPUCs, but not in any inverted papilloma. FGFR3 mutations were observed more frequently in PUNLMP and low-grade NIPUC than in inverted papillomas (P = 0.009), whereas the opposite trend was noted for HRAS mutations (P low-grade NIPUC (P = 0.530). Notably, PUNLMP cases with TERT promoter mutations had a similar recurrence rate to that in low-grade NIPUC cases (P = 0.487). Our results suggest that the status of the TERT promoter mutation may serve as a biomarker of prognostic stratification in patients with PUNLMP. © 2017 John Wiley & Sons Ltd.

  20. Telomerase reverse transcriptase promoter mutations in glandular lesions of the urinary bladder.

    Science.gov (United States)

    Vail, Eric; Zheng, Xiaoyong; Zhou, Ming; Yang, Ximing; Fallon, John T; Epstein, Jonathan I; Zhong, Minghao

    2015-10-01

    Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign to primary and secondary malignancies. The accurate diagnosis of these lesions is both important and challenging. Recently, studies suggest that telomerase reverse transcriptase (TERT) promoter mutations could be a biomarker for urothelial carcinoma (UC). We hypothesized that these mutations can distinguish UC with glandular differentiation from nephrogenic adenoma, primary adenocarcinoma of the urinary bladder (PAUB), or secondary malignancies. Twenty-five cases of benign glandular lesions (including nephrogenic adenoma); 29 cases of UC with glandular differentiation; 10 cases of PAUB; and 10 cases each of metastatic colon cancer, prostatic carcinoma, and carcinoma from Mullerian origin were collected. Slides were reviewed and selected to make sure the lesion was at least 10% to 20% of all tissue. Macrodissection was performed in some of cases, and genomic DNA was extracted from the tissue. Telomerase reverse transcriptase promoter mutations were determined by standard polymerase chain reaction sequencing. Twenty-one cases (72%) of UC with glandular differentiation were positive for TERT promoter mutations. However, none of the remaining cases (total 65 cases of benign lesions, PAUB, and metastatic carcinomas) was positive for TERT promoter mutation. Telomerase reverse transcriptase promoter mutations were highly associated with UC including UC with glandular differentiation but not other glandular lesions of bladder. Therefore, in conjunction with morphologic features, Immunohistochemistry stain profile, and clinical information, TERT promoter mutations could distinguish UC with glandular differentiation from other bladder glandular lesions. In addition, lack of TERT promoter mutations in primary adenocarcinoma of bladder suggests that this entity may have different origin or carcinogenesis from those of UC. Published by Elsevier Inc.

  1. TERT promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas.

    Science.gov (United States)

    Gao, Ke; Li, Gang; Qu, Yiping; Wang, Maode; Cui, Bo; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2016-02-23

    Increasing evidences have implicated somatic gain-of-function mutations at the telomerase reverse transcriptase (TERT) promoter as one of the major mechanisms that promote transcriptional activation of TERT and subsequently maintain telomere length in human cancers including glioma. To investigate the prognostic value of these mutations and telomere length, individually and their coexistence, in gliomas, we analyzed two somatic mutations C228T and C250T in the TERT promoter, relative telomere length (RTL), IDH1 mutation and MGMT methylation in 389 glioma patients, and explored their associations with patient characteristics and clinical outcomes. Our data showed that C228T and C250T mutations were found in 17.0% (66 of 389) and 11.8% (46 of 389) of gliomas, respectively, and these two mutations were mutually exclusive in this cancer. Moreover, they were significantly associated with WHO grade. We also found that the RTL was significant longer in gliomas than in meningiomas and normal brain tissues (Median, 0.89 vs. 0.44 and 0.50; P radiotherapy. Collectively, TERT promoter mutations and long RTL are not only prognostic factors for poor clinical outcomes, but also the predictors of radiotherapy resistance in gliomas.

  2. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

    Science.gov (United States)

    Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

    2016-06-01

    Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

  3. Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment.

    Science.gov (United States)

    Gomez, James E; Kaufmann-Malaga, Benjamin B; Wivagg, Carl N; Kim, Peter B; Silvis, Melanie R; Renedo, Nikolai; Ioerger, Thomas R; Ahmad, Rushdy; Livny, Jonathan; Fishbein, Skye; Sacchettini, James C; Carr, Steven A; Hung, Deborah T

    2017-02-21

    Antibiotic resistance arising via chromosomal mutations is typically specific to a particular antibiotic or class of antibiotics. We have identified mutations in genes encoding ribosomal components in Mycobacterium smegmatis that confer resistance to several structurally and mechanistically unrelated classes of antibiotics and enhance survival following heat shock and membrane stress. These mutations affect ribosome assembly and cause large-scale transcriptomic and proteomic changes, including the downregulation of the catalase KatG, an activating enzyme required for isoniazid sensitivity, and upregulation of WhiB7, a transcription factor involved in innate antibiotic resistance. Importantly, while these ribosomal mutations have a fitness cost in antibiotic-free medium, in a multidrug environment they promote the evolution of high-level, target-based resistance. Further, suppressor mutations can then be easily acquired to restore wild-type growth. Thus, ribosomal mutations can serve as stepping-stones in an evolutionary path leading to the emergence of high-level, multidrug resistance.

  4. “Technology packages” for crop improvement using mutation induction and biotechnology

    Energy Technology Data Exchange (ETDEWEB)

    Lavi, U. [ARO-Volcani Center, P.O. Box 6, Bet Dagan 50250 (Israel); Heslop-Harrison, J. S. [Department of Biology, University of Leicester, Leicester LE1 7RH (United Kingdom); Spencer, M. M.; Lagoda, P. J.L. [International Atomic Energy Agency, Vienna (Austria)

    2009-05-15

    “Technology packages” in crop breeding may be defined as sets of various technologies used in synergy in order to achieve specific research goals. The tremendous advances in cell, molecular, atomic and even nano-technology afford scientists with powerful tools for exploring the Living Kingdom to the benefit of Human Kind. Mutation induction is undoubtedly one of these technologies, which has resulted in tremendous changes in the way genetics and derived genomics can be applied for crop improvement. Classical breeding approaches associated with agronomy and biotechnologies allow less than 2% of the population of industrialized countries to produce ample food to satisfy their national needs. The rapid expansion in science-based knowledge, relating to genetics, genomics, exploitation of biodiversity and induced mutations now has the potential to bridge the gap from research to application in agriculture in developing countries. In a timescale of decades some important changes could be efficiently implemented. In addition to the current goals of plant breeding new ones such as the following are emerging continuously: a demand for more meat in global diets - requiring serious increase of primary production; the demand for bioenergy crops other than just fuel woods mean that there is a new range of target plants for domestication and improvement where minimal or no classical breeding has been applied so far. When considering the major technological developments together with their potential in crop improvement for developing countries, there is a great need of clear and wise assessment of their usefulness and applicability. Various approaches such as DNA, markers, TILLING, high-throughput sequencing and reverse genetics are applicable to breeding programmes in developing countries. In the present chapter, all approaches considered appropriate are assessed on the basis of their advantages and constraints. (author)

  5. Use of gamma rays for in vitro mutation induction in taro

    International Nuclear Information System (INIS)

    Medero Vega, Victor R.; Lopez Torres, J.; Basail Perez, Milagros

    2015-01-01

    A methodology for genetic improvement of taro (Colocasia esculenta) for in vitro mutation induction using physical mutagens to guarantee the increased variability and the possibility of selecting superior genotypes to commercial clones with higher yield potential, better nutritional quality and response to biotic and abiotic stress was established. Irradiations were performed at the National Center for Studies Applied to Nuclear Energy (CEADEN). Nine radiation doses with Co 60 gamma rays (10, 15, 20, 25, 30, 35, 40, 50 and 60 Gy) were studied. The control was based on three clones: 'INIVIT MC-2001', 'INIVIT MC-2006' and 'INIVIT MC-2012'. 50 meristematic apices per clone were used. The survival percentages of explants were evaluated after 30 days of culture for the calculation of the dose-effect curve. The survival percentage of in vitro produced plants in field conditions and the agronomic response 9 months after plantation were evaluated. The Median Lethal Dose (LD 50 ) for the genotypes studied was 20 Gy, and doses higher than 25 Gy to cause practically 100% deaths of explants irradiated were also determined. Two possible mutants with better agronomic characteristics than the donor and better response to water stress were selected in field conditions. (Author)

  6. Induction of mutation in Aspergillus niger for conversion of cellulose into fuel precursor

    International Nuclear Information System (INIS)

    Helmi, S.; Khalil, A.; Tahoun, M.K.; Khairy, A.H.

    1990-01-01

    Induction of mutation in Aspergillus niger ATCC 1004 was achieved by exposure of conidia suspension to uv-light 2,400 erg/m 2 (240 J/m 2 ) for 120 s to obtain 5% survivors. The mutants were tested for the activity of different cellulases and were selected according to (1) rate and percentage of germination, (2) mycelial dry weight, (3) colony morphology, and (4) diameter of conidia. The efficiency of the mutants to convert celllose into reducing sugars was detected by the assay of the activity of different cellulases. Three of the selected mutants indicated higher Avicel activity, 0.0183, 0.0205, and 0.0295 μ mol reducing sugars/ml/min compared to 0.0153 for the wild type. The uv-irradiation also induced mutants that gave elevated CMCase activity, 3.06, 3.44, 5.30, 6.47, and 7.20 μmol reducing sugars/ml/min as compared with the wild type, 2.94 μmol reducing sugars/ml/min. Highly significant (F-test) increases in the activity of β-glucosidase were obtained for some of the selected mutants, 196.50, 255.00, 255.70, and 267.5 μmol P-nitrophenol/ml/min compared to the parent strain, 167.20 μmol P-nitrophenol/ml/min

  7. Development Procedure in Mutation Induction and Tracer Technique for Good Agriculture Practices for Under used Crops

    International Nuclear Information System (INIS)

    Faiz Ahmad; Rusli Ibrahim; Khairuddin Abdul Rahim

    2015-01-01

    Under used crops are those crop species which have high potential value in the supply of important raw material for secondary economy sector in food processing. The yield production of new Under used crops varieties can be used as an important input in food production process for export products. The optimum production cost can be minimized since the price of raw material supplied from agriculture sector is cheaper compared with the international markets. Agriculture output can be increased through the development of Under used crops using radiation mutagenesis and tracer technique for good agricultural practices. This paper work will discuss the development procedure of mutation induction method which includes irradiation of samples such as seeds of groundnut and in vitro shoots of banana using gamma rays and application of N-15 for nutrient use efficiency and screening of potential mutant lines with high yield and resistance to drought. These management practices using established procedures of water and nutrient use efficiency will be recommended to the growers. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Tahoun, M.K.; Khalil, A.I.; Helmi, S.; Khairy, A.H. [Univ. of Alexandria Research Centre, Alexandria (Egypt)

    1991-12-31

    The production of cellulolytic enzymes from fungi has been extensively studied. Several mutants of Trichoderma reesei were selected. Most of the studies were carried out on T. reesei, T. viride, T. harzianum, Penicillium funiculosum, Altemaria alternata. Aspergillus phoenicis, A. ustus, A. tamarii, A. japonicus, and A. niger. T. koningii is one of the most active producers of the so-called C, factor, which is indispensable for the rapid and extensive attack on crystal-line cellulose. However, Trichodenna is known to excrete only small amounts of {beta}-glucosidase. Therefore, Trichoderma is supplemented with {beta}-glucosidase from Aspergillus to increase the saccharification rate of cellulose to glucose as the main sugar. Induction of mutations in Trichodenna spp. rather than T. viride as a tool for the enhancement of {beta}-glucosidase activity was reported. Unfortunately, T. reesei is a poor producer of {beta}-glucosidase. On the other hand, T. harzianum M{sub 5}, a mutant that was induced by gamma radiation, produced high yields, not only of Avicelase and carboxy methyl cellulose, but also of {beta}-glucosidase, than its respective wild type.

  9. Comparison on Promotion Effect of Various Types of Surfactants on HCFC-141b Hydrate Induction Time

    Science.gov (United States)

    Li, Juan; Sun, Zhigao; Liu, Chenggang; Zhu, Minggui

    2018-03-01

    Cold storage in air conditioning based on refrigerant hydrate is a new-type energy saving technology to reduce initial investment and running cost of air conditioning equipments and improve system stability. Refrigerant hydrate is generated under critical temperature and pressure condition, while surfactant is an effective medium to promote its phase equilibrium. In this paper, in order to research such promotion effect, different type of surfactants with unique mechanism, SDS, Tween80 and Span80, n-BA were selected to compare the respective impact on HCFC141b hydrate induction time based on temperature curve. Experimental results showed that no obvious change had been discovered when no surfactant was added into pure water system, which coincided with phase equilibrium diagram of HCFC141b. All the four kinds of surfactants had realized promotion effect to various degrees. For each hydration system, a large gap existed between the longest and the shortest induction time in 6 groups of parallel experiments, meaning relatively poor system stability. Under the combined effect of Tween80 (2wt%), Span80 (0.1wt%) and n-BA (0.1wt%), average and the shortest induction time was 20.9min and 17.5min respectively, corresponding to the best promotion effect.

  10. Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events.

    Science.gov (United States)

    Nagashima, Haruki; Shiraishi, Kumiko; Ohkawa, Saori; Sakamoto, Yuki; Komatsu, Kenshi; Matsuura, Shinya; Tachibana, Akira; Tauchi, Hiroshi

    2017-10-19

    It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of 0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  11. Induction of mutation on mulberry (morus alba L.) by using in vitro techniques in combination with gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen Van Vinh [Nuclear Research Institute, Department of Biotechnology, Dalat (Viet Nam)

    2001-03-01

    Mutation induction and selection of desired characters on mulberry will contribute to industrialization and modernization in agricultural development in Vietnam. The objectives are to conduct biochemical and physiological analyses of collected mulberry varieties and to improve techniques for boosting yield and better quality in some mulberry genotypes by using in vitro technique combined with gamma irradiation. Two mulberry varieties named BauDen and VA 186 were used. Cuts of them were treated with gamma rays of Co-60, cultivated in experimental field with use of vitro technique to rapidly isolate mutants in irradiated population and investigated for plantlets, color of leaves, etc 30 days after cultivation. The results on the mutation frequency and spectrum of variation as well as the results of selection and isolation are presented. Eleven mutated clones from the two starting varieties were obtained during 1993-99. Three of them are now being cultivated in LamDong province fields. (S. Ohno)

  12. Induction of mutation on mulberry (morus alba L.) by using in vitro techniques in combination with gamma irradiation

    International Nuclear Information System (INIS)

    Nguyen Van Vinh

    2001-01-01

    Mutation induction and selection of desired characters on mulberry will contribute to industrialization and modernization in agricultural development in Vietnam. The objectives are to conduct biochemical and physiological analyses of collected mulberry varieties and to improve techniques for boosting yield and better quality in some mulberry genotypes by using in vitro technique combined with gamma irradiation. Two mulberry varieties named BauDen and VA 186 were used. Cuts of them were treated with gamma rays of Co-60, cultivated in experimental field with use of vitro technique to rapidly isolate mutants in irradiated population and investigated for plantlets, color of leaves, etc 30 days after cultivation. The results on the mutation frequency and spectrum of variation as well as the results of selection and isolation are presented. Eleven mutated clones from the two starting varieties were obtained during 1993-99. Three of them are now being cultivated in LamDong province fields. (S. Ohno)

  13. Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

    Science.gov (United States)

    Metcalf, Alexander M; Spurdle, Amanda B

    2014-03-01

    Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

  14. Mutation induction in a mouse lymphoma cell mutant sensitive to 4-nitroquinoline 1-oxide and ultraviolet radiation

    International Nuclear Information System (INIS)

    Sato, K.; Hieda, N.

    1980-01-01

    The mutant mouse lymphoma cell Q31, which is sensitive to 4-nitroquinoline 1-oxide and ultraviolet radiation (UV), was compared with the parental L5178Y cell for the effect of caffeine and mutation induction after UV irradiation. Caffeine potentiated the lethal effect of UV in both cell strains to a similar extent, indicating that the defective process in Q31 cells was caffeine-insensitive. UV-induced mutation to 6-thioguanine resistance was determined in L5178Y and Q31 cells. The maximal yield of mutants was obtained 7 days post-irradiation in L5178Y cells and 14 days in Q31 cells for higher UV doses. It appears that a much longer time is required for the mutant cells than for the parental cells for full expression of the resistance phenotype even at equitoxic UV doses. A substantially higher frequency in induced mutations was observed in Q31 cells than in L5178Y cells at a given dose of UV. A plot of induced mutation frequency as a function of logarithm of surviving fraction again indicates hypermutability of Q31 cells as compared with the parental strain. In contrast, X-rays induced a similar frequency of mutations to 6-thioguanine resistance in L5178Y and Q31 cells. (orig.)

  15. BRAF mutation-specific promoter methylation of FOX genes in colorectal cancer

    NARCIS (Netherlands)

    E.H.J. van Roon (Eddy); A. Boot (Arnoud); A.A. Dihal (Ashwin); R.F. Ernst (Robert); T. van Wezel (Tom); H. Morreau (Hans); J.M. Boer (Judith)

    2013-01-01

    textabstractBackground: Cancer-specific hypermethylation of (promoter) CpG islands is common during the tumorigenesis of colon cancer. Although associations between certain genetic aberrations, such as BRAF mutation and microsatellite instability, and the CpG island methylator phenotype (CIMP), have

  16. The effect of mutations in the AmpC promoter region on β-lactam ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... between the -10 and -35 boxes affects the resistance of bacteria to β-lactam antibiotics. .... The chromosomal cephalosporinase gene, ampC, of E. .... mutation in the ampC promoter increasing resistance to β-lactams in.

  17. Effect of tumor promoters on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kunz, B.A.; Hannan, M.A.; Haynes, R.H.

    1980-01-01

    Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodacetate, anthralin, and 12-0-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-0-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters

  18. Induction of different types of mutations in yeast Saccharomyces serevisiae by γ-radiation

    International Nuclear Information System (INIS)

    Lyubimova, K.A.; Shvaneva, N.V.; Koltovaya, N.A.

    2005-01-01

    Several tester systems were used to study a wide spectrum of genetic changes induced by γ-radiation in the yeast Saccharomyces cerevisiae. The tester systems allow one to identify a loss of chromosomes, recombination (crossing over) and point mutations (frame shifts and base-pair substitutions.) Large genome changes were induced by γ-rays more efficiently than the point mutations. The dose dependence of the point mutations frequency was linear. Spontaneous and induced mutation rates per base pair corresponded with the known literature data for the same tester systems. Our finding shows that the used tester systems are not specific. They are useful for further study of mutations induced by ionizing radiation with various physical characteristics

  19. The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

    Directory of Open Access Journals (Sweden)

    Mohammad Zare-Bidaki

    2015-04-01

    Full Text Available Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32 in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  20. Mutation to ouabain-resistance in Chinese hamster cells: induction by ethyl methanesulphonate and lack of induction by ionising radiation

    International Nuclear Information System (INIS)

    Thacker, J.; Stephens, M.A.; Stretch, A.

    1978-01-01

    The spontaneous frequency of mutants resistant to growth inhibition by ouabian (OUAsup(R) mutants) was found to be about 5.10 -5 per viable cell in uncloned cultures of Chinese hamster V79-4 cells. In freshly-isolated clones or cultures started from a few cells this frequency was initially reduced to about 1.10 -6 in 1 mM ouabain. No increase in the frequency of OUAsup(R) mutants was found in cultures treated with γ-rays despite exploration of such variables as radiation dose, ouabain concentration, post-treatment interval before selection, cell density in selective medium, and clonal state of the cells at the time of adding ouabain (in situ vs. respreading method). A similar negative result was found for accelerated helium ions, for which the mutagenic effectiveness per unit dose has been shown to be about 10 times higher than γ-rays for the induction of thioguanine-resistant mutants in these cells. Recent evidence is reviewed in support of the suggestion that ionising radiation is unable to induce OUAsup(R) mutants because of the severity of the genetic damage it causes. (Auth.)

  1. Plant cultivars derived from mutation induction or the use of induced mutants in cross breeding

    International Nuclear Information System (INIS)

    Micke, A.; Maluszynski, M.; Donini, B.

    1985-01-01

    Since 1969 we have collected information on cultivated varieties of plants, developed by using induced mutations. Whenever we learn about a cultivar presumably derived from an induced mutant or from use of mutants in crosses. we mail a questionnaire to the breeder. The information gathered in this way is stored in our file on ''Mutant Varieties''. Excerpts are published regularly in the form of a list in the FAO/IAEA Mutation Breeding Newsletter. Our mutant variety list has repeatedly provided a basis for analyses on the value and prospects of mutation breeding

  2. Plant cultivars derived from mutation induction or the use of induced mutants in cross breeding

    Energy Technology Data Exchange (ETDEWEB)

    Micke, A; Maluszynski, M; Donini, B [Joint FAO/IAEA Division, Plant Breeding and Genetics Section, Vienna (Austria)

    1985-05-01

    Since 1969 we have collected information on cultivated varieties of plants, developed by using induced mutations. Whenever we learn about a cultivar presumably derived from an induced mutant or from use of mutants in crosses. we mail a questionnaire to the breeder. The information gathered in this way is stored in our file on ''Mutant Varieties''. Excerpts are published regularly in the form of a list in the FAO/IAEA Mutation Breeding Newsletter. Our mutant variety list has repeatedly provided a basis for analyses on the value and prospects of mutation breeding.

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

    International Nuclear Information System (INIS)

    Abdul Rahim Harun

    2001-01-01

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  5. In vitro mutation induction for resistance to Fusarium wilt in the banana

    Energy Technology Data Exchange (ETDEWEB)

    Tulmann Neto, A; Mendes, B M.J.; Latado, R [Centro de Energia Nuclear na Agricultura, Piracicaba, SP (Brazil); Cesar Santos, P dos; Boliani, A [Universidade Estadual Paulista, Ilha Solteira, SP (Brazil). Faculdade de Agronomia

    1995-11-01

    In Brazil, which is one of the world`s principal banana production regions, almost all production is consumed within the country. Consumers show high preference for the cultivar Maca (AAB group). However, it is becoming increasingly difficult to produce bananas of this type because of their high susceptibility to Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense. Sexual breeding, which consists of recombination and selection, is limited in the banana because of polyploidy and sterility. Spontaneous somatic mutations are an important source of new cultirvars, and mutation breeding might be particularly important to generate genetic variation. Because of this, the mutation breeding approach has been used in Brazil. The objective of this research was to induce gamma ray mutations for resistance or to increase the level of tolerance to Fusarium wilt in the banana cultivar Maca on the basis of screening under field conditions. 4 refs.

  6. A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

    Science.gov (United States)

    Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

    2017-12-15

    Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical

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

    International Nuclear Information System (INIS)

    Barber, Ruth C.; Hardwick, Robert J.; Shanks, Morag E.; Glen, Colin D.; Mughal, Safeer K.; Voutounou, Mariel; Dubrova, Yuri E.

    2009-01-01

    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 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 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 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.

  8. The estimation of risks from the induction of recessive mutations after exposure to ionising radiation

    International Nuclear Information System (INIS)

    Searle, A.G.; Edwards, J.H.

    1986-01-01

    Induced recessive mutations can cause harm by (1) partnership with a defective allele already established in the population; (2) partnership with another recessive mutation induced at the same locus; (3) the formation of homozygous descendants, that is, identify by descent; and (4) heterozygous effects. Calculations based on a combination of data from observations on human populations and from mouse experiments suggest that an extra genetically significant dose of 1 cGy X or γ irradiation received by each parent in a stable population with a million liveborn offspring would induce up to 1200 extra recessive mutations. From partnership effects, about one extra case of recessive disease would be expected in the following 10 generations. Homozygosity resulting from identity by descent could not normally occur until the fourth generation after exposure but, on certain assumptions, about ten extra cases of recessive disease would be expected from this cause by the tenth generation. In the same period, about 250 recessive alleles would be eliminated in heterozygotes given 2.5% heterozygous disadvantage. These deleterious heterozygous effects should not be combined with those of dominants, as has been done in some previous risk estimates. It is considered unlikely that many radiation induced recessives would show heterozygous advantage. Certain dominants should be excluded from calculations of mutational risk because they are unlikely to be maintained by mutation. (author)

  9. Induction of specific-locus mutations in the mouse by tritiated water

    International Nuclear Information System (INIS)

    Russell, W.L.; Cumming, R.B.; Kelly, E.M.; Phipps, E.L.

    1978-01-01

    The results reported are the first obtained on transmtted gene mutations induced by tritium in any form in any mammal. They are, therefore, of obvious practical importance in the estimaton of the possible biological hazards of man-made tritium in the environment. Male mice were injected intraperitoneally with either 0.75 or 0.50 mCi per gram of body weight of tritiated water. They were then used in our standard specific-locus mutation test in which the treated wild-type stock of mice is mated to a stock homozygous for seven recessive marker genes. Mutations at any of the seven loci are scored in the offspring. The earlier matings provided information on the mutation frequency in germ cells irradiated in postspermatogonial stages, and the later matings gave the mutation frequency in treated spermatogonia. The spermatogonia are the important cells so far as human risks are concerned, and the mouse results for this germ-cell stage yielded a relative biological effectiveness (RBE) of approximately 2 for tritiated water compared with low-dose-rate gamma irradiation. There are various uncertainties involved in arriving at this figure, and the difference between it and l is probably not statistically significant. However, for risk estimation, it seems prudent to use the RBE value of 2, which is, after all, the best point estimate computed from the present data

  10. K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder

    Directory of Open Access Journals (Sweden)

    Imran Ahmad

    2011-07-01

    The human fibroblast growth factor receptor 3 (FGFR3 gene is frequently mutated in superficial urothelial cell carcinoma (UCC. To test the functional significance of FGFR3 activating mutations as a ‘driver’ of UCC, we targeted the expression of mutated Fgfr3 to the murine urothelium using Cre-loxP recombination driven by the uroplakin II promoter. The introduction of the Fgfr3 mutations resulted in no obvious effect on tumorigenesis up to 18 months of age. Furthermore, even when the Fgfr3 mutations were introduced together with K-Ras or β-catenin (Ctnnb1 activating mutations, no urothelial dysplasia or UCC was observed. Interestingly, however, owing to a sporadic ectopic Cre recombinase expression in the skin and lung of these mice, Fgfr3 mutation caused papilloma and promoted lung tumorigenesis in cooperation with K-Ras and β-catenin activation, respectively. These results indicate that activation of FGFR3 can cooperate with other mutations to drive tumorigenesis in a context-dependent manner, and support the hypothesis that activation of FGFR3 signaling contributes to human cancer.

  11. Induction of mutations in the blue-green alga Plectonema boryanum Gomont

    International Nuclear Information System (INIS)

    Singh, R.N.; Kashyap, A.K.

    1977-01-01

    Mutations to cyanophage and streptomycin resistance were induced in the filamentous blue-gree alga Plectonema boryanum IU 594 after treatment with ultraviolet irradiation, N-methyl-N'-nitro-Nnitrosoguanidine, acriflavine, 2-aminopurine and caffeine. Phage-resistant mutants were obtained with all the mutagens tested. Their efficiencies were in the order: MNNG>UV>acriflavine >2-AP>caffeine. In contrast, the drug-resistant mutants were not induced by base analogues: the efficiencies were: acriflavine>MNNG>UV. Lethal and mutational lesions induced with UV were efficiently repaired under photo-reactivating conditions whereas post-treatment with caffeine resulted in enhanced mutation frequencies especially at low UV doses. Neither survival nor mutagenesis was enhanced by keeping the MNNG-treated population in subdued light

  12. Induction of mutation with gamma irradiation in camellia (Camellia Japonica L.)

    International Nuclear Information System (INIS)

    Zhou Diying; Shen Shoujiang; Wang Yanjun

    1990-01-01

    Studies on the radiosensitivity and mutagenic effects in Camellia (Camellia Japonica L.) were carried out with the shoot cuttings, one-year seedlings and three or four-year plants irradiated with 60 Co-γ rays. Results obtained showed that the radiosensitivities varied greatly in cultivars and in different parts of the plant. The suitable irradiation doses for shoot cuttings are 1-3 krad. The treatment of low doses (bellow 2 kard) resulted in higher frequency of mutation with plants of high sensitivity to γ-rays. The frequencies of mutation in flower color and type were 2.5-12.0%. The mutant with ornamental value has been obtained

  13. Induction of chlorophyll chimeras and chlorophyll mutations in mungbean (Vigna radiata) cv. T44

    International Nuclear Information System (INIS)

    Singh, V.P.; Yadav, R.D.S.

    1993-01-01

    Uniform and healthy seeds of mungbean (Vigna radiata) cv. T44 were exposed to varying doses of gamma rays, ethyl methane sulphonate (EMS) and combination treatment of gamma rays with EMS. The data were recorded for seed germination, plant survival, frequency and spectrum of chlorophyll chimeras in M 1 and chlorophyll mutations in M 2 generation. Among all, the combination treatments were found most effective for inducing chlorophyll chimeras and chlorophyll mutations than the gamma rays or EMS alone. Of the mutants under reference, the albino, xantha and chlorina showed monogenic recessive while viridis exhibited digenic recessive inheritance. (author). 8 refs., 2 tabs

  14. Valproic acid promotes neuronal differentiation by induction of proneural factors in association with H4 acetylation.

    Science.gov (United States)

    Yu, In Tag; Park, Jin-Yong; Kim, Sung Hyun; Lee, Jeong-Sik; Kim, Yong-Seok; Son, Hyeon

    2009-02-01

    Valproate (VPA) influences the proliferation and differentiation of neuronal cells. However, little is known about the downstream events, such as alterations in gene transcription, that are associated with cell fate choice. To determine whether VPA plays an instructive role in cell fate choice during hippocampal neurogenesis, the expression of genes involved in the cell cycle and neuronal differentiation was investigated. Treatment with VPA during the progenitor stages resulted in strong inhibition of cell proliferation and induction of neuronal differentiation, accompanied by increases in the expression of proneural transcription factors and in neuronal cell numbers. The increased expression of Ngn1, Math1 and p15 points to a shift towards neuronal fate in response to histone deacetylase inhibitors (HDACi). Chromatin immunoprecipitation (ChIP) analysis showed that acetylated histone H4 (Ac-H4) was associated with the Ngn1, Math1 and p15 promoters in cultured hippocampal neural progenitor cells. VPA-induced hippocampal neurogenesis was also accompanied by association of Ac-H4 with the Ngn1 promoter in hippocampal extracts. The discovery of an association between HDACi and the Ngn1, Math1 and p15 promoters extends the importance of HDAC inhibition as a key regulator of neuronal differentiation at the transcriptional level.

  15. Synergism in mutations induction in Tradescantia by plants protection agents acting jointly with ionizing radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.; Smagala, J.

    1990-01-01

    Tradescantia was first treated by plants protection agents such as: Ambusz, Afalton, Ripcord, Decis, deltametryne and after that irradiated with X radiation. The synergism of both factors was observed. The mutation frequency dependence on radiation doses was studied. 7 figs., 4 refs. (A.S.)

  16. Mutation induction in rice by radiation combined with chemical protectants and mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A [Agricultural College, University of Sao Paulo, Sao Paulo (Brazil)

    1970-03-01

    Seeds of the rice variety 'Dourado Precoce' were treated with different combinations of gamma rays, cysteine and EMS or gamma rays, cysteine and dES. Cysteine showed some protection against the effects of gamma radiation and combined gamma-ray + chemical treatments with regard to germination, seedling height and fertility. There are also indications of changes in the spectra of chlorophyll mutations. (author)

  17. Mutation Induction with UV- and X-radiations in spores and vegetative cells of Bacillus subtilis

    International Nuclear Information System (INIS)

    Tanooka, H.; Munakata, N.; Kitahara, S.

    1978-01-01

    Spores and vegetative cells of Bacillus subtilis strains with various defects in DNA-repair capacities (hcr - , ssp - , hcr - ssp - ) were irradiated with UV radiation or X-rays. Induced mutation frequency was determined from the observed frequency of prototrophic reversion of a suppressible auxotropic mutation. At equal physical dose, after either UV- or X-irradiation, spores were more resistant to mutations as well as to killing than were vegetative cells. However, quantitative comparison revealed that, at equally lethal doses, spores and vegetative cells were almost equally mutable by X-rays whereas spores were considerably less mutable by UV than were vegetative cells. Thus, as judged from their mutagenic efficiency relative to the lethality, X-ray-induced damage in the spore DNA and the vegetative DNA were equally mutagenic, while UV-induced DNA photoproducts in the spore were less mutagenic than those in vegetative cells. Post-treatment of UV-irradiated cells with caffeine decreased the survival and the induced mutation frequency for either spores or vegetative cells for all the strains. In X-irradiated spores however, a similar suppressing effect of caffeine was observed only for mutability of a strain lacking DNA polymerase I activity

  18. Local anesthetics inhibit induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.

    OpenAIRE

    Yuspa, S H; Lichti, U; Ben, T

    1980-01-01

    The induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in mouse epidermal cells in vivo and in vitro occurs rapidly after exposure to the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). This induction has characteristics of a cell surface receptor-mediated process. Local anesthetics modify a variety of cellular responses mediated by membrane receptors. When cultured mouse epidermal cells were exposed to the local anesthetics lidocaine, tetracaine...

  19. Characterization of three Agrobacterium tumefaciens avirulent mutants with chromosomal mutations that affect induction of vir genes.

    OpenAIRE

    Metts, J; West, J; Doares, S H; Matthysse, A G

    1991-01-01

    Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum diagremontiana, Nicotiana tabacum, N. debneyi, N. glauca, and Daucus carota but was virulent on Zinnia elegans and Lycopersicon esculentum (tomato). That the mutant phenotype was due to the transposon insertion was d...

  20. Studies on in vitro induction mutation for wheat mutant of resistance to root rot and its resistance mechanism

    International Nuclear Information System (INIS)

    Sun Guangzu

    1992-06-01

    The screening wheat mutant which has the resistance to root rot was completed in 37 varieties by in vitro induction mutation method. The effect of irradiation on in vitro culture of different wheat explants and the effectiveness of screening rude toxin were studied. Two wheat mutants, RB500 and RB501, which have the resistance to root rot, were obtained. Changes of the ultrastructure and defensive enzymes (SOD, ROD and PAL) were investigated by using mutants and parent under the action of rude toxin. The results showed that the rude toxin could induce changes of enzyme activity, isoenzyme pattern and ultrastructure of the mitochondria and chloroplast. These change correspond to their ability of resistance to disease. The mutant under the action of toxin has the ability to increase the defensive enzyme activity and to reduce the damage of cell membrane system that would result in resistance increasing

  1. Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Su X

    2016-11-01

    Full Text Available Xingyun Su,1 Xiaoxia Jiang,1 Weibin Wang,1 Haiyong Wang,1 Xin Xu,2 Aihui Lin,1 Xiaodong Teng,3 Huiling Wu,4 Lisong Teng1 1Department of Surgical Oncology, 2Department of Medical Oncology, 3Department of Pathology, 4Department of Plastic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: The clinicopathological and prognostic significance of telomerase reverse transcriptase (TERT promoter mutations have been widely investigated in thyroid cancer; however, the results are still discrepant. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, and the Cochran Library databases for relevant articles prior to April 2016. Mutation rates were synthesized by R statistical software. The odds ratio or standardized mean difference with 95% confidence interval was pooled by Stata. A total of 22 studies with 4,907 cases were included in this meta-analysis. TERT promoter mutations tended to present in aggressive histological types including poorly differentiated thyroid cancer (33.37%, anaplastic thyroid cancer (38.69%, and tall-cell variant papillary thyroid cancer (30.23%. These promoter mutations were likely to exist in older patients and males and were well associated with larger tumor size, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, advanced tumor stage, disease recurrence/persistence, and mortality. In addition, TERT promoter mutations (especially C228T tended to coexist with BRAFV600E mutation, which indicated more aggressive tumor behavior. Therefore, TERT promoter mutations may be promising biomarkers for early diagnosis, risk stratification, prognostic prediction, and management of thyroid cancer. Keywords: TERT promoter mutations, thyroid cancer, clinicopathological features, prognosis, BRAFV600E mutation

  2. Prefoldin Promotes Proteasomal Degradation of Cytosolic Proteins with Missense Mutations by Maintaining Substrate Solubility.

    Directory of Open Access Journals (Sweden)

    Sophie A Comyn

    2016-07-01

    Full Text Available Misfolded proteins challenge the ability of cells to maintain protein homeostasis and can accumulate into toxic protein aggregates. As a consequence, cells have adopted a number of protein quality control pathways to prevent protein aggregation, promote protein folding, and target terminally misfolded proteins for degradation. In this study, we employed a thermosensitive allele of the yeast Guk1 guanylate kinase as a model misfolded protein to investigate degradative protein quality control pathways. We performed a flow cytometry based screen to identify factors that promote proteasomal degradation of proteins misfolded as the result of missense mutations. In addition to the E3 ubiquitin ligase Ubr1, we identified the prefoldin chaperone subunit Gim3 as an important quality control factor. Whereas the absence of GIM3 did not impair proteasomal function or the ubiquitination of the model substrate, it led to the accumulation of the poorly soluble model substrate in cellular inclusions that was accompanied by delayed degradation. We found that Gim3 interacted with the Guk1 mutant allele and propose that prefoldin promotes the degradation of the unstable model substrate by maintaining the solubility of the misfolded protein. We also demonstrated that in addition to the Guk1 mutant, prefoldin can stabilize other misfolded cytosolic proteins containing missense mutations.

  3. Mutational analysis of the promoter and the coding region of the 5-HT1A gene

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, J.; Noethen, M.M.; Shimron-Abarbanell, D. [Univ. of Bonn (Germany)] [and others

    1994-09-01

    Disturbances of serotonergic pathways have been implicated in many neuropsychiatric disorders. Serotonin (5HT) receptors can be subdivided into at least three major families (5HT1, 5HT2, and 5HT3). Five human 5HT1 receptor subtypes have been cloned, namely 1A, 1D{alpha}, 1D{beta}, 1E, and 1F. Of these, the 5HT1A receptor is the best characterized subtype. In the present study we sought to identify genetic variation in the 5HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetics of neuropsychiatric diseases. The coding region and the 5{prime} promoter region of the 5HT1A gene from 159 unrelated subjects (45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 controls) were analyzed using SSCA. SSCA revealed the presence of two mutations both located in the coding region of the 5HT1A receptor gene. The first mutation is a rare silent C{r_arrow}T substitution at nucleotide position 549. The second mutation is characterized by a base pair substitution (A{r_arrow}G) at the first position of codon 28 and results in an amino acid exchange (Ile{r_arrow}Val). Since Val28 was found only in a single schizophrenic patient and in none of the other patients or controls, we decided to extend our samples and to use a restriction assay for screening a further 74 schizophrenic, 95 bipolar affective, and 49 patients with Tourette`s syndrome, as well as 185 controls, for the presence of the mutation. In total, the mutation was found in 2 schizophrenic patients, in 3 bipolars, in 1 Tourette patient, and in 5 controls. To our knowledge the Ile-28-Val substitution reported here is the first natural occuring molecular variant which has been identified for a serotonin receptor so far.

  4. Application of GAMMA ray for induction of mutation and combination with biotechnology for induce desirable genetic variation in Tangerine

    International Nuclear Information System (INIS)

    Rahimi, M.; Majd, F.; Rastegari, J.; Vedadi, S.; Naseri, M.; Jahangirzadeh, E.

    2002-01-01

    Combined application of physical mutagen and tissue culture for induction of somatic mutation in some characters without affecting the whole genome proved to be an efficient tool for improvement of plant trees.Up to now substantial breeding research has not been done on fruit trees in Iran. We are intending to begin a new era in fruit trees improvement through mutation and biotechnology. On this basis we selected tangerine as a well-adapted and highly consumed citrus fruit which has a disadvantage of too many seeds in it's flesh. Through this technique the aim is to produce seedless/less seeded tangerine in order to motivate increase in cultivation area and potential for export. We used physical mutagen (γ-ray) with doses of (30,35 and 40 Gy) for lateral bud in vivo and doses of (10, 15 and 20 Gy) for bud in-vitro. To produce explant free of pathogen we used shoot tip grafting (stg) technique, and micropropagation of bud in modified MS medium for multiplication of buds

  5. Induction of somatic mutations in some vegetatively Propagated ornamentals by gamma radiation

    International Nuclear Information System (INIS)

    Das, P.K.; Ghosh, P.; Dube, S.; Dhua, S.P.

    1974-01-01

    Attempts were made to produce mutations in some vegetatively propagated ornamentals by acute and chronic gamma irradiation. Rooted cutting of Chrysanthemums and dormant bulbs of Dahlias were exposed to 1.5, 2.5, 3.5 and 2.0, 3.0 kR of acute doses respectively. In chronic irradiation, potted plants of Bougainvillea, Hibiscus, Allamanda, Achania, Jasminum, Chrysanthemum were exposed to several dose rates at different isodose arcs in the gamma field. Isolated mutants are being vegetatively multiplied and some of them have already been stabilized as pure forms. (M.G.B.)

  6. In vitro induction of mutation and separation of chimeras in Gerbera jamesonii

    International Nuclear Information System (INIS)

    Jerzy, M.; Zalewska, M.; Garczewska, A.

    1994-01-01

    Using ex vitro leaves as objects to be irradiated and to induce variation in sixteen Gerbera jamesonii cultivars, reproduced from adventitious buds, resulted in obtaining the mutants which inflorescence color was uniformly changed and which newly acquired traits recurred in the second generation of plants reproduced vegetatively from the isolated shoot tips. However, chimeras appeared among the vM 1 plants exposed to various doses of gamma rays (5-25 Gy and they constituted almost half of the mutated plants. A further propagation of chimeras from leaf explants forming adventitious shoots significantly increased the number of solid mutants with uniformly changed inflorescence color in the vM 1 generation. (author)

  7. Mutation induction in γ-irradiated primary human bronchial epithelial cells and molecular analysis of the HPRT- mutants

    International Nuclear Information System (INIS)

    Suzuki, Keiji; Hei, Tom K.

    1996-01-01

    We have examined various radiobiological parameters using commercially-available primary normal human bronchial epithelial (NHBE) cells, which can be subcultured more than 20 population doublings, and have established the mutation system in order to characterize the molecular changes in γ-irradiated primary cells. The survival curve, obtained after irradiation of cells with 137 Cs γ-rays, indicates that the D 0 , D q , and n values are 1.34 Gy, 1.12 Gy, and 2.3, respectively. The induction of HPRT - mutation was dose-dependent and the mutant fraction increased in a non-linear fashion. Since the doubling number of NHBE cells is limited, DNA was extracted directly from the single mutant colonies and alteration in the HPRT gene locus was analyzed using multiplex PCR technique. Among spontaneous mutants, the proportion with total and partial deletions of the gene was 10.0% (2/20) and 60.0% (12/20), respectively, while 30.0% (6/20) did not have any detectable changes in the nine exons examined. On the other hand, the fraction of total deletion increased by more than 2-fold among mutants induced by γ-rays in that 26.3% (10/38) of them showed the total gene deletions. Twenty-five out of 38 γ-induced mutants (65.8%) had partial deletions and 3 mutants (7.9%) had no detectable alteration. The present results showed that γ-irradiation efficiently induced HPRT gene mutation in primary human epithelial cells and that most of the induced mutants suffered larger deletions compared to that observed in spontaneous mutants. This system provides a useful tool for determination of mutagenicity and understanding the molecular mechanisms of environmental carcinogens in primary human bronchial cells

  8. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    -κB activation inhibited CCL20 expression in mtBALB cybrids and decreased their migratory capabilities. Thus, acquired mtDNA mutations may promote tumorigenic phenotypes through up-regulation of chemokine CCL20.

  9. INDUCTION OF DNA ADDUCTS, TUMORS, AND KI-RAS ONCOGENE MUTATIONS IN STRAIN A/J MOUSE LUNG BY IP. ADMINISTRATION OF DIBENZ[A,H]ANTHRACENE

    Science.gov (United States)

    Induction of DNA adducts, tumors, and Ki-ras oncogene mutations in strain AlJ mouse lung by ip. administration of dibenz[a,h]anthracene Previous studies of polycyclic aromatic hydrocarbon (P AH) induced lung tumors in the strain NJ mouse model system have demonstrated qua...

  10. Primary experiment aimed at selecting the suitable dose to mutation induction in vicia faba major

    International Nuclear Information System (INIS)

    Nabulsi, Imad; Mir Ali, Nizar

    1992-08-01

    Seeds of a local faba been variety (Mahali) (Vicia faba major) were irradiated with (0, 5, 10, 15, 20, 40, 60, 80, and 100 Gy) of gamma rays and sown under greenhouse and field conditions in Deir Al-Hajar Research Station near Damascus. Four replicates were used in a randomized complete block design. Germination percentage, seedling height, and daily growth rate, were estimated one month and two months after planting for the greenhouse and field treatments respectively. The results showed a stimulation effect in the 5 Gy dose, whereas, the higher doses showed a gradual decrease in seedling height. Doses up to 20 Gy had a similar germination percentage to that of the control (about 75%) whereas, the germination percentage decreased sharply at the higher doses (3% and 0.2% for the 100 Gy under greenhouse and the field respectively). The doses between 20 and 40 Gy were considered optimal for mutation from the plant breeder point of view where the lethality was moderate and an acceptable rate of mutation was shown. (author). 6 refs., 3 tabs., 1 fig

  11. Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, J; Grom, A; Csuka, J; Kindlova, L [Poultry Research Institute, Ivanka pri Dunaji (Czechoslovakia)

    1977-01-01

    Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000, and 3000 R at the exposure rate of 5.86 Rs/sup -1/. After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F/sub 1/ was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000, and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had a linear course, the value of the lethal hit per gamete for 1 R was 1.04x10/sup -4/.

  12. Caffeine sensitive repair and mutation induction in UV- or γ-ray-irradiated Dictyostelium discoideum

    International Nuclear Information System (INIS)

    Kanishi, Nobuji; Kinjo, Yasuhito; Watanabe, Makoto.

    1990-01-01

    It seems that certain kinds of chemical substances increase the distortion in molecules, change the high order microstructures of nuclei and chromosomes, and exert large variation to the function of repairing the damage of genes due to radiation and others, by coupling with DNA, protein or enzyme system. It has been well known that caffeine is one of such compounds, and by coupling with DNA, it increases the damage due to ultraviolet ray and gives the action of obstructing repair in addition to the action of inducing the abnormality of chromosomes and mutation. Dictyostelium discoideum has the simplest nuclear structure, and shows extremely high resistance to radiation by its high restoration ability. The authors have advanced the research by paying attention to its characteristics, and comparing the Dictyostelium discoideum as one model system with the lymphocyte system of higher animals. This time, the authors analyzed the characteristics of two kinds of sensitivity repair process of caffeine, and investigated into their relation with the occurrence of mutation. The experimental method and the results are reported. (K.I.)

  13. Caffeine sensitive repair and mutation induction in UV- or. gamma. -ray-irradiated Dictyostelium discoideum

    Energy Technology Data Exchange (ETDEWEB)

    Kanishi, Nobuji (Tokyo Metropolitan Research Lab. of Public Health (Japan)); Kinjo, Yasuhito; Watanabe, Makoto

    1990-01-01

    It seems that certain kinds of chemical substances increase the distortion in molecules, change the high order microstructures of nuclei and chromosomes, and exert large variation to the function of repairing the damage of genes due to radiation and others, by coupling with DNA, protein or enzyme system. It has been well known that caffeine is one of such compounds, and by coupling with DNA, it increases the damage due to ultraviolet ray and gives the action of obstructing repair in addition to the action of inducing the abnormality of chromosomes and mutation. Dictyostelium discoideum has the simplest nuclear structure, and shows extremely high resistance to radiation by its high restoration ability. The authors have advanced the research by paying attention to its characteristics, and comparing the Dictyostelium discoideum as one model system with the lymphocyte system of higher animals. This time, the authors analyzed the characteristics of two kinds of sensitivity repair process of caffeine, and investigated into their relation with the occurrence of mutation. The experimental method and the results are reported. (K.I.).

  14. Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

    International Nuclear Information System (INIS)

    Baumgartner, J.; Grom, A.; Csuka, J.; Kindlova, L.

    1977-01-01

    Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000 and 3000 R at the exposure rate of 5.86 Rs -1 . After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F 1 was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000 and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had linear course, the value of the lethal hit per gamete for 1 R was 1.04x10 -4 . (author)

  15. In-vitro induction of mutations in Chrysanthemum using x- and gamma-radiation

    International Nuclear Information System (INIS)

    Jerzy, M.

    1990-01-01

    Full text: Spontaneous and induced mutations occur frequently in the hexaploid and very heterozygous Chrysanthemum. Alterations in flower colours can thus be obtained for an outstanding cultivar produced by cross-breeding. Whole families of mutants have been reported for cultivars like 'Westland', 'Indianapolis', 'Horim' and 'Bravo'. The mutation-breeding programme in Poland started in 1986 with the use of in vitro techniques to obtain early cultivars flowering in unheated plastic greenhouses. One of the successful examples was the irradiation of cv. 'Richmond'. Leaves from plants regenerated through shoot tip culture were treated with 15 Gy x- and gamma-rays. Each treatment comprised 400 leaf explants on MS medium with IAA 2 mg/l and BA 0,6 mg/l. After 6 weeks, regenerated adventitious shoots were transferred to the rooting medium with HAA 0,02 mg/l. Rooted plantlets were used as stock plants for the production of shoot cuttings to be subjected to mutant selection. Many plants with drastically changed flower colours were obtained. The violet-pink colour, which is typical for 'Richmond' flowers changed to 13 different colours: white, yellow, golden, pink, salmon, lilac, violet, purple, orange, apricot, amber, bronze and red. Eleven colours occurred as a result of x-ray treatment, eight colours after gamma irradiation. Chimeras were not observed. Among irradiated plants there were also inflorescences with all-ligulate florets scrolled up into tubes. (author)

  16. Induction of mutations in garlic by combined use of gamma-rays and tissue culture

    Energy Technology Data Exchange (ETDEWEB)

    Rou, Zhen Hai [Horticultural Research Inst., Shanghai Academy of Agricultural Sciences, Shanghai (China)

    1997-07-01

    Callus cultures were initiated from leaf explants of garlic on MS medium supplemented with 1.0 mg/l KIN + 1.0 mg/l IAA + 2.0 mg/l 2,4-D. Plantlets were induced from leaf calli on MS medium with 2.0 mg/l BA + 2.0 mg/l IAA. Bulblets were induced from plantlets on MS medium containing 3.0 mg/l ITA. Callus growth and plantlets induction were remarkably inhibited with irradiation doses of 8 and 10 Gy. It was found that doses of 3 and 5 Gy were suitable to induce variation. Somatic embryos were induced on MS medium supplemented with 2.0 mg/l 2,4-D + 500 mg/l casein, 1000 mg/l yeast extract and 3 to 5% sucrose. (author). 11 tabs.

  17. Induction of mutations in garlic by combined use of gamma-rays and tissue culture

    International Nuclear Information System (INIS)

    Zhen Hai Rou

    1997-01-01

    Callus cultures were initiated from leaf explants of garlic on MS medium supplemented with 1.0 mg/l KIN + 1.0 mg/l IAA + 2.0 mg/l 2,4-D. Plantlets were induced from leaf calli on MS medium with 2.0 mg/l BA + 2.0 mg/l IAA. Bulblets were induced from plantlets on MS medium containing 3.0 mg/l ITA. Callus growth and plantlets induction were remarkably inhibited with irradiation doses of 8 and 10 Gy. It was found that doses of 3 and 5 Gy were suitable to induce variation. Somatic embryos were induced on MS medium supplemented with 2.0 mg/l 2,4-D + 500 mg/l casein, 1000 mg/l yeast extract and 3 to 5% sucrose. (author). 11 tabs

  18. Mutation induction as a tool for varietal development in ornamental plants

    International Nuclear Information System (INIS)

    Mohd Nazir Basiran

    2000-01-01

    Although the current advancement in biotechnology has tremendously change the modern breeding approach, the induced mutation techniques is still very much in use as complementary tools. MINT experiences in using the techniques for varietal development in ornamental plants has helped to increase genetic variabilities in several ornamental plant species, produced twelve new mutant cultivars as well as developed efficient tissue culture system for six ornamental plant species as tool for in vitro mutagenesis procedures and micropropagation. The technology and expertise that have been established are ready for transfer to the horticulture industry. Sharing of capability and capacity between research institutions and private sector is one possible way by improving and maintaining long-term sustenance of the floriculture industry. (author)

  19. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

    Science.gov (United States)

    Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

    2014-10-01

    The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

  20. DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Yang, Tao; Li, Xiao-Na; Li, Xing-Guang; Li, Ming; Gao, Peng-Zhi

    2014-01-01

    Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC

  1. DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Tao [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Li, Xiao-Na [General Surgery, Sports Science Institute of Hebei Province, Shijiazhuang 050011 (China); Li, Xing-Guang; Li, Ming [General Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Gao, Peng-Zhi, E-mail: pengzhigaovip@163.com [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China)

    2014-12-12

    Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC.

  2. Radiation promotes cancer cell metastasis via EMT induction in mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jongkuk; Kang, Sungwook; Hwang, Sanggu; Um, Hongduck [Department of Radiation Cancer, New York (United States); Jang, Su Jin; Kang, Joohyun [Molecular Imaging Research Center, Charlestown (United States); Park, Sunhoo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Wunjae [Chungbuk National Univ., Cheongju (Korea, Republic of)

    2013-05-15

    Whether γ-IR-induced invasion and metastasis are stimulated in our in vitro C6L cell line and in vivo systems, and further identify the associated changes in signal pathways or mice physiology. We constructed an animal model system with a view to clarifying the intracellular molecular events underlying the promotion of metastasis after γ-IR treatment for primary cancer and developing effective anti-metastatic reagents. Our results demonstrate that γ-IR treatment of cancer cell lines and mice xenografts triggers invasion and metastasis. In particular, γ-IR-treated cancer cells or mouse xenografts and metastatic lesions in mice bearing γ-IR-treated xenografts also display typical EMT marker expression patterns, such as increased venetum or MMP-2 expression, decreased E-chondron, and enhanced activity of MMP-2. Our results collectively suggest that γ-IR-induced invasion or metastasis results from induction of EMT, and inhibition of EMT may thus be a means to enhance the effectiveness of radiation therapy. Our results also suggested EMT might be one of the major therapeutic targets to block metastasis.

  3. Radiation promotes cancer cell metastasis via EMT induction in mouse model

    International Nuclear Information System (INIS)

    Park, Jongkuk; Kang, Sungwook; Hwang, Sanggu; Um, Hongduck; Jang, Su Jin; Kang, Joohyun; Park, Sunhoo; Kim, Wunjae

    2013-01-01

    Whether γ-IR-induced invasion and metastasis are stimulated in our in vitro C6L cell line and in vivo systems, and further identify the associated changes in signal pathways or mice physiology. We constructed an animal model system with a view to clarifying the intracellular molecular events underlying the promotion of metastasis after γ-IR treatment for primary cancer and developing effective anti-metastatic reagents. Our results demonstrate that γ-IR treatment of cancer cell lines and mice xenografts triggers invasion and metastasis. In particular, γ-IR-treated cancer cells or mouse xenografts and metastatic lesions in mice bearing γ-IR-treated xenografts also display typical EMT marker expression patterns, such as increased venetum or MMP-2 expression, decreased E-chondron, and enhanced activity of MMP-2. Our results collectively suggest that γ-IR-induced invasion or metastasis results from induction of EMT, and inhibition of EMT may thus be a means to enhance the effectiveness of radiation therapy. Our results also suggested EMT might be one of the major therapeutic targets to block metastasis

  4. Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

    Science.gov (United States)

    Annunziata, Clorinda; Pezzuto, Francesca; Greggi, Stefano; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2018-03-31

    Two recurrent mutations (-124 G > A and -146 G > A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position -124 or -146. TERT promoter was mutated at nucleotide -146 (G > A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (-124G > A or -146G > A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression. © 2018 UICC.

  5. Survival and mutagenesis in UV-irradiated phage: Multi-hit kinetics of mutation induction and lack of indirect induction by infection with UV-irradiated phage of error-prone repair

    International Nuclear Information System (INIS)

    Krauss, G.; Mennigmann, H.D.; Kaplan, R.W.

    1980-01-01

    The paper is concerned with the question of whether Weigle-reactivation (WR) and Weigle-mutagenesis (WM) can be indirectly induced by infection with UV-irradiated phage. Experiments neither with phage lambda of Escherichia coli nor with phage kappa of Serratia marcescens show such induction. In this respect phage DNA differs from F'-DNA or Hfr-DNA; possible explanations are discussed. In both systems clear plaque mutations can also be induced by UV without irradiation of the host cells; they appear, in unirradiated and irradiated host cells, with an increase in frequency which is greater than proportional to the UV dose. It is concluded that mutation induction of phage in the unirradiated host cells is due to a low level constitutive mutagenic repair; this could either be due to 'spontaneous' induction of the mutagenic SOS function or it could be a mechanism different from this one. Host irradiation would give rise to additional activity by the induced SOS function leading to WR and WM. It is further concluded that deviation of the induction kinetics from a linear dose-dependence is not due to the necessary induction of SOS functions. (author)

  6. Primary experiment aimed at selecting the suitable dose to mutation induction in two soybean cultivars

    International Nuclear Information System (INIS)

    Nabulsi, I.; Mir Ali, N

    1991-07-01

    Seeds from two soybean [Glycine Max L. (Merrill)] cultivars K-25 and K-38 were irradiated with the following doses of gamma rays: 100, 150, 200, 250, 300, 350, 400 and 500 Gy. The dose rate was 9.25 Gy/minute. A week after irradiation 25 seeds were sown from each variety in pots (26.5 x 26.5 cm) with 4 replicates in a randomized complete block design under greenhouse conditions. The distance between the cotyledon and the first leaf was measured 4 weeks after sowing and the results showed stimualtion effect in the 100 and 150 Gy doses in comparison to the control whereas in the higher doses, a gradual reduction was realized in addition to the appearance of the necrotic spots on the leaves which was increased in percentages along with the dose. The results indicated that doses between 100 and 200 Gy achieved the highest rate of mutations with minimal rate of lethality hence achieving the aim of this preliminary experiment. (author). 5 refs., 2 tabs., 2 figs

  7. Induction of mutations in Thai rice varieties and subsequent selection and testing of beneficial mutant lines

    Energy Technology Data Exchange (ETDEWEB)

    Dasananda, S; Khambanonda, P [Ministry of Agriculture, Bangkok (Thailand)

    1970-03-01

    Ionizing radiations were first used in the Thailand Rice Breeding Program in 1955 when seeds of two recommended varieties were sent to the United States of America for treatment. As a result, five promising mutant lines are at present in regional yield tests where they are being considered for recommendation to rice growers. During the period 1960-1961 an unsuccessful attempt was made to induce resistance to blast in three susceptible varieties by exposing seeds to a local source of ionizing radiation In 1964, after an elapse of about 4 years, another attempt was made to utilize ionizing radiations in the breeding program by treating seeds of two recommended varieties. In 1965, a co-ordinated rice mutation breeding program was initiated under the auspices of the Joint FAO/IAEA Division of Atomic Energy in Food and Agriculture which resulted in treating seeds of twelve different rice varieties with both ethyl methane sulphonate and gamma rays from a {sup 60}Co gamma cell. The results so far indicate that mutagenic agents have been successful in producing genetic variability. Differences in heading date, mature plant height and plant type are frequently observed in the M{sub 2} and M{sub 3} generations. Several lines obtained from two of the irradiated varieties have exhibited a higher degree of resistance to blast than the parental material. From 15-kR treatments of non-glutinous varieties, mutants with glutinous endosperm have been obtained. Not all varieties gave the same response to treatment. (author)

  8. Induction of materials for mutation breeding of strawberry (FragariaxAnanassa) by gamma irradiation (Phase 2)

    International Nuclear Information System (INIS)

    Le Tien Thanh; Huynh Thi Trung; Pham Van Nhi; Vu Thi Trac

    2016-01-01

    In this study, New Zaeland strawberry runners was propagated in vitro to create clump of buds for Gamma irradiation. The experimental result showed that LD_5_0 was 52 Gy. Basing on the LD_5_0, we selected the 5 doses of 20, 40, 60, 80 and 100 Gy to irradiate in vitro materials for creating the potential mutants. Irradiated materials were propagated continuously in vitro to complete 300 in vitro plants per dose. On farm, ex vitro plants were planted on the spout (from the ground) by hydroponic method with the number of 200 plants per dose. Some mutant characteristics increased gradually toward the increasing of gamma doses as dwarf plants (in the dose of 60 Gy, 80 Gy and 100 Gy), plants had small fruits (in the dose of 60 Gy, 80 Gy, 100 Gy), plants had deformed fruits (in the dose of 20 Gy, 40 Gy, 60 Gy, 80 Gy and 100 Gy). In this study, we selected four mutants with 2 mutation fruits were changed to fruit heart-shape with symbol DT 1 (dose 60 Gy) and DT 2 (dose 80 Gy); 2 mutants were dwarf plants, the ungrown bud, wrinkled leaf, deformed fruits, high sweetness with symbol DN 1 (dose 60 Gy) and DN 2 (dose 80 Gy). (author)

  9. Sesame improvement through mutation induction for reduction of seed loss at harvest (semi-shattering capsules)

    International Nuclear Information System (INIS)

    Maneekao, S.; Srikul, N.; Poo-Sri, B.; Kumphai, S.

    2001-01-01

    In 1994, the study of sesame improvement for reduction of seed loss by mutation was conducted at Ubonratchathani Field Crops Research Center (UBFCRC). There were two experiments carried out to improve sesame capsule for non-shattering characteristics using gamma rays and fast neutrons. The first experiment was performed to study the effect of irradiation doses on sesame when applied at doses varying from 200 to 750 Gy. Results of the experiments showed that all sesame lines had LD 50 levels between 300-750 Gy when irradiated with gamma rays, and 20-80 Gy with fast neutron. The second experiment was done to investigate the effect of irradiation on shattering types of sesame capsules. Three local varieties, Red Pitsanulok, Black Burirum and white Granuan were irradiated with 500 Gy of gamma rays. In the dry season 1997-98, 24 plants of M 7 generation (black- and red- seeded lines) and 8 plants of M 5 generation (white-seeded lines) were selected for yield evaluation with three local varieties. The results show 3 shatter resistant lines, PMUB 1, PMUB 19 (both with shatter resistance scale 537) and GMUB 7 (with scale 637) in 1997-98 (772 in 1997) gave 27% higher seed yield than the original variety; 2 black seeded mutant lines BMUB 21 and BMUB 23 of which seed colour slowly fades and 2 mutant lines (GMUB 1, GMUB 3) with a high degree of tolerance to powdery mildew. (author)

  10. Sesame mutation induction: Improvement of non-shattering capsule by using gamma rays and EMS

    International Nuclear Information System (INIS)

    Wongyai, W.; Saengkaewsook, W.; Veerawudh, J.

    2001-01-01

    Improvement of non-shattering capsule by using gamma rays and EMS in the Kasetsart University Sesame Breeding Project has been carried out since November 1994. Seed treatments with gamma rays (500 Gy) and EMS (0.5 and 1.0%, 4 hrs) were used. Growth characteristics, delayed shattering and shatter resistance of capsule were investigated in M 2 through M 8 lines. The seed yield of thirty promising M 7 lines was evaluated in April 1997 at Suwan Farm, Pakchong, Nakorn Ratchasima. Most of the tested lines gave higher seed yields than the check variety, MK 60. M 6026 gave the highest seed yield (1,477 kg/ha). All the tested mutant lines had a longer period of growth during flowering (GF). However, three promising lines had a shorter flowering period (FP) and a degree of stem termination (DST) when they were planted both in April and August 1997. Based on the criteria of determinate growth studied, these mutant lines would be classified as having a determinate growth habit. Delayed shattering and shatter resistant capsule were obtained. It is noted that the promising mutant lines were obtained from EMS treatment. Thus, the study of these mutant lines revealed that the improvement of sesame by mutation breeding for reduced seed losses before or during the harvest can be successful. (author)

  11. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    Directory of Open Access Journals (Sweden)

    Wen-bin He

    2018-01-01

    Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

  12. Induction of dominant lethal mutations by alkylating agnets in germ-cells of the silkworm, Bombyx mori

    International Nuclear Information System (INIS)

    Murota, Tetsuo; Murakami, Akio.

    1977-01-01

    The comparison of the intensity of activity was made by measuring radiation equivalent chemical (REC) dose in the experiment of the induction of dominant lethal mutation, using the germ cells of pupae five days before the moths will be hatched. The alkylating agents employed in the experiment are methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), diethyl sulfate (DSC) and mitomycine-C (MC). X-ray irradiation was employed in order to indicate the capability of inducing mutation of the alkylating agents with the radiation equivalent chemical dose (REC dose). The dose-hatchability curves for the alkylating agents showed sigmoidal fashion as observed in X-ray, regardless of germ cells. The REC value at LD (50) was estimated by comparing the relative mutagenic capability of these chemicals. In sperm, EMS and DES with concentration of 1.0 x 10 -7 M/g showed the same lethality as about 2.3 kR and 0.6 kR of X-ray. However, no significant reduction of embryonic lethality after the treatment of pupae with MC (up to 2.1 x 10 -7 M/g) and MMS (up to 1.0 x 10 -6 M/g) was observed. As the results, the order of mutagenic effectiveness was as follows: EMS>DES>MMS approximately equal to MC. When oocytes in the mid-pupae were treated with MMS, EMS and MC with concentration of 1.0 x 10 -7 M/g, MMS and EMS showed the same effects as 12.8 kR and 0.6 kR. Surprisingly, MC showed the same lethality as 232.3 kR. This extremely high sensitivity of oocytes to MC may be ascribed to the inhibiting effect of the drug on the meiotic division. (Iwakiri, K.)

  13. Improving Peanut Productivity and Resistance to Aspergillus flavus L Through mutation Induction

    International Nuclear Information System (INIS)

    Ragab, A.I; Korani, W.A.A.; Rashed, M.A.; Salam, M.A

    2008-01-01

    The present study was conducted to improve peanut productivity and resistance to Aspergillus flavus that caused aflatoxin formation in peanut seeds . To achieve these goals , dry seeds of the two local varieties (Giza 4 and Giza5) were irradiated with gamma ray doses of 0 , 50 , 100 , 150 , 200 , 250 , 300 Gy. The irradiated seeds were sown to get the M1 and M2 generations. Six high yielding mutants were selected in M2 from irradiated populations of 150 Gy and 200 Gy for Giza 4 and Giza 5 respectively. These mutants were evaluated in M3 generation for yield and yield components , quality traits (protein and oil content) and the resistance to Aspergillus flavus infection. The obtained results revealed that analysis of variance for Giza 4 selected mutants showed significant differences between genotypes for different studied characters except for plant height and no. of branches /plant .However, for Giza5 selected mutants, significant differences between genotypes were only obtained for plant height , no of pods/plant, weight of pods/plant, weight of seeds/plant, and weight of 100 seeds. Different M3 mutants that selected from irradiated populations of both two peanut cultivars Giza4 and Giza5 shod marked improvement for yield and yield components, and quality traits in comparison with their mother varieties.The results of M3 progeny test indicated that most selected mutants retained the features of their M2 selectors, suggesting that they were considered true breeding materials. For Giza 4 selected mutants, aflatoxin concentrations ranged from 31.11 μg for mutant 1 to 188.46 μ g for mutant3 in comparison with 42.76 μg for the mother variety Giza 4. The lowest yielding progenies of mutant1 (1 ) showed the lowest aflatoxin concentrations as compared with the mother variety Giza 4 and other mutants, therefore the use of induced mutations for peanut improvement may be led to the development of improved varieties .However, for Giza 5 selected mutants aflatoxin

  14. Mutation induction in haploid yeast after split-dose radiation exposure. II. Combination of UV-irradiation and X-rays.

    Science.gov (United States)

    Keller, B; Zölzer, F; Kiefer, J

    2004-01-01

    Split-dose protocols can be used to investigate the kinetics of recovery from radiation damage and to elucidate the mechanisms of cell inactivation and mutation induction. In this study, a haploid strain of the yeast, Saccharomyces cerevisiae, wild-type with regard to radiation sensitivity, was irradiated with 254-nm ultraviolet (UV) light and then exposed to X-rays after incubation for 0-6 hr. The cells were incubated either on nutrient medium or salt agar between the treatments. Loss of reproductive ability and mutation to canavanine resistance were measured. When the X-ray exposure immediately followed UV-irradiation, the X-ray survival curves had the same slope irrespective of the pretreatment, while the X-ray mutation induction curves were changed from linear to linear quadratic with increasing UV fluence. Incubations up to about 3 hr on nutrient medium between the treatments led to synergism with respect to cell inactivation and antagonism with respect to mutation, but after 4-6 hr the two treatments acted independently. Incubation on salt agar did not cause any change in the survival curves, but there was a strong suppression of X-ray-induced mutation with increasing UV fluence. On the basis of these results, we suggest that mutation after combined UV and X-ray exposure is affected not only by the induction and suppression of DNA repair processes, but also by radiation-induced modifications of cell-cycle progression and changes in the expression of the mutant phenotype. Copyright 2004 Wiley-Liss, Inc.

  15. Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

    Science.gov (United States)

    Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

    2015-01-01

    Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

  16. Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma

    International Nuclear Information System (INIS)

    Yuan, Yang; Wang, Weixing; Li, Huizhong; Yu, Yongwei; Tao, Jin; Huang, Shengdong; Zeng, Zhiyong

    2015-01-01

    Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS

  17. Mechanisms of EDDHA effects on the promotion of floral induction in the long-day plant Lemna minor (L.).

    Science.gov (United States)

    Krajncic, Bozidar; Nemec, Joze

    2003-02-01

    EDDHA added in an optimal concentration (20.5 mumol.L-1) to a modified Pirson-Seidel nutrient solution induces flowering in some clones of the species Lemna minor, Lemna gibba and Spirodela polyrrhiza, which in the absence of EDDHA in the same nutrient solution do not flower. By adding EDDHA (20.5 mumol.L-1), floral induction under LD conditions is optimally promoted in the long-day (LD) species Lemna minor. After adding EDDHA to the nutrient solution, before floral induction and during flowering, Zn, Mn and Cu content is significantly increased in plants. Zn-EDDHA (0.86 mumol.L-1), Mn-EDDHA (1.51 mumol.L-1) and Cu-EDDHA (0.12 mumol.L-1), when used individually, greatly promote flowering under LD conditions as compared to flowering in the same nutrient solution with an equivalent quantity of Zn, Mn or Cu in the nonchelate form. If, on the other hand, Zn-EDDHA and Mn-EDDHA are added to the nutrient solution together (instead of Zn and Mn in nonchelate form), their effect on the promotion of flowering is less than in the case of their individual use. This shows that there is antagonism between Zn-EDDHA and Mn-EDDHA that is eliminated by adding EDDHA to the nutrient solution. We obtained the highest percentage of flowering plants (i.e. 74%) if we added EDDHA (20.5 mumol.L-1) to the nutrient solution containing Mn, Zn and Cu in chelate form. 74% of flowering plants actually means that flowering was achieved in all physiologically mature plants. Our results show that EDDHA promotes floral induction in Lemna minor under LD conditions, especially through chelating Zn, Mn and Cu, and, in addition, through eliminating the antagonism between Mn and Zn chelates EDDHA. Zn-EDDHA (0.86 mumol.L-1) also promote floral differentiation, especially cell division of microspore mother cells into dyads and those into microspore tetrads, which can be seen in microphotographs. When investigating possible pathways through which Mn-EDDHA, Zn-EDDHA and Cu-EDDHA promote flowering, we studied

  18. Wee1 Kinase Inhibitor AZD1775 Radiosensitizes Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C., E-mail: kcuneo@umich.edu; Morgan, Meredith A.; Davis, Mary A.; Parcels, Leslie A.; Parcels, Joshua; Karnak, David; Ryan, Caila; Liu, Na; Maybaum, Jonathan; Lawrence, Theodore S.

    2016-06-01

    Purpose: Wee1 kinase inhibitors are effective radiosensitizers in cells lacking a G{sub 1} checkpoint. In this study we examined the potential effect of Wee1 kinase inhibition on inducing replication stress in hepatocellular carcinoma (HCC). Methods and Materials: Five independent datasets from the Oncomine database comparing gene expression in HCC compared to normal tissue were combined and specific markers associated with Wee1 sensitivity were analyzed. We then performed a series of in vitro experiments to study the effect of Wee1 inhibition on irradiated HCC cell lines with varying p53 mutational status. Clonogenic survival assays and flow cytometry using anti-γH2AX and phospho-histone H3 antibodies with propidium iodide were performed to study the effect of AZD1775 on survival, cell cycle, and DNA repair. Additionally, nucleoside enriched medium was used to examine the effect of altering nucleotide pools on Wee1 targeted radiation sensitization. Results: Our analysis of the Oncomine database found high levels of CDK1 and other cell cycle regulators indicative of Wee1 sensitivity in HCC. In our in vitro experiments, treatment with AZD1775 radiosensitized and chemosensitized Hep3B, Huh7, and HepG2 cell lines and was associated with delayed resolution of γH2AX foci and the induction of pan-nuclear γH2AX staining. Wee1 inhibition attenuated radiation-induced G{sub 2} arrest in the Hep3B (TP53 null) and Huh7 (TP53 mutant) cell lines but not in the TP53 wild-type cell line HepG2. Supplementation with nucleosides reversed the radiation-sensitizing effect of AZD1775 and reduced the amount of cells with pan-nuclear γH2AX staining after radiation. Conclusions: Radiation sensitization with Wee1 inhibition occurs in cells regardless of their p53 mutational status. In this study we show for the first time that replication stress via the overconsumption of nucleotides plays an important role in AZD1775-induced radiation sensitization.

  19. Key tumor suppressor genes inactivated by "greater promoter" methylation and somatic mutations in head and neck cancer

    NARCIS (Netherlands)

    Guerrero-Preston, Rafael; Michailidi, Christina; Marchionni, Luigi; Pickering, Curtis R.; Frederick, Mitchell J.; Myers, Jeffrey N.; Yegnasubramanian, Srinivasan; Hadar, Tal; Noordhuis, Maartje G.; Zizkova, Veronika; Fertig, Elana; Agrawal, Nishant; Westra, William; Koch, Wayne; Califano, Joseph; Velculescu, Victor E.; Sidransky, David

    Tumor suppressor genes (TSGs) are commonly inactivated by somatic mutation and/or promoter methylation; yet, recent high-throughput genomic studies have not identified key TSGs inactivated by both mechanisms. We pursued an integrated molecular analysis based on methylation binding domain sequencing

  20. Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease.

    Science.gov (United States)

    Akinbami, Anthony O; Campbell, Andrew D; Han, Zeqiu J; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

    2016-01-01

    Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.

  1. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

    Science.gov (United States)

    He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  2. Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63.

    Science.gov (United States)

    Ozaki, Toshinori; Nakamura, Mizuyo; Ogata, Takehiro; Sang, Meijie; Yoda, Hiroyuki; Hiraoka, Kiriko; Sang, Meixiang; Shimozato, Osamu

    2016-11-01

    Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM sensitivity. Under our experimental conditions, RUNX2 knockdown caused a significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc-1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion, forced expression of TAp63α in Panc-1 cells promoted cell cycle arrest and/or cell death, and massively increased luciferase activities driven by TAp63-target gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells. Taken together, our current observations strongly suggest that depletion of RUNX2 enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the stimulation of TAp63-dependent cell death pathway even in the presence of a large amount of pro-oncogenic mutant p53, and might provide an attractive strategy to treat pancreatic cancer patients with p53 mutations.

  3. Mutational studies reveal a complex set of positive and negative control elements within the chicken vitellogenin II promoter.

    Science.gov (United States)

    Seal, S N; Davis, D L; Burch, J B

    1991-05-01

    The endogenous chicken vitellogenin II (VTGII) gene is transcribed exclusively in hepatocytes in response to estrogen. We previously identified two estrogen response elements (EREs) upstream of this gene. We now present an analysis of the VTGII promoter activated by these EREs in response to estrogen. Chimeric VTGII-CAT genes were cotransfected into LMH chicken hepatoma cells along with an estrogen receptor expression vector, and transient CAT expression was assayed after culturing the cells in the absence or presence of estrogen. An analysis of constructs bearing deletions downstream of the more proximal ERE indicated that promoter elements relevant to transcription in LMH cells extend to between -113 and -96. The relative importance of sequences within the VTGII promoter was examined by using 10 contiguous linker scanner mutations spanning the region from -117 to -24. Although most of these mutations compromised VTGII promoter function, one dramatically increased expression in LMH cells and also rendered the VTGII promoter capable of being activated by cis-linked EREs in fibroblasts cotransfected with an estrogen receptor expression vector. Gel retardation and DNase I footprinting assays revealed four factor-binding sites within this promoter. We demonstrate that three of these sites bind C/EBP, SP1, and USF (or related factors), respectively; the fourth site binds a factor that we denote TF-V beta. The biological relevance of these findings is suggested by the fact that three of these binding sites map to sites previously shown to be occupied in vivo in response to estrogen.

  4. Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone

    International Nuclear Information System (INIS)

    Koenig, R.J.; Brent, G.A.; Warne, R.L.; Larsen, P.R.; Moore, D.D.

    1987-01-01

    Transcription of the rat growth hormone (rGH) gene in pituitary cells is increased by addition of thyroid hormone (T3). This induction is dependent on the presence of specific sequences just upstream of the rGH promoter. The authors have partially purified T3 receptor from rat liver and examined its interaction with these rGH sequences. They show here that T3 receptor binds specifically to a site just upstream of the basal rGH promoter. This binding site includes two copies of a 7-base-pair direct repeat, the centers of which are separated by 10 base pairs. Deletions that specifically remove the T3 receptor binding site drastically reduce response to T3 in transient transfection experiments. These results demonstrate that T3 receptor can recognize specific DNA sequences and suggest that it can act directly as a positive transcriptional regulatory factor

  5. Induction of mutations by chemicals and gamma rays in mutants of yeast refractory to UV-mutagenesis

    International Nuclear Information System (INIS)

    Nasim, A.; Hannan, M.A.

    1977-01-01

    Radiation-sensitive mutants of Schizosaccharomyces pombe, known to be refractory to UV-mutagenesis, were tested for mutability caused by treatments with chemicals and gamma rays. One such mutant (rad3) was studied over a wide range of UV doses to compare the kinetics of its mutational response to that of the wild type. All such comparisons were carried out using a forward mutation system. Data show that, unlike UV, the chemical mutagens as well as gamma rays produced mutations (although at reduced frequency), in the strains of S. pombe tested, indicating the existence of an additional mechanism(s) for chemical and gamma ray induced mutations. These observations are discussed as these relate to the pathways for repair of mutational damage in yeast. (author)

  6. Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex.

    Science.gov (United States)

    Ruan, Hongyu; Yao, Wei-Dong

    2017-01-25

    Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP). After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons is induced at +30 ms, a normally ineffective timing interval for t-LTP induction in saline-exposed mice. This cocaine-induced, extended-timing t-LTP lasts for ∼1 week after terminating cocaine and is accompanied by an increased susceptibility to potentiation by fewer pre-post spike pairs, indicating a reduced t-LTP induction threshold. Basal synaptic strength and the maximal attainable t-LTP magnitude remain unchanged after cocaine exposure. We further show that the cocaine facilitation of t-LTP induction is caused by sensitized D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons, which then pathologically recruits voltage-gated l-type Ca 2+ channels that synergize with GluN2A-containing NMDA receptors to drive t-LTP at extended timing. Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifies the coincidence detection window during Hebbian plasticity to facilitate associative synaptic potentiation in prefrontal excitatory circuits. By modifying rules that govern activity-dependent synaptic plasticity, addictive drugs can derail the experience-driven neural circuit remodeling process important for executive control of reward and addiction. It is believed that addictive drugs often render an addict's brain reward system hypersensitive, leaving the individual more susceptible to

  7. Rosette growth of shoots in chrysanthemum (Dendranthema grandiflora Tzvelev) as a result of in vitro propagation of plants and gamma irradiation used for mutation induction

    International Nuclear Information System (INIS)

    Jerzy, M.; Zalewska, M.; Lema, J.

    1999-01-01

    Rosette growth of chrysanthemum shoots in 'Mrs. R.C. Puling' was observed after in vitro propagation with explants obtained from vernalised and non-vernalised stock plants. The phenomenon was also observed as a result of the exposure of leaf explants to gamma radiation used for in vitro regeneration of plants in mutation induction. The higher the irradiation dose, the more considerable the rosette growth. Following the 4th pinching of shoot tips, only elongating growth of plants was observed

  8. Rationally designed turn promoting mutation in the amyloid-β peptide sequence stabilizes oligomers in solution.

    Directory of Open Access Journals (Sweden)

    Jayakumar Rajadas

    Full Text Available Enhanced production of a 42-residue beta amyloid peptide (Aβ(42 in affected parts of the brain has been suggested to be the main causative factor for the development of Alzheimer's Disease (AD. The severity of the disease depends not only on the amount of the peptide but also its conformational transition leading to the formation of oligomeric amyloid-derived diffusible ligands (ADDLs in the brain of AD patients. Despite being significant to the understanding of AD mechanism, no atomic-resolution structures are available for these species due to the evanescent nature of ADDLs that hinders most structural biophysical investigations. Based on our molecular modeling and computational studies, we have designed Met35Nle and G37p mutations in the Aβ(42 peptide (Aβ(42Nle35p37 that appear to organize Aβ(42 into stable oligomers. 2D NMR on the Aβ(42Nle35p37 peptide revealed the occurrence of two β-turns in the V24-N27 and V36-V39 stretches that could be the possible cause for the oligomer stability. We did not observe corresponding NOEs for the V24-N27 turn in the Aβ(21-43Nle35p37 fragment suggesting the need for the longer length amyloid peptide to form the stable oligomer promoting conformation. Because of the presence of two turns in the mutant peptide which were absent in solid state NMR structures for the fibrils, we propose, fibril formation might be hindered. The biophysical information obtained in this work could aid in the development of structural models for toxic oligomer formation that could facilitate the development of therapeutic approaches to AD.

  9. Oncogenic IDH1 Mutations Promote Enhanced Proline Synthesis through PYCR1 to Support the Maintenance of Mitochondrial Redox Homeostasis

    Directory of Open Access Journals (Sweden)

    Kate E.R. Hollinshead

    2018-03-01

    Full Text Available Summary: Since the discovery of mutations in isocitrate dehydrogenase 1 (IDH1 in gliomas and other tumors, significant efforts have been made to gain a deeper understanding of the consequences of this oncogenic mutation. One aspect of the neomorphic function of the IDH1 R132H enzyme that has received less attention is the perturbation of cellular redox homeostasis. Here, we describe a biosynthetic pathway exhibited by cells expressing mutant IDH1. By virtue of a change in cellular redox homeostasis, IDH1-mutated cells synthesize excess glutamine-derived proline through enhanced activity of pyrroline 5-carboxylate reductase 1 (PYCR1, coupled to NADH oxidation. Enhanced proline biosynthesis partially uncouples the electron transport chain from tricarboxylic acid (TCA cycle activity through the maintenance of a lower NADH/NAD+ ratio and subsequent reduction in oxygen consumption. Thus, we have uncovered a mechanism by which tumor cell survival may be promoted in conditions associated with perturbed redox homeostasis, as occurs in IDH1-mutated glioma. : Hollinshead et al. demonstrate a role for PYCR1 in control of mitochondrial redox homeostasis. Expression of IDH1 R132H mutation leads to increased NADH-coupled proline biosynthesis, mediated by PYCR1. The resulting metabolic phenotype partially uncouples mitochondrial NADH oxidation from respiration, representing an oxygen-sparing metabolic phenotype. Keywords: glioma, IDH1, redox, metabolism, proline

  10. Combined effect of gamma irradiation methods and in vitro explant sources on mutation induction of flower color in Chrysanthemum morifoliun Ramat

    International Nuclear Information System (INIS)

    Nagatomi, Shigeki; Miyahira, Eiken; Degi, Konosuke

    1997-01-01

    Effective radiation breeding method was searched by establishing an effective exposure method to induce a mutation involved in flower color of chrysanthemum and clarifying the effects of its combined use with cultured explants. A chrysanthemum 'Taihei', a variety suitable for cut-flower use was used as the subject, which was irradiated at a dose ranging from 0.25-1.5 Gy/day for 20 days. The floral petals, buds and leaves were used as the explants for callus induction culture. The flower color was evaluated using Japanese Standard Color chart for Horticultural Plants. The color spectrum of the adaxial surface of a petal was recorded by spectro-photometer TC-1800 MK-2. Thus, six mutants of flower color were registered as new varieties. Either of these mutants was derived from chronic irradiation. Three varieties from petal culture, two from bud one and one from cutting culture were obtained, showing that the combined method of chronic irradiation and organ culture is useful in practice for mutation breeding of flower species. Further, this method is applicable for production of non-chimeric mutants, enhancement of the mutation rate and widening the mutation spectra in vegetatively propagated plants. (M.N.)

  11. Promoting Picture Word Inductive Model (PWIM to Develop Students’ Writing Skill

    Directory of Open Access Journals (Sweden)

    Fitri Novia

    2015-04-01

    Full Text Available Abstract: The objective of this study was to find out whether or not there was significant difference between students who were taught using picture word inductive model (PWIM and that of those who were not. The experimental method was used to conduct the study. The population of this study was the eighth grade students in SMP N 1 Sirah Pulau Padang.  Out of this pouplation, 68 students were taken as a sample and were divided  equally into two groups by using purposive sampling method. Therefore, class VIII 1 was the experimental group whereas VIII 3 as the control group, each of them consists of 34 students. The data were collected by asking students to write descriptive paragraph. To find out the validity, content validity was used. Inter-rater reliability was used to find out the reliability. T-test was used to analyze the data. Based on the result, the value of t-obtained was 3.155, at the significant level p<0.05 in two tailed testing with do = 66, the critical value of t-table = 1.9966. Since the value of t-obtained was higher than t-table, the Null Hypotheses (Ho was rejected and Alternative Analysis (Ha was accepted. It meant that there was significant difference between students who were taught using picture word inductive model (PWIM and that of those who were not. In conclusion, PWIM could help students to develop writing skill.   Key Word: Writing skill, Picture Word Inductive Model (PWIM.

  12. A mutation in a functional Sp1 binding site of the telomerase RNA gene (hTERC promoter in a patient with Paroxysmal Nocturnal Haemoglobinuria

    Directory of Open Access Journals (Sweden)

    Mason Philip J

    2004-06-01

    Full Text Available Abstract Background Mutations in the gene coding for the RNA component of telomerase, hTERC, have been found in autosomal dominant dyskeratosis congenita (DC and aplastic anemia. Paroxysmal nocturnal hemoglobinuria (PNH is a clonal blood disorder associated with aplastic anemia and characterized by the presence of one or more clones of blood cells lacking glycosylphosphatidylinositol (GPI anchored proteins due to a somatic mutation in the PIGA gene. Methods We searched for mutations in DNA extracted from PNH patients by amplification of the hTERC gene and denaturing high performance liquid chromatography (dHPLC. After a mutation was found in a potential transcription factor binding site in one patient electrophoretic mobility shift assays were used to detect binding of transcription factors to that site. The effect of the mutation on the function of the promoter was tested by transient transfection constructs in which the promoter is used to drive a reporter gene. Results Here we report the finding of a novel promoter mutation (-99C->G in the hTERC gene in a patient with PNH. The mutation disrupts an Sp1 binding site and destroys its ability to bind Sp1. Transient transfection assays show that mutations in this hTERC site including C-99G cause either up- or down-regulation of promoter activity and suggest that the site regulates core promoter activity in a context dependent manner in cancer cells. Conclusions These data are the first report of an hTERC promoter mutation from a patient sample which can modulate core promoter activity in vitro, raising the possibility that the mutation may affect the transcription of the gene in hematopoietic stem cells in vivo, and that dysregulation of telomerase may play a role in the development of bone marrow failure and the evolution of PNH clones.

  13. MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T1

    Directory of Open Access Journals (Sweden)

    Olsson Hans

    2013-01-01

    Full Text Available Abstract Background Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors. Methods After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression. Results Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038. Conclusions MDM2 SNP309 promoter polymorphism and mutations in

  14. Dosimetry and mutation induction with cobalt-60, on the three potato species: sani imilla, imilla negra and waycha pacena

    International Nuclear Information System (INIS)

    Mendoza, Victor Hugo; Arizaca, Jaime

    2000-01-01

    This paper presents the research on dosimetry of three species of the potato widely consumed in the bolivian plateau, aiming to obtain the optimum irradiation doses to induce mutations for the research to come

  15. Induction of an altered lipid phenotype by two cancer promoting treatments in rat liver.

    Science.gov (United States)

    Riedel, S; Abel, S; Swanevelder, S; Gelderblom, W C A

    2015-04-01

    Changes in lipid metabolism have been associated with tumor promotion in rat liver. Similarities and differences of lipid parameters were investigated using the mycotoxin fumonisin B1 (FB1) and the 2-acetylaminofluorene/partial hepatectomy (AAF/PH) treatments as cancer promoters in rat liver. A typical lipid phenotype was observed, including increased membranal phosphatidylethanolamine (PE) and cholesterol content, increased levels of C16:0 and monounsaturated fatty acids in PE and phosphatidylcholine (PC), as well as a decrease in C18:0 and long-chained polyunsaturated fatty acids in the PC fraction. The observed lipid changes, which likely resulted in changes in membrane structure and fluidity, may represent a growth stimulus exerted by the cancer promoters that could provide initiated cells with a selective growth advantage. This study provided insight into complex lipid profiles induced by two different cancer promoting treatments and their potential role in the development of hepatocyte nodules, which can be used to identify targets for the development of chemopreventive strategies against cancer promotion in the liver. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Mutation induction and neoplastic transformation in human and human-hamster hybrid cells: dependence on photon energy and modulation in the low-dose range

    Energy Technology Data Exchange (ETDEWEB)

    Frankenberg, D.; Frankenberg-Schwager, M.; Garg, I.; Pralle, E. [Abt. Klin. Strahlenbiologie und Klin. Strahlenphysik, Universitaet Goettingen, Goettingen (Germany); Uthe, D.; Greve, B.; Severin, E.; Goehde, W. [Institut fuer Strahlenbiologie, Universitaet Muenster, Munster (Germany)

    2002-09-01

    Mutation induction in the HPRT gene of human fibroblasts after irradiation with mammography-like 29 kVp or 200 kVp x-rays shows radiohypersensitivity for doses smaller than {approx}0.5 Gy. Similarly, mutation induction in the CD 59 gene on human chromosome 11 in A{sub L} cells shows radiohypersensitivity for doses smaller than {approx}0.5 Gy after exposure to 200 kVp x-rays, but not after irradiation with low-filtered 30 kVp x-rays. The RBE values of 29 and 30 kVp x-rays relative to 200 kVp x-rays are strongly dose dependent. For neoplastic transformation of human hybrid (CGL1) cells after irradiation with 29 or 200 kVp x-rays or {sup 60}Co gamma rays a linear-quadratic dose relationship was observed with RBE values of approximately four and eight for mammography relative to 200 kVp x-rays and {sup 60}Co gamma rays, respectively. (author)

  17. Induction and maintenance of DNA methylation in plant promoter sequences by apple latent spherical virus-induced transcriptional gene silencing

    Directory of Open Access Journals (Sweden)

    Tatsuya eKon

    2014-11-01

    Full Text Available Apple latent spherical virus (ALSV is an efficient virus-induced gene silencing vector in functional genomics analyses of a broad range of plant species. Here, an Agrobacterium-mediated inoculation (agroinoculation system was developed for the ALSV vector, and virus-induced transcriptional gene silencing (VITGS is described in plants infected with the ALSV vector. The cDNAs of ALSV RNA1 and RNA2 were inserted between the CaMV 35S promoter and the NOS-T sequences in a binary vector pCAMBIA1300 to produce pCALSR1 and pCALSR2-XSB or pCALSR2-XSB/MN. When these vector constructs were agroinoculated into Nicotiana benthamiana plants with a construct expressing a viral silencing suppressor, the infection efficiency of the vectors was 100%. A recombinant ALSV vector carrying part of the 35S promoter sequence induced transcriptional gene silencing of the green fluorescent protein gene in a line of N. benthamiana plants, resulting in the disappearance of green fluorescence of infected plants. Bisulfite sequencing showed that cytosine residues at CG and CHG sites of the 35S promoter sequence were highly methylated in the silenced generation 0 plants infected with the ALSV carrying the promoter sequence as well as in progeny. The ALSV-mediated VITGS state was inherited by progeny for multiple generations. In addition, induction of VITGS of an endogenous gene (chalcone synthase-A was demonstrated in petunia plants infected with an ALSV vector carrying the native promoter sequence. These results suggest that ALSV-based vectors can be applied to study DNA methylation in plant genomes, and provide a useful tool for plant breeding via epigenetic modification.

  18. Induction of lethal mutations in the x-chromosome of unirradiated Drosophila oocytes after fertilization by irradiated spermatozoa

    International Nuclear Information System (INIS)

    Shaposhnikov, M.V.; Zainullin, V.G.

    2003-01-01

    Full text: In primary study on Drosophila it was found that irradiated male X-chromosomes induce recessive lethals in unirradiated female homologues (Abeleva et al., 1961, Radiobiologya. 1:123-126). The same effects were obtained in Drosophila in some recent investigations. The mechanisms of these effects is unknown. However it may be responsible for low-dose radiation effects as it induce mutations in unirradiated DNA. We assume that this effect may be a result of activation of error prone repair in response to preliminary DNA lesions in irradiated chromosome. In this research we analyse the frequencies of the recessive lethal mutations in the X-chromosome of Drosophila females mated with irradiated Basc males. We used acute irradiation with a dose rate of 10 Gy. For testing our hypothesis we use the mus209 and mei-41 mutant females. Mus209 is a PCNA gene homologue and mei-41 is a homologue of ATM gene. These genes are involved in post-replication DNA repair which may be error prone repair in Drosophila. It was obtained the tendency to decreasing the mutation rate at the mei-41[D5] background and decreasing mutation rate in mus209[B1] background in comparison with wild type strains CS (p<0.05). The obtained results demonstrate the possible role of mus209[B1] and mei-41[D5] genes in the inducing of mutations in the unirradiated X-chromosome in the presence of irradiated homologue

  19. Protection against radiation-induced mutations at the hprt locus by spermine and N,N double-prime-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278). WR-33278 and spermine protect against mutation induction

    International Nuclear Information System (INIS)

    Grdina, D.J.; Shigematsu, N.; Schwartz, J.L.

    1994-01-01

    The polyamine spermine and the disulfide N,N double-prime-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278) are structurally similar agents capable of binding to DNA. WR-33278 is the disulfide moiety of the clinically studied radioprotective agent S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). Because of their reported structural and functional similarities, it was of interest to characterize and compare their radioprotective properties using the endpoints of cell survival and mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in Chinese hamster AA8 cells. In order to facilitate both the uptake of WR-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents (at concentrations of 0.01 mM and 0.001 mM) were electroporated into cells. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction, with the sequence of irradiation followed 3 h later by electroporation being the more toxic protocol. Enhanced cell survival was observed following electroporation of 0.01 mM of spermine and WR-33278 30 min prior to irradiation; protection factors (PF) of 1.3 and 1.8, respectively. Neither agent was protective at a concentration of 0.001 mM. Protection against radiation-induced hprt mutations was observed for both spermine and WR-33278 under all experimental conditions tested. These data suggest that the properties of radioprotection and chemoprevention exhibited by the phosphorothioate (WR-2721) and associated aminothiol (WR-1065) and disulfide (WR-33278) metabolites may be mediated via endogenous spermine-like polyamine processes. Such a mechanism would have important implications with respect to the design and development of new generation drugs for use in radioprotection and chemoprevention

  20. Synergism between caffeine and γ-radiation in the induction of dominant lethal mutations in oocytes and spermatozoa of Musca domestica

    International Nuclear Information System (INIS)

    Targa, H.J.

    1983-01-01

    Caffeine was studied with regard to its synergism with γ-radiation in the induction of dominant lethal mutations in S14 oocytes and mature spermatozoa of M. domestica. In S14 oocytes an increase in the frequency of such a type of mutation was observed only when the exposure to γ-radiation followed a pretreatment with a diet containing 0.2% of caffeine. Negative results were obtained with (a) post-treatment with the same kind of diet, (b) pretreatment with diets containing 0.1 and 0.02% of caffeine and (c) exposure to the radiation 6 h after interruption of the feeding treatment with the diet containing 0.2% of caffeine. Such influence of the conditions under which the treatment is performed and the synergistic effects is probably related to the food intake pattern and the rapid metabolism of the caffeine. When the 0.2% caffeine pretreatment was combined with an exposure of the oocytes to variable doses of γ-radiation, the increments in the mutations observed seemed to be negatively correlated to the radiation doses used. Also, under such conditions, the dose/survival relationship fits well an exponential curve expressed by in y=-0.866chi. With mature spermatozoa, synergism by caffeine was found only when the females, after having been mated with the irradiated males, were fed for 24 h on a diet supplemented with 0.2% of caffeine. (orig.)

  1. Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation.

    Science.gov (United States)

    Diehl, Sean; Chow, Chi-Wing; Weiss, Linda; Palmetshofer, Alois; Twardzik, Thomas; Rounds, Laura; Serfling, Edgar; Davis, Roger J; Anguita, Juan; Rincón, Mercedes

    2002-07-01

    Interleukin (IL)-6 is produced by professional antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells. It has been previously shown that APC-derived IL-6 promotes the differentiation of naive CD4+ T cells into effector T helper type 2 (Th2) cells. Here, we have studied the molecular mechanism for IL-6-mediated Th2 differentiation. During the activation of CD4+ T cells, IL-6 induces the production of IL-4, which promotes the differentiation of these cells into effector Th2 cells. Regulation of IL-4 gene expression by IL-6 is mediated by nuclear factor of activated T cells (NFAT), as inhibition of NFAT prevents IL-6-driven IL-4 production and Th2 differentiation. IL-6 upregulates NFAT transcriptional activity by increasing the levels of NFATc2. The ability of IL-6 to promote Th2 differentiation is impaired in CD4+ T cells that lack NFATc2, demonstrating that NFATc2 is required for regulation of IL-4 gene expression by IL-6. Regulation of NFATc2 expression and NFAT transcriptional activity represents a novel pathway by which IL-6 can modulate gene expression.

  2. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos

    Science.gov (United States)

    Tu, Zhuchi; Yang, Weili; Yan, Sen; Yin, An; Gao, Jinquan; Liu, Xudong; Zheng, Yinghui; Zheng, Jiezhao; Li, Zhujun; Yang, Su; Li, Shihua; Guo, Xiangyu; Li, Xiao-Jiang

    2017-01-01

    CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing. PMID:28155910

  3. Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

    Science.gov (United States)

    Morafraile, Esther C; Diffley, John F X; Tercero, José Antonio; Segurado, Mónica

    2015-01-20

    The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

  4. Small-Molecule Induction Promotes Corneal Epithelial Cell Differentiation from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Alexandra Mikhailova

    2014-02-01

    Full Text Available Human induced pluripotent stem cells (hiPSCs offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

  5. Mouse Norovirus infection promotes autophagy induction to facilitate replication but prevents final autophagosome maturation

    International Nuclear Information System (INIS)

    O’Donnell, Tanya B.; Hyde, Jennifer L.; Mintern, Justine D.; Mackenzie, Jason M.

    2016-01-01

    Autophagy is a cellular process used to eliminate intracellular pathogens. Many viruses however are able to manipulate this cellular process for their own advantage. Here we demonstrate that Mouse Norovirus (MNV) infection induces autophagy but does not appear to utilise the autophagosomal membrane for establishment and formation of the viral replication complex. We have observed that MNV infection results in lipidation and recruitment of LC3 to the autophagosome membrane but prevents subsequent fusion of the autophagosomes with lysosomes, as SQSTM1 (an autophagy receptor) accumulates and Lysosome-Associated Membrane Protein1 is sequestered to the MNV replication complex (RC) rather than to autophagosomes. We have additionally observed that chemical modulation of autophagy differentially affects MNV replication. From this study we can conclude that MNV infection induces autophagy, however suppresses the final maturation step of this response, indicating that autophagy induction contributes to MNV replication independently of RC biogenesis. - Highlights: • MNV induces autophagy in infected murine macrophages. • MNV does not utilise autophagosomal membranes for replication. • The MNV-induced autophagosomes do not fuse with lysosomes. • MNV sequesters SQSTM1 to prevent autophagy degradation and turnover. • Chemical modulation of autophagy enhances MNV replication.

  6. Mouse Norovirus infection promotes autophagy induction to facilitate replication but prevents final autophagosome maturation

    Energy Technology Data Exchange (ETDEWEB)

    O’Donnell, Tanya B. [Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3010 (Australia); Hyde, Jennifer L. [School of Chemical and Biological Sciences, University of Queensland, St. Lucia, Brisbane, Queensland 4072 (Australia); Mintern, Justine D. [Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010 (Australia); Mackenzie, Jason M., E-mail: jason.mackenzie@unimelb.edu.au [Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3010 (Australia)

    2016-05-15

    Autophagy is a cellular process used to eliminate intracellular pathogens. Many viruses however are able to manipulate this cellular process for their own advantage. Here we demonstrate that Mouse Norovirus (MNV) infection induces autophagy but does not appear to utilise the autophagosomal membrane for establishment and formation of the viral replication complex. We have observed that MNV infection results in lipidation and recruitment of LC3 to the autophagosome membrane but prevents subsequent fusion of the autophagosomes with lysosomes, as SQSTM1 (an autophagy receptor) accumulates and Lysosome-Associated Membrane Protein1 is sequestered to the MNV replication complex (RC) rather than to autophagosomes. We have additionally observed that chemical modulation of autophagy differentially affects MNV replication. From this study we can conclude that MNV infection induces autophagy, however suppresses the final maturation step of this response, indicating that autophagy induction contributes to MNV replication independently of RC biogenesis. - Highlights: • MNV induces autophagy in infected murine macrophages. • MNV does not utilise autophagosomal membranes for replication. • The MNV-induced autophagosomes do not fuse with lysosomes. • MNV sequesters SQSTM1 to prevent autophagy degradation and turnover. • Chemical modulation of autophagy enhances MNV replication.

  7. Induction of apoptosis by tomato using space mutation breeding in human colon cancer SW480 and HT-29 cells.

    Science.gov (United States)

    Shi, Jiahui; Yang, Bin; Feng, Pan; Li, Duo; Zhu, Jiajin

    2010-03-15

    As far as we know, there have been no reports concerning the functional characteristics of tomatoes using space mutation breeding. The aim of this study was to evaluate the anti-colon cancer effect of tomatoes M1 and M2 using space mutation breeding. In the present study, obvious anti-cancer activity was shown with tomato juice of M1 and M2 and their parent CK treatment in colon cancer cell lines SW480 and HT-29 in cell growth inhibition. In addition, SW480 cells were more sensitive to M1 and M2 than HT-29 cells in cell apoptosis. Furthermore, M1 and M2 induced cell cycle arrest both in G0-G1 and G2/M phases. These data suggest that consumption of tomato using space mutation breeding may provide benefits to inhibit growth of colon cancer cells. Therefore, tomato production using space mutation breeding may be a good candidate for development as a dietary supplement in drug therapy for colon cancer.

  8. Synergistic interaction of gamma rays and some metallic salts in the induction of chlorophyll mutations in rice

    International Nuclear Information System (INIS)

    Reddy, T.P.; Vaidyanath, K.

    1978-01-01

    In this study the mutagenic activity of 9 metallic salts was tested in comparison and conjunction with gamma rays on rice seed. In M 2 , barium and cadmium produced chlorophyll mutation and mutant frequencies on a par with those of 20 kR gamma rays. Similarly, copper and mercury induced moderately high mutation and mutant frequencies. Salts of strontium, iron and lead showed rather weak mutagenic effects. On the other hand, two metals - manganese anc calcium - failed to provoke chlorophyll mutations in rice seed. Sequential treatments of gamma rays + 5 metals, namely Sr, Cd, Hg, Pb and Cu, produced synergistic yields of chlorophyll mutants in the M 2 generation. Two genetically active metals, Ba and Fe, showed less than additive effects when post-treated after gamma irradiation. Manganese, which failed to induce chlorophyll mutations in independent treatment, potentiated the mutagenic activity of gamma radiation in sequential treatment. On the other hand, sequential treatment with calcium seemed to confer a substantial protection against gamma-ray-induced genetic lesions. The probable mechanisms of synergistic interaction, mutagenic potentiation and protection, observed in sequential treatments, are discussed. (Auth.)

  9. Pachymic acid promotes induction of autophagy related to IGF-1 signaling pathway in WI-38 cells.

    Science.gov (United States)

    Lee, Su-Gyeong; Kim, Moon-Moo

    2017-12-01

    The insulin-like growth factor 1 (IGF-1) signaling pathway has spotlighted as a mechanism to elucidate aging associated with autophagy in recent years. Therefore, we have tried to screen an effective compound capable of inducing autophagy to delay aging process. The aim of this study is to investigate whether pachymic acid, a main compound in Poria cocos, induces autophagy in the aged cells. The aging of young cells was induced by treatment with IGF-1 at 50 ng/ml three times every two days. The effect of pachymic acid on cell viability was evaluated in human lung fibroblasts, WI-38 cells, using MTT assay. The induction of autophagy was detected using autophagy detection kit. The expression of proteins related to autophagy and IGF-1 signaling pathway was examined by western blot analysis and immunofluorescence assay. In this study, pachymic acid showed cytotoxic effect in a dose dependent manner and remarkably induced autophagy at the same time. Moreover, pachymic acid increased the expression of proteins related to autophagy such as LC3-II and Beclin1 and decreased the levels of mTor phosphorylation and p70S6K in the aged cells. In particular, pachymic acid increased the expression of p-PI3K, p-FoxO and Catalase. In addition, pachymic acid remarkably increased the expression of IGFBP-3. Above results suggest that pachymic acid could induce autophagy related to IGF-1 signaling pathway in the aged cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Absence of mutation at the 5'-upstream promoter region of the TPM4 gene from cardiac mutant axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Denz, Christopher R; Zhang, Chi; Jia, Pingping; Du, Jianfeng; Huang, Xupei; Dube, Syamalima; Thomas, Anish; Poiesz, Bernard J; Dube, Dipak K

    2011-09-01

    Tropomyosins are a family of actin-binding proteins that show cell-specific diversity by a combination of multiple genes and alternative RNA splicing. Of the 4 different tropomyosin genes, TPM4 plays a pivotal role in myofibrillogenesis as well as cardiac contractility in amphibians. In this study, we amplified and sequenced the upstream regulatory region of the TPM4 gene from both normal and mutant axolotl hearts. To identify the cis-elements that are essential for the expression of the TPM4, we created various deletion mutants of the TPM4 promoter DNA, inserted the deleted segments into PGL3 vector, and performed promoter-reporter assay using luciferase as the reporter gene. Comparison of sequences of the promoter region of the TPM4 gene from normal and mutant axolotl revealed no mutations in the promoter sequence of the mutant TPM4 gene. CArG box elements that are generally involved in controlling the expression of several other muscle-specific gene promoters were not found in the upstream regulatory region of the TPM4 gene. In deletion experiments, loss of activity of the reporter gene was noted upon deletion which was then restored upon further deletion suggesting the presence of both positive and negative cis-elements in the upstream regulatory region of the TPM4 gene. We believe that this is the first axolotl promoter that has ever been cloned and studied with clear evidence that it functions in mammalian cell lines. Although striated muscle-specific cis-acting elements are absent from the promoter region of TPM4 gene, our results suggest the presence of positive and negative cis-elements in the promoter region, which in conjunction with positive and negative trans-elements may be involved in regulating the expression of TPM4 gene in a tissue-specific manner.

  11. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak, E-mail: Siamak.haghdoost@su.se

    2015-10-15

    Highlights: • 50 mGy at 1.4 mGy/h induces adaptive response in MCF-10A at mutation level. • Low dose rate γ-radiation does not induce adaptive response at survival level. • Overall, a dose rate effect is absent at the level of mutation in MCF-10A cells. - Abstract: A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50 mGy adapting dose administered acutely (0.40 Gy/min) or chronically (1.4 mGy/h or 4.1 mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100 mGy and 1 Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50 mGy at 1.4 mGy/h followed by 1 Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100 mGy), no differences at the level of mutation were found comparing different dose rates.

  12. Analysis of clustered point mutations in the human ribosomal RNA gene promoter by transient expression in vivo

    International Nuclear Information System (INIS)

    Jones, M.H.; Learned, R.M.; Tjian, R.

    1988-01-01

    The authors have mapped the cis regulatory elements required in vivo for initiation at the human rRNA promoter by RNA polymerase I. Transient expression in COS-7 cells was used to evaluate the transcription phenotype of clustered base substitution mutations in the human rRNA promoter. The promoter consists of two major elements: a large upstream region, composed of several domains, that lies between nucleotides -234 and -107 relative to the transcription initiation site and affects transcription up to 100-fold and a core element that lies between nucleotides -45 and +20 and affects transcription up to 1000-fold. The upstream regions is able to retain partial function when positioned within 100-160 nucleotides of the transcription initiation site, but it cannot stimulate transcription from distances of ≥ 600 nucleotides. In addition, they demonstrate, using mouse-human hybrid rRNA promoters, that the sequences responsible for human species-specific transcription in vivo appear to reside in both the core and upstream elements, and sequences from the mouse rRNA promoter cannot be substituted for them

  13. IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

    Science.gov (United States)

    Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

    2012-05-10

    Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

  14. Induction of mutation in Jujube (Zizyphus jujuba Mill) using tissue culture combined with {sup 60}Coγ-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, H. R. [Horticultural Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai (China); Liu, Z. C. [Shanghai Agrobiological Gene Center, Shanghai (China); Ye, Z. W.; Su, M. S.; Jin, Y. F.

    2009-05-15

    In vivo and in vitro mutagenesis techniques were assayed to explore effects of irradiation in jujube (Ziziphus jujuba Mill) improvement. {sup 60}Co γ-ray irradiated seeds and shoot tips of a land race of jujube originating in Shangdong province of China were micropropagated up to M{sub 1}V{sub 4} generation on MS basal medium containing 2 mg/L BA and 0.4 mg/L IBA. The rooting MS medium contained 1 mg/L BA and 0.6 mg/L IAA, ZEA 1 mg/L, 2, 4-D 0.5 mg/L, and NAA 0.5 mg/L in different combinations. Adventitious buds were also produced from irradiated calli derived from leaf and hypocotyl fragments and the elongated adventitious buds rooted in vitro prior to green house transfer. Different doses (20 to 900Gy) were tested for in vitro explants as well as the jujube kernels irradiation. Six types of leaf shape and seven types of fruit shape mutations were observed and different ripening characters and growth habits were recorded in the orchard on putatively mutated mature trees. Even though there is a need for confirmation and molecular characterization, these mutations may be considered as a new and powerful way for jujube improvement in order to develop genotypes with promising value added traits. (author)

  15. The development of ideas about the effect of DNA repair on the induction of gene mutations and chromosomal aberrations by radiation and by chemicals

    International Nuclear Information System (INIS)

    Kimball, R.F.

    1987-01-01

    An historical overview is given of the development of ideas about chromosomal and DNA repair as they relate to the induction of mutations, chromosomal aberrations, and sister-chromatid exchanges by radiations and chemicals. The genetic and molecular bases of the various repair pathways are reviewed whenever possible. Work on both prokaryotes and eukaryotes is included. Mention is made, when deemed appropriate, of major developments in other areas that served as essential background for the repair work, but no attempt is made to cover these background developments in any detail. Near the end, a brief review is given of factors affecting polymerase fidelity. The history is subdivided into approximately 10-year intervals. For the most part, references are to reviews and symposia in which the ideas of the time were brought together. The implications of these findings for some practical problems in genetic toxicology and for our understanding of the maintenance of the genome are discussed at the end. 147 refs

  16. Development of ideas about the effect of DNA repair on the induction of gene mutations and chromosomal aberrations by radiation and by chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Kimball, R F

    1987-07-01

    An historical overview is given of the development of ideas about chromosomal and DNA repair as they relate to the induction of mutations, chromosomal aberrations, and sister-chromatid exchanges by radiations and chemicals. The genetic and molecular bases of the various repair pathways are reviewed whenever possible. Work on both prokaryotes and eukaryotes is included. Mention is made, when deemed appropriate, of major developments in other areas that served as essential background for the repair work, but no attempt is made to cover these background developments in any detail. Near the end, a brief review is given of factors affecting polymerase fidelity. The history is subdivided into approximately 10-year intervals. For the most part, references are to reviews and symposia in which the ideas of the time were brought together. The implications of these findings for some practical problems in genetic toxicology and for our understanding of the maintenance of the genome are discussed at the end. 147 refs.

  17. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tian-Li [Department of General Surgery, The People’s Hospital of Wuqing, Tianjin (China); Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Yue [Department of Respiration, Affiliated Hospital of Medical College of Chinese People’s Armed Police Force, Tianjin (China); Chen, Ao-Xiang; Sun, Xuan [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie, E-mail: gejie198003@163.com [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2014-04-04

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.

  18. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Chu, Tian-Li; Zhao, Hong-Meng; Li, Yue; Chen, Ao-Xiang; Sun, Xuan; Ge, Jie

    2014-01-01

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy

  19. Cellular and subcellular effect of heavy ions: A comparison of the induction of strand breaks and chromosomal aberration with the incidence of inactivation and mutation

    International Nuclear Information System (INIS)

    Kraft, G.; Kraft-Weyrather, W.; Ritter, S.; Scholz, M.; Stanton, J.

    1988-10-01

    Radiobiological effects of heavy charged particles are compared for a large variety of ions from Helium to Uranium and energies between 1 and 1000 MeV/u which correspond to LET values between 10 and 16000 keV/μm. The different cross section for the induction of strand breaks and chromosomal aberrations as well as for inactivation and mutation induction exhibit striking similarities when compared as function of the linear energy transfer (LET). At LET values below 100 keV/μm all data points of one specific effect form one single curve as a function of LET, independent of the atomic number of the ion. In this LET range, the biological effects are independent from the particle energy or track structure and depend only on the energy transfer. Therefore, LET is a good parameter in tis regime. For LET values greater than 100 keV/μm, the curves for the different ions separate from the common curve in order of increasing atomic numbers. In this regime LET is no longer a good parameter and the physical parameters of the formation of particle tracks are important. The similarity of the σ-LET curves for different endpoints indicates that the 'hook-structure' is produced by physical and chemical effects which occur before the biologically relevant lesions are formed. However, from the existing data of biological effects, it can be concluded that the efficiencies for cell killing are always smaller than those extrapolated from X-ray data on the basis of the energy deposition only. Therefore, cells which are directly hit by an HZE particle are not killed and undergo a finite risk of mutation and transformation. (orig.)

  20. T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination

    Directory of Open Access Journals (Sweden)

    Masahisa Hemmi

    2017-11-01

    Full Text Available Few current vaccines can establish antigen (Ag-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2−/− mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.

  1. Mutational analysis of the UCP2 core promoter and relationships of variants with obesity

    DEFF Research Database (Denmark)

    Dalgaard, Louise T; Andersen, Gitte; Larsen, Lesli H

    2003-01-01

    To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain.......To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain....

  2. Induction of interferon-stimulated genes by IRF3 promotes replication of Toxoplasma gondii.

    Science.gov (United States)

    Majumdar, Tanmay; Chattopadhyay, Saurabh; Ozhegov, Evgeny; Dhar, Jayeeta; Goswami, Ramansu; Sen, Ganes C; Barik, Sailen

    2015-03-01

    Innate immunity is the first line of defense against microbial insult. The transcription factor, IRF3, is needed by mammalian cells to mount innate immune responses against many microbes, especially viruses. IRF3 remains inactive in the cytoplasm of uninfected cells; upon virus infection, it gets phosphorylated and then translocates to the nucleus, where it binds to the promoters of antiviral genes and induces their expression. Such genes include type I interferons (IFNs) as well as Interferon Stimulated Genes (ISGs). IRF3-/- cells support enhanced replication of many viruses and therefore, the corresponding mice are highly susceptible to viral pathogenesis. Here, we provide evidence for an unexpected pro-microbial role of IRF3: the replication of the protozoan parasite, Toxoplasma gondii, was significantly impaired in IRF3-/- cells. In exploring whether the transcriptional activity of IRF3 was important for its pro-parasitic function, we found that ISGs induced by parasite-activated IRF3 were indeed essential, whereas type I interferons were not important. To delineate the signaling pathway that activates IRF3 in response to parasite infection, we used genetically modified human and mouse cells. The pro-parasitic signaling pathway, which we termed PISA (Parasite-IRF3 Signaling Activation), activated IRF3 without any involvement of the Toll-like receptor or RIG-I-like receptor pathways, thereby ruling out a role of parasite-derived RNA species in activating PISA. Instead, PISA needed the presence of cGAS, STING, TBK1 and IRF3, indicating the necessity of DNA-triggered signaling. To evaluate the physiological significance of our in vitro findings, IRF3-/- mice were challenged with parasite infection and their morbidity and mortality were measured. Unlike WT mice, the IRF3-/- mice did not support replication of the parasite and were resistant to pathogenesis caused by it. Our results revealed a new paradigm in which the antiviral host factor, IRF3, plays a cell

  3. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

    Science.gov (United States)

    Harley, Margaret E; Murina, Olga; Leitch, Andrea; Higgs, Martin R; Bicknell, Louise S; Yigit, Gökhan; Blackford, Andrew N; Zlatanou, Anastasia; Mackenzie, Karen J; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A M; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B; Nürnberg, Peter; Jackson, Stephen P; Hurles, Matthew E; Wollnik, Bernd; Stewart, Grant S; Jackson, Andrew P

    2016-01-01

    DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.

  4. Systematic screening for mutations in the promoter and the coding region of the 5-HT{sub 1A} gene

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, J.; Shimron-Abarbanell, D.; Cichon, S. [Univ. of Bonn (Germany)] [and others

    1995-10-09

    In the present study we sought to identify genetic variation in the 5-HT{sub 1A} receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains a functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A{yields}G) in nucleotide position 82 which leads to an amino acid exchange (Ile{yields}Val) in position 28 of the receptor protein and a silent mutation (C{yields}T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT{sub 1A} gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette`s syndrome. 29 refs., 4 figs., 1 tab.

  5. Induction and evaluation of mutations for improved protein production in certain species of yeasts in the Philippines

    International Nuclear Information System (INIS)

    Borromeo, J.D.

    1976-02-01

    The species of yeasts included in the studies are Saccharomyces cerevisiae, Rhodeterula rubra, Rhodeterula pilimane and those isolated from fruits such as citrus, papaya and banana. Part of the project involved induction of sporulation to obtain haploid cells for crossing to produce stable disploids exhibiting improved protein production. Although S. cerevisiae produce less protein than Rhodeterula, it produces ascesperes which are haploid cells. These haploid cells can be used to obtain stable diploids with the desirable characteristics by crossing cultures. Rhodeterula, a fungus that does not produce ascesperes will be subjected to certain adverse conditions to induce, hopefully, sperulation

  6. Induction of lacI- mutations in Escherichia coli cells after single and split-dose irradiation

    International Nuclear Information System (INIS)

    Kozubek, S.; Ryznar, L.

    1992-01-01

    In the lacI system of Escherichia coli, X-ray mutagenesis follows a linear-quadratic curve with suppression; the survival curve is exponential. Dose fractionation leads to nearly complete repair of premutational lesions during an incubation interval of 3.5 h. Repair starts with a delay of 1.5-2 h, suggesting the involvement of an inducible repair/mutation fixation system. The dose-dependence of mutagenesis is described by a simple model assuming two hits being required. A probable explanation might be that the premutagenic lesions consist of two closely spaced lesions on the opposite strands of the DNA molecule. (author)

  7. Mutation induction by 365-nm radiation and far-ultraviolet light in Escherichia coli differing in near- and far-ultraviolet light sensitivity

    International Nuclear Information System (INIS)

    Leonardo, J.M.; Reynolds, P.R.; Tuveson, R.W.

    1984-01-01

    The his-4 locus derived from Escherichia coli strain AB1157 has been transduced into 4 E. coli strains that exhibit all 4 possible combinations of genes controlling sensitivity to near-ultraviolet light (nur versus nur + ) and far-ultraviolet light (uvrA6 versus uvrA + ). The 4 strains exhibited the predicted sensitivity to 254-nm radiation based on the sensitivity of the parent strains from which they were derived and the frequency of his + mutations predicted from experiments with AB1157 from which the his-4 locus was derived. When the 4 strains were treated with 365-nm radiation, they exhibited the predicted sensitivity based on the near-ultraviolet light sensitivity of the strains from which they were derived while his + mutations were undetectable with the 4 strains as well as with strain AB1157. When treated with 365-nm radiation, cells of a WP2sub(s) strain (a derivative of B/r transduced to his-4) plated on semi-enriched medium prepared with casamino acids did not yield induced mutations, whereas plating on semi-enriched medium prepared with nutrient broth did yield mutants at both the his-4 and trp loci at frequencies at least an order of magnitude lower than that observed with far-ultraviolet light. The induction of nutritionally independent mutants by 365-nm radiation is strongly dependent on the supplement used for semi-enrichment. When compared at equivalent survival levels, mutant frequencies are significantly less following 365-nm radiation when compared with far-ultraviolet radiation. (Auth.)

  8. Facilitators and Barriers to Health-Seeking Behaviours among Filipino Migrants: Inductive Analysis to Inform Health Promotion

    Directory of Open Access Journals (Sweden)

    D. Maneze

    2015-01-01

    Full Text Available Understanding factors that influence health-seeking behaviour of migrants is necessary to intervene for behaviour change. This paper explores Filipino migrants’ perceptions of facilitators and barriers to maintaining health in Australia. Open-ended survey item responses reflecting factors that assisted and hindered health following migration to Australia were inductively analysed. Three hundred and thirty-seven of the 552 survey respondents (61% provided open-ended responses. Responses were grouped into two major categories: individual factors, including personal resources and cultural influences, and environmental factors encompassing both the physical conditions in the host country and health service access. Awareness of practices that enhance health was a major personal facilitator of health-seeking behaviour; however, competing priorities of daily living were perceived as barriers. Cultural beliefs and practices influenced health-seeking behaviour. Despite high self-rated English language skills in this population, new migrants and the elderly cited communication difficulties as barriers to accessing health services. Insight into facilitators and barriers to health-seeking behaviour in this less researched migrant population revealed tools for enhancing engagement in health promotion programs addressing healthy lifestyle.

  9. Facilitators and Barriers to Health-Seeking Behaviours among Filipino Migrants: Inductive Analysis to Inform Health Promotion.

    Science.gov (United States)

    Maneze, D; DiGiacomo, M; Salamonson, Y; Descallar, J; Davidson, P M

    2015-01-01

    Understanding factors that influence health-seeking behaviour of migrants is necessary to intervene for behaviour change. This paper explores Filipino migrants' perceptions of facilitators and barriers to maintaining health in Australia. Open-ended survey item responses reflecting factors that assisted and hindered health following migration to Australia were inductively analysed. Three hundred and thirty-seven of the 552 survey respondents (61%) provided open-ended responses. Responses were grouped into two major categories: individual factors, including personal resources and cultural influences, and environmental factors encompassing both the physical conditions in the host country and health service access. Awareness of practices that enhance health was a major personal facilitator of health-seeking behaviour; however, competing priorities of daily living were perceived as barriers. Cultural beliefs and practices influenced health-seeking behaviour. Despite high self-rated English language skills in this population, new migrants and the elderly cited communication difficulties as barriers to accessing health services. Insight into facilitators and barriers to health-seeking behaviour in this less researched migrant population revealed tools for enhancing engagement in health promotion programs addressing healthy lifestyle.

  10. Facilitators and Barriers to Health-Seeking Behaviours among Filipino Migrants: Inductive Analysis to Inform Health Promotion

    Science.gov (United States)

    Salamonson, Y.; Descallar, J.; Davidson, P. M.

    2015-01-01

    Understanding factors that influence health-seeking behaviour of migrants is necessary to intervene for behaviour change. This paper explores Filipino migrants' perceptions of facilitators and barriers to maintaining health in Australia. Open-ended survey item responses reflecting factors that assisted and hindered health following migration to Australia were inductively analysed. Three hundred and thirty-seven of the 552 survey respondents (61%) provided open-ended responses. Responses were grouped into two major categories: individual factors, including personal resources and cultural influences, and environmental factors encompassing both the physical conditions in the host country and health service access. Awareness of practices that enhance health was a major personal facilitator of health-seeking behaviour; however, competing priorities of daily living were perceived as barriers. Cultural beliefs and practices influenced health-seeking behaviour. Despite high self-rated English language skills in this population, new migrants and the elderly cited communication difficulties as barriers to accessing health services. Insight into facilitators and barriers to health-seeking behaviour in this less researched migrant population revealed tools for enhancing engagement in health promotion programs addressing healthy lifestyle. PMID:26380277

  11. Ultraviolet B (UVB) induction of the c-fos promoter is mediated by phospho-cAMP response element binding protein (CREB) binding to CRE and c-fos activator protein 1 site (FAP1) cis elements.

    Science.gov (United States)

    Gonzales, Melissa; Bowden, G Tim

    2002-06-26

    The ultraviolet B (UVB) portion (280-320 nm) of the ultraviolet spectrum has been shown to contribute to the development of non-melanoma skin cancer in humans. Research in the human keratinocyte cell line, HaCaT, revealed that UVB irradiation caused the upregulation of the transcription factor activator protein-1 (AP-1). The AP-1 complex formed in UVB-irradiated HaCaT cells is specifically composed of c-fos and Jun D. c-Fos expression was induced in a manner that correlated with the UVB-induced activation of AP-1. To investigate how c-fos expression is regulated by UVB irradiation, the role of each of four cis elements within the c-fos promoter was evaluated. Clustered point mutations at the sis inducible element (SIE), serum response element (SRE), c-fos AP-1 site (FAP1), or cyclic AMP response elements (CRE) significantly inhibited UVB induction of the c-fos promoter. This indicated that all four cis elements are required for maximum promoter activity. The CRE and FAP1 elements were the two most active cis elements that mediate the UVB transactivation of c-fos. Homodimers of phosphorylated cAMP response element binding protein (CREB) were induced by UVB irradiation to bind to each of these elements. Therefore, CREB may function as an important regulatory protein in the UVB-induced expression of c-fos.

  12. PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions.

    Science.gov (United States)

    Kraus, Allison; Raymond, Gregory J; Race, Brent; Campbell, Katrina J; Hughson, Andrew G; Anson, Kelsie J; Raymond, Lynne D; Caughey, Byron

    2017-11-01

    Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro , only some are transmissible and pathogenic in vivo To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood

  13. Induction patterns of structural mutations in barley leaf meristem upon the combined action of ionizing radiation and heavy metals

    International Nuclear Information System (INIS)

    Geras'kin, S.A.; Dikarev, V.G.; Udalova, A.A.

    1995-01-01

    Environmental protection requires the development of principles, universal methods, and quantitative criteria for estimating the ecological risk of the combined effects of various factors on natural ecosystems. The combined action of these factors may induce complex multidirectional processes, e.g., the induction and inhibition of separation systems that result in a broad spectrum of cell responses (from antagonism to synergism), depending on the relative involvement of the factors. This was confirmed by numerous examples of nonlinear responses of biological systems to alterations in the order and level of damaging agents, as well as in the duration of their action. For this reason, the response of a biological system to the combined action of various damaging factors cannot be predicted from the data on the separate action of factors. 7 refs., 3 figs., 2 tabs

  14. ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis.

    Science.gov (United States)

    Jin, Shengfang; Chen, Jiang; Chen, Lizao; Histen, Gavin; Lin, Zhizhong; Gross, Stefan; Hixon, Jeffrey; Chen, Yue; Kung, Charles; Chen, Yiwei; Fu, Yufei; Lu, Yuxuan; Lin, Hui; Cai, Xiujun; Yang, Hua; Cairns, Rob A; Dorsch, Marion; Su, Shinsan M; Biller, Scott; Mak, Tak W; Cang, Yong

    2015-07-21

    Mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the liver removes toxic aldehydes including acetaldehyde, an intermediate of ethanol metabolism. Nearly 40% of East Asians inherit an inactive ALDH2*2 variant, which has a lysine-for-glutamate substitution at position 487 (E487K), and show a characteristic alcohol flush reaction after drinking and a higher risk for gastrointestinal cancers. Here we report the characterization of knockin mice in which the ALDH2(E487K) mutation is inserted into the endogenous murine Aldh2 locus. These mutants recapitulate essentially all human phenotypes including impaired clearance of acetaldehyde, increased sensitivity to acute or chronic alcohol-induced toxicity, and reduced ALDH2 expression due to a dominant-negative effect of the mutation. When treated with a chemical carcinogen, these mutants exhibit increased DNA damage response in hepatocytes, pronounced liver injury, and accelerated development of hepatocellular carcinoma (HCC). Importantly, ALDH2 protein levels are also significantly lower in patient HCC than in peritumor or normal liver tissues. Our results reveal that ALDH2 functions as a tumor suppressor by maintaining genomic stability in the liver, and the common human ALDH2 variant would present a significant risk factor for hepatocarcinogenesis. Our study suggests that the ALDH2*2 allele-alcohol interaction may be an even greater human public health hazard than previously appreciated.

  15. Radiosensitivity, mutation and tetraploid induction in the gamma-ray-irradiated growing shoots in mulberry, Morus alba L

    International Nuclear Information System (INIS)

    Katagiri, Koitsu

    1976-01-01

    The vigorously developing mulberry shoots on the 1 year old grafted trees of the variety Inchinose were separately exposed to 60 Co γ-ray of 6KR at 120 R/hr and 7.5 KR at 150 R/hr in early July, early August and early September. After the irradiation, all of the irradiated shoots developed axially buds with malformed narrow leaves, and after that, all plants subjected to the irradiation in September and 30% of the July irradiation group and 40% of the August irradiation group both with higher exposure ceased shoot development. This type of radiation damage was large for the plants with higher exposure as compared with those with lower one, and it was also severe for the plants irradiated in July in comparison with those in August. From the ceasing of shoot development the LD 50 value of 150 R/hr irradiation was estimated to be a little more than 7.5 KR. The frequencies of mutation and tetraploid in the grafts produced by the propagation of the axially buds below the leafless portion were high in the grafts with higher exposure than those with lower one, and also the frequencies were high in July irradiation in comparison with August irradiation. It was confirmed that the size of mutation or tetraploid sector was large in the shoots derived from the less advanced axially bud primordia at the time of irradiation than that from the advanced ones. All of tetraploids were the cytochimeras having diploid epidermises over tetraploid internal tissues. (Kobatake, H.)

  16. H2A/K pseudogene mutation may promote cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jisheng; Jing, Ruirui; Lv, Xin; Wang, Xiaoyue; Li, Junqiang; Li, Lin; Li, Cuiling; Wang, Daoguang; Bi, Baibing; Chen, Xinjun [Cancer Research Center, Shandong University School of Medicine, Jinan 250012 (China); Yang, Jing-Hua, E-mail: sdu_crc_group1@126.com [Cancer Research Center, Shandong University School of Medicine, Jinan 250012 (China); Department of Surgery, VA Boston Healthcare System, Boston University School of Medicine, Boston 510660, MA (United States)

    2016-05-15

    Highlights: • The mutant H2A/K pseudogene is active. • The mutant H2A/K pseudogene can promote cell proliferation. - Abstract: Little attention has been paid to the histone H2A/K pseudogene. Results from our laboratory showed that 7 of 10 kidney cancer patients carried a mutant H2A/K pseudogene; therefore, we were interested in determining the relationship between mutant H2A/K and cell proliferation. We used shotgun and label-free proteomics methods to study whether mutant H2A/K lncRNAs affected cell proliferation. Quantitative proteomic analysis indicated that the expression of mutant H2A/K lncRNAs resulted in the upregulation of many oncogenes, which promoted cell proliferation. Further interaction analyses revealed that a proliferating cell nuclear antigen (PCNA)-protein interaction network, with PCNA in the center, contributes to cell proliferation in cells expressing the mutant H2A/K lncRNAs. Western blotting confirmed the critical upregulation of PCNA by mutant H2A/K lncRNA expression. Finally, the promotion of cell proliferation by mutant H2A/K lncRNAs (C290T, C228A and A45G) was confirmed using cell proliferation assays. Although we did not determine the exact mechanism by which the oncogenes were upregulated by the mutant H2A/K lncRNAs, we confirmed that the mutant H2A/K lncRNAs promoted cell proliferation by upregulating PCNA and other oncogenes. The hypothesis that cell proliferation is promoted by the mutant H2A/K lncRNAs was supported by the protein expression and cell proliferation assay results. Therefore, mutant H2A/K lncRNAs may be a new factor in renal carcinogenesis.

  17. Resistance or tolerance to the golden mosaic virus of bean plant (Phaseolus vulgaris L.), obtained by mutation induction

    International Nuclear Information System (INIS)

    Tulmann Neto, A.

    1979-09-01

    Experiments were carried out with the objective of selecting, evaluation and using induced mutants of Phaseolus vulgaris L. resistant or tolerant to golden mosaic - a virus disease of beans. Seeds from three bean cultivars were treated with gamma-ray or the chemical mutagen ethyl methanesulphonate (EMS). After golden mosaic inoculation of 50,000 M 2 seedlings, in a insectary, screening was made and a tolerant mutant (TMD-1) was selected. Evaluation of TMD-1 was carried out by comparing it with the parent cultivar Carioca, indicating that, although showing lower productivity than the original material, (what prevented it from being used directly on a commercial basis), it maintained the same reaction to rust, bacterial blight, and common mosaic. Studies on the genetic basis of the mutation were also done. The possibility of using this mutant in a plant breeding programme aimed at obtaining resistance to golden mosaic was demonstrated in crosses between TMD-1 and two cultivars, to which transference of tolerance was possible. (Author) [pt

  18. MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

    Science.gov (United States)

    Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

    2016-10-01

    Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (PMLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas can harbor KRAS mutations and arise from precursor polyps resembling conventional tubular/tubulovillous adenomas.

  19. The influence of the wavelength of ultraviolet radiation on survival, mutation induction and DNA repair in irradiated Chinese hamster cells

    International Nuclear Information System (INIS)

    Zelle, B.; Reynolds, R.J.; Kottenhagen, M.J.; Schuite, A.; Lohmann, P.H.M.

    1980-01-01

    Chinese hamster ovary cells were used to compare the cytotoxicity and mutagenicity of far-UV radiation emitted by a low-pressure mercury, germicidal lamp (wavelength predominantly 254 nm) with that of near UV radiation emitted by a fluorescent lamp with a continuous spectrum (Westinghouse Sun Lamp), of which only the radiation with wavelengths greater than 290 nm or greater than 310 nm was transmitted to the cells. The radiation effects were compared on the basis of an equal number of pyrimidine dimers, the predominant lesion induced in DNA by far-UV, for the induction of which much more energy is needed with near-UV than with 254-nm radiation. The numbers of dimers induced were determined by a biochemical method detecting UV-endonuclease-susceptible sites. The equivalence of these sites with pyrimidine dimers was established, qualitatively and quantitatively, in studies with enzymic photoreactivation in vitro and chromatographic analysis of dimers. On the basis of induced dimers, more cells were killed by UE 310-nm UV than by UE 290-nm UV; both forms of radiation were more cytotoxic than 254-nm UV when equal numbers of dimers were induced. Moreover, 5-6 times as many mutants were induced per dimer by UE 310-nm UV than by UE 290-nm UV; the latter appeared approximately as mutagenic as 254-nm UV. The differences in lethality and mutagenicity were not caused by differences in repair of dimers: cells with an equal number of dimers induced by either 254-nm or near-UV showed the same removal of sites susceptible to a UV endonuclease specific for dimers, as well as an identical amount of repair replication. The results indicate that near-UV induces, besides pyrimidine dimers, other lesions that appear to be of high biological significance. (orig.)

  20. Induction of mutation for increased sulfur content in the CFI strain of yeast by gamma-irradiation

    International Nuclear Information System (INIS)

    Faustino, C.C.

    1977-08-01

    From all current source of protein concentration the food yeast offers the greatest potential for development. Yeast protein is a good source of lysine and has adeqouate acounts of other essential amino acids such as trytophan and threonine, however, it was found to be relatively poor in the sulfur-containing amino acids which limits its nutrient value. A lasting remedy is genetic modification of the microorganisms to produce protein with a better amino acid balance. Gamma radiation from Co-60 was tried in these experiments being reported to induce mutations in the new CFI strain. A way of screening for increased sulfur content was devised. These are; 1) Incorporation of (NH 4 ) 2 35 S0 4 into the yeast cells; 2) Autoradiography; and 3) Quantitative determination of S-incorporation in submerse cultures of yeasts by use of a liquid scintillation counter. About seven hundred individual colonies were carefully and meticulously autQradiographically screened for high-S0 4 incorporation. Based on the results of autoradiography, 7.8% (50 strains) of the whole population were considered high in 35 S0 4 incorporation. The 50 yeast strains selected by autoradiography to be high in S0 4 incorporation were analyzed with the use of a liquid scintillation counter. From the data gathered, 29 mutants were se--lected. The data from these 29 mutants are presented in tabulated form. Only yeast strains no. 1, 42, 44, 47, 4, 3, 49, 50, 2 and 39 appear to show any promise as putative high-S mutants

  1. Chemical inducible promoter used to obtain transgenic plants with a silent marker and organisms and cells and methods of using same for screening for mutations

    Science.gov (United States)

    Zuo, Jianru [New York, NY; Chua, Nam-Hai [Scarsdale, NY

    2007-06-12

    Disclosed is a chemically inducible promoter for transforming plants or plant cells with genes which are regulatable by adding the plants or cells to a medium containing an inducer or by removing them from such medium. The promoter is inducible by a glucocorticoid, estrogen or inducer not endogenous to plants. Such promoters may be used with any plant genes that can promote shoot regeneration and development to induce shoot formation in the presence of a glucocorticoid, estrogen or inducer. The promoter may be used with antibiotic or herbicide resistance genes or other genes which are regulatable by the presence or absence of a given inducer. Also presented are organisms or cells comprising a gene wherein the natural promoter of the gene is disrupted and the gene is placed under the control of a transgenic inducible promoter. These organisms and cells and their progeny are useful for screening for conditional gain of function and loss of function mutations.

  2. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

    OpenAIRE

    Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to...

  3. Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism

    Science.gov (United States)

    Mandriota, Stefano J.; Valentijn, Linda J.; Lesne, Laurence; Betts, David R.; Marino, Denis; Boudal-Khoshbeen, Mary; London, Wendy B.; Rougemont, Anne-Laure; Attiyeh, Edward F.; Maris, John M.; Hogarty, Michael D.; Koster, Jan; Molenaar, Jan J.; Versteeg, Rogier

    2015-01-01

    Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified. Chromosome bands 11q22-q23 contain ATM, a cell cycle checkpoint kinase and tumor suppressor playing a pivotal role in the DNA damage response. Here, we report that haploinsufficiency of ATM in neuroblastoma correlates with lower ATM expression, event-free survival, and overall survival. ATM loss occurs in high stage neuroblastoma without MYCN amplification. In SK-N-SH, CLB-Ga and GI-ME-N human neuroblastoma cells, stable ATM silencing promotes neuroblastoma progression in soft agar assays, and in subcutaneous xenografts in nude mice. This effect is dependent on the extent of ATM silencing and does not appear to involve MYCN. Our findings identify ATM as a potential haploinsufficient neuroblastoma tumor suppressor, whose inactivation mirrors the increased aggressiveness associated with 11q deletion in neuroblastoma. PMID:26053094

  4. Deletion mutations of bacteriophage

    International Nuclear Information System (INIS)

    Ryo, Yeikou

    1975-01-01

    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.)

  5. Two co-existing germline mutations P53 V157D and PMS2 R20Q promote tumorigenesis in a familial cancer syndrome.

    Science.gov (United States)

    Wang, Zuoyun; Sun, Yihua; Gao, Bin; Lu, Yi; Fang, Rong; Gao, Yijun; Xiao, Tian; Liu, Xin-Yuan; Pao, William; Zhao, Yun; Chen, Haiquan; Ji, Hongbin

    2014-01-01

    Germline mutations are responsible for familial cancer syndromes which account for approximately 5-10% of all types of cancers. These mutations mainly occur at tumor suppressor genes or genome stability genes, such as DNA repair genes. Here we have identified a cancer predisposition family, in which eight members were inflicted with a wide spectrum of cancer including one diagnosed with lung cancer at 22years old. Sequencing analysis of tumor samples as well as histologically normal specimens identified two germline mutations co-existing in the familial cancer syndrome, the mutation of tumor suppressor gene P53 V157D and mismatch repair gene PMS2 R20Q. We further demonstrate that P53 V157D and/or PMS2 R20Q mutant promotes lung cancer cell proliferation. These two mutants are capable of promoting colony formation in soft agar as well as tumor formation in transgenic drosophila system. Collectively, these data have uncovered the important role of co-existing germline P53 and PMS2 mutations in the familial cancer syndrome development. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Genomic instability in mutation induction on normal human fibroblasts irradiated with chronic low-dose radiations in heavy-ion radiation field

    International Nuclear Information System (INIS)

    Suzuki, M.; Tsuruoka, C.; Uchihori, Y.; Yasuda, H.; Fujitaka, K.

    2003-01-01

    Full text: At a time when manned space exploration is more a reality with the planned the International Space Station (ISS) underway, the potential exposure of crews in a spacecraft to chronic low-dose radiations in the field of low-flux galactic cosmic rays (GCR) and the subsequent biological effects have become one of the major concerns of space science. We have studied both in vitro life span and genomic instability in cellular effects in normal human skin fibroblasts irradiated with chronic low-dose radiations in heavy-ion radiation field. Cells were cultured in a CO2 incubator, which was set in the irradiation room for the biological study of heavy ions in the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS), and irradiated with scattered radiations produced from heavy ions. Absorbed dose measured using a thermoluminescence dosimeter (TLD) and a Si-semiconductor detector was to be around 1.4 mGy per day when operating the HIMAC machine for biological experiments. The total population doubling number (tPDN) of low-dose irradiated cells was significantly smaller (79-93%) than that of unirradiated cells. The results indicate that the life span of the cell population shortens by irradiating with low-dose scattered radiations in the heavy-ion irradiation field. Genomic instability in cellular responses was examined to measure either cell killing or mutation induction in low-dose accumulated cells after exposing to X-ray challenging doses. The results showed that there was no enhanced effect on cell killing between low-dose accumulated and unirradiated cells after exposing to defined challenging doses of 200kV X rays. On the contrary, the mutation frequency on hprt locus of low-dose accumulated cells was much higher than that of unirradiated cells. The results suggested that genomic instability was induced in mutagenesis by the chronic low-dose irradiations in heavy-ion radiation field

  7. KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer.

    Science.gov (United States)

    Kohonen-Corish, Maija R J; Tseung, Jason; Chan, Charles; Currey, Nicola; Dent, Owen F; Clarke, Stephen; Bokey, Les; Chapuis, Pierre H

    2014-06-15

    Colonic and rectal cancers differ in their clinicopathologic features and treatment strategies. Molecular markers such as gene methylation, microsatellite instability and KRAS mutations, are becoming increasingly important in guiding treatment decisions in colorectal cancer. However, their association with clinicopathologic variables and utility in the management of rectal cancer is still poorly understood. We analyzed CDKN2A gene methylation, CpG island methylator phenotype (CIMP), microsatellite instability and KRAS/BRAF mutations in a cohort of 381 rectal cancers with extensive clinical follow-up data. BRAF mutations (2%), CIMP-high (4%) and microsatellite instability-high (2%) were rare, whereas KRAS mutations (39%), CDKN2A methylation (20%) and CIMP-low (25%) were more common. Only CDKN2A methylation and KRAS mutations showed an association with poor overall survival but these did not remain significant when analyzed with other clinicopathologic factors. In contrast, this prognostic effect was strengthened by the joint presence of CDKN2A methylation and KRAS mutations, which independently predicted recurrence of cancer and was associated with poor overall and cancer-specific survival. This study has identified a subgroup of more aggressive rectal cancers that may arise through the KRAS-p16 pathway. It has been previously shown that an interaction of p16 deficiency and oncogenic KRAS promotes carcinogenesis in the mouse and is characterized by loss of oncogene-induced senescence. These findings may provide avenues for the discovery of new treatments in rectal cancer. © 2013 UICC.

  8. TNF-α and IL-1β Dependent Induction of CCL3 Expression by Nucleus Pulposus Cells Promotes Macrophage Migration through CCR1

    Science.gov (United States)

    Wang, Jianru; Tian, Ye; Phillips, Kate L.E.; Chiverton, Neil; Haddock, Gail; Bunning, Rowena A.; Cross, Alison K.; Shapiro, Irving M.; LeMaitre, Christine L.; Risbud, Makarand V.

    2012-01-01

    Objective To investigate TNF-α and IL-1β regulation of CCL3 expression in nucleus pulposus (NP) cells and in macrophage migration. Methods qRT-PCR and immunohistochemistry were used to measure CCL3 expression in NP cells. Transfections were used to determine the role of NF-κB, C/EBP-β and MAPK on cytokine mediated CCL3 promoter activity. Effect of NP-conditioned medium on macrophage migration was measured using a transwell system. Results An increase in CCL3 expression and promoter activity was observed in NP cells after TNF-α or IL-1β treatment. Treatment of cells with NF-κB and MAPK inhibitors abolished the effect of the cytokines on CCL3 expression. The inductive effect of p65 and C/EBP-β on CCL3 promoter was confirmed through gain- and loss-of-function studies. Noteworthy, co-transfection of p50 completely blocked cytokine and p65 dependent induction. In contrast, c-Rel and RelB had little effect on promoter activity. Lentiviral transduction with Sh-p65 and Sh-Ikkβ significantly decreased TNF-α dependent increase in CCL3 expression. Analysis of degenerate human NP tissues showed that CCL3, but not CCL4 expression correlated positively with the grade of tissue degeneration. Importantly, treatment of macrophages with conditioned medium of NP cells treated with TNF-α or IL-1β promoted their migration; pretreatment of macrophages with antagonist to CCR1, primary receptor for CCL3 and CCL4, blocked cytokine mediated migration. Conclusions By controlling the activation of MAPK, NF-κB and C/EBPβ signaling, TNF-α and IL-1β modulate the expression of CCL3 in NP cells. The CCL3-CCR1 axis may play an important role in promoting macrophage infiltration in degenerate, herniated discs. PMID:23233369

  9. A novel ATM-dependent checkpoint defect distinct from loss of function mutation promotes genomic instability in melanoma.

    Science.gov (United States)

    Spoerri, Loredana; Brooks, Kelly; Chia, KeeMing; Grossman, Gavriel; Ellis, Jonathan J; Dahmer-Heath, Mareike; Škalamera, Dubravka; Pavey, Sandra; Burmeister, Bryan; Gabrielli, Brian

    2016-05-01

    Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. Here, we report a novel defect of the ATM-dependent cell cycle checkpoint in melanoma cell lines that promotes genomic instability. In defective cells, ATM signalling to CHK2 is intact, but the cells are unable to maintain the cell cycle arrest due to elevated PLK1 driving recovery from the arrest. Reducing PLK1 activity recovered the ATM-dependent checkpoint arrest, and over-expressing PLK1 was sufficient to overcome the checkpoint arrest and increase genomic instability. Loss of the ATM-dependent checkpoint did not affect sensitivity to ionizing radiation demonstrating that this defect is distinct from ATM loss of function mutations. The checkpoint defective melanoma cell lines over-express PLK1, and a significant proportion of melanomas have high levels of PLK1 over-expression suggesting this defect is a common feature of melanomas. The inability of ATM to impose a cell cycle arrest in response to DNA damage increases genomic instability. This work also suggests that the ATM-dependent checkpoint arrest is likely to be defective in a higher proportion of cancers than previously expected. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Predictive and prognostic impact of TP53 mutations and MDM2 promoter genotype in primary breast cancer patients treated with epirubicin or paclitaxel.

    Directory of Open Access Journals (Sweden)

    Ranjan Chrisanthar

    Full Text Available BACKGROUND: TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP T309G increases MDM2 activity and may reduce wild-type p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy. EXPERIMENTAL DESIGN: Each patient was randomly assigned to treatment with epirubicin 90 mg/m(2 (n = 109 or paclitaxel 200 mg/m(2 (n = 114 every 3rd week as monotherapy for 4-6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy. PRINCIPAL FINDINGS: While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007 but also MDM2 309TG/GG genotype status (p = 0.012 were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039 but not among individuals with TP53 mutated tumors (p>0.5. CONCLUSION: TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy.

  11. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model

    NARCIS (Netherlands)

    Wildenberg, Manon E.; Levin, Alon D.; Ceroni, Alessandro; Guo, Zhen; Koelink, Pim J.; Hakvoort, Theodorus B. M.; Westera, Liset; Bloemendaal, Felicia M.; Brandse, Johannan F.; Simmons, Alison; D'Haens, Geert R.; Ebner, Daniel; van den Brink, Gijs R.

    2017-01-01

    Background and Aims: Regulatory macrophages play a critical role in tissue repair, and we have previously shown that anti-tumour necrosis factor [TNF] antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the

  12. Use of the Lactococcal nisA Promoter To Regulate Gene Expression in Gram-Positive Bacteria : Comparison of Induction Level and Promoter Strength

    NARCIS (Netherlands)

    Eichenbaum, Zehava; Federle, Michael J.; Marra, Diana; Vos, Willem M. de; Kuipers, Oscar P.; Kleerebezem, Michiel; Scott, June R.

    1998-01-01

    We characterized the regulated activity of the lactococcal nisA promoter in strains of the gram-positive species Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, and Bacillus subtilis. nisA promoter activity was dependent on the proteins NisR and

  13. Cyclosporine promotes the induction of thymic lymphomas in C57BL/6 mice initiated by a single dose of γ-radiation

    International Nuclear Information System (INIS)

    Yabu, Koji; Warty, V.S.; Gorelik, E.; Shinozuka, Hisashi

    1991-01-01

    We previously demonstrated that a single dose of γ-radiation (350 rads) was able to induce thymic lymphomas in C57BL mice when followed by promoting treatment with oral cyclosporine (CsA), a non-genotoxic immunosuppressant. We have now tested the efficacy of various doses of γ-radiation as an initiator of CsA promotion of the induction of thymic lymphomas in male C57BL mice. The effects of oral CsA on the splenic natural killer (NK) cell activity of non-irradiated and irradiated (400 rads, 1X) mice were tested by the standard 51 Cr release assays against YAC-1 cells. The cumulative incidence of thymic lymphomas induced by a single dose of γ-radiation at 100, 200, 400 and 600 rads were 10, 25, 63 and 75% respectively, after 42 weeks of CsA promotion. The splenic NK cell activity in non-irradiated mice given CsA for 4 weeks was twice as high as that in the control mice. CsA inhibited poly I:C-induced augmentation of the splenic NK cell activity. In mice given a single dose (400 rads) of γ-radiation and CsA for 4 weeks, a similar but reduced enhancement of the splenic NK cell activity as seen in non-irradiated mice was observed. These results indicate that the efficacy of CsA promotion in the induction of thymic lymphomas is dependent on the initiating doses of γ-radiation, and that CsA enhances host splenic NK cell activity during the early stage of tumor promotion. (author)

  14. Mutation induction in durum wheat

    International Nuclear Information System (INIS)

    Senay, A.; Sekerci, S.

    2009-01-01

    The aim of this research was to determine the separate and combine effects of different doses of gamma rays and EMS concentrations on some characteristics of M1 plants of durum wheat, cv. Kunduru 1149. The seeds of durum wheat, cv. Kunduru 1149 which were irradiated with 50 Gy, 150 Gy and 250 Gy gamma rays and/or treated EMS for 6 hours at 30 C in 0,2 % and 0,4 % concentrated. According to the results of this research; separate and combine treatments of different doses of gamma rays and EMS have shown significant difference all of the observed traits at M1 plants of durum wheat cv. Kunduru 1149. The negative effects of increasing doses of mutagens on all plant characteristics for M1 plants were found statistically significant. Combined treatments were found to be more efficient than the sum of effects of the single treatments. In followed generation 3 mutant lines were selected according to plant height, spike height, number of seed, leaf relative water lost, and some quality traits. In M6 generation 3 desirable lines have been sown for preliminary field yield tests.

  15. Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers

    International Nuclear Information System (INIS)

    Liu, Yang; Gao, Weimin; Siegfried, Jill M; Weissfeld, Joel L; Luketich, James D; Keohavong, Phouthone

    2007-01-01

    Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are frequent in lung tumors from smokers but rare in those from never-smokers. In this study, we analyzed promoter methylation in the ras-association domain isoform A (RASSF1A) and the death-associated protein kinase (DAPK) genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region. We compare the results with the smoking status of the patients and the mutation status of the K-ras, p53, and EGFR genes determined previously on these same lung tumors. Promoter methylation of the RASSF1A and DAPK genes was analyzed by using a modified two-stage methylation-specific PCR. Data on mutations of K-ras, p53, and EGFR were obtained from our previous studies. The RASSF1A gene promoter methylation was found in tumors from 46.7% (57/122) of the patients and was not significantly different between smokers and never-smokers, but was associated significantly in multiple variable analysis with tumor histology (p = 0.031) and marginally with tumor stage (p = 0.063). The DAPK gene promoter methylation frequency in these tumors was 32.8% (40/122) and did not differ according to the patients' smoking status, tumor histology, or tumor stage. Multivariate analysis adjusted for age, gender, smoking status, tumor histology and stage showed that the frequency of promoter methylation of the RASSF1A or DAPK genes did not correlate with the frequency of mutations of the K-ras, p53, and EGFR gene. Our results showed that RASSF1A and DAPK genes' promoter methylation occurred frequently in lung tumors, although the prevalence of this alteration in these genes was not associated with the smoking status of the patients or the occurrence of mutations in the K-ras, p53 and EGFR genes, suggesting each of

  16. Heterozygous Null Bone Morphogenetic Protein Receptor Type 2 Mutations Promote SRC Kinase-dependent Caveolar Trafficking Defects and Endothelial Dysfunction in Pulmonary Arterial Hypertension*

    Science.gov (United States)

    Prewitt, Allison R.; Ghose, Sampa; Frump, Andrea L.; Datta, Arumima; Austin, Eric D.; Kenworthy, Anne K.; de Caestecker, Mark P.

    2015-01-01

    Hereditary pulmonary arterial hypertension (HPAH) is a rare, fatal disease of the pulmonary vasculature. The majority of HPAH patients inherit mutations in the bone morphogenetic protein type 2 receptor gene (BMPR2), but how these promote pulmonary vascular disease is unclear. HPAH patients have features of pulmonary endothelial cell (PEC) dysfunction including increased vascular permeability and perivascular inflammation associated with decreased PEC barrier function. Recently, frameshift mutations in the caveolar structural protein gene Caveolin-1 (CAV-1) were identified in two patients with non-BMPR2-associated HPAH. Because caveolae regulate endothelial function and vascular permeability, we hypothesized that defects in caveolar function might be a common mechanism by which BMPR2 mutations promote pulmonary vascular disease. To explore this, we isolated PECs from mice carrying heterozygous null Bmpr2 mutations (Bmpr2+/−) similar to those found in the majority of HPAH patients. We show that Bmpr2+/− PECs have increased numbers and intracellular localization of caveolae and caveolar structural proteins CAV-1 and Cavin-1 and that these defects are reversed after blocking endocytosis with dynasore. SRC kinase is also constitutively activated in Bmpr2+/− PECs, and localization of CAV-1 to the plasma membrane is restored after treating Bmpr2+/− PECs with the SRC kinase inhibitor 3-(4-chlorophenyl)-1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP2). Late outgrowth endothelial progenitor cells isolated from HPAH patients show similar increased activation of SRC kinase. Moreover, Bmpr2+/− PECs have impaired endothelial barrier function, and barrier function is restored after treatment with PP2. These data suggest that heterozygous null BMPR2 mutations promote SRC-dependent caveolar trafficking defects in PECs and that this may contribute to pulmonary endothelial barrier dysfunction in HPAH patients. PMID:25411245

  17. The hepcidin gene promoter nc.-1010C > T; -582A > G haplotype modulates serum ferritin in individuals carrying the common H63D mutation in HFE gene.

    Science.gov (United States)

    Silva, Bruno; Pita, Lina; Gomes, Susana; Gonçalves, João; Faustino, Paula

    2014-12-01

    Hereditary hemochromatosis is an autosomal recessive disorder characterized by severe iron overload. It is usually associated with homozygosity for the HFE gene mutation c.845G > A; p.C282Y. However, in some cases, another HFE mutation (c.187C > G; p.H63D) seems to be associated with the disease. Its penetrance is very low, suggesting the possibility of other iron genetic modulators being involved. In this work, we have screened for HAMP promoter polymorphisms in 409 individuals presenting normal or increased serum ferritin levels together with normal or H63D-mutated HFE genotypes. Our results show that the hepcidin gene promoter TG haplotype, originated by linkage of the nc.-1010C > T and nc.-582A > G polymorphisms, is more frequent in the HFE_H63D individuals presenting serum ferritin levels higher than 300 μg/L than in those presenting the HFE_H63D mutation but with normal serum ferritin levels or in the normal control group.Moreover, it was observed that the TG haplotype was associated to increased serum ferritin levels in the overall pool of HFE_H63D individuals. Thus, our data suggest that screening for these polymorphisms could be of interest in order to explain the phenotype. However, this genetic condition seems to have no clinical significance.

  18. Induction of short-term biomarkers of tumor promotion in skin of CD-1 mice by petroleum middle distillates: preliminary observations.

    Science.gov (United States)

    Skisak, C; DiGiovanni, J; Conti, C J; Slaga, T J; Sharma, S; Sagartz, J W; Walborg, E F

    1995-01-01

    The induction of sustained epidermal hyperplasia in mouse skin has been shown to be a reliable predictor of tumor promoting activity for chemicals as diverse as phorbol esters, anthralins, n-dodecane and organic peroxides (DiGiovanni, 1992). The results contained herein demonstrate that API 81-07 and API 81-10, petroleum middle distillates that exhibit tumor promoting activity in mouse skin, induce epidermal hyperplasia and ODC activity. Other petroleum middle distillates (odorless light petroleum hydrocarbons, a light vacuum distillate, and a mineral seal oil) were also shown to share these activities. It should be emphasized that the relevance of these observations to human skin remains unresolved; however, the availability of these short-term biomarkers offers the opportunity to address the issue by performing comparative investigations on the effects of petroleum middle distillates on human skin xenografted to athymic (nude) mice. Such studies are being initiated.

  19. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    International Nuclear Information System (INIS)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

    2013-01-01

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA

  20. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  1. PB2 mutations D701N and S714R promote adaptation of an influenza H5N1 virus to a mammalian host.

    Science.gov (United States)

    Czudai-Matwich, Volker; Otte, Anna; Matrosovich, Mikhail; Gabriel, Gülsah; Klenk, Hans-Dieter

    2014-08-01

    Mutation D701N in the PB2 protein is known to play a prominent role in the adaptation of avian influenza A viruses to mammalian hosts. In contrast, little is known about the nearby mutations S714I and S714R, which have been observed in some avian influenza viruses highly pathogenic for mammals. We have generated recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the mammalian signature 701N and serine, isoleucine, and arginine at position 714 and compared them for polymerase activity and virus growth in avian and mammalian cells, as well as for pathogenicity in mice. Mutation D701N led to an increase in polymerase activity and replication efficiency in mammalian cells and in mouse pathogenicity, and this increase was significantly enhanced when mutation D701N was combined with mutation S714R. Stimulation by mutation S714I was less distinct. These observations indicate that PB2 mutation S714R, in combination with the mammalian signature at position 701, has the potential to promote the adaptation of an H5N1 virus to a mammalian host. Influenza A/H5N1 viruses are avian pathogens that have pandemic potential, since they are spread over large parts of Asia, Africa, and Europe and are occasionally transmitted to humans. It is therefore of high scientific interest to understand the mechanisms that determine the host specificity and pathogenicity of these viruses. It is well known that the PB2 subunit of the viral polymerase is an important host range determinant and that PB2 mutation D701N plays an important role in virus adaptation to mammalian cells. In the present study, we show that mutation S714R is also involved in adaptation and that it cooperates with D701N in exposing a nuclear localization signal that mediates importin-α binding and entry of PB2 into the nucleus, where virus replication and transcription take place. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation: indicators of tumor staging and metastasis in adenocarcinomatous sporadic colorectal cancer in Indian population.

    Directory of Open Access Journals (Sweden)

    Rupal Sinha

    Full Text Available Colorectal cancer (CRC development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease.One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed.Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12 and MGMT methylation (p-value <0.049. Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044 and methylated RASSF1A (p-values 0.034, 0.044, FHIT (p-values 0.001, 0.047 and MGMT (p-values 0.018, 0.044 genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025. Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes.Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.

  3. Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Yingying; Chen, Xi; Yu, Dehai [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Tao [Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Cui, Jiuwei; Wang, Guanjun [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Hu, Ji-Fan, E-mail: jifan@stanford.edu [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China); Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304 (United States); Li, Wei, E-mail: jdyylw@163.com [Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun, Jilin 130061 (China)

    2015-09-10

    Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phase blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.

  4. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  5. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.; Arold, Stefan T.; Chauhan, Gaurav B.; Blachno, Korina V.; Deng, Nanfu; Chang, Wei-Chao; Jin, Quanri; Huang, Tzu-Hsuan; Hsu, Jung-Mao; Brady, Samuel W.; Bartholomeusz, Chandra; Ladbury, John E.; Stone, Steve; Yu, Dihua; Hung, Mien-Chie; Esteva, Francisco J.

    2014-01-01

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  6. An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

    Science.gov (United States)

    Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

    2016-06-24

    Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

  7. Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1

    DEFF Research Database (Denmark)

    Serup, P; Jensen, J; Andersen, F G

    1996-01-01

    Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London...

  8. Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A.

    Directory of Open Access Journals (Sweden)

    Stephanie Jamison

    Full Text Available Evidence is accumulating that activation of the pancreatic endoplasmic reticulum kinase (PERK in response to endoplasmic reticulum (ER stress adapts tumor cells to the tumor microenvironment and enhances tumor angiogenesis by inducing vascular endothelial growth factor A (VEGF-A. Recent studies suggest that VEGF-A can act directly on certain tumor cell types in an autocrine manner, via binding to VEGF receptor 2 (VEGFR2, to promote tumor cell migration and invasion. Although several reports show that PERK activation increases VEGF-A expression in medulloblastoma, the most common solid malignancy of childhood, the role that either PERK or VEGF-A plays in medulloblastoma remains elusive. In this study, we mimicked the moderate enhancement of PERK activity observed in tumor patients using a genetic approach and a pharmacologic approach, and found that moderate activation of PERK signaling facilitated medulloblastoma cell migration and invasion and increased the production of VEGF-A. Moreover, using the VEGFR2 inhibitor SU5416 and the VEGF-A neutralizing antibody to block VEGF-A/VEGFR2 signaling, our results suggested that tumor cell-derived VEGF-A promoted medulloblastoma cell migration and invasion through VEGFR2 signaling, and that both VEGF-A and VEGFR2 were required for the promoting effects of PERK activation on medulloblastoma cell migration and invasion. Thus, these findings suggest that moderate PERK activation promotes medulloblastoma cell migration and invasion through enhancement of VEGF-A/VEGFR2 signaling.

  9. Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

    Science.gov (United States)

    Yokoyama, Takanori; Takehara, Kazuhiro; Sugimoto, Nao; Kaneko, Keika; Fujimoto, Etsuko; Okazawa-Sakai, Mika; Okame, Shinichi; Shiroyama, Yuko; Yokoyama, Takashi; Teramoto, Norihiro; Ohsumi, Shozo; Saito, Shinya; Imai, Kazuho; Sugano, Kokichi

    2018-05-21

    Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

  10. Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line.

    Science.gov (United States)

    Meng, Ran; Zhou, Jin; Sui, Meng; Li, ZhiYong; Feng, GuoSheng; Yang, BaoFeng

    2010-01-01

    This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-As2O3)=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As(2)O(3) aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As(2)O(3) in APL treatment.

  11. Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.

    Science.gov (United States)

    Springuel, Lorraine; Losdyck, Elisabeth; Saussoy, Pascale; Turcq, Béatrice; Mahon, François-Xavier; Knoops, Laurent; Renauld, Jean-Christophe

    2016-12-01

    Genomic instability drives cancer progression by promoting genetic abnormalities that allow for the multi-step clonal selection of cells with growth advantages. We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect in mutation avoidance mechanisms. In the first part of this paper, we discovered that the gene encoding mutL homolog-1 (MLH1), a key component of the DNA mismatch repair system, is silenced by promoter methylation in TS1 cells. By means of stable ectopic expression and RNA interference methods, we showed that the high frequencies of growth factor-independent and inhibitor-resistant cells with activating JAK mutations can be attributed to the absence of MLH1 expression. In the second part of this paper, we confirm the clinical relevance of our findings by showing that chronic myeloid leukemia relapses upon ABL-targeted therapy correlated with a lower expression of MLH1 messenger RNA. Interestingly, the mutational profile observed in our TS1 model, characterized by a strong predominance of T:A>C:G transitions, was identical to the one described in the literature for primitive cells derived from chronic myeloid leukemia patients. Taken together, our observations demonstrate for the first time a causal relationship between MLH1-deficiency and incidence of oncogenic point mutations in tyrosine kinases driving cell transformation and acquired resistance to kinase-targeted cancer therapies.

  12. Loss of metal ions, disulfide reduction and mutations related to familial ALS promote formation of amyloid-like aggregates from superoxide dismutase.

    Directory of Open Access Journals (Sweden)

    Zeynep A Oztug Durer

    Full Text Available Mutations in the gene encoding Cu-Zn superoxide dismutase (SOD1 are one of the causes of familial amyotrophic lateral sclerosis (FALS. Fibrillar inclusions containing SOD1 and SOD1 inclusions that bind the amyloid-specific dye thioflavin S have been found in neurons of transgenic mice expressing mutant SOD1. Therefore, the formation of amyloid fibrils from human SOD1 was investigated. When agitated at acidic pH in the presence of low concentrations of guanidine or acetonitrile, metalated SOD1 formed fibrillar material which bound both thioflavin T and Congo red and had circular dichroism and infrared spectra characteristic of amyloid. While metalated SOD1 did not form amyloid-like aggregates at neutral pH, either removing metals from SOD1 with its intramolecular disulfide bond intact or reducing the intramolecular disulfide bond of metalated SOD1 was sufficient to promote formation of these aggregates. SOD1 formed amyloid-like aggregates both with and without intermolecular disulfide bonds, depending on the incubation conditions, and a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1 formed amyloid-like aggregates at neutral pH under reducing conditions. ALS mutations enhanced the ability of disulfide-reduced SOD1 to form amyloid-like aggregates, and apo-AS-SOD1 formed amyloid-like aggregates at pH 7 only when an ALS mutation was also present. These results indicate that some mutations related to ALS promote formation of amyloid-like aggregates by facilitating the loss of metals and/or by making the intramolecular disulfide bond more susceptible to reduction, thus allowing the conversion of SOD1 to a form that aggregates to form resembling amyloid. Furthermore, the occurrence of amyloid-like aggregates per se does not depend on forming intermolecular disulfide bonds, and multiple forms of such aggregates can be produced from SOD1.

  13. Comparative effects of ionizing radiation and two gaseous chemical mutagens on somatic mutation induction in one mutable and two non-mutable clones of Tradescantia

    International Nuclear Information System (INIS)

    Nauman, C.H.; Sparrow, A.H.; Schairer, L.A.

    1976-01-01

    The X-ray dose responses of mutable clone 0106 of Tradescantia (mutable for blue to pink), and its parent clone 02 have been determined for pink and colorless mutations in stamen hair cells, and are compared to the previously determined X-ray response for pink mutations of a third unrelated clone, clone 4430 (hybrid of T. subacaulis and T. hirsutiflora). X-ray response curves are compared to the response curves of the same three clones after exposure to the gaseous phase of the alkylating agent ethyl methanesulfate (EMS) and the fumigant and gasoline additive 1,2-dibromoethane (DBE). X-irradiation induces a pink mutation rate in mutable clone 0106 that is significantly higher than that of the nearly identical pink mutation rates in clones 02 and 4430. However, the colorless mutation rates of clones 02 and 0106 are not significantly different from one another. In clones 02 and 0106, pink mutations occur more frequently than colorless mutations at lower doses, but colorless dose-response curves saturate at higher doses than do those for pink mutations. Exposure-response curves for EMS and DBE have characteristics similar to those of X-ray response curves: exponential rise followed by an area of saturation. However, it was found that the relative sensitivities of the three clones to the gaseous mutagens and to ionizing radiation do not parallel one another. Where clones 02 and 4430 are equally sensitive to X-rays, at equal mutagen concentration clone 4430 is 6-7 times more sensitive to EMS and 7-9 times more sensitive to DBE than is clone 02. Mutable clone 0106 shows intermediate sensitivities to both EMS and DBE

  14. Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction.

    Science.gov (United States)

    Meephansan, Jitlada; Thummakriengkrai, J; Ponnikorn, S; Yingmema, W; Deenonpoe, R; Suchonwanit, P

    2017-11-01

    Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.

  15. Genetic and Epigenetic Tumor Suppressor Gene Silencing are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Non small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Marsit, C. J.; Kelsey, K. T.; Houseman, E. A.; Kelsey, K. T.; Houseman, E. A.; Nelson, H. H.

    2008-01-01

    Both genetic and epigenetic alterations characterize human non small cell lung cancer (NSCLC), but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hyper methylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hyper methylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hyper methylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hyper methylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

  16. Genetic and Epigenetic Tumor Suppressor Gene Silencing Are Distinct Molecular Phenotypes Driven by Growth Promoting Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Carmen J. Marsit

    2008-01-01

    Full Text Available Both genetic and epigenetic alterations characterize human nonsmall cell lung cancer (NSCLC, but the biological processes that create or select these alterations remain incompletely investigated. Our hypothesis posits that a roughly reciprocal relationship between the propensity for promoter hypermethylation and a propensity for genetic deletion leads to distinct molecular phenotypes of lung cancer. To test this hypothesis, we examined promoter hypermethylation of 17 tumor suppressor genes, as a marker of epigenetic alteration propensity, and deletion events at the 3p21 region, as a marker of genetic alteration. To model the complex biology between these somatic alterations, we utilized an item response theory model. We demonstrated that tumors exhibiting LOH at greater than 30% of informative alleles in the 3p21 region have a significantly reduced propensity for hypermethylation. At the same time, tumors with activating KRAS mutations showed a significantly increased propensity for hypermethylation of the loci examined, a result similar to what has been observed in colon cancer. These data suggest that NSCLCs have distinct epigenetic or genetic alteration phenotypes acting upon tumor suppressor genes and that mutation of oncogenic growth promoting genes, such as KRAS, is associated with the epigenetic phenotype.

  17. Extensive overproduction of the AdhE protein by rng mutations depends on mutations in the cra gene or in the Cra-box of the adhE promoter.

    Science.gov (United States)

    Kaga, Naoko; Umitsuki, Genryou; Clark, David P; Nagai, Kazuo; Wachi, Masaaki

    2002-07-05

    Escherichia coli RNase G encoded by the rng gene is involved in degradation of adhE mRNA. Overproduction of the AdhE protein by rng mutants was found to depend on the genetic background of strains derived from DC272 (adhC81) or MC1061. We found that DC272 carried a point mutation in the Cra-binding site of the adhE promoter. The Cra protein encoded by the cra gene is known to act as a repressor of adhE. P1-phage-mediated transduction and lacZ fusion analysis with the mutant adhE promoter confirmed that this mutation is responsible for overproduction. On the other hand, Southern hybridization revealed that MC1061 had a 0.85-kb deletion of the cra gene. Overproduction of AdhE in the MC1061 background was reversed to the wild-type levels by introduction of a plasmid carrying the cra(+) gene. These results indicated that expression of the adhE gene was regulated transcriptionally by Cra and posttranscriptionally by RNase G. (c) 2002 Elsevier Science (USA).

  18. Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

    Energy Technology Data Exchange (ETDEWEB)

    Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Cerretani, Daniela [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Di Paolo, Marco [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fiaschi, Anna Ida [Pharmacology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena (Italy); Frati, Paola [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy); Neri, Margherita [Department of Forensic Pathology, University of Foggia, Foggia (Italy); Pedretti, Monica [Department of Forensic Pathology, University of Pisa, Pisa (Italy); Fineschi, Vittorio, E-mail: vfinesc@tin.it [Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, University of Rome Sapienza, Viale Regina Elena 336, 00161 Rome (Italy)

    2014-10-01

    Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.

  19. An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers.

    Science.gov (United States)

    Tang, H M; Kuay, K T; Koh, P F; Asad, M; Tan, T Z; Chung, V Y; Lee, S C; Thiery, J P; Huang, Ry-J

    2016-01-01

    Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality.

  20. Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

    International Nuclear Information System (INIS)

    Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

    2014-01-01

    Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney

  1. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

    OpenAIRE

    In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A

    1997-01-01

    Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, delet...

  2. Core promoter mutations 3 years after anti-hepatitis B e seroconversion in patients with chronic hepatitis B or hepatitis B and C infection and cancer remission.

    Science.gov (United States)

    Zampino, Rosa; Marrone, Aldo; Karayiannis, Peter; Cirillo, Grazia; del Giudice, Emanuele Miraglia; Rania, Giovanni; Utili, Riccardo; Ruggiero, Giuseppe

    2002-09-01

    In this study, we aimed to evaluate the persistence of hepatitis B virus (HBV) DNA and the role of HBV core promoter and precore region mutations in 28 young cancer survivor patients with HBV or HBV and hepatitis C virus (HCV) infections, and persistently normal ALT levels, after spontaneous or interferon (IFN)-induced anti-hepatitis B e (HBe) seroconversion. Sera from 15 patients with HBV and 13 with dual HBV-HCV infection were analyzed for the presence of HBV-DNA and HCV-RNA by polymerase chain reaction 3 yr after anti-HBe seroconversion. A total of 21 patients had seroconverted spontaneously and seven did so after IFN treatment. The core promoter and the precore regions were amplified sequenced directly. Among patients with HBV infection, HBV-DNA was detected in five of nine (55%) with spontaneous anti-HBe and in all six treated patients (p = 0.092). In the coinfected patients, four had cleared both HBV-DNA and HCV-RNA, five were HBV-DNA negative/HCV-RNA positive and four had the reverse viral pattern. Among the 15 patients with persistence of HBV-DNA, a 7-base pair nucleotide deletion in the core promoter (1757-1763) was present in seven of 10 patients with spontaneous and in one of five patients with IFN-induced seroconversion (p = 0.033). The G1896A precore stop codon mutation was never observed. HBV-DNA levels were significantly lower in patients with the core promoter deletion (p = 0.011). The 7-base pair deletion generated a truncated X protein at amino-acid position 132. A core promoter deletion after anti-HBe seroconversion was associated with low HBV-DNA levels, probably because of downregulation of pregenomic RNA production and truncation of the X protein. HBV-DNA persistence was a frequent event, even in the absence of active liver disease.

  3. Dual roles of palladin protein in in vitro myogenesis: inhibition of early induction but promotion of myotube maturation.

    Directory of Open Access Journals (Sweden)

    Ngoc-Uyen-Nhi Nguyen

    Full Text Available Palladin is a microfilament-associated phosphoprotein whose function in skeletal muscle has rarely been studied. Therefore, we investigate whether myogenesis is influenced by the depletion of palladin expression known to interfere with the actin cytoskeleton dynamic required for skeletal muscle differentiation. The inhibition of palladin in C2C12 myoblasts leads to precocious myogenic differentiation with a concomitant reduction in cell apoptosis. This premature myogenesis is caused, in part, by an accelerated induction of p21, myogenin, and myosin heavy chain, suggesting that palladin acts as a negative regulator in early differentiation phases. Paradoxically, palladin-knockdown myoblasts are unable to differentiate terminally, despite their ability to perform some initial steps of differentiation. Cells with attenuated palladin expression form thinner myotubes with fewer myonuclei compared to those of the control. It is noteworthy that a negative regulator of myogenesis, myostatin, is activated in palladin-deficient myotubes, suggesting the palladin-mediated impairment of late-stage myogenesis. Additionally, overexpression of 140-kDa palladin inhibits myoblast differentiation while 200-kDa and 90-kDa palladin-overexpressed cells display an enhanced differentiation rate. Together, our data suggest that palladin might have both positive and negative roles in maintaining the proper skeletal myogenic differentiation in vitro.

  4. IGF-1 Gene Transfer to Human Synovial MSCs Promotes Their Chondrogenic Differentiation Potential without Induction of the Hypertrophic Phenotype

    Directory of Open Access Journals (Sweden)

    Yasutoshi Ikeda

    2017-01-01

    Full Text Available Mesenchymal stem cell- (MSC- based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1 to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.

  5. Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B

    DEFF Research Database (Denmark)

    Stofega, M R; Herrington, J; Billestrup, Nils

    2000-01-01

    phosphorylation. Consistent with the effects on STAT5B phosphorylation, tyrosine-to-phenylalanine mutation of tyrosine 595 prolongs the duration of tyrosyl phosphorylation of GHR and JAK2. These data suggest that tyrosine 595 is a major site of interaction of GHR with SHP-2, and that GHR-bound SHP-2 negatively......Binding of GH to GH receptor (GHR) rapidly and transiently activates multiple signal transduction pathways that contribute to the growth-promoting and metabolic effects of GH. While the events that initiate GH signal transduction, such as activation of the Janus tyrosine kinase JAK2, are beginning...

  6. HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

    Science.gov (United States)

    Gargan, Siobhan; Ahmed, Suaad; Mahony, Rebecca; Bannan, Ciaran; Napoletano, Silvia; O'Farrelly, Cliona; Borrow, Persephone; Bergin, Colm; Stevenson, Nigel J

    2018-04-01

    Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBΔVif), partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3 expression and IFN-α-induced ISG15 were reduced in PBMCs from HIV-infected patients, compared to healthy controls. Furthermore, IFN-α pre-treatment of a CEM T lymphoblast cells significantly inhibited HIV infection/replication (measured by cellular p24), only in the absence of Vif (IIIBΔVif), but was unable to suppress full length IIIB infection. When analysing the mechanism by which Vif might target the JAK/STAT pathway, we found Vif interacts with both STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin-SOCS-box binding motif enables the formation of an active E3 ligase complex, which we found to be required for Vif's degradation of STAT1 and STAT3. In fact, the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be

  7. PmrB Mutations Promote Polymyxin Resistance of Pseudomonas aeruginosa Isolated from Colistin-Treated Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Moskowitz, Samuel M; Brannon, Mark K; Dasgupta, Nandini

    2012-01-01

    Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of colistin (polymyxin E) resistance in laboratory strains and clinical isolates...

  8. Effects of a tumor promoter and an anti-promoter on spontaneous and UV-induced 6-thioguanine-resistant mutations and sister-chromatid exchanges in V79 Chinese hamster cells

    International Nuclear Information System (INIS)

    Fujiwara, Y.; Kano, Y.; Tatsumi, M.; Paul, P.

    1980-01-01

    The effects of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or an anti-promoter antipain (protease inhibitor) on spontaneous and ultraviolet-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6TGsup(r)) recessive mutations were examined in V79 Chinese hamster cells in culture. TPA and/or antipain neither significantly altered base-line and UV-induced immediate SCE frequencies, nor decreased the level of delayed SCEs which persisted 6-7 days after irradiation. TPA and/or antipain appeared to enhance the recovery of UV-induced 6TGsup(r) colonies at the plateau expression phase despite non-mutagenicity by themselves and unaltered metabolic cooperation. Thus, the results conceivably imply that the 6TGsup(r)-recessive mutation expression, but not fixation, can be modulated at the cell level by TPA and/or antipain. Our results, together with the recent results of Loveday and Latt, may argue against the notion that TPA enhances the antipain-suppressible SCEs as an index of mitotic recombination in relevance with a tumor-promotion mechanism. (orig.)

  9. Mutations of Profilin-1 Associated with Amyotrophic Lateral Sclerosis Promote Aggregation Due to Structural Changes of Its Native State.

    Science.gov (United States)

    Del Poggetto, Edoardo; Bemporad, Francesco; Tatini, Francesca; Chiti, Fabrizio

    2015-11-20

    The PFN1 gene, coding for profilin-1, has recently been associated with familial amyotrophic lateral sclerosis (fALS), as three mutations, namely C71G, M114T, and G118V, have been found in patients with familial forms of the disease and another, E117G, has been proposed to be a moderate risk factor for disease onset. In this work, we have purified the four profilin-1 variants along with the wild-type protein. The resulting aggregates appear to be fibrillar, to have a weak binding to ThT, and to possess a significant amount of intermolecular β-sheet structure. Using ThT fluorescence assays, far-UV circular dichroism, and dynamic light scattering, we found that all four variants have an aggregation propensity higher than that of the wild-type counterpart. In particular, the C71G mutation was found to induce the most dramatic change in aggregation, followed by the G118V and M114T substitutions and then the E117G mutation. Such a propensity was found not to strictly correlate with the conformational stability in this group of profilin-1 variants, determined using both urea-induced denaturation at equilibrium and folding/unfolding kinetics. However, it correlated with structural changes of the folded states, as monitored with far-UV circular dichroism, intrinsic fluorescence spectroscopy, ANS binding, acrylamide quenching, and dynamic light scattering. Overall, the results suggest that all four mutations increase the tendency of profilin-1 to aggregate and that such aggregation behavior is largely determined by the mutation-induced structural changes occurring in the folded state of the protein.

  10. Biological effects of dyes on bacteria. VI. Mutation induction by acridine orange and methylene blue in the dark with special reference to Escherichia coli WP6 (polA1)

    Energy Technology Data Exchange (ETDEWEB)

    Webb, R.B.; Hass, B.S.

    1984-01-01

    Acridine orange (AO) and methylene blue (MB) in the dark were shown to be weak to moderate mutagens (induction of resistance to T5 phage) in repair-deficient strains of Escherichia coli B/r. However, strain WP2, (wild-type) was not mutated by AO in the dark, in confirmation of earlier data. The presence of 2 ..mu..M AO reduced by 41% the spontaneous mutation rate in strain WP2, from 4.1 to 2.4 mutants/10/sup 8/ cells/generation. In the polymerase I-deficient strain WP6 (polA1), 2 ..mu..M AO increased the mutation rate in the dark 14-fold. It is proposed that both spontaneous and AO-induced mutagenesis in the absence of light occur at the site of semiconservative DNA replication. If the intercalation mechanism for the effects in the absence of light is valid, the wild-type strain (WP2) may be resistant to frameshift mutagenesis induced by intercalated compounds, while the polymerase I-deficient strain (WP6) may be highly susceptible to the presence of an intercalated dye such as AO at the DNA-replication fork. MB and AO likely act through different mechanisms since MB is only a moderate mutagen in strain WP6 and the other repair-deficient strains tested.

  11. A Threshold Exists in the Dose-response Relationship for Somatic Mutation Frequency Inducted by X-ray Irradiation of Drosophia

    International Nuclear Information System (INIS)

    Koana, T.; Takashima, Y.; Okada, M. O.; Ikehata, M.; Miyakoshi, J.; Sakai, K.

    2004-01-01

    The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds. The basic data for this model was obtained from mutational assays in the male germ cells of fruits fly Drosophila melanogaster. However, carcinogenic activity should be examined more appropriately in somatic cells than in germ cells. Here, the dose-response relationship of X- ray irradiation and somatic mutation is examined in Drosophila. A threshold at approximately 1Gy was observed in the DNA repair proficient flies. In the repair deficient siblings, the threshold was smaller and the inclination of the dose-response curve was much steeper. These results suggest that the dose-response relationship between X-ray irradiation and somatic mutation has a threshold, and that the DNA repair function contributes to its formation. (Author) 35 refs

  12. Mutation induction, evaluation and utilization for development of high yielding varieties in Indian mustard and sunflower: an overview of BARC work

    International Nuclear Information System (INIS)

    Jambhulkar, S.J.; Shitre, A.S.

    2009-01-01

    Mutation breeding programme in Indian mustard and sunflower at BARC has resulted into the development of wide spectrum of mutations for seed coat colour, chlorophyll, plant height, maturity, flower morphology, seed weight and oil content. In Indian mustard, TM1 and TM50 are high yielding yellow seed coat mutants, which were exploited in hybridisation to develop bold, yellow seed coat and high yielding genotypes. Light green leaf and variegated leaf are novel mutation in mustard. Putative mutants for drought tolerance have been isolated. Variability for zero erucic acid and zero glucosinolates genotypes have been developed in B. napus and B. juncea. In sunflower, high yielding black seed coat mutant were isolated. Extreme dwarf measuring only 11 cm is novel. Three high yielding varieties namely TM2, TM4, and TPM1 in mustard and one i.e.TAS82 in sunflower have been released for cultivation in collaboration with state agricultural universities. (author)

  13. Determinants of Plant Growth-promoting Ochrobactrum lupini KUDC1013 Involved in Induction of Systemic Resistance against Pectobacterium carotovorum subsp. carotovorum in Tobacco Leaves

    Directory of Open Access Journals (Sweden)

    Marilyn Sumayo

    2013-06-01

    Full Text Available The plant growth-promoting rhizobacterium Ochrobactrum lupini KUDC1013 elicited induced systemic resistance (ISR in tobacco against soft rot disease caused by Pectobacterium carotovorum subsp. carotovorum. We investigated of its factors involved in ISR elicitation. To characterize the ISR determinants, KUDC1013 cell suspension, heat-treated cells, supernatant from a culture medium, crude bacterial lipopolysaccharide (LPS and flagella were tested for their ISR activities. Both LPS and flagella from KUDC1013 were effective in ISR elicitation. Crude cell free supernatant elicited ISR and factors with the highest ISR activity were retained in the n-butanol fraction. Analysis of the ISR-active fraction revealed the metabolites, phenylacetic acid (PAA, 1-hexadecene and linoleic acid (LA, as elicitors of ISR. Treatment of tobacco with these compounds significantly decreased the soft rot disease symptoms. This is the first report on the ISR determinants by plant growth-promoting rhizobacteria (PGPR KUDC1013 and identifying PAA, 1-hexadecene and LA as ISR-related compounds. This study shows that KUDC1013 has a great potential as biological control agent because of its multiple factors involved in induction of systemic resistance against phytopathogens.

  14. Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

    Directory of Open Access Journals (Sweden)

    Jin Liu

    2018-03-01

    Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

  15. GCK-MODY diabetes as a protein misfolding disease: the mutation R275C promotes protein misfolding, self-association and cellular degradation.

    Science.gov (United States)

    Negahdar, Maria; Aukrust, Ingvild; Molnes, Janne; Solheim, Marie H; Johansson, Bente B; Sagen, Jørn V; Dahl-Jørgensen, Knut; Kulkarni, Rohit N; Søvik, Oddmund; Flatmark, Torgeir; Njølstad, Pål R; Bjørkhaug, Lise

    2014-01-25

    GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C>T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (kcat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Ultraviolet light induction of diphtheria toxin-resistant mutations in normal and DNA repair-deficient human and Chinese hamster fibroblasts

    International Nuclear Information System (INIS)

    Trosko, J.E.; Schultz, R.S.; Chang, C.C.; Glover, T.

    1980-01-01

    The role on unrepaired DNA lesions in the production of mutations is suspected of contributing to the initiation phase of carcinogenesis. Since the molecular basis of mutagenesis is not understood in eukaryotic cells, development of new genetic markers for quantitative in vitro measurement of mutations for mammalian cells is needed. Furthermore, mammalian cells, genetically deficient for various DNA repair enzymes, will be needed to study the role of unrepaired DNA lesions in mutagenesis. The results in this report relate to preliminary attempts to characterize the diphtheria toxin resistance marker as a useful quantitative genetic marker in human cells and to isolate and characterize various DNA repair-deficient Chinese hamster cells

  17. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

    Science.gov (United States)

    In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A; Rubin, P; Kemp, J; Israel, E; Busse, W; Ledford, D; Murray, J J; Segal, A; Tinkleman, D; Drazen, J M

    1997-03-01

    Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

  18. Y682 mutation of amyloid precursor protein promotes endo-lysosomal dysfunction by disrupting APP-SorLA interaction

    Directory of Open Access Journals (Sweden)

    Luca Rosario La Rosa

    2015-04-01

    Full Text Available The intracellular transport and localization of amyloid precursor protein (APP are critical determinants of APP processing and β-amyloid peptide production, thus crucially important for the pathophysiology of Alzheimer’s disease (AD. Notably, the C-terminal Y682ENPTY687 domain of APP binds to specific adaptors controlling APP trafficking and sorting in neurons. Mutation on the Y682 residue to glycine (Y682G leads to altered APP sorting in hippocampal neurons that favors its accumulation in intracellular compartments and the release of soluble APPα. Such alterations induce premature aging and learning and cognitive deficits in APP Y682G mutant mice (APPYG/YG. Here, we report that Y682G mutation affects formation of the APP complex with sortilin-related receptor (SorLA, resulting in endo-lysosomal dysfunctions and neuronal degeneration. Moreover, disruption of the APP/SorLA complex changes the trafficking pathway of SorLA, with its consequent increase in secretion outside neurons. Mutations in the SorLA gene are a prognostic factor in AD, and increases in SorLA levels in cerebrospinal fluid are predictive of AD in humans. These results might open new possibilities in comprehending the role played by SorLA in its interaction with APP and in the progression of neuronal degeneration. In addition, they further underline the crucial role played by Y682 residue in controlling APP trafficking in neurons.

  19. Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

    Science.gov (United States)

    Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

    2009-06-01

    It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

  20. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis.

    Science.gov (United States)

    Esteller, M; Toyota, M; Sanchez-Cespedes, M; Capella, G; Peinado, M A; Watkins, D N; Issa, J P; Sidransky, D; Baylin, S B; Herman, J G

    2000-05-01

    O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from the O6 position of guanine. O6-methylguanine mispairs with thymine during replication, and if the adduct is not removed, this results in conversion from a guanine-cytosine pair to an adenine-thymine pair. In vitro assays show that MGMT expression avoids G to A mutations and MGMT transgenic mice are protected against G to A transitions at ras genes. We have recently demonstrated that the MGMT gene is silenced by promoter methylation in many human tumors, including colorectal carcinomas. To study the relevance of defective MGMT function by aberrant methylation in relation to the presence of K-ras mutations, we studied 244 colorectal tumor samples for MGMT promoter hypermethylation and K-ras mutational status. Our results show a clear association between the inactivation of MGMT by promoter hypermethylation and the appearance of G to A mutations at K-ras: 71% (36 of 51) of the tumors displaying this particular type of mutation had abnormal MGMT methylation, whereas only 32% (12 of 37) of those with other K-ras mutations not involving G to A transitions and 35% (55 of 156) of the tumors without K-ras mutations demonstrated MGMT methylation (P = 0.002). In addition, MGMT loss associated with hypermethylation was observed in the small adenomas, including those that do not yet contain K-ras mutations. Hypermethylation of other genes such as p16INK4a and p14ARF was not associated with either MGMT hypermethylation or K-ras mutation. Our data suggest that epigenetic silencing of MGMT by promoter hypermethylation may lead to a particular genetic change in human cancer, specifically G to A transitions in the K-ras oncogene.

  1. Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis.

    Science.gov (United States)

    Esteller, M; Risques, R A; Toyota, M; Capella, G; Moreno, V; Peinado, M A; Baylin, S B; Herman, J G

    2001-06-15

    Defects in DNA repair may be responsible for the genesis of mutations in key genes in cancer cells. The tumor suppressor gene p53 is commonly mutated in human cancer by missense point mutations, most of them G:C to A:T transitions. A recognized cause for this type of change is spontaneous deamination of the methylcytosine. However, the persistence of a premutagenic O(6)-methylguanine can also be invoked. This last lesion is removed in the normal cell by the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). In many tumor types, epigenetic silencing of MGMT by promoter hypermethylation has been demonstrated and linked to the appearance of G to A mutations in the K-ras oncogene in colorectal tumors. To study the relevance of defective MGMT function by aberrant methylation in relation to the presence of p53 mutations, we studied 314 colorectal tumors for MGMT promoter hypermethylation and p53 mutational spectrum. Inactivation of MGMT by aberrant methylation was associated with the appearance of G:C to A:T transition mutations at p53 (Fischer's exact test, two-tailed; P = 0.01). Overall, MGMT methylated tumors displayed p53 transition mutations in 43 of 126 (34%) cases, whereas MGMT unmethylated tumors only showed G:C to A:T changes in 37 of 188 (19%) tumors. A more striking association was found in G:C to A:T transitions in non-CpG dinucleotides; 71% (12 of 17) of the total non-CpG transition mutations in p53 were observed in MGMT aberrantly methylated tumors (Fischer's exact test, two-tailed; P = 0.008). Our data suggest that epigenetic silencing of MGMT by promoter hypermethylation may lead to G:C to A:T transition mutations in p53.

  2. Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress.

    Science.gov (United States)

    Yang, Changwon; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

    2017-07-28

    Myricetin is a bioactive compound found in a variety of vegetables and fruits, and its anti-cancer effects are well known. In this study, we confirmed that myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3) and also promoted apoptosis and regulated cell cycle progression in a dose-dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In addition, we found that ROS production, lipid peroxidation, glutathione depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca 2+ release from the endoplasmic reticulum associated with modulation of ER stress in JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic antiproliferative effects with current chemotherapeutics, etoposide and cisplatin, on choriocarcinoma cells. Collectively, results of the present study provide strong evidence for the potential of myricetin to be an effective therapeutic for the prevention of human placental choriocarcinomas. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment.

    Science.gov (United States)

    Ségaliny, Aude I; Mohamadi, Amel; Dizier, Blandine; Lokajczyk, Anna; Brion, Régis; Lanel, Rachel; Amiaud, Jérôme; Charrier, Céline; Boisson-Vidal, Catherine; Heymann, Dominique

    2015-07-01

    Interleukin-34 (IL-34) was recently characterized as the M-CSF "twin" cytokine, regulating the proliferation/differentiation/survival of myeloid cells. The implication of M-CSF in oncology was initially suspected by the reduced metastatic dissemination in knock-out mice, due to angiogenesis impairment. Based on this observation, our work studied the involvement of IL-34 in the pathogenesis of osteosarcoma. The in vivo effects of IL-34 were assessed on tissue vasculature and macrophage infiltration in a murine preclinical model based on a paratibial inoculation of human osteosarcoma cells overexpressing or not IL-34 or M-CSF. In vitro investigations using endothelial cell precursors and mature HUVEC cells were performed to analyse the involvement of IL-34 in angiogenesis and myeloid cell adhesion. The data revealed that IL-34 overexpression was associated with the progression of osteosarcoma (tumor growth, lung metastases) and an increase of neo-angiogenesis. In vitro analyses demonstrated that IL-34 stimulated endothelial cell proliferation and vascular cord formation. Pre-treatment of endothelial cells by chondroitinases/heparinases reduced the formation of vascular tubes and abolished the associated cell signalling. In addition, IL-34 increased the in vivo recruitment of M2 tumor-associated macrophages into the tumor tissue. IL-34 increased in vitro monocyte/CD34(+) cell adhesion to activated HUVEC monolayers under physiological shear stress conditions. This work also demonstrates that IL-34 is expressed by osteosarcoma cells, is regulated by TNF-α, IL-1β, and contributes to osteosarcoma growth by increasing the neo-angiogenesis and the recruitment of M2 macrophages. By promoting new vessel formation and extravasation of immune cells, IL-34 may play a key role in tumor development and inflammatory diseases. © 2014 UICC.

  4. Induction of drought tolerance in cucumber plants by a consortium of three plant growth-promoting rhizobacterium strains.

    Directory of Open Access Journals (Sweden)

    Chun-Juan Wang

    Full Text Available Our previous work showed that a consortium of three plant growth-promoting rhizobacterium (PGPR strains (Bacillus cereus AR156, Bacillus subtilis SM21, and Serratia sp. XY21, termed as BBS for short, was a promising biocontrol agent. The present study investigated its effect on drought tolerance in cucumber plants. After withholding watering for 13 days, BBS-treated cucumber plants had much darker green leaves and substantially lighter wilt symptoms than control plants. Compared to the control, the BBS treatment decreased the leaf monodehydroascorbate (MDA content and relative electrical conductivity by 40% and 15%, respectively; increased the leaf proline content and the root recovery intension by 3.45-fold and 50%, respectively; and also maintained the leaf chlorophyll content in cucumber plants under drought stress. Besides, in relation to the control, the BBS treatment significantly enhanced the superoxide dismutase (SOD activity and mitigated the drought-triggered down-regulation of the expression of the genes cAPX, rbcL, and rbcS encoding cytosolic ascorbate peroxidase, and ribulose-1,5-bisphosphate carboxy/oxygenase (Rubisco large and small subunits, respectively, in cucumber leaves. However, 1-aminocyclopropane-1-carboxylate (ACC deaminase activity was undetected in none of the culture solutions of three BBS constituent strains. These results indicated that BBS conferred induced systemic tolerance to drought stress in cucumber plants, by protecting plant cells, maintaining photosynthetic efficiency and root vigor and increasing some of antioxidase activities, without involving the action of ACC deaminase to lower plant ethylene levels.

  5. Better plants through mutations

    International Nuclear Information System (INIS)

    1988-01-01

    This is a public relations film describing problems associated with the genetic improvement of crop plants through induced mutations. Mutations are the ultimate source of genetic variation in plants. Mutation induction is now established as a practical tool in plant breeding. The Joint FAO/IAEA Division and the IAEA's laboratory at Seibersdorf have supported research and practical implementation of mutation breeding of both seed propagated and vegetatively propagated plants. Plant biotechnology based on in vitro culture and recombinant DNA technology will make a further significant contribution to plant breeding

  6. Positive signature-tagged mutagenesis in Pseudomonas aeruginosa: tracking patho-adaptive mutations promoting airways chronic infection.

    Directory of Open Access Journals (Sweden)

    Irene Bianconi

    2011-02-01

    Full Text Available The opportunistic pathogen Pseudomonas aeruginosa can establish life-long chronic infections in the airways of cystic fibrosis (CF patients. Persistent lifestyle is established with P. aeruginosa patho-adaptive variants, which are clonal with the initially-acquired strains. Several reports indicated that P. aeruginosa adapts by loss-of-function mutations which enhance fitness in CF airways and sustain its clonal expansion during chronic infection. To validate this model of P. aeruginosa adaptation to CF airways and to identify novel genes involved in this microevolution, we designed a novel approach of positive-selection screening by PCR-based signature-tagged mutagenesis (Pos-STM in a murine model of chronic airways infection. A systematic positive-selection scheme using sequential rounds of in vivo screenings for bacterial maintenance, as opposed to elimination, generated a list of genes whose inactivation increased the colonization and persistence in chronic airways infection. The phenotypes associated to these Pos-STM mutations reflect alterations in diverse aspects of P. aeruginosa biology which include lack of swimming and twitching motility, lack of production of the virulence factors such as pyocyanin, biofilm formation, and metabolic functions. In addition, Pos-STM mutants showed altered invasion and stimulation of immune response when tested in human respiratory epithelial cells, indicating that P. aeruginosa is prone to revise the interaction with its host during persistent lifestyle. Finally, sequence analysis of Pos-STM genes in longitudinally P. aeruginosa isolates from CF patients identified signs of patho-adaptive mutations within the genome. This novel Pos-STM approach identified bacterial functions that can have important clinical implications for the persistent lifestyle and disease progression of the airway chronic infection.

  7. Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia.

    Science.gov (United States)

    Khan, Anis; Al Balwi, Mohammed A; Tanaka, Yasuhito; Hajeer, Ali; Sanai, Faisal M; Al Abdulkarim, Ibrahim; Al Ayyar, Latifah; Badri, Motasim; Saudi, Dib; Tamimi, Waleed; Mizokami, Masashi; Al Knawy, Bandar

    2013-12-15

    In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non-HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme-linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non-HCC and 45 HCC patients infected with HBV/D, followed by age-matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti-HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non-HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age- and gender-adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8-118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3-17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3-84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high-risk patients and improving diagnostic and treatment strategies for HBV/D1. Copyright © 2013 UICC.

  8. The influence of continuous γ-irradiation at decreasing dose-rate on the survival rote and induction of gene mutations in cultured Chinese hamster cells

    International Nuclear Information System (INIS)

    Feoktistova, T.P.; Elisova, E.V.; Stavrakova, N.M.

    1991-01-01

    Continuous γ-irradiation at decreasing dose-rate was shown to be less effective than acute exposure with regard to the lethal effect and frequency of mutations of resistance to 6-thioguanine in cultured Chinese hamster cells. The cell population subjected to continuons irradiation was d more radioresistant than the intact one. Lethal and genetic effects of continuous irradiation at decreasing dose-rate were mainly determined by the contribution of the radiation dose received during the first 24 h of exposure

  9. Comparative studies of the induction of somatic eye-color mutations in an unstable strain of Drosophila melanogaster by MMS and X-rays at different developmental stages

    International Nuclear Information System (INIS)

    Rasmuson, Aa.

    1985-01-01

    The UZ system in Drosophila melanogaster can be used as a screening system for mutagens. This survey is an attempt to correlate the size of the mutated area of the eyes with the age of the larvae at mutagen treatment. X-rays and MMS were used to give an indication of the mechanism of the instability, according to the different kinds of DNA damage induced. The results show that the mean size of red spots decreased with increasing age of larvae at treatment, while the mutation frequencies were increased because of the multiplication of the cells in the eye anlage susceptible to the mutagens. Red spots induced with MMS are smaller in size than X-ray-induced red spots, indicating a delay in the establishment of mutations from chemically-induced lesions compared to irradiation damage. White spots on the other hand were equally large in size, irrespective of inducing agent and about twice the size of the chemically-induced red spots, implying a faster and more direct action for fixation of deletions than for the production of MMS induced shifts in eye color from zeste to red. (Auth.)

  10. Influence of anoxia on the induction of mutations by phenylalanine radicals during gamma-irradiation of plasmid DNA in aqueous solution.

    Science.gov (United States)

    Kuipers, Gitta K; Slotman, Ben J; Reitsma-Wijker, Carola A; van Andel, Rob J; Poldervaart, Hester A; Lafleur, M Vincent M

    2004-12-21

    When DNA is irradiated in aqueous solution, most of the damage is inflicted by water-derived radicals. This is called the indirect effect of ionizing radiation. However in whole cells not only the primary formed water radicals play a role, because some cellular compounds form secondary radicals which can also damage DNA. It is known that the amino acid phenylalanine is able to react with water radicals, resulting in the production of secondary phenylalanine radicals which can damage and inactivate DNA. In a previous study the influence of the presence of phenylalanine during gamma-irradiation of DNA in aqueous solution under oxic conditions was studied. Under anoxic irradiation conditions different amounts and types of reactive water-derived radicals are formed compared to oxic conditions and also different phenylalanine radicals are formed. Therefore, this study examines the influence of the presence of phenylalanine under anoxic conditions on the gamma-radiation-induced mutation spectrum. The results indicate that phenylalanine radicals are damaging to DNA, but less effective compared to primary water radicals. On the mutational level, in the presence of phenylalanine radicals under anoxic conditions, the amount of mutations on G:C base pairs was significantly decreased as compared to oxic conditions. Furthermore, the results of this study indicate that nucleotide excision repair is involved in repair of both inactivating and mutagenic damage induced by phenylalanine radicals under anoxic conditions.

  11. Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene plus okadaic acid class tumor promoters.

    Science.gov (United States)

    Fujiki, H; Suganuma, M; Yoshizawa, S; Kanazawa, H; Sugimura, T; Manam, S; Kahn, S M; Jiang, W; Hoshina, S; Weinstein, I B

    1989-01-01

    Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation at the second nucleotide of codon 61 (CAA----CTA) in the c-Ha-ras gene, determined by the polymerase chain reaction procedure and DNA sequencing. Three potent 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, TPA, teleocidin, and aplysiatoxin, showed the same effects. These results provide strong evidence that this mutation in the c-Ha-ras gene is due to a direct effect of DMBA rather than a selective effect of specific tumor promoters.

  12. Induction of host defences by Rhizobium during ineffective nodulation of pea (Pisum sativum L.) carrying symbiotically defective mutations sym40 (PsEFD), sym33 (PsIPD3/PsCYCLOPS) and sym42.

    Science.gov (United States)

    Ivanova, Kira A; Tsyganova, Anna V; Brewin, Nicholas J; Tikhonovich, Igor A; Tsyganov, Viktor E

    2015-11-01

    Rhizobia are able to establish a beneficial interaction with legumes by forming a new organ, called the symbiotic root nodule, which is a unique ecological niche for rhizobial nitrogen fixation. Rhizobial infection has many similarities with pathogenic infection and induction of defence responses accompanies both interactions, but defence responses are induced to a lesser extent during rhizobial infection. However, strong defence responses may result from incompatible interactions between legumes and rhizobia due to a mutation in either macro- or microsymbiont. The aim of this research was to analyse different plant defence reactions in response to Rhizobium infection for several pea (Pisum sativum) mutants that result in ineffective symbiosis. Pea mutants were examined by histochemical and immunocytochemical analyses, light, fluorescence and transmission electron microscopy and quantitative real-time PCR gene expression analysis. It was observed that mutations in pea symbiotic genes sym33 (PsIPD3/PsCYCLOPS encoding a transcriptional factor) and sym40 (PsEFD encoding a putative negative regulator of the cytokinin response) led to suberin depositions in ineffective nodules, and in the sym42 there were callose depositions in infection thread (IT) and host cell walls. The increase in deposition of unesterified pectin in IT walls was observed for mutants in the sym33 and sym42; for mutant in the sym42, unesterified pectin was also found around degrading bacteroids. In mutants in the genes sym33 and sym40, an increase in the expression level of a gene encoding peroxidase was observed. In the genes sym40 and sym42, an increase in the expression levels of genes encoding a marker of hypersensitive reaction and PR10 protein was demonstrated. Thus, a range of plant defence responses like suberisation, callose and unesterified pectin deposition as well as activation of defence genes can be triggered by different pea single mutations that cause perception of an otherwise

  13. Radiation induced mutations for plant selection

    International Nuclear Information System (INIS)

    Brunner, H.

    1994-01-01

    The successful use of plant breeding for improving crops requires the existence of genetic variation of useful traits. Unfortunately, the desired variation is often lacking. However, radiation can be used to induce mutations and thereby generate genetic variation from which desired mutants may be selected. Mutation induction has become a proven way of creating variation within a crop variety. It offers the possibility of inducing desired attributes that either cannot be expressed in nature or have been lost during evolution. More than 1700 mutant cultivars of crop plants with significantly improved attributes such as increased yield, improved quality, disease and stress resistance, have been released worldwide in the last thirty years. The Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has contributed to these achievements through the promotion of research and development in mutation breeding techniques using nuclear and related biotechnological methods and the provision of in plant breeding is then transferred to Member States of the IAEA and the FAO through training in mutation breeding methods and the provision of technical advice. Moreover, radiation treatment services are provided to foster applications of nuclear techniques in crop improvement programmes of member states and more specifically to render direct support to plant breeders by efficient generation of mutations. Plant materials are standardized prior to radiation exposure to warrant reproducibility of the induced effects within practical limits and a radiosensitivity test is implemented to affirm useful doses for applied objectives of a request. This review deals with irradiation methods applied at the IAEA laboratories for the efficient induction of mutations in seeds, vegetative propagules and tissue and cell cultures and the establishment of genetically variable populations upon which selection of desired traits can be based. 3 tabs., 18 refs. (author)

  14. Induction and identification of somatic mutations with particular reference to perennial plants. Part of a coordinated programme on improvement of vegetatively propagated crops and tree crops through radiation-induced mutations

    International Nuclear Information System (INIS)

    Zubrzycki, H.M.

    1980-06-01

    An attempt was made to obtain resistance of oranges (Citrus sinensis L. Osbeck) and grapefruit (C. paradisi Macf.) to Tristeza virus by induced mutation breeding. Two methods were used. In one, buds were treated with X or gamma radiation. The detached sprouts were subsequently grafted. In the other, a number of chemical mutagens were used: diethyl sulfate or propylenoxide on buds; diethyl sulfate or nitrosemethylurethane on seeds (2400). The selection and isolation of mutants from treated buds and seeds, respectively, are described. Intermediate results only are given and discussed

  15. Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation. Detection by LOH analysis

    International Nuclear Information System (INIS)

    Umebayashi, Yukihiro; Iwaki, Masaya; Yatagai, Fumio; Honma, Masamitsu; Suzuki, Masao; Suzuki, Hiromi; Shimazu, Toru; Ishioka, Noriaki

    2007-01-01

    To study the genetic effects of low-doses and low-dose-rate ionizing radiation (IR), human lymphoblastoid TK6 cells were exposed to 30 mGy of γ-rays at a dose-rate of 1.2 mGy/hr. The frequency of early mutations (EMs) in the thymidine kinase (TK) gene locus was determined to be 1.7 x 10 -6 , or 1.9-fold higher than the level seen in unirradiated controls. These mutations were analyzed with a loss of heterozygosity (LOH) detection system, a methodology which has been shown to be sensitive to the effects of radiation. Among the 15 EMs observed after IR exposure, 8 were small interstitial-deletion events restricted to the TK gene locus. However, this specific type of event was not found in unirradiated controls. Although these results were observed under the limited conditions, they strongly suggest that the LOH detection system can be used for estimating the genetic effects of a low-dose IR exposure delivered at a low-dose-rate. (author)

  16. Mutations that promote furin-independent growth of Semliki Forest virus affect p62-E1 interactions and membrane fusion

    International Nuclear Information System (INIS)

    Zhang Xinyong; Kielian, Margaret

    2004-01-01

    The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1's fusion activity is regulated by its heterodimeric interaction with a companion membrane protein E2. Mature E2 protein is generated by furin processing of the precursor p62. Processing destabilizes the heterodimer, allowing dissociation at acidic pH, E1 conformational changes, and membrane fusion. We used a furin-deficient cell line, FD11, to select for SFV mutants that show increased growth in the absence of p62 processing. We isolated and characterized 7 such pci mutants (p62 cleavage independent), which retained the parental furin cleavage site but showed significant increases in their ability to carry out membrane fusion in the p62 form. Sequence analysis of the pci mutants identified mutations primarily on the E2 protein, and suggested sites important in the interaction of p62 with E1 and the regulation of fusion

  17. Mutation breeding in peas

    Energy Technology Data Exchange (ETDEWEB)

    Jaranowski, J [Institute of Genetics and Plant Breeding, Academy of Agriculture, Poznan (Poland); Micke, A [Joint FAO/IAEA Division of Isotope and Radiation Applications of Atomic Energy for Food and Agricultural Development, International Atomic Energy Agency, Vienna (Austria)

    1985-02-01

    The pea as an ancient crop plant still today has wide uses and is an import source of food protein. It is also an important object for genetic studies and as such has been widely used in mutation induction experiments. However, in comparison with cereals this ancient crop plant (like several other grain legumes) has gained relatively little from advances in breeding. The review focuses on the prospects of genetic improvement of pea by induced mutations, discusses principles and gives methodological information. (author)

  18. Mutation breeding in peas

    International Nuclear Information System (INIS)

    Jaranowski, J.; Micke, A.

    1985-01-01

    The pea as an ancient crop plant still today has wide uses and is an import source of food protein. It is also an important object for genetic studies and as such has been widely used in mutation induction experiments. However, in comparison with cereals this ancient crop plant (like several other grain legumes) has gained relatively little from advances in breeding. The review focuses on the prospects of genetic improvement of pea by induced mutations, discusses principles and gives methodological information. (author)

  19. A Specific Mutation in the Promoter Region of the Silent cel Cluster Accounts for the Appearance of Lactose-Utilizing Lactococcus lactis MG1363

    Science.gov (United States)

    Solopova, Ana; Bachmann, Herwig; Teusink, Bas; Kok, Jan; Neves, Ana Rute

    2012-01-01

    The Lactococcus lactis laboratory strain MG1363 has been described to be unable to utilize lactose. However, in a rich medium supplemented with lactose as the sole carbon source, it starts to grow after prolonged incubation periods. Transcriptome analyses showed that L. lactis MG1363 Lac+ cells expressed celB, encoding a putative cellobiose-specific phosphotransferase system (PTS) IIC component, which is normally silent in MG1363 Lac− cells. Nucleotide sequence analysis of the cel cluster of a Lac+ isolate revealed a change from one of the guanines to adenine in the promoter region. We showed here that one particular mutation, taking place at increased frequency, accounts for the lactose-utilizing phenotype occurring in MG1363 cultures. The G-to-A transition creates a −10 element at an optimal distance from the −35 element. Thus, a fully active promoter is created, allowing transcription of the otherwise cryptic cluster. Nuclear magnetic resonance (NMR) spectroscopy results show that MG1363 Lac+ uses a novel pathway of lactose utilization. PMID:22660716

  20. Progressive adult primary glioblastoma in the medulla oblongata with an unmethylated MGMT promoter and without an IDH mutation.

    Science.gov (United States)

    Yoshikawa, Akifumi; Nakada, Mitsutoshi; Watanabe, Takuya; Hayashi, Yutaka; Sabit, Hemragul; Kato, Yukinari; Suzuki, Shioto; Ooi, Akishi; Sato, Hiroshi; Hamada, Jun-ichiro

    2013-07-01

    A 63-year-old woman presented with dizziness followed by gait disturbance and loss of appetite. Magnetic resonance image (MRI) showed that a lesion located in the medulla oblongata, appearing as hyperintense on T2-weighted image and with slight enhancement area, appeared in the ventral aspect of the mass on T1-weighted MR imaging with gadolinium. It was diagnosed as high-grade brain-stem glioma and the patient underwent chemoradiotherapy. However, she died 18 days after treatment, and autopsy was performed. The pathological diagnosis was glioblastoma (GBM) with unmethylated O-6-methylguanine-DNA methyltransferase promoter and wild isocitrate dehydrogenase 1 gene. We report an extremely short clinical course of adult GBM in medulla oblongata with genetic analysis and present a review of the literature.

  1. Labor Induction

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ154 LABOR, DELIVERY, AND POSTPARTUM CARE Labor Induction • What is labor induction? • Why is labor induced? • What is the Bishop score? • What is “ripening ...

  2. Induction of somaclonal variation and mutations in sugarcane calli for selecting mutants with resistance to red-rot and tolerance to water-logged conditions

    International Nuclear Information System (INIS)

    Shaikh, M.A.Q.; Begum, S.; Samad, M.A.; Shmsuzzaman, K.M.

    1997-01-01

    Immature leaves of cv. 'Isd-16' of sugarcane were cultured on modified MS medium supplemented with 3.0 mg/l 2,4-D for callus induction. The calli were transferred to MS medium supplemented with 5.0 mg/l IAA and 2.0 mg/l KIN for shoot regeneration. The shoots were rooted on MS medium supplemented with 5.0 mg/1NAA and 70 g/l sucrose. The regenerated plants were screened against red-rot disease and water-logged condition in a field. Of the 368 plants inoculated with red-rot pathogen, only one was moderately resistant and two were moderately susceptible. In another set of 500 R 1 plants, six clones were tolerant to water-logged condition. Four week-old callus cultures were irradiated with doses of 2, 3, 4, 5, 6, 7, 8 and 10 Gy gamma-rays. Survival of calli decreased with increase in radiation dose and ranged from 58 to 91%. Regenerated shoots were obtained from all irradiated calli except those treated with 8 and 10 Gy. Shoot regeneration from the irradiated calli ranged from 8 to 50%, and gave 768 R 1 plants. The highest regeneration of plants was obtained from calli treated with 3 Gy. These plants are being grown in a field for screening against red-rot and water-logged conditions. (author). 10 refs, 2 tabs

  3. Induction of somaclonal variation and mutations in sugarcane calli for selecting mutants with resistance to red-rot and tolerance to water-logged conditions

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, M A.Q.; Begum, S; Samad, M A; Shmsuzzaman, K M [Bangladesh Inst. of Nuclear Agriculture, Mymensingh (Bangladesh)

    1997-07-01

    Immature leaves of cv. `Isd-16` of sugarcane were cultured on modified MS medium supplemented with 3.0 mg/l 2,4-D for callus induction. The calli were transferred to MS medium supplemented with 5.0 mg/l IAA and 2.0 mg/l KIN for shoot regeneration. The shoots were rooted on MS medium supplemented with 5.0 mg/1NAA and 70 g/l sucrose. The regenerated plants were screened against red-rot disease and water-logged condition in a field. Of the 368 plants inoculated with red-rot pathogen, only one was moderately resistant and two were moderately susceptible. In another set of 500 R{sub 1} plants, six clones were tolerant to water-logged condition. Four week-old callus cultures were irradiated with doses of 2, 3, 4, 5, 6, 7, 8 and 10 Gy gamma-rays. Survival of calli decreased with increase in radiation dose and ranged from 58 to 91%. Regenerated shoots were obtained from all irradiated calli except those treated with 8 and 10 Gy. Shoot regeneration from the irradiated calli ranged from 8 to 50%, and gave 768 R{sub 1} plants. The highest regeneration of plants was obtained from calli treated with 3 Gy. These plants are being grown in a field for screening against red-rot and water-logged conditions. (author). 10 refs, 2 tabs.

  4. Early evaluation and on field conditions of resistance to Mycosphaerella fijiensis Morelet of plants from Grande naine (AAA cultivar, obtained through out tissue culture and mutations induction

    Directory of Open Access Journals (Sweden)

    Lourdes R. García

    2003-04-01

    Full Text Available The present work was carried out in the Plants Biotechnology Institute of the Central University of Las Villas. The plant material from the cv. Grande Naine (AAA was treated with physical mutagenic agents(gamma radiation 60Co source to induce genetic variability. The behaviour of the population to the black Sigatoka was evaluated. A somaclone was selected by its disease resistance and was in vitro multiplied and the plants were acclimatized to evaluate its behaviour facing the disease on greenhouse conditions and in a second cycle of multiplication in the field. The results showed that in the majority of the plants were not found differences respect cv Grande Naine, just one presented similar reaction to cv. ‘FHIA 18’ (AAAB (partially resistant as for the variable evaluated, being obtained a frequency of 0.018% for this character. This plant was named IBP 446. After 60 days of application of the mycelial homogenized of M. fijiensis in micropropagated plants of this somaclone, differences in the respect affectation states were found at susceptible witness in greenhouse conditions. When plants of the IBP 446 were evaluated in a second cycle of multiplication differences were found with the susceptible control only at flowering, while they behaved similar at susceptible control in the crop. Key words: early detection, breeding, mutation, Black Sigatoka

  5. Induction linacs

    International Nuclear Information System (INIS)

    Keefe, D.

    1986-07-01

    The principle of linear induction acceleration is described, and examples are given of practical configurations for induction linacs. These examples include the Advanced Technology Accelerator, Long Pulse Induction Linac, Radial Line Accelerator (RADLAC), and Magnetically-Insulated Electron-Focussed Ion Linac. A related concept, the auto accelerator, is described in which the high-current electron-beam technology in the sub-10 MeV region is exploited to produce electron beams at energies perhaps as high as the 100 to 1000 MeV range. Induction linacs for ions are also discussed. The efficiency of induction linear acceleration is analyzed

  6. A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes

    DEFF Research Database (Denmark)

    Ek, Jakob; Hansen, Sara P; Lajer, Maria

    2006-01-01

    Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp...... of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4......,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total...

  7. Mutation Induction In White Oyster Mushroom (Pleurotus Ostreatus) Using GAMMA Irradiation And Analyzing Genetic Diversity Of Induced Mutants By RAPD.PCR

    International Nuclear Information System (INIS)

    Mohammed, H.M; Soliman, S.S.A; Shawky, A.S.H; Mahgoub, E.M.I

    2013-01-01

    The present study aimed to understand the effect of gamma rays on three strains of white oyster mushroom Pleurotus ostreatus and induction of new benefit mutants. Five different doses, i.e., 0.25,0.5,0.75, and 1.00 KGy of gamma rays were used. Twelve morphological criteria were measured. The result confirmed the existence of different response of three strains to different doses of radiation. The 21 strain as a control, the first flush was misshapen, but the second flush gave normal fruit, while mutant Po 21-3 gave excellent growth performance for the shape, colour, fruit diameter and stem length, while slightly decrease in wet and dry total matter per bag and flushes numbers were found.The po 21-2 mutant considered as important mutant because slightly increased in wet and dry total matter than the control, and had short stem length. This mutant Po 21 -2 gave spores, while the control was sporeless. Control of strain 22 possessed good performance for fruit characterization but it forms fruits less than its primordial it formed (semi maturation less strain) per bag, While po 22-l and Po 22-2 appeared good performance, in addition high yielding as wet and dry total matter and faster flushing. The control of strain 66 had a good growth performance, and the four mutants for this strain is very good too they had excellent growth performance; Po 66-1 and Po 66-3 mutants had significant and highly significant values for wet matter than the control (21.04, 21.64 and 12.27) for (Po 66-1, Po 66-4, control). As well as more important criteria there were taken as short fruit stem length and fruit number/bag. These results confirmed the important of Po 66-4 followed by po 66-1 in next breeding and production programs for white oyster mushroom (Pleurotus ostreatus).the RAPD PCR results showed the oligonucleotide OPB-10, OPA-05 and OPC-02 presented the highest percentage of RAPD polymorphism (80⁒, 80⁒, 66.6⁒). The pattern obtained with OPB-10 oligonucleotide for strains

  8. Haploid rice plants in mutation studies

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, S [Institute of Radiation Breeding, Ministry of Agriculture and Forestry, Ohmiya, Ibaraki-ken (Japan)

    1970-03-01

    Studies were made on chlorophyll-deficient sectors and diploid-like sectors in haploid rice plants exposed to chronic gamma irradiation, and on germinal mutations in diploid strains derived from the haploid plants. The induction and elimination of somatic mutations in haploid plants and the occurrence of drastic germinal mutations in diploid strains from haploid plants are discussed. (author)

  9. Inductive reasoning.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan; Swendsen, Haruka

    2010-03-01

    Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category-based induction as well as theoretical models of these results, including similarity-based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity-based phenomena but not knowledge-based phenomena. Recent models that aim to account for both similarity-based and knowledge-based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well-established and emerging lines of induction research is the need to develop well-articulated and empirically testable formal models of induction. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

  10. A point mutation in the DNA-binding domain of HPV-2 E2 protein increases its DNA-binding capacity and reverses its transcriptional regulatory activity on the viral early promoter

    Directory of Open Access Journals (Sweden)

    Gao Chen

    2012-02-01

    Full Text Available Abstract Background The human papillomavirus (HPV E2 protein is a multifunctional DNA-binding protein. The transcriptional activity of HPV E2 is mediated by binding to its specific binding sites in the upstream regulatory region of the HPV genomes. Previously we reported a HPV-2 variant from a verrucae vulgaris patient with huge extensive clustered cutaneous, which have five point mutations in its E2 ORF, L118S, S235P, Y287H, S293R and A338V. Under the control of HPV-2 LCR, co-expression of the mutated HPV E2 induced an increased activity on the viral early promoter. In the present study, a series of mammalian expression plasmids encoding E2 proteins with one to five amino acid (aa substitutions for these mutations were constructed and transfected into HeLa, C33A and SiHa cells. Results CAT expression assays indicated that the enhanced promoter activity was due to the co-expressions of the E2 constructs containing A338V mutation within the DNA-binding domain. Western blots analysis demonstrated that the transiently transfected E2 expressing plasmids, regardless of prototype or the A338V mutant, were continuously expressed in the cells. To study the effect of E2 mutations on its DNA-binding activity, a serial of recombinant E2 proteins with various lengths were expressed and purified. Electrophoresis mobility shift assays (EMSA showed that the binding affinity of E2 protein with A338V mutation to both an artificial probe with two E2 binding sites or HPV-2 and HPV-16 promoter-proximal LCR sequences were significantly stronger than that of the HPV-2 prototype E2. Furthermore, co-expression of the construct containing A338V mutant exhibited increased activities on heterologous HPV-16 early promoter P97 than that of prototype E2. Conclusions These results suggest that the mutation from Ala to Val at aa 338 is critical for E2 DNA-binding and its transcriptional regulation.

  11. Teacher induction

    NARCIS (Netherlands)

    Beijaard, D.; Buitink, J.; Kessels, C.; Peterson, P.; Baker, E.; McGraw, B.

    2010-01-01

    Teacher induction programs are intended to support the professional development of beginning teachers and thereby contribute to the reduction of teacher attrition during the early teaching years. Teacher induction programs are often based upon a deficit model with a focus on the better organization

  12. Conditional induction of Math1 specifies embryonic stem cells to cerebellar granule neuron lineage and promotes differentiation into mature granule neurons.

    Science.gov (United States)

    Srivastava, Rupali; Kumar, Manoj; Peineau, Stéphane; Csaba, Zsolt; Mani, Shyamala; Gressens, Pierre; El Ghouzzi, Vincent

    2013-04-01

    Directing differentiation of embryonic stem cells (ESCs) to specific neuronal subtype is critical for modeling disease pathology in vitro. An attractive means of action would be to combine regulatory differentiation factors and extrinsic inductive signals added to the culture medium. In this study, we have generated mature cerebellar granule neurons by combining a temporally controlled transient expression of Math1, a master gene in granule neuron differentiation, with inductive extrinsic factors involved in cerebellar development. Using a Tetracyclin-On transactivation system, we overexpressed Math1 at various stages of ESCs differentiation and found that the yield of progenitors was considerably increased when Math1 was induced during embryonic body stage. Math1 triggered expression of Mbh1 and Mbh2, two target genes directly involved in granule neuron precursor formation and strong expression of early cerebellar territory markers En1 and NeuroD1. Three weeks after induction, we observed a decrease in the number of glial cells and an increase in that of neurons albeit still immature. Combining Math1 induction with extrinsic factors specifically increased the number of neurons that expressed Pde1c, Zic1, and GABAα6R characteristic of mature granule neurons, formed "T-shaped" axons typical of granule neurons, and generated synaptic contacts and action potentials in vitro. Finally, in vivo implantation of Math1-induced progenitors into young adult mice resulted in cell migration and settling of newly generated neurons in the cerebellum. These results show that conditional induction of Math1 drives ESCs toward the cerebellar fate and indicate that acting on both intrinsic and extrinsic factors is a powerful means to modulate ESCs differentiation and maturation into a specific neuronal lineage. Copyright © 2012 AlphaMed Press.

  13. Erythroid Kruppel-like factor (EKLF) is recruited to the γ-globin gene promoter as a co-activator and is required for γ-globin gene induction by short-chain fatty acid derivatives

    Science.gov (United States)

    Perrine, Susan P.; Mankidy, Rishikesh; Boosalis, Michael S.; Bieker, James J.; Faller, Douglas V.

    2011-01-01

    Objectives The erythroid Kruppel-like factor (EKLF) is an essential transcription factor for β-type globin gene switching, and specifically activates transcription of the adult β-globin gene promoter. We sought to determine if EKLF is also required for activation of the γ-globin gene by short-chain fatty acid (SCFA) derivatives, which are now entering clinical trials. Methods The functional and physical interaction of EKLF and co-regulatory molecules with the endogenous human globin gene promoters was studied in primary human erythroid progenitors and cell lines, using chromatin immunoprecipitation (ChIP) assays and genetic manipulation of the levels of EKLF and co-regulators. Results and conclusions Knockdown of EKLF prevents SCFA-induced expression of the γ-globin promoter in a stably expressed μLCRβprRlucAγprFluc cassette, and prevents induction of the endogenous γ-globin gene in primary human erythroid progenitors. EKLF is actively recruited to endogenous γ-globin gene promoters after exposure of primary human erythroid progenitors, and murine hematopoietic cell lines, to SCFA derivatives. The core ATPase BRG1 subunit of the human SWI/WNF complex, a ubiquitous multimeric complex that regulates gene expression by remodeling nucleosomal structure, is also required for γ-globin gene induction by SCFA derivatives. BRG1 is actively recruited to the endogenous γ-globin promoter of primary human erythroid progenitors by exposure to SCFA derivatives, and this recruitment is dependent upon the presence of EKLF. These findings demonstrate that EKLF, and the co-activator BRG1, previously demonstrated to be required for definitive or adult erythropoietic patterns of globin gene expression, are co-opted by SCFA derivatives to activate the fetal globin genes. PMID:19220418

  14. Prophage induction and cell division in E. coli. Pt. 3

    International Nuclear Information System (INIS)

    George, J.; Castellazzi, M.; Buttin, G.

    1975-01-01

    In E. coli K12, cell filamentation promoted by tif is enhanced by the lon mutation; in contrast, prophage induction and repair of UV-irradiated phage lambda, also promoted by tif, are not affected by lon. From a tif lon double mutant, 'revertants' having recovered the ability to divide at 41 0 were isolated, among which most (95%) had also lost heir Lon filamentous phenotype after ultraviolet (UV) irradiation. From these 95% of revertants 94% are suppressed for the whole Tif phenotype, by additional mutations that render them deficient in DNA repair, as judged from their high UV sensitivity; some have been characterized as recA mutants. 1% have recovered a control on cell division at 41% or after UV irradiation by means of secondary mutations altering neither the other phenotypic properties of tif and lon, nor the repair and recombination ability of the cells: in particular, this class of 'revertants' remains thermoinducible upon lysogenisation; the mutations which specifically supress filamentation have been mapped at two loci, sfiA and sfiB, cotransducible respectively with pyrD and leu. In the remaining 5% of revertants that still exhibit an UV-induced filamentous growth, 3% can be tentatively classified as true tif + revertants; 2% behave as tif thermodependent revertants, showing suppression of Tif (and Lon) phenotype only at 41 0 : 2 recAts have been identified in this class. Non-lysogenic tif lon sfi and tif sfi strains remain viable during prolonged growth at 41 0 . Under these conditions, tif expresses mutator properties, which can be conveniently analyzed in this sfi background. The action of tif, lon and sfi mutations is tentatively interpreted on the basis of a negative control of cell division specifically associated with DNA repair. (orig.) [de

  15. Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

    Science.gov (United States)

    Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

    2016-07-01

    Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of

  16. The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin

    DEFF Research Database (Denmark)

    Wang, Yifan; Bernhardy, Andrea J; Cruz, Cristina

    2016-01-01

    Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and...

  17. Mutation induction in sesame in Uganda

    International Nuclear Information System (INIS)

    Anyanga, W.

    2001-01-01

    Seeds of five sesame cultivars: T-85, Serra, EM-14, Anyana and S were irradiated with 0, 200, 300, 400, 600 and 800 Gy doses of gamma rays. Irradiated seeds together with their controls were planted in 1995 to produce M 1 plants. Records were taken on germination percentage after four days and three weeks, and vigour also after three weeks of germination. Much decline in growth was recorded from the doses of 600 and 800 Gy. Five capsules/plant from each variety per dose were harvested to grow M 2 progenies. 276 single plants were selected out of 2,636 plants from all the treated varieties. Out of 276 plants selected and planted, 30 progeny rows of those single plants were further selected to be tested in a preliminary yield trial. From five varieties about 7,000 seeds per dose per variety have again been irradiated with 300, 400, 500, and 600 Gy gamma rays. (author)

  18. Induction and utilization of mutations in rice

    Energy Technology Data Exchange (ETDEWEB)

    Viado, G B [Philippine Atomic Energy Commission, Manila (Philippines); Santos, I S [Philippine Atomic Research Center, Diliman, Quezon City (Philippines); Cada, E [Maligaya Rice Research and Training Center, Munoz, Nueva Ecija (Philippines); Escuro, P B [U.P. College of Agriculture, College, Laguna (Philippines); Soriano, J D [University of the Philippines, Diliman, Quezon City (Philippines)

    1970-03-01

    Experiments at the Philippine Atomic Research Center with gamma-irradiated seeds of IR-8-288-3 showed a pronounced inhibition of germination at 60 and 70 kR. The LD{sub 50} was calculated to be about 54 kR at 8 days from seeding. Fertility decreased with increase in gamma radiation dose in an approximately linear fashion. Numerous types of variants have been obtained in the M{sub 2} generation of which the following may be of particular interest: (1) Plant height slightly shorter and leaves darker green, narrower and more erect than IR-8; 99 days from seeding to harvest, fertile. (2) Plant height distinctly shorter than IR-8, leaves dark green small and stiff, culms small, produced as many as 27 panicle-bearing culms, grains very narrow. (3) Typically IR-8 in early growth but at maturity exhibits long panicle exertion, longer grains than IR-8, 111 days from seeding to harvest, produced as many as 20 productive tillers. At the U.P. College of Agriculture, Los Banos 308 plants were selected from the M{sub 2} generation of BE-3 and BPI-121, and 85 from the M3 generation of Bengawan, Peta and Intan after irradiation with fast neutrons. All these selections were early to medium-early and short to medium-short. More beneficial mutants were obtained with the lower dose treatments of BE-3, BPI-121 and Bengawan and with the higher dose treatments of Peta. Plant-progeny rows of these selections, except those from the photoperiod-sensitive varieties BE-3 and BPI-121, are being grown this 1968 dry season for further evaluation. In the M{sub 4} generation of Peta a larger number of short to medium-short and early to medium-early plants were selected from the 35 to 45 kR gamma treatments and the 0.5 to 1.0% EMS treatments. A total of 2430 plant selections were harvested and are now being grown in plant-progeny rows. Seventy-three uniform lines were selected from the M 3 generation of Peta and Intan irradiated with fast neutrons and from the Ma generation of Peta treated with gamma rays, mixed radiations and EMS. All these lines were earlier and mostly shorter than the Peta check. They are now growing in a two-replicate preliminary test with the control. Work at the Maligaya Rice Research and Training Center has included (1) further selection of mutants in the M{sub 3} of several varieties after different mutagenic treatments, and (2) field tests and observations on 12 indica and 15 japonica mutants. From BPI-121, 140 non-seasonal lines were selected. The range of maturity of the selected lines was 120 - 125 days from sowing to harvesting. From BE-3, 547 lines were selected for non-seasonal characteristics with a range of maturity from 125 to 140 days. Of these selections 12 from BPI-121 and 28 from BE-3 were practically uniform and are now being tested for preliminary yield trials during the 1968 dry season. In the field trials four of the indica mutants gave higher yields than the check. All the indica mutants were non-lodging and relatively early. The japonica mutants did not perform as well as the indica mutants. All were non-lodging but only the irradiated Taichung 65 Mut. gave a higher yield than BPI-76 (check). A study on the selection for eating quality in M{sub 2} IR-8 rice at the College of Arts and Sciences, University of the Philippines indicated that improved eating quality may be induced in IR-8 by mutagenic agents. (author)

  19. Induction of mutations in hexaploid triticale

    International Nuclear Information System (INIS)

    Svec, M.

    1989-01-01

    Full text: Several different triticale lines were seed treated with NEH or NaN 3 . In M 2 , chlorophyll mutants were mainly observed in line V2-30 (from 46 x Toemzsi), while short stem, compact spikes and early maturity mutants were found mainly in lines KS126 (from 57 x Stamm 300) and V2-2Z (from Boekoekoe x Rosner). Lines KS60 (from 46 x Toemzsi) and PS728 (from Toemzsi x 72) showed low mutability. (author)

  20. Practicing induction:

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Rohde, Nicolas

    2009-01-01

    We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning.......We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning....

  1. Mutation Breeding Newsletter. No. 39

    International Nuclear Information System (INIS)

    1992-01-01

    This newsletter contains brief articles on the use of radiation to induce mutations in plants; radiation-induced mutants in Chrysanthemum; disrupting the association between oil and protein content in soybean seeds; mutation studies on bougainvillea; a new pepper cultivar; and the use of mutation induction to improve the quality of yam beans. A short review of the seminar on the use of mutation and related biotechnology for crop improvement in the Middle East and Mediterranean regions, and a description of a Co-ordinated Research Programme on the application of DNA-based marker mutations for the improvement of cereals and other sexually reproduced crop species are also included. Two tables are given: these are based on the ''FAO/IAEA Mutant Varieties Database'' and show the number of mutated varieties and the number of officially released mutant varieties in particular crops/species. Refs and tabs

  2. Role of heteroplasmic mutations in the mitochondrial genome and the ID4 gene promoter methylation region in the pathogenesis of chronic aplastic anemia in patients suffering from Kidney yin deficiency.

    Science.gov (United States)

    Cui, Xing; Wang, Jing-Yi; Liu, Kui; Cui, Si-Yuan; Zhang, Jie; Luo, Ya-Qin; Wang, Xin

    2016-06-01

    To analyze changes in gene amplification in the mitochondrial genome and in the ID4 gene promoter methylation region in patients with chronic aplastic anemia (CAA) suffering from Kidney (Shen) yin deficiency or Kidney yang deficiency. Bone marrow and oral epithelium samples were collected from CAA patients with Kidney yin deficiency or Kidney yang deficiency (20 cases). Bone marrow samples were collected from 20 healthy volunteers. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and PCR products were used for sequencing and analysis. Higher mutational rates were observed in the ND1-2, ND4-6, and CYTB genes in CAA patients suffering from Kidney yin deficiency. Moreover, the ID4 gene was unmethylated in bone marrow samples from healthy individuals, but was methylated in some CAA patients suffering from Kidney yin deficiency (positive rate, 60%) and Kidney yang deficiency (positive rate, 55%). These data supported that gene mutations can alter the expression of respiratory chain enzyme complexes in CAA patients, resulting in energy metabolism impairment and promoting the physiological and pathological processes of hematopoietic failure. Functional impairment of the mitochondrial respiration chain induced by gene mutation may be an important reason for hematopoietic failure in patients with CAA. This change is closely related to maternal inheritance and Kidney yin deficiency. Finally, these data supported the assertion that it is easy to treat disease in patients suffering from yang deficiency and difficult to treat disease in patients suffering from yin deficiency.

  3. 8-methoxypsoralen and ultraviolet A radiation activate the human elastin promoter in transgenic mice: in vivo and in vitro evidence for gene induction

    International Nuclear Information System (INIS)

    Bernstein, E.F.; Brown, D.B.; Takeuchi, Tsunemichi; Kong, S.K.; Uitto, Jouni; Gasparro, F.P.

    1996-01-01

    Treatment of skin diseases with the combination of 8-methoxypsoralen and ultraviolet A radiation (PUVA) results in clinical alterations in treated skin that resemble those observed in chronically photodamaged skin. The PUVA-treated patients develop nonmelanoma skin cancers, pigmentary alterations and wrinkling characteristic of sun-induced changes. The major alteration in the dermis of sun-damaged skin is the deposition of abnormal elastic fibers, termed solar elastosis. Up-regulation of elastin promoter activity in dermal fibroblasts explains the excess elastic tissue but not the reason for the aberrant morphology of the elastotic material. In order to study photoaging in an experimental system we utilized a transgenic mouse line that expresses the human elastin promoter/chloramphenicol acetyltransferase construct in a tissue-specific and developmentally regulated manner. Although UVB radiation has been demonstrated to increase promoter activity in vitro, UVA fails to demonstrate a similar effect at the doses utilized. In this study, we demonstrate the ability of PUVA treatment to up regulate elastin promoter activity both in vitro and in vivo. These data help to explain the development of photoaging in sun-protected PUVA-treated skin. We attribute the up-regulation of elastin promoter activity in response to PUVA to the formation of DNA photoadducts, which do not occur in response to UVA radiation alone. (UK)

  4. Regulation of ATM induction

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.M.; Kearsley, J.H.; Lee, C.S.; Sarris, M.; De Murrell, D.

    2000-01-01

    Full text: ATM, the tumour suppressor protein mutated in ataxia-telangiectasia, is of pivotal importance in controlling the cells primary response to ionising radiation (IR) induced DNA damage. Mutations in ATM which reduce the level of the ATM protein and/or compromise ATM functions are known to give rise to radiosensitivity and defective cell cycle checkpoint control. In response to DNA damage ATM kinase is rapidly activated and initiates downstream signalling to cell cycle control molecules including p53. To investigate additional mechanisms of ATM control we have employed ATM antisense expression in cultured cells, western analyses and immunohistochemistry in situ. We report that ATM can be up-regulated up to 10-fold following exposure to low levels of ionising radiation. ATM radiation-induction was radiation dose dependent while the rapidity of the response indicates a post translational pathway. The concurrent time frames for the radiation-induction of ATM levels and the activation of ATM kinase activity appear to be complimentary in boosting ATM's protective response to IR induced DNA damage, especially in ATM 'low expressing' systems. We also provide the first report of ATM misregulation in 2 cancer patients, indicating that ATM is not only radio-protective but has possible implications in cancer, particularly breast cancer. These results have particular importance in defining the regulation of the ATM protein as an: adaptive radio-response; radio-prognostic market in tumours and normal tissue, and breast cancer marker

  5. Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter

    Directory of Open Access Journals (Sweden)

    Surleen Kaur

    2016-03-01

    Full Text Available Insulin receptor substrate-2 (IRS-2 plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS, insulin resistance and cancer. To predict the transcription factors (TFs responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]. The ibid data is part of author׳s publication (Anjali et al., 2015 [2] that explains Follicle stimulating hormone (FSH mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer. Keywords: IRS-2, TFBS, FSH, SP1, ChIP

  6. Loss of function mutations in PTPN6 promote STAT3 deregulation via JAK3 kinase in diffuse large B-cell lymphoma

    Science.gov (United States)

    Demosthenous, Christos; Han, Jing Jing; Hu, Guangzhen; Stenson, Mary; Gupta, Mamta

    2015-01-01

    PTPN6 (SHP1) is a tyrosine phosphatase that negatively controls the activity of multiple signaling pathways including STAT signaling, however role of mutated PTPN6 is not much known. Here we investigated whether PTPN6 might also be a potential target for diffuse large B cell lymphoma (DLBCL) and performed Sanger sequencing of the PTPN6 gene. We have identified missense mutations within PTPN6 (N225K and A550V) in 5% (2/38) of DLBCL tumors. Site directed mutagenesis was performed to mutate wild type (WT) PTPN6 and stable cell lines were generated by lentiviral transduction of PTPN6WT, PTPN6N225K and PTPN6A550V constructs, and effects of WT or mutated PTPN6 on STAT3 signaling were analyzed. WT PTPN6 dephosphorylated STAT3, but had no effect on STAT1, STAT5 or STAT6 phosphorylation. Both PTPN6 mutants were unable to inhibit constitutive, as well as cytokines induced STAT3 activation. Both PTPN6 mutants also demonstrated reduced tyrosine phosphatase activity and exhibited enhanced STAT3 transactivation activity. Intriguingly, a lack of direct binding between STAT3 and WT or mutated PTPN6 was observed. However, compared to WT PTPN6, cells expressing PTPN6 mutants exhibited increased binding between JAK3 and PTPN6 suggesting a more dynamic interaction of PTPN6 with upstream regulators of STAT3. Consistent with this notion, both the mutants demonstrated increased resistance to JAK3 inhibitor, WHIP-154 relative to WT PTPN6. Overall, this is the first study, which demonstrates that N225K and A550V PTPN6 mutations cause loss-of-function leading to JAK3 mediated deregulation of STAT3 pathway and uncovers a mechanism that tumor cells can use to control PTPN6 substrate specificity. PMID:26565811

  7. FLT3 and JAK2 Mutations in Acute Myeloid Leukemia Promote Interchromosomal Homologous Recombination and the Potential for Copy Neutral Loss of Heterozygosity.

    Science.gov (United States)

    Gaymes, Terry J; Mohamedali, Azim; Eiliazadeh, Anthony L; Darling, David; Mufti, Ghulam J

    2017-04-01

    Acquired copy neutral LOH (CN-LOH) is a frequent occurrence in myeloid malignancies and is often associated with resistance to standard therapeutic modalities and poor survival. Here, we show that constitutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (iHR), a precedent for CN-LOH. Using a targeted recombination assay, we determined significant iHR activity in internal tandem duplication FLT3 (FLT3-ITD) and JAK2V617F-mutated cells. Sister chromatid exchanges, a surrogate measure of iHR, was significantly elevated in primary FLT3-ITD normal karyotype acute myeloid leukemia (NK-AML) compared with wild-type FLT3 NK-AML. HR was harmonized to S phase of the cell cycle to repair broken chromatids and prevent iHR. Increased HR activity in G 0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML. Cells expressing mutated FLT3-ITD demonstrated a relative increase in mutation frequency as detected by thymidine kinase (TK) gene mutation assay. Moreover, resistance was associated with CN-LOH at the TK locus. Treatment of FLT3-ITD- and JAK2V617F-mutant cells with the antioxidant N -acetylcysteine diminished reactive oxygen species (ROS), restoring iHR and HR levels. Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellular milieu toward illegitimate recombination events such as iHR and CN-LOH. Therapeutic reduction of ROS may thus prevent leukemic progression and relapse in myeloid malignancies. Cancer Res; 77(7); 1697-708. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

    2013-01-01

    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  9. Induction practice -

    DEFF Research Database (Denmark)

    Rohde, Nicolas; Sprogøe, Jonas

    2007-01-01

    that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and the organization, what we call agenerative dance, ignites both kinds of learning. We focus on and describe the interplay , ignites both kinds...

  10. Probable Chemical Hypoxia Effects on Progress of CNV Through Induction of Promoter CpG Demethylation and Overexpression of IL17RC in Human RPE Cells.

    Science.gov (United States)

    Alivand, Mohammad Reza; Sabouni, Farzaneh; Soheili, Zahra-Soheila

    2016-09-01

    To survey the changes of promoter CpG methylation status and mRNA expression of IL17RC (interleukin 17 receptor C) gene in retinal pigment epithelium (RPE) cells under chemical hypoxia condition for choroidal neovascularization (CNV) modeling in vitro. RPE cells were cultured in both untreated as a control group and treated by cobalt chloride media as a hypoxia group for various concentrations (100-150μM) and times (24-36 hrs.) To confirm chemical hypoxia condition, mRNA expression of HIF (Hypoxia Inducible Factor) -1α, -2α, and Vascular Endothelial Growth Factor (VEGF) was compared between two groups by Real-time PCR. Also, in normoxia and hypoxia conditions, IL17RC expression changes and promoter CpG methylation status were evaluated by Real-time PCR and methylation-specific PCR (MSP) techniques, respectively. Overexpression of HIF-1α, HIF-2α, and VEGF was significant in hypoxia versus normoxia conditions. Our data showed overexpression of IL17RC (2.1- to 6.3-fold) and decreasing of its promoter methylation in comparison with hypoxia and normoxia conditions. It was found that there are significant association between promoter methylation status and expression of IL17RC in chemical hypoxia condition. Therefore, methylation of IL17RC could play as a marker in CNV and degeneration of RPE cells in vitro. Additionally, HIF-α and methylation phenomena may be considered as critical targets for blocking in angiogenesis of age-related degeneration in future studies.

  11. PhoQ mutations promote lipid A modification and polymyxin resistance of Pseudomonas aeruginosa found in colistin-treated cystic fibrosis patients

    DEFF Research Database (Denmark)

    Miller, Amanda K; Brannon, Mark K; Stevens, Laurel

    2011-01-01

    Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 - 64 mg/L) in laboratory and clinical strains...

  12. Mutations in the estrogen receptor alpha hormone binding domain promote stem cell phenotype through notch activation in breast cancer cell lines.

    Science.gov (United States)

    Gelsomino, L; Panza, S; Giordano, C; Barone, I; Gu, G; Spina, E; Catalano, S; Fuqua, S; Andò, S

    2018-04-24

    The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behavior of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44 + /CD24 - ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities. Mutant clones exhibited high expression of NOTCH receptors/ligands/target genes and blockade of NOTCH signaling reduced MFE and migratory potential. Mutant BCSC activity was dependent on ERα phosphorylation at serine 118, since its inhibition decreased MFE and NOTCH4 activation only in mutant cells. Collectively, we demonstrate that the expression of HBD-ESR1 mutations may drive BC cells to acquire stem cell traits through ER/NOTCH4 interplay. We propose the early detection of HBD-ESR1 mutations as a challenge in precision medicine strategy, suggesting the development of tailored-approaches (i.e. NOTCH inhibitors) to prevent disease development and metastatic spread in BC mutant-positive patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Mutation breeding in ornamental plants

    International Nuclear Information System (INIS)

    Datta, S.K.

    1990-01-01

    Full text: Mutation induction produced a large number of new promising varieties in ornamental species. 37 new mutants of Chrysanthemum and 14 of rose have been developed by mutations and released for commercialisation. The mutations in flower colour/shape were detected as chimeras in M 1 V 1 , M 1 V 2 , M 1 V 3 generations. The mutation frequency varied with the cultivar and exposure to gamma rays. Comparative analysis of original cultivars and their respective induced mutants on cytomorphological, anatomical and biochemical characters are being carried out for better understanding of the mechanism involved in the origin and evolution of somatic flower colour/shape mutations. Cytological analysis with reference to chromosomal aberrations, chromosome number, ICV, INV and DNA content gave no differences between the original and mutant cultivars. Analysis of florets/petal pigments by TLC and spectrophotometric methods indicated both qualitative and quantitative changes. (author)

  14. Induction Brazing

    DEFF Research Database (Denmark)

    Henningsen, Poul

    , or if the hottest area is located outside the joint interface, a number of defects may appear: the braze metal may flow away from the joint, the flux may burn off, poor binding of the braze metal may appear or the braze metal may be overheated. Joint geometry as well as electro-magnetic properties of the work piece...... presents a combined numerical and experimental method for determination of appropriate/optimiged coil geometry and position in induction brazing tube-to-plate joints of different ratios between tube and plate thickness and different combinations of the materials stainless steel, brass and copper....... The method has proven to give successful results in brazing tube-plate joints of copper-brass, copper-stainless steel, stainless steel-brass, and stainless steel-stainless steel. A new design of an adjustable flux concentrator for induction heating tube-to-plate joints is proposed and tested on a variety...

  15. Radiation-induced mutation at minisatellite loci

    International Nuclear Information System (INIS)

    Dubrova, Y.E.; Nesterov, V.N.; Krouchinsky, N.G.

    1997-01-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of γ-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure 137 Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed

  16. FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it

    International Nuclear Information System (INIS)

    Tanabe, Yuko; Fujita, Eriko; Momoi, Takashi

    2011-01-01

    Highlights: → We isolated protection of telomeres 1 (POT1) as a FOXP2-associated protein by a yeast two-hybrid. → FOXP2 associated and co-localized with POT1 in the nuclei. → FOXP2(R553H) also co-localized with POT1 in both the cytoplasm and nuclei. → FOXP2(R553H) partially prevented the nuclear translocation of POT1. → FOXP2(R553H) mutation may be associated with the pathogenesis of speech-language disorder. -- Abstract: FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.

  17. FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Yuko [Division of Development and Differentiation, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigasi, Kodaira 187-8511 (Japan); Fujita, Eriko [Division of Development and Differentiation, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigasi, Kodaira 187-8511 (Japan); Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498 (Japan); Momoi, Takashi, E-mail: momoi@iuhw.ac.jp [Division of Development and Differentiation, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigasi, Kodaira 187-8511 (Japan); Center for Medical Science, International University of Health and Welfare, 2600-1 Kitakanamaru, Otawara, Tochigi 324-8501 (Japan)

    2011-07-08

    Highlights: {yields} We isolated protection of telomeres 1 (POT1) as a FOXP2-associated protein by a yeast two-hybrid. {yields} FOXP2 associated and co-localized with POT1 in the nuclei. {yields} FOXP2(R553H) also co-localized with POT1 in both the cytoplasm and nuclei. {yields} FOXP2(R553H) partially prevented the nuclear translocation of POT1. {yields} FOXP2(R553H) mutation may be associated with the pathogenesis of speech-language disorder. -- Abstract: FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.

  18. Induction of chinook salmon growth hormone promoter activity by the adenosine 3',5'-monophosphate (cAMP)-dependent pathway involves two cAMP-response elements with the CGTCA motif and the pituitary-specific transcription factor Pit-1.

    Science.gov (United States)

    Wong, A O; Le Drean, Y; Liu, D; Hu, Z Z; Du, S J; Hew, C L

    1996-05-01

    In this study, the functional role of two cAMP-response elements (CRE) in the promoter of the chinook salmon GH gene and their interactions with the transcription factor Pit-1 in regulating GH gene expression were examined. A chimeric construct of the chloramphenicol acetyltransferase (CAT) reporter gene with the CRE-containing GH promoter (pGH.CAT) was transiently transfected into primary cultures of rainbow trout pituitary cells. The expression of CAT activity was stimulated by an adenylate cyclase activator forskolin as well as a membrane-permeant cAMP analog 8-bromo-cAMP. Furthermore, these stimulatory responses were inhibited by a protein kinase A inhibitor H89, suggesting that these CREs are functionally coupled to the adenylate cyclase-cAMP-protein kinase A cascade. This hypothesis is supported by parallel studies using GH4ZR7 cells, a rat pituitary cell line stably transfected with dopamine D2 receptors. In this cell line, D2 receptor activation is known to inhibit adenylate cyclase activity and cAMP synthesis. Stimulation with a nonselective dopamine agonist, apomorphine, or a D2-specific agonist, Ly171555, suppressed the expression of pGH.CAT in GH4ZR7 cells, and this inhibition was blocked by simultaneous treatment with forskolin. These results indicate that inhibition of the cAMP-dependent pathway reduces the basal promoter activity of the CRE-containing pGH.CAT. The functionality of these CREs was further confirmed by deletion analysis and site-specific mutagenesis. In trout pituitary cells, the cAMP inducibility of pGH.CAT was inhibited after deleting the CRE-containing sequence from the GH promoter. When the CRE-containing sequence was cloned into a CAT construct with a viral thymidine kinase promoter, a significant elevation of cAMP inducibility was observed. This stimulatory response, however, was abolished by mutating the core sequence, CGTCA, in these CREs, suggesting that these cis-acting elements confer cAMP inducibility to the salmon GH gene

  19. Mutation breeding in jute

    International Nuclear Information System (INIS)

    Joshua, D.C.

    1980-01-01

    Mutagenic studies in jute in general dealt with the morphological abnormalities of the M 1 generation in great detail. Of late, induction of a wide spectrum of viable mutations have been reported in different varieties of both the species. Mutations affecting several traits of agronomic importance such as, plant height, time of flowering, fibre yield and quality, resistance to pests and diseases are also available. Cytological analysis of a large collection of induced mutants resulted in the isolation of seven trisomics in an olitorius variety. Several anatomical parameters which are the components of fibre yield, have also received attention. Some mutants with completely altered morphology were used for interpreting the evolution of leaf shape in Tiliaceas and related families. A capsularis variety developed using mutation breeding technique has been released for cultivation. Several others, including derivatives of inter-mutant hybridization have been found to perform well at different locations in the All India Coordinated Trials. Presently, chemical mutagenesis and induction of mutants of physiological significance are receiving considerable attention. The induced variability is being used in genetic and linkage studies. (author)

  20. Phytohormones and induction of plant-stress tolerance and defense genes by seed and foliar inoculation with Azospirillum brasilense cells and metabolites promote maize growth.

    Science.gov (United States)

    Fukami, Josiane; Ollero, Francisco Javier; Megías, Manuel; Hungria, Mariangela

    2017-12-01

    Azospirillum spp. are plant-growth-promoting bacteria used worldwide as inoculants for a variety of crops. Among the beneficial mechanisms associated with Azospirillum inoculation, emphasis has been given to the biological nitrogen fixation process and to the synthesis of phytohormones. In Brazil, the application of inoculants containing A. brasilense strains Ab-V5 and Ab-V6 to cereals is exponentially growing and in this study we investigated the effects of maize inoculation with these two strains applied on seeds or by leaf spray at the V2.5 stage growth-a strategy to relieve incompatibility with pesticides used for seed treatment. We also investigate the effects of spraying the metabolites of these two strains at V2.5. Maize growth was promoted by the inoculation of bacteria and their metabolites. When applied via foliar spray, although A. brasilense survival on leaves was confirmed by confocal microscopy and cell recovery, few cells were detected after 24 h, indicating that the effects of bacterial leaf spray might also be related to their metabolites. The major molecules detected in the supernatants of both strains were indole-3-acetic acid, indole-3-ethanol, indole-3-lactic acid and salicylic acid. RT-PCR of genes related to oxidative stress (APX1, APX2, CAT1, SOD2, SOD4) and plant defense (pathogenesis-related PR1, prp2 and prp4) was evaluated on maize leaves and roots. Differences were observed according to the gene, plant tissue, strain and method of application, but, in general, inoculation with Azospirillum resulted in up-regulation of oxidative stress genes in leaves and down-regulation in roots; contrarily, in general, PR genes were down-regulated in leaves and up-regulated in roots. Emphasis should be given to the application of metabolites, especially of Ab-V5 + Ab-V6 that in general resulted in the highest up-regulation of oxidative-stress and PR genes both in leaves and in roots. We hypothesize that the benefits of inoculation of Azospirillum on

  1. Effect of Promoter Region Mutations and mgrA Overexpression on Transcription of norA, Which Encodes a Staphylococcus aureus Multidrug Efflux Transporter

    OpenAIRE

    Kaatz, Glenn W.; Thyagarajan, Rama V.; Seo, Susan M.

    2005-01-01

    NorA is a Staphylococcus aureus multidrug transporter that confers resistance to structurally distinct compounds. The MgrA global regulatory protein is reported to augment norA expression when mgrA is overexpressed from an undefined plasmid-based promoter. Further details about norA regulatory mechanisms are scant. A chromosomal norA::lacZ transcriptional fusion was constructed in different S. aureus strains, and allele replacement was used to define the relevance of promoter region sequences...

  2. Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice

    International Nuclear Information System (INIS)

    Andres, A.C.; Schoenenberger, C.A.; Groner, B.; Henninghausen, L.; LeMeur, M.; Gelinger, P.

    1987-01-01

    The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and four females). Wap-ras expression was observed in the mammary glands of lactating females in two lines derived from female founders. The tissue-directed and hormone-dependent Wap expression was conferred on the Ha-ras oncogene. The signals governing Wap expression are located within 2.5 kilobases of 5' flanking sequence. The other two lines derived from female founders did not express the chimeric gene. In the line derived from the male founder the Wap-ras gene is integrated into the Y chromosome. Expression was found in the salivary gland of male animals only. After a long latency, Wap-ras-expressing mice developed tumors. The tumors arose in tissues expressing Wap-ras - i.e., mammary or salivary glands. Compared to the corresponding nonmalignant tissues, Wap-ras expression was enhanced in the tumors

  3. TIMP-1 is under regulation of the EGF signaling axis and promotes an aggressive phenotype in KRAS-mutated colorectal cancer cells

    DEFF Research Database (Denmark)

    Tarpgaard, Line S; Ørum-Madsen, Maj Sofie; Christensen, Ib J

    2016-01-01

    EGFR inhibitors. Metalloproteinase inhibitor 1 (TIMP-1) is a pleiotropic factor predictive of survival outcome of CRC patients. Levels of TIMP-1 were measured in pre-treatment plasma samples (n = 426) of metastatic CRC patients randomized to Nordic FLOX (5-fluorouracil and oxaliplatin) +/- cetuximab...... (NORDIC VII study). Multivariate analysis demonstrated a significant interaction between plasma TIMP-1 protein levels, KRAS status and treatment with patients bearing KRAS mutated tumors and high TIMP-1 plasma level (> 3rd quartile) showing a significantly longer overall survival if treated with cetuximab...

  4. Molecular Mechanisms of Mouse Skin Tumor Promotion

    International Nuclear Information System (INIS)

    Rundhaug, Joyce E.; Fischer, Susan M.

    2010-01-01

    Multiple molecular mechanisms are involved in the promotion of skin carcinogenesis. Induction of sustained proliferation and epidermal hyperplasia by direct activation of mitotic signaling pathways or indirectly in response to chronic wounding and/or inflammation, or due to a block in terminal differentiation or resistance to apoptosis is necessary to allow clonal expansion of initiated cells with DNA mutations to form skin tumors. The mitotic pathways include activation of epidermal growth factor receptor and Ras/Raf/mitogen-activated protein kinase signaling. Chronic inflammation results in inflammatory cell secretion of growth factors and cytokines such as tumor necrosis factor-α and interleukins, as well as production of reactive oxygen species, all of which can stimulate proliferation. Persistent activation of these pathways leads to tumor promotion

  5. Human hepatocytes apoptosis induced by replication of hepatitis B virus subgenotypes F1b and F4: Role of basal core promoter and preCore mutations.

    Science.gov (United States)

    Elizalde, María Mercedes; Sevic, Ina; González López Ledesma, María Mora; Campos, Rodolfo Héctor; Barbini, Luciana; Flichman, Diego Martin

    2018-01-01

    In the context of pathogenesis of HBV infection, HBV genotypes and mutants have been shown to affect the natural course of chronic infection and treatment outcomes. In this work, we studied the induction of apoptosis by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. Both subgenotypes F1b and F4 HBV genome transfections induced cell death by apoptosis in human hepatocytes. The BCPdm (A1762T/G1764A) and preCore (G1896A) mutants induced higher levels of apoptosis than the wt virus. This increase in apoptosis was not associated with the enhanced viral replication of the variants. HBV-mediated apoptosis was independent of viral subgenotypes, and associated with the modulation of members of the regulatory Bcl-2 family proteins expression in the mitochondrial apoptotic pathway. Finally, the apoptosis induction increase observed for the preCore mutants suggests that HBeAg might have an anti-apoptotic effect in human hepatocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Mutation breeding in pepper

    Energy Technology Data Exchange (ETDEWEB)

    Daskalov, S [Plant Breeding Unit, Joint FAO/IAEA Division of Isotope and Radiation Applications of Atomic Energy for Food and Agricultural Development, Seibersdorf Laboratory, International Atomic Energy Agency, Vienna (Austria)

    1986-03-01

    Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F{sub 1} hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M{sub 1} effects, handling the treated material in M{sub 1}, M{sub 2} and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

  7. Mutation breeding in pepper

    International Nuclear Information System (INIS)

    Daskalov, S.

    1986-01-01

    Pepper (Capsicum sp.) is an important vegetable and spice crop widely grown in tropical as well as in temperate regions. Until recently the improvement programmes were based mainly on using natural sources of germ plasma, crossbreeding and exploiting the heterosis of F 1 hybrids. However, interest in using induced mutations is growing. A great number of agronomically useful mutants as well as mutants valuable for genetic, cytological and physiological studies have been induced and described. In this review information is presented about suitable mutagen treatment procedures with radiation as well as chemicals, M 1 effects, handling the treated material in M 1 , M 2 and subsequent generations, and mutant screening procedures. This is supplemented by a description of reported useful mutants and released cultivars. Finally, general advice is given on when and how to incorporate mutation induction in Capsicum improvement programmes. (author)

  8. Induced mutations in citrus

    International Nuclear Information System (INIS)

    Spiegel-Roy, P.; Vardi, Aliza

    1990-01-01

    Full text: Parthenocarpic tendency is an important prerequisite for successful induction of seedlessness in breeding and especially in mutation breeding. A gene for asynapsis and accompanying seedless fruit has been found by us in inbred progeny of cv. 'Wilking'. Using budwood irradiation by gamma rays, seedless mutants of 'Eureka' and 'Villafranca' lemon (original clone of the latter has 25 seeds) and 'Minneola' tangelo have been obtained. Ovule sterility of the three mutants is nearly complete, with some pollen fertility still remaining. A semi-compact mutant of Shamouti orange has been obtained by irradiation. A programme for inducing seedlessness in easy peeling citrus varieties and selections has been initiated. (author)

  9. v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element.

    Science.gov (United States)

    Xie, W; Fletcher, B S; Andersen, R D; Herschman, H R

    1994-10-01

    We recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factors and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5' of the TIS10/PGS2 transcription start site that mediates pp60v-src induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the ATF/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60v-src induction. E-box mutation has no effect on the fold induction in response to pp60v-src. In contrast, ATF/CRE mutation attenuates the pp60v-src response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. Our data suggest that Ras mediates pp60v-src activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element.

  10. Position of the axillary bud and mutation induction in Chrysanthemum (Dendranthema grandiflora Tzvelev) plant lets; Posicao da gema axilar e a inducao de mutacao em mudas de crisantemo (Dendranthema grandiflora Tzvelev)

    Energy Technology Data Exchange (ETDEWEB)

    Adames, Alvis Hernan; Latado, Rodrigo Rocha; Camargo, Nalza Maria; Tulmann Neto, Augusto [Centro de Energia Nuclear na Agricultura (CENA), Piracicaba, SP (Brazil). Lab. de Melhoramento de Plantas. E-mail: rrlatado@cena.usp.br

    1999-12-01

    Mutagenic treatment of multicellular meristems from vegetatively propagated plants generally results in the formation of chimeric plants. Mutated sectors can be increased and stabilized through the cutting-back method. The objective of the present research was to study the influence of application of this method in the M{sub 1}V{sub 2} population, originated from six different axillary buds from the M{sub 1}V{sub 1} chrysanthemum branches. For this purpose, rooted plants of the cultivar Ingrid (dark ping) were irradiated with 20 Gy of gamma-rays and the prune was carried out 40 days after planting. Frequency and spectrum of flower color mutants were evaluated. No mutants were observed in the control population. In the M{sub 1}V{sub 1} population, 22.1% of the total plants were mutants (white color, dark bronze, pale pink, yellow, wine, variegated and cream). Among them, 1.8% were periclinal chimeras (with only one different color from the original) and the others showed mutated sectors. No differences were observed in mutation frequency and size of mutated sector among six M{sub 1}V{sub 1} populations. The wine colored mutant was selected, multiplied and evaluated in a yield trial. This mutant named Magali was multiplied and was released as a new cultivar. (author)

  11. Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene.

    Science.gov (United States)

    Walker, L C; Teebi, A S; Marini, J C; De Paepe, A; Malfait, F; Atsawasuwan, P; Yamauchi, M; Yeowell, H N

    2004-12-01

    The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized by tissue fragility, hyperelasticity of the skin and joint hypermobility. This phenotype, accompanied by kyphoscoliosis and/or ocular fragility, is present in patients with the autosomal recessive type VI form of EDS. These patients have significantly decreased levels of lysyl hydroxylase (LH) activity, due to mutations in the LH1 gene. LH hydroxylates specific lysine residues in the collagen molecule that are precursors for the formation of cross-links which provide collagen with its tensile strength. No disorder has been directly linked to decreased expression of LH2 and LH3, two other isoforms of LH. This study describes 3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 mRNAs, in their skin fibroblasts. In contrast to the effect of LH1 deficiency in EDS VI patients, the decreased expression of LH2 does not affect LH activity, bifunctional collagen cross-links (measured after reduction as dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL)), or helical lysine hydroxylation in these cell lines. Sequence analysis of full length LH2 cDNAs and 1kb of the promoter region of LH2 does not show mutations that could explain the decreased expression of LH2. These results suggest that the deficiency of LH2 in these fibroblasts may be caused by changes in other factors required for the expression of LH2.

  12. Mutation breeding in Philippine fruits

    International Nuclear Information System (INIS)

    Espino, R.R.C.

    1987-09-01

    Studies were made to establish standard conditions for mutation induction by gamma-irradiation to be performed in combination with in-vitro culture for banana and citrus spp. Besides this, radio-sensitivity of seeds and/or plantlets of mango, sugar apple, soursop, lanzones and Jack fruit was investigated and primary observation on the occurrence of mutation was made. For the mutagenesis of banana shoot tip cultures, radio-sensitivity of plantlets derived from the culture as well as fresh-cultured shoots was examined and phenotypes indicative of mutation, such as chlorophyl streaking, slow growth, pigmentation and varied bunch orientation were recorded. Isozyme analysis for mutated protein structure was not conclusive. In the in-vitro culture of Citrus spp., seeds placed on fresh media as well as germinating seeds and two-leaf stage seedlings in test tubes were examined for their radio-sensitivity. Irradiated materials were propagated for further observation. In these two crops, basic methodology for mutation induction with combined use of in-vitro culture and gamma-irradiation was established. In mango, sugar apple, soursop, lanzones and Jack fruit, basic data on radiosensitivity were obtained. In mango, leaf abnormalities were observed after the treatment of scions

  13. Induction of autophagy by spermidine promotes longevity.

    Science.gov (United States)

    Eisenberg, Tobias; Knauer, Heide; Schauer, Alexandra; Büttner, Sabrina; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Ring, Julia; Schroeder, Sabrina; Magnes, Christoph; Antonacci, Lucia; Fussi, Heike; Deszcz, Luiza; Hartl, Regina; Schraml, Elisabeth; Criollo, Alfredo; Megalou, Evgenia; Weiskopf, Daniela; Laun, Peter; Heeren, Gino; Breitenbach, Michael; Grubeck-Loebenstein, Beatrix; Herker, Eva; Fahrenkrog, Birthe; Fröhlich, Kai-Uwe; Sinner, Frank; Tavernarakis, Nektarios; Minois, Nadege; Kroemer, Guido; Madeo, Frank

    2009-11-01

    Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

  14. Meclozine promotes longitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene.

    Science.gov (United States)

    Matsushita, Masaki; Hasegawa, Satoru; Kitoh, Hiroshi; Mori, Kensaku; Ohkawara, Bisei; Yasoda, Akihiro; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2015-02-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias causing short stature owing to a gain-of-function mutation in the FGFR3 gene, which encodes the fibroblast growth factor receptor 3. We found that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cells. To examine the feasibility of meclozine administration in clinical settings, we investigated the effects of meclozine on ACH model mice carrying the heterozygous Fgfr3(ach) transgene. We quantified the effect of meclozine in bone explant cultures employing limb rudiments isolated from developing embryonic tibiae from Fgfr3(ach) mice. We found that meclozine significantly increased the full-length and cartilaginous primordia of embryonic tibiae isolated from Fgfr3(ach) mice. We next analyzed the skeletal phenotypes of growing Fgfr3(ach) mice and wild-type mice with or without meclozine treatment. In Fgfr3(ach) mice, meclozine significantly increased the body length after 2 weeks of administration. At skeletal maturity, the bone lengths including the cranium, radius, ulna, femur, tibia, and vertebrae were significantly longer in meclozine-treated Fgfr3(ach) mice than in untreated Fgfr3(ach) mice. Interestingly, meclozine also increased bone growth in wild-type mice. The plasma concentration of meclozine during treatment was within the range that has been used in clinical settings for motion sickness. Increased longitudinal bone growth in Fgfr3(ach) mice by oral administration of meclozine in a growth period suggests potential clinical feasibility of meclozine for the improvement of short stature in ACH.

  15. Development of technique on the induction and selection of in vitro mutant lines (Potato, Solanum tuberosum L.)

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jang Ryoel; Lee, Yeong Il; Song, Hee Seop; Kim, Jae Seong; Sin, In Cheol; Lee, Sang Jae; Lee, Ki Un; Lim, Yong Taek [Korea Atomic Energy Res. Inst., Taejon (Korea, Republic of)

    1993-09-01

    For the development of the technique on the plant tissue culture and application of nuclear technique in the in vitro mutation breeding, present research laid emphasis on the development of techniques of potato tissue culture, and on the induction and selection of radiation mutation. Another culture for haploid induction, optimum radiation dosage for cybrid formation of potato and mutation induction from in vitro cultured microtuber and plantlets were investigated for modelling the technique on the induction and selection of in vitro mutant lines. Inheritance stability of the selected mutants were also studied in field condition. In vitro system of micropropagation and selection of mutation was summarized.

  16. Development of technique on the induction and selection of in vitro mutant lines (Potato, Solanum tuberosum L.)

    International Nuclear Information System (INIS)

    Yoo, Jang Ryoel; Lee, Yeong Il; Song, Hee Seop; Kim, Jae Seong; Sin, In Cheol; Lee, Sang Jae; Lee, Ki Un; Lim, Yong Taek

    1993-09-01

    For the development of the technique on the plant tissue culture and application of nuclear technique in the in vitro mutation breeding, present research laid emphasis on the development of techniques of potato tissue culture, and on the induction and selection of radiation mutation. Another culture for haploid induction, optimum radiation dosage for cybrid formation of potato and mutation induction from in vitro cultured microtuber and plantlets were investigated for modelling the technique on the induction and selection of in vitro mutant lines. Inheritance stability of the selected mutants were also studied in field condition. In vitro system of micropropagation and selection of mutation was summarized

  17. MLH1-93 G/a polymorphism is associated with MLH1 promoter methylation and protein loss in dysplastic sessile serrated adenomas with BRAFV600E mutation.

    Science.gov (United States)

    Fennell, Lochlan J; Jamieson, Saara; McKeone, Diane; Corish, Tracie; Rohdmann, Megan; Furner, Tori; Bettington, Mark; Liu, Cheng; Kawamata, Futoshi; Bond, Catherine; Van De Pols, Jolieke; Leggett, Barbara; Whitehall, Vicki

    2018-01-05

    Sessile serrated adenomas with BRAF mutation progress rapidly to cancer following the development of dysplasia (SSAD). Approximately 75% of SSADs methylate the mismatch repair gene MLH1, develop mismatch repair deficiency and the resultant cancers have a good prognosis. The remaining SSADs and BRAF mutant traditional serrated adenomas (TSA) develop into microsatellite stable cancers with a poor prognosis. The reason for this dichotomy is unknown. In this study, we assessed the genotypic frequency of the MLH1-93 polymorphism rs1800734 in SSADs and TSAs to determine if the uncommon variant A allele predisposes to MLH1 promoter hypermethylation. We performed genotyping for the MLH1-93 polymorphism, quantitative methylation specific PCR, and MLH1 immunohistochemistry on 124 SSAD, 128 TSA, 203 BRAF mutant CRCs and 147 control subjects with normal colonoscopy. The minor A allele was significantly associated with a dose dependent increase in methylation at the MLH1 promoter in SSADs (p = 0.022). The AA genotype was only observed in SSADs with MLH1 loss. The A allele was also overrepresented in BRAF mutant cancers with MLH1 loss. Only one of the TSAs showed loss of MLH1 and the overall genotype distribution in TSAs did not differ from controls. The MLH1-93 AA genotype is significantly associated with promoter hypermethylation and MLH1 loss in the context of SSADs. BRAF mutant microsatellite stable colorectal cancers with the AA genotype most likely arise in TSAs since the A allele does not predispose to methylation in this context.

  18. Use of induced mutations in soybean breeding

    International Nuclear Information System (INIS)

    Zakri, A.H.; Jalani, B.S.; Ng, K.F.

    1981-01-01

    Artificial induction of mutation in plants is carried out using #betta#-irradiation and ethyl metanesulphonate (EMS) to expand the genetic variability of locally-grown soybean. This aspect of mutation breeding complements of conventional breeding approach undertaken by the Joint Malaysia Soybean Breeding Project group. Recovery of agronomically-important mutants such as earliness, lateness, bigger seed size and improved plant architecture were recorded. The significance of these findings is discussed. (author)

  19. Recent trends on crop genetic improvement using mutation techniques

    International Nuclear Information System (INIS)

    Kang, Siyong

    2008-01-01

    The radiation breeding technology has been significantly achieved on creation of mutation genetic resources of plants for commercial cultivation and genomic study since 1920s. According to the FAO-IAEA Mutant Variety Database, more than 2600 varieties have been released in the world. Induction of mutations with radiation has been the most frequently used by sources of X-ray and gamma ray, but in recent Japanese scientist have been used the heavy ion beam as a new radiation sources. And China has been made remarkable outcomes in the mutant creation using new space breeding technology since 1990s. In Korea, more about 40 varieties have been developed by using the mutation breeding method since the mid-1960s. Most of the released mutant varieties in Korea were food and oil seed crops, especially for improving agronomic traits such as yield, lodging tolerance, maturity, and functional compounds. Currently the mutation breeding program in Korea has assigned more resources to develop high functional crops and ornamental plants. These functional and ornamental plants are ideal systems for a mutation breeding. A research program for the development of potential varieties of flowering and ornamental crops as rose, chrysanthemum, lily, carnation, orchids, and wild flowers was started with financial support from the Bio green 21 project of Korean government. The potential outcomes from the program will be new highly valued-added varieties which will provide greater money gains to Korean farmers and lots of valued mutants used for a gene isolation of interest and reverse genetics or functional genomic. Scientific interest in mutation breeding has drastically be ed focused to the field of functional genomic. Scientific interest in mutation breeding has drastically be ed focused to the field of functional genomic after a completion of genome sequencing of some model plant species. A direct approach of discovering the function of a novel gene is to use a mutant which has altered

  20. Recent trends on crop genetic improvement using mutation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Siyong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-04-15

    The radiation breeding technology has been significantly achieved on creation of mutation genetic resources of plants for commercial cultivation and genomic study since 1920s. According to the FAO-IAEA Mutant Variety Database, more than 2600 varieties have been released in the world. Induction of mutations with radiation has been the most frequently used by sources of X-ray and gamma ray, but in recent Japanese scientist have been used the heavy ion beam as a new radiation sources. And China has been made remarkable outcomes in the mutant creation using new space breeding technology since 1990s. In Korea, more about 40 varieties have been developed by using the mutation breeding method since the mid-1960s. Most of the released mutant varieties in Korea were food and oil seed crops, especially for improving agronomic traits such as yield, lodging tolerance, maturity, and functional compounds. Currently the mutation breeding program in Korea has assigned more resources to develop high functional crops and ornamental plants. These functional and ornamental plants are ideal systems for a mutation breeding. A research program for the development of potential varieties of flowering and ornamental crops as rose, chrysanthemum, lily, carnation, orchids, and wild flowers was started with financial support from the Bio green 21 project of Korean government. The potential outcomes from the program will be new highly valued-added varieties which will provide greater money gains to Korean farmers and lots of valued mutants used for a gene isolation of interest and reverse genetics or functional genomic. Scientific interest in mutation breeding has drastically be ed focused to the field of functional genomic. Scientific interest in mutation breeding has drastically be ed focused to the field of functional genomic after a completion of genome sequencing of some model plant species. A direct approach of discovering the function of a novel gene is to use a mutant which has altered

  1. Sample preparation method for induced mutation on orchid

    International Nuclear Information System (INIS)

    Suhaimi Musa; Sakinah Ariffin

    2005-01-01

    Studies on the induction of mutation in Dendrobium orchid at MINT has produced a number of new orchid mutant cultivars. Tissue culture techniques on orchid seeds and meristem cloning are employed in preparing the samples for the mutation induction. Solid medium based on the Murashige and Skoog (1962) and liquid medium based on Vacin and Went (1949) were found to be suitable in producing protocorm like bodies (PLBs) that are required for the irradiation treatment. (Author)

  2. Mutation breeding in chickpea

    International Nuclear Information System (INIS)

    2009-01-01

    Chickpea is an important food legume in Turkey. Turkey is one of the most important gene centers in the world for legumes. The most widely known characteristic of chickpea is that it is an important vegetable protein source used in human and animal nutrition. However, the dry grains of chickpea, has 2-3 times more protein than our traditional food of wheat. In addition, cheakpea is also energy source because of its high carbohydrate content. It is very rich in some vitamin and mineral basis. In the plant breeding, mutation induction has become an effective way of supplementing existing germplasm and improving cultivars. Many successful examples of mutation induction have proved that mutation breeding is an effective and important approach to food legume improvement. The induced mutation technique in chickpea has proved successful and good results have been attained. Realizing the potential of induced mutations, a mutation breeding programme was initiated at the Nuclear Agriculture Section of the Saraykoey Nuclear Research and Training Center in 1994. The purpose of the study was to obtain high yielding chickpea mutants with large seeds, good cooking quality and high protein content. Beside this some characters such as higher adaptation ability, tolerant to cold and drought, increased machinery harvest type, higher yield, resistant to diseases especially to antracnose and pest were investigated too. Parents varieties were ILC-482, AK-7114 and AKCIN-91 (9 % seed moisture content and germination percentage 98 %) in these experiments. The irradiation doses were 0 (control), 50, 100, 150, 200, 250, 300, 350, 400, 500 ve 600 Gy for greenhouse experiments and 0 (control), 50, 100, 150, 200, 250, 300, 350 ve 400 Gy for field experiments, respectively. One thousand seeds for per treatment were sown in the field for the M 1 . At maturity, 3500 single plants were harvested and 20 seeds were taken from each M 1 plant and planted in the following season. During plant growth

  3. Induced mutations in pomoid trees breeding

    International Nuclear Information System (INIS)

    Hamed, Faysal

    1986-01-01

    Induction of mutations in fruit trees by ionizing radiation complements a cross-breeding program. The objectives are: 1) the improvements of methods of induction, identification and selection of useful mutations, and 2) the initiation of useful mutations either for immediate use as improved cultivars or as a parent material for conventional cross-breeding. The induction of mutants in pomoid fruits, with special emphasis on apple, was realized by gamma-ray treatment of dormant scions subsequently propagated on a rootstoch in the nursery. The aim was to obtain compacts, presuming the feasibility of selecting compact shoots formed by the irradiated scions in the first vegetative generation and also assuming that chance of finding (e.g. fruit mutants) would be thus increased rather than lessened. Selection was carried out on one-season old shoots, formed on the same material for two or three seasons, by using a cut-back at the end of the first and second season. The procedure was highly effective. Moderate exposures, resulting in 60% survival gave high mutation frequencies. Buds 6-10 on the primary shoot gave higher frequencies of recognizable mutations than either buds 1-5 or 11-15. Preliminary results seem to indicate that, at least in some apple cultivars, there is opportunity to obtain compact growth types with good biological characteristics. 8 refs. (author)

  4. Inductive Monitoring System (IMS)

    Data.gov (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  5. MUTANTES DE LARANJA - 'PÊRA' COM NÚMERO REDUZIDO DE SEMENTES, OBTIDOS ATRAVÉS DE MUTAÇÕES INDUZIDAS SWEET ORANGE 'PÊRA' MUTANTS WITH LOW NUMBER OF SEEDS OBTAINED THROUGH MUTATION INDUCTION

    Directory of Open Access Journals (Sweden)

    RODRIGO ROCHA LATADO

    2001-08-01

    Full Text Available A obtenção de cultivares de citros com pequeno número de sementes é importante quando o objetivo é a produção de frutas para o consumo in natura. O objetivo deste trabalho foi o de avaliar, por três anos (1997, 1998 e 1999, o número médio de sementes e 15 outras características agronômicas, de 127 mutantes putativos de laranja-'Pêra', selecionados após irradiação de borbulhas com raios-gama e 8 plantas selecionadas do controle não irradiado. Os mutantes foram divididos em 16 grupos baseados nos tipos de mutações observados e em cada grupo, como controle comum, foram incluídas plantas de laranja-'Pêra' comercial. Observou-se que 46 mutantes putativos e uma planta do controle não irradiado (PSC apresentaram redução significativa no número de sementes por fruto, nos três anos consecutivos, sendo que 15 mutantes apresentaram frutos com média entre uma e duas sementes e 9 mutantes, frutos com média inferior a uma semente. Dentre estes 9 mutantes, os de número 27, 28 e 58, que apresentaram também alterações significativas no diâmetro de copa ou na altura de planta, além do 59 e 101, que não apresentaram alterações nas outras 15 características avaliadas, possuem um maior potencial para serem lançados como novos mutantes de laranja-'Pêra' com pequeno número de sementes.Citrus varieties with low number of seeds are important for in natura fruit market. The objective of the present work was to evaluate, for three years (1997, 1998 and 1999, the average number of seeds per fruit and 15 other agronomic characteristics of 127 putative mutated clones of sweet orange 'Pêra', selected after gamma-irradiation of budwood and 8 non irradiated control clones. Mutants were divided in 16 groups based on the type of mutation observed 'Pêra' commercial control plants (PCC were included. It was observed that 46 putative mutants and one non-irradiated plant (PSC showed significant reduction in seed number per fruit. Fifteen

  6. Inductive Reasoning and Writing

    Science.gov (United States)

    Rooks, Clay; Boyd, Robert

    2003-01-01

    Induction, properly understood, is not merely a game, nor is it a gimmick, nor is it an artificial way of explaining an element of reasoning. Proper understanding of inductive reasoning--and the various types of reasoning that the authors term inductive--enables the student to evaluate critically other people's writing and enhances the composition…

  7. Mutations induced by X-radiation in the yeast Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Loprieno, N.; Barale, R.; Baroncelli, S.; Cammellini, A.; Melani, M.; Nieri, R.; Nozzolini, M.; Rossi, A.M.; Pisa Univ.

    1975-01-01

    Experiments on strains of yeast with different genetic backgrounds were done to evaluate the kinetics of inactivation and mutation induction by X-radiation. A system of forward mutation induction in five loci was used and a specific mutation rate was evaluated for the wild type. From a comparison of observations with wild type and radiation-sensitive strains, it may be assumed that in this yeast, mutations are mainly the result of a repair-active process. The range of genotypic and phenotypic influence upon the specific locus mutation rate was evaluated with appropriate biological material and experiments

  8. Promotion and inhibition of mutation in pathogens

    Directory of Open Access Journals (Sweden)

    Maurice Samuel Devaraj

    2014-03-01

    Findings from this research may be used to prevent development of drug resistance, whether epigenetic or arising due to deoxyribonucleic acid (DNA modification, in several pathogens, especially Mycobacterium tuberculosis through the co-administration of adenosine along with antibiotic treatment.

  9. Induction machine handbook

    CERN Document Server

    Boldea, Ion

    2002-01-01

    Often called the workhorse of industry, the advent of power electronics and advances in digital control are transforming the induction motor into the racehorse of industrial motion control. Now, the classic texts on induction machines are nearly three decades old, while more recent books on electric motors lack the necessary depth and detail on induction machines.The Induction Machine Handbook fills industry's long-standing need for a comprehensive treatise embracing the many intricate facets of induction machine analysis and design. Moving gradually from simple to complex and from standard to

  10. Induced mutations for crop improvement

    International Nuclear Information System (INIS)

    Micke, A.; Donini, B.; Maluszynski, M.

    1990-01-01

    Mutation induction has become an established tool in plant breeding to supplement existing germ plasma and to improve cultivars in certain specific traits. Hundreds of improved varieties have been released to farmers for many different crop species, demonstrating the economic value of the technology. Limitations arise mainly from the large mutagenized populations to be screened and from the unsatisfactory selection methods. Both limitations may be eased to some extent by advances in techniques of plant in-vitro culture. (author). Refs, 1 fig., 7 tabs

  11. Mutational specificity of SOS mutagenesis

    International Nuclear Information System (INIS)

    Kato, Takeshi

    1986-01-01

    In an approach to the isolation of mutants of E. coli unable to produce mutations by ultraviolet light, the author has found new umuC-mutants. Their properties could be explained by ''SOS hypothesis of Radman and Witkin'', which has now been justified by many investigators. Analysis of the umuC region of E. coli chromosome cloned in pSK 100 has led to the conclusion that two genes, umuD and umuC, having the capacity of mutation induction express in the same mechanism as that of SOS genes, which is known to be inhibited by LexA protein bonding to ''SOS box'' found at promotor region. Suppressor analysis for mutational specificity has revealed: (i) umuDC-independent mutagens, such as EMS and (oh) 4 Cy, induce selected base substitution alone; and (ii) umuDC-dependent mutagens, such as X-rays and gamma-rays, induce various types of base substitution simultaneously, although they have mutational specificity. In the umuDC-dependent processes of basechange mutagenesis, the spectra of base substitution were a mixture of base substitution reflecting the specific base damages induced by individual mutagens and nonspecific base substitution. In conclusion, base substitution plays the most important role in umuDC-dependent mutagenesis, although mutagenesis of umuDC proteins remains uncertain. (Namekawa, K.)

  12. Modification of mutation frequency in Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Vashishat, R.K.; Kakar, S.N.

    1976-01-01

    In a reverse mutation system, using haploid, histidine-requirinq strain of Saccharomyces cerevisiae, the frequency of uv-induced prototrophs increased if the post-irradiation minimal medium was supplemented with limited amounts of histidine. Addition of natural amino acids or RNA bases in the post-irradiation minimal medium, with or without histidine, also increased the uv-induced mutation frequency. Thus, post-irradiation conditions favouring protein and RNA synthesis, are effective in increasing uv-induced mutations in yeast. As compared to uv light, nitrous acid was more effective in inducing reversions in this strain and the frequency increased if the treated cells were plated on minimal medium supplemented with limited amounts of histidine. However, the addition of amino acids or RNA bases decreased the number of revertants. An additional inclusion of histidine reversed the suppressive effect of these metabolites. The mutation induction processes are thus different or differently modifiable in uv and nitrous acid. (author)

  13. DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression

    International Nuclear Information System (INIS)

    Straehle, U.; Klock, G.; Schuetz, G.

    1987-01-01

    To define the recognition sequence of the glucocorticoid receptor and its relationship with that of the progesterone receptor, oligonucleotides derived from the glucocorticoid response element of the tyrosine aminotransferase gene were tested upstream of a heterologous promoter for their capacity to mediate effects of these two steroids. The authors show that a 15-base-pair sequence with partial symmetry is sufficient to confer glucocorticoid inducibility on the promoter of the herpes simplex virus thymidine kinase gene. The same 15-base-pair sequence mediates induction by progesterone. Point mutations in the recognition sequence affect inducibility by glucocorticoids and progesterone similarly. Together with the strong conservation of the sequence of the DNA-binding domain of the two receptors, these data suggest that both proteins recognize a sequence that is similar, if not the same

  14. The use of radiations to induce useful mutations in fruit trees

    International Nuclear Information System (INIS)

    Donini, B.

    1976-01-01

    The researches carried out at Casaccia in this field had covered the problems of technique of mutagenic treatment, mechanism of mutation induction and methodology of somatic mutation isolation. To enhance the efficiency of somatic mutation induction several conditions during and after the treatment have been studied. More experience has been gained with regard to the induction of somatic mutation which raises from genetical event or by tissue arrangement of a chimaeric shoot apex. To increase the size of mutated sector treatment have been carried out on the primordia in a very early stages and to improve the methodology of somatic mutation special techniques have been adapted of handling the material in the propagation. Possibility for early detection of mutants has been explored in cherry by establishing a correlation between mutants and hormonal content. By using the above mentioned techniques, useful mutants have been isolated in cherries, grapes, olives and peaches. (author)

  15. New mutations affecting induced mutagenesis in yeast.

    Science.gov (United States)

    Lawrence, C W; Krauss, B R; Christensen, R B

    1985-01-01

    Previously isolated mutations in baker's yeast, Saccharomyces cerevisiae, that impair induced mutagenesis were all identified with the aid of tests that either exclusively or predominantly detect base-pair substitutions. To avoid this bias, we have screened 11 366 potentially mutant clones for UV-induced reversion of the frameshift allele, his4-38, and have identified 10 mutants that give much reduced yields of revertants. Complementation and recombination tests show that 6 of these carry mutations at the previously known REV1, REV1 and REV3 loci, while the remaining 4 define 3 new genes, REV4 (2 mutations), REV5 and REV6. The rev4 mutations are readily suppressed in many genetic backgrounds and, like the rev5 mutation, impart only a limited deficiency for induced mutagenesis: it is likely, therefore that the REV4+ and REV5+ gene functions are only remotely concerned with this process. The rev6 mutants have a more general deficiency, however, as well as marked sensitivity to UV and an increased spontaneous mutation rate, properties that suggest the REV6 gene is directly involved in mutation induction. The REV5 gene is located about 1 cM proximal to CYC1 on chromosome X.

  16. Induced mutations for disease resistance in wheat

    International Nuclear Information System (INIS)

    Cerny, J.; Hanis, M.; Hanisova, A.; Knytl, V.; Sasek, A.

    1983-01-01

    Mutation induction has been used over a period of 20 years to obtain mutants of wheat with improved disease resistance. 34 wheat cultivars have been treated with X-rays, gamma rays, thermal neutrons or EMS. A great number of mutants were selected. Their mutational origin was verified by electrophoretic analysis of gliadin spectra. Resistances have been confirmed over several generations. None of the mutants have been released yet for commercial cultivation because of shortcomings in yield or susceptibility to other diseases. The use of mutants in cross-breeding is considered. (author)

  17. Induction of homologous recombination in Saccharomyces cerevisiae.

    Science.gov (United States)

    Simon, J R; Moore, P D

    1988-09-01

    We have investigated the effects of UV irradiation of Saccharomyces cerevisiae in order to distinguish whether UV-induced recombination results from the induction of enzymes required for homologous recombination, or the production of substrate sites for recombination containing regions of DNA damage. We utilized split-dose experiments to investigate the induction of proteins required for survival, gene conversion, and mutation in a diploid strain of S. cerevisiae. We demonstrate that inducing doses of UV irradiation followed by a 6 h period of incubation render the cells resistant to challenge doses of UV irradiation. The effects of inducing and challenge doses of UV irradiation upon interchromosomal gene conversion and mutation are strictly additive. Using the yeast URA3 gene cloned in non-replicating single- and double-stranded plasmid vectors that integrate into chromosomal genes upon transformation, we show that UV irradiation of haploid yeast cells and homologous plasmid DNA sequences each stimulate homologous recombination approximately two-fold, and that these effects are additive. Non-specific DNA damage has little effect on the stimulation of homologous recombination, as shown by studies in which UV-irradiated heterologous DNA was included in transformation/recombination experiments. We further demonstrate that the effect of competing single- and double-stranded heterologous DNA sequences differs in UV-irradiated and unirradiated cells, suggesting an induction of recombinational machinery in UV-irradiated S. cerevisiae cells.

  18. Urofollitropin and ovulation induction

    NARCIS (Netherlands)

    van Wely, Madelon; Yding Andersen, Claus; Bayram, Neriman; van der Veen, Fulco

    2005-01-01

    Anovulation is a common cause of female infertility. Treatment for women with anovulation is aimed at induction of ovulation. Ovulation induction with follicle-stimulating hormone (FSH) is indicated in women with WHO type II anovulation in whom treatment with clomifene citrate (clomifene) has

  19. Inductance loop and partial

    CERN Document Server

    Paul, Clayton R

    2010-01-01

    "Inductance is an unprecedented text, thoroughly discussing "loop" inductance as well as the increasingly important "partial" inductance. These concepts and their proper calculation are crucial in designing modern high-speed digital systems. World-renowned leader in electromagnetics Clayton Paul provides the knowledge and tools necessary to understand and calculate inductance." "With the present and increasing emphasis on high-speed digital systems and high-frequency analog systems, it is imperative that system designers develop an intimate understanding of the concepts and methods in this book. Inductance is a much-needed textbook designed for senior and graduate-level engineering students, as well as a hands-on guide for working engineers and professionals engaged in the design of high-speed digital and high-frequency analog systems."--Jacket.

  20. Half Bridge Inductive Heater

    Directory of Open Access Journals (Sweden)

    Zoltán GERMÁN-SALLÓ

    2015-12-01

    Full Text Available Induction heating performs contactless, efficient and fast heating of conductive materials, therefore became one of the preferred heating procedure in industrial, domestic and medical applications. During induction heating the high-frequency alternating currents that heat the material are induced by means of electromagnetic induction. The material to be heated is placed inside the time-varying magnetic field generated by applying a highfrequency alternating current to an induction coil. The alternating electromagnetic field induces eddy currents in the workpiece, resulting resistive losses, which then heat the material. This paper describes the design of a power electronic converter circuit for induction heating equipment and presents the obtained results. The realized circuit is a low power half bridge resonant inverter which uses power MOS transistors and adequate driver circuits.

  1. v-src Induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element

    Energy Technology Data Exchange (ETDEWEB)

    Xie, W.; Fletcher, B.S.; Andersen, R.D.; Herschman, H.R. [Univ. of California, Los Angeles, CA (United States)

    1994-10-01

    The authors recently reported the cloning of a mitogen-inducible prostaglandin synthase gene, TIS10/PGS2. In addition to growth factor and tumor promoters, the v-src oncogene induces TIS10/PGS2 expression in 3T3 cells. Deletion analysis, using luciferase reporters, identifies a region between -80 and -40 nucleotides 5{prime} of the TIS10/PGS2 transcription start site that mediates pp60{sup v-src} induction in 3T3 cells. This region contains the sequence CGTCACGTG, which includes overlapping ATF/CRE (CGTCA) and E-box (CACGTG) sequences. Gel shift-oligonucleotide competition experiments with nuclear extracts from cells stably transfected with a temperature-sensitive v-src gene demonstrate that the CGTCACGTG sequence can bind proteins at both the AFT/CRE and E-box sequences. Dominant-negative CREB and Myc proteins that bind DNA, but do not transactivate, block v-src induction of a luciferase reporter driven by the first 80 nucleotides of the TIS10/PGS2 promoter. Mutational analysis distinguishes which TIS10/PGS2 cis-acting element mediates pp60{sup v-src} induction. E-box mutation has no effect on the fold induction in response to pp60{sup v-src}. In contrast, ATF/CRE mutation attenuates the pp{sup v-src} response. Antibody supershift and methylation interference experiments demonstrate that CREB and at least one other ATF transcription factor in these extracts bind to the TIS10/PGS2 ATF/CRE element. Expression of a dominant-negative ras gene also blocks TIS10/PGS2 induction by v-src. The data suggest that Ras mediates pp60{sup v-src} activation of an ATF transcription factor, leading to induced TIS10/PGS2 expression via the ATF/CRE element of the TIS10/PGS2 promoter. This is the first description of v-src activation of gene expression via an ATF/CRE element. 64 refs., 8 figs.

  2. SOS gene induction and possible mutagenic effects of freeze-drying in Escherichia coli and Salmonella typhimurium.

    Science.gov (United States)

    Rosen, Rachel; Buchinger, Sebastian; Pfänder, Ramona; Pedhazur, Rami; Reifferscheid, Georg; Belkin, Shimshon

    2016-11-01

    We report the results of a study of the potential negative effects of the freeze-drying process, normally considered a benign means for long-term conservation of living cells and the golden standard in bacterial preservation. By monitoring gene induction using a whole-cell Escherichia coli bioreporter panel, in which diverse stress-responsive gene promoters are fused to luminescent or fluorescent reporting systems, we have demonstrated that DNA repair genes belonging to the SOS operon (recA, sulA, uvrA, umuD, and lexA) were induced upon resuscitation from the freeze-dried state, whereas other stress-responsive promoters such as grpE, katG, phoA, soxS, and sodA were not affected. This observation was confirmed by the UMU-chromotest (activation of the umuD gene promoter) in Salmonella typhimurium, as well as by real-time PCR analyses of selected E. coli SOS genes. We further show that a functional SOS operon is important in viability maintenance following resuscitation, but that at the same time, this repair system may introduce significantly higher mutation rates, comparable to those induced by high concentrations of a known mutagen. Our results also indicate that the entire freeze-drying process, rather than either freezing or drying separately, is instrumental in the induction of DNA damage.

  3. Survival of mutations arising during invasions.

    Science.gov (United States)

    Miller, Judith R

    2010-03-01

    When a neutral mutation arises in an invading population, it quickly either dies out or 'surfs', i.e. it comes to occupy almost all the habitat available at its time of origin. Beneficial mutations can also surf, as can deleterious mutations over finite time spans. We develop descriptive statistical models that quantify the relationship between the probability that a mutation will surf and demographic parameters for a cellular automaton model of surfing. We also provide a simple analytic model that performs well at predicting the probability of surfing for neutral and beneficial mutations in one dimension. The results suggest that factors - possibly including even abiotic factors - that promote invasion success may also increase the probability of surfing and associated adaptive genetic change, conditioned on such success.

  4. Induction and evaluation of beneficial mutations in Volvariella volvacea mushroom

    International Nuclear Information System (INIS)

    Borromeo, J.D.

    1976-03-01

    The present strains of Volvariella volvacea are difficult to grow, hence the need for developing a wild-type mushroom that can be grown without the stringent cultural requirements. This would be suitable for backyard or small-scale production. A vigorous white mushroom that responds to the controlled conditions in mushroom houses is appropriate for large-scale or commercial production. The percentages success in getting the ''first flushes'' has been no more than 30%. There was a certain amount of difficulty in recognizing mutants based on their morphological features in laboratory culture. The first irradiation series utilizing 200 and 400 kR and using the box-type method of cultivation in growing the mushroom have given us the needed information in planning the next irradiation series

  5. In vitro methods for mutation induction in potato (Solanum ...

    African Journals Online (AJOL)

    BADO, Souleymane

    2016-09-28

    Sep 28, 2016 ... In addition to high starch levels, potato tubers contain significant ... 2000; Li et al., 2005) modified histological and texture properties (Nayak et al., ..... transported or shipped over long distances and stored for over 6 months.

  6. Induction of mutation in mango (Mangifera indica L.)

    International Nuclear Information System (INIS)

    Sharma, D.K.; Majumder, P.K.; Singh, R.N.

    1983-01-01

    Studies on evolving of improved plant types through physical and chemical mutagens are, in general, lacking in tree fruits, more particularly in Mango. The present study showed that the LD 50 values (γ-irradiation) for the mango cultivars Neelum, Dashehari and Mallika were 3.9, 2.9 and 2.4 Krad, respectively. The effective dosages of EMS and NMU for the cvs Dashehari and Neelum were 1.50 and 0.05 per cent, respectively. Primary effects of both physical and chemical mutagens were found to be more or less the same. Some interesting changes in vegetative characters have also been stabilised. Out of these a few plants appeared to be promising for dwarfness whereas in some others, fruit quality improved. (author)

  7. Induction of mutation in peas (Pisum sativum) in Peru

    International Nuclear Information System (INIS)

    Gomez Pando, L.; Torres Aranda, M.; Romero Loli, M.

    1984-01-01

    The production of peas, a staple food in Peru, can be increased by crop rotation with cereals in high lands (3000 m and above). Cultivation in high lands not only gives cultivar of higher proteic content but also improves the fertility of the soils. However, the low temperature (in the freezing region) in the high lands and the associated plant diseases are the major problems for this kind of cultivation. The present report describes the development of freezing and disease resistant mutants through mutagenesis with gamma radiation. Two varieties, Alderman and Amarilla, which had been adopted to high lands are selected for the present study. Two doses were used, 14 and 18 Krad, employing 4600 seeds/dose for the Alderman variety and 3600 seeds/dose for Amarilla. Preliminary results are presented

  8. Mutation induction in two crops by gamma rays

    African Journals Online (AJOL)

    PC-sonia

    2012-04-24

    Apr 24, 2012 ... dipsaci), rust (Uromyces fabae virus diseases and root rot (Rhizoctonia spp.) were also present (Hooper, 1983;. Kerkoud et al. 2007). Chocolate ..... utilized and neglected crops in low income food deficit countries through irradiation and related techniques, Pretoria, South Africa, pp. 127-130. Chaudhuri S ...

  9. Mutation induction of protein variability in wheat and rice

    International Nuclear Information System (INIS)

    Narahari, P.; Bhatia, C.R.; Gopalakrishna, T.; Mitra, R.K.

    1976-01-01

    No high protein mutants of wheat have been obtained without depression of grain yield after screening a few thousand lines. The best wheat mutant identified in our programme so far is an erectoid mutant that has consistently shown about 1.5-2% points increase in protein over Kalyan sona for the last four years. Grain yield of the mutant is about 89% of the parent. No significant variation in amino composition is noted in the mutant. Preliminary analysis of over 200 macro mutants in three varieties of rice has resulted in identification of mutants with high protein content (10-22%) compared with 8.0 to 8.5% in the high yielding controls. The amino-acid composition of some of the mutant kernels do not show great deviation from the controls. All the high protein percentage mutants are lower in grain yield. Despite very high F 1 sterility in a cross involving the high protein genotype GMPR-51 and high yielding IR-8, several fertile F 2 plants resembling IR-8 have been isolated which on preliminary analysis have shown still higher protein content than GMPR-51, suggesting a transgressive mode of inheritance of this trait. (author)

  10. Induction of mutation, through gamma rays, in sugarcane

    International Nuclear Information System (INIS)

    Vieira, M.A.S.; Matsuoka, S.; Ruschel, R.

    1984-01-01

    Variety buds Co-740 of sugar cane were irradiated with gamma rays 60 Co at 0.0, 3.0, 4.0, 5.0, 6.0 and 7.0 kR to study changes in the obtained progeny. Evaluation of the germination capacity, height of plants and morphological changes were studied in the different treatments. (M.A.C.) [pt

  11. Mutated genes as research tool

    International Nuclear Information System (INIS)

    1981-01-01

    Green plants are the ultimate source of all resources required for man's life, his food, his clothes, and almost all his energy requirements. Primitive prehistoric man could live from the abundance of nature surrounding him. Man today, dominating nature in terms of numbers and exploiting its limited resources, cannot exist without employing his intelligence to direct natural evolution. Plant sciences, therefore, are not a matter of curiosity but an essential requirement. From such considerations, the IAEA and FAO jointly organized a symposium to assess the value of mutation research for various kinds of plant science, which directly or indirectly might contribute to sustaining and improving crop production. The benefit through developing better cultivars that plant breeders can derive from using the additional genetic resources resulting from mutation induction has been assessed before at other FAO/IAEA meetings (Rome 1964, Pullman 1969, Ban 1974, Ibadan 1978) and is also monitored in the Mutation Breeding Newsletter, published by IAEA twice a year. Several hundred plant cultivars which carry economically important characters because their genes have been altered by ionizing radiation or other mutagens, are grown by farmers and horticulturists in many parts of the world. But the benefit derived from such mutant varieties is without any doubt surpassed by the contribution which mutation research has made towards the advancement of genetics. For this reason, a major part of the papers and discussions at the symposium dealt with the role induced-mutation research played in providing insight into gene action and gene interaction, the organization of genes in plant chromosomes in view of homology and homoeology, the evolutionary role of gene duplication and polyploidy, the relevance of gene blocks, the possibilities for chromosome engineering, the functioning of cytroplasmic inheritance and the genetic dynamics of populations. In discussing the evolutionary role of

  12. Review of induction LINACS

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1981-10-01

    There has been a recent upsurge of activity in the field of induction linacs, with several new machines becoming operational and others in the design stages. The performance levels of electron machines have reached 10's of kiloamps of current and will soon reach 10's of MeV's of energy. Acceleration of ion current has been demonstrated, and the study of a 10 GeV heavy ion induction linac for ICF continues. The operating principles of induction linacs are reviewed with the emphasis on design choices which are important for increasing the maximum beam currents

  13. Review of induction linacs

    International Nuclear Information System (INIS)

    Faltens, A.; Keefe, D.

    1982-01-01

    There has been a recent upsurge of activity in the field of induction linacs, with several new machines becoming operational and others in the design stages. The performance levels of electron machines have reached 10's of kiloamps of current and will soon reach 10's of MeV's of energy. Acceleration of several kiloamps of ion current has been demonstrated, and the study of a 10 GeV heavy ion induction linac for ICF continues. The operating principles of induction linacs are reviewed with the emphasis on design choices which are important for increasing the maximum beam currents

  14. Properties of inductive reasoning.

    Science.gov (United States)

    Heit, E

    2000-12-01

    This paper reviews the main psychological phenomena of inductive reasoning, covering 25 years of experimental and model-based research, in particular addressing four questions. First, what makes a case or event generalizable to other cases? Second, what makes a set of cases generalizable? Third, what makes a property or predicate projectable? Fourth, how do psychological models of induction address these results? The key results in inductive reasoning are outlined, and several recent models, including a new Bayesian account, are evaluated with respect to these results. In addition, future directions for experimental and model-based work are proposed.

  15. In vivo identification of promoter elements and transcription factors mediating activation of hepatic HMG-CoA reductase by T{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Lindsey R.; Niesen, Melissa I. [Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL (United States); Jaroszeski, Mark [Department of Chemical and Biomedical Engineering, College of Engineering, University of South Florida, Tampa, FL (United States); Ness, Gene C., E-mail: gness@hsc.usf.edu [Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL (United States)

    2009-07-31

    The promoter elements and transcription factors necessary for triiodothyronine (T{sub 3}) induction of hepatic HMG-CoA reductase (HMGR) were investigated by transfecting rat livers with wild type and mutant HMGR promoter-luciferase constructs using in vivo electroporation. Mutations in the sterol response element (SRE), nuclear factor-y (NF-Y) site, and the newly identified upstream transcription factor-2 (USF-2) site essentially abolished the T{sub 3} response. Chromatin immunoprecipitation (ChIP) analysis demonstrated that T{sub 3} treatment caused a 4-fold increase in in vivo binding of USF-2 to the HMGR promoter. Co-transfection of the wild type HMGR promoter with siRNAs to USF-2, SREBP-2, or NF-Y nearly abolished the T{sub 3} induction, as measured by promoter activity. These data provide in vivo evidence for functional roles for USF-2, SREBP-2, and NF-Y in mediating the T{sub 3}-induction of hepatic HMGR transcription.

  16. R and D activities on radiation induced mutation breeding

    International Nuclear Information System (INIS)

    Lapade, A.G.; Asencion, A.B.; Santos, I.S.; Grafia, A.O.; Veluz, AM.S.; Barrida, A.C.; Marbella, L.J.

    1996-01-01

    This paper summarizes the accomplishments, prospects and future plans of mutation breeding for crop improvement at the Philippine Nuclear Research Institute (PNRI). Mutation induction has become a proven way creating variation within a crop variety and inducing desired attributes that cannot be found in nature or have been lost during evolution. Several improved varieties with desirable traits were successfully developed through induced mutation breeding at our research institute. In rice, mutation breeding has resulted in the development of new varieties: (1) PARC 2, (2) Milagrosa mutant, (3) Bengawan mutant and (4) Azmil mutant. Mutation breeding in leguminous crops has led to the induction of an improved L 114 soybean mutant that is shorter that the original variety but yield about 40% more. Several PAEC mungbean varieties characterized with long pods that are non-shattering were also induced. In asexually propagated crops, an increase in yield and chlorophyll mutants were obtained in sweet potatos. Likewise, chlorophyll mutant which look-like 'ornamental bromeliads' and a mutant with reduced spines have been developed in pineapple Queen variety. At present, we have started a new project in mutation breeding in ornamentals. Tissue culture is being utilized in our mutation breeding program. In the near future, radiation induced mutagenesis coupled with in vitro culture techniques on protoplast culture and somatic hybridization will be integrated into our mutation breeding program to facilitate the production of new crop varieties. (author)

  17. Plant mutation reports, Vol. 2, No. 1, December 2008

    International Nuclear Information System (INIS)

    2008-12-01

    The International Symposium on Induced Mutations in Plants (ISIMP) was successfully held in Vienna, Austria 12-15 August 2008. It attracted more almost 500 participants, demonstrating a broad interest in induced mutations in the plant breeding and research community. The titles of oral presentations are included in this issue. Some papers submitted to the Symposium by authors who were unable to attend the Symposium are included in this issue. In this issue, you will learn that mutations can be induced in uncommon plants using various means and utilized for various purposes. For example, Kacholam, guar and cocoyam are not widely cultivated crop species and there is very limited genetic variability, Kanakamanay, Arora et al. and Ndzana et al. reported the induction of mutations as a valuable source of genetic variability in these crops. Rice is a staple food crop and has a history of successful application of mutation techniques for its improvement; however, the virus resistant mutant varieties released in the United Republic of Tanzania, the cold tolerant mutant lines developed in Madagascar and the use of proton radiation for mutation induction in this field. The use of mutation techniques for improving tomato productivity in low water supply area, for increasing crossability and progeny fertility of mungbean crossed with its wild relative species and for investigating leaf structure in mungbean are convincing examples of the usefulness of mutation techniques

  18. Hyperthermia-induced alteration of yeast susceptibility to mutation

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Morrison, D.P.

    1985-01-01

    Diploid yeast (s. cerevisiae) were examined for alterations in susceptibility to induced mutation following hyperthermia treatment. In cells grown at 23 0 C, a non-lethal heat exposure (38 0 C, 30 min) markedly suppressed mutation induced by a subsequent non-killing dose of MNNG of MNU. Mutation by ENU, 8-MOP + UVA, or γ-rays was not affected. An intermediate level of mutation suppression was observed for mutation by 254nm UV or MMS. Mutation by MNNG was not suppressed by the same heat treatment delivered after the mutagen exposure. In a split dose experiment (two MNNG treatments separated by a heat exposure) no suppression of mutation was observed. Treatment with cycloheximide mimicked the effect of heat treatment. These data suggest that mutation induction by MNNG or MNU is protein synthesis dependent, i.e. an error-prone repair system is induced by exposure to MNNG or MNU but not by ENU, 8-MOP+UVA or γ-irradiation. We propose that hyperthermia treatment, by inducing stress protein synthesis at the expense of normal protein synthesis, precludes induction of this error-prone system. Therefore, in heat treated cells, DNA lesions produced by MNNG or MNU exposure must be resolved by an essentially constitutive system which is less error-prone than the inducible one

  19. Induction melter apparatus

    Science.gov (United States)

    Roach, Jay A [Idaho Falls, ID; Richardson, John G [Idaho Falls, ID; Raivo, Brian D [Idaho Falls, ID; Soelberg, Nicholas R [Idaho Falls, ID

    2008-06-17

    Apparatus and methods of operation are provided for a cold-crucible-induction melter for vitrifying waste wherein a single induction power supply may be used to effect a selected thermal distribution by independently energizing at least two inductors. Also, a bottom drain assembly may be heated by an inductor and may include an electrically resistive heater. The bottom drain assembly may be cooled to solidify molten material passing therethrough to prevent discharge of molten material therefrom. Configurations are provided wherein the induction flux skin depth substantially corresponds with the central longitudinal axis of the crucible. Further, the drain tube may be positioned within the induction flux skin depth in relation to material within the crucible or may be substantially aligned with a direction of flow of molten material within the crucible. An improved head design including four shells forming thermal radiation shields and at least two gas-cooled plenums is also disclosed.

  20. Induction of gastrin expression in gastrointestinal cells by hypoxia or cobalt is independent of hypoxia-inducible factor (HIF).

    Science.gov (United States)

    Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2012-07-01

    Gastrin and its precursors have been shown to promote mitogenesis and angiogenesis in gastrointestinal tumors. Hypoxia stimulates tumor growth, but its effect on gastrin gene regulation has not been examined in detail. Here we have investigated the effect of hypoxia on the transcription of the gastrin gene in human gastric cancer (AGS) cells. Gastrin mRNA was measured by real-time PCR, gastrin peptides were measured by RIA, and gastrin promoter activity was measured by dual-luciferase reporter assay. Exposure to a low oxygen concentration (1%) increased gastrin mRNA concentrations in wild-type AGS cells (AGS) and in AGS cells overexpressing the gastrin receptor (AGS-cholecystokinin receptor 2) by 2.1 ± 0.4- and 4.1 ± 0.3-fold (P factor hypoxia-inducible factor 1 (HIF-1) or knockdown of either the HIF-1α or HIF-1β subunit did not affect gastrin promoter inducibility under hypoxia indicated that the hypoxic activation of the gastrin gene is likely HIF independent. Mutational analysis of previously identified Sp1 regulatory elements in the gastrin promoter also failed to abrogate the induction of promoter activity by hypoxia. The observations that hypoxia up-regulates the gastrin gene in AGS cells by HIF-independent mechanisms, and that this effect is enhanced by the presence of gastrin receptors, provide potential targets for gastrointestinal cancer therapy.

  1. Linear induction accelerator

    Science.gov (United States)

    Buttram, M.T.; Ginn, J.W.

    1988-06-21

    A linear induction accelerator includes a plurality of adder cavities arranged in a series and provided in a structure which is evacuated so that a vacuum inductance is provided between each adder cavity and the structure. An energy storage system for the adder cavities includes a pulsed current source and a respective plurality of bipolar converting networks connected thereto. The bipolar high-voltage, high-repetition-rate square pulse train sets and resets the cavities. 4 figs.

  2. Radiation-induced mutations and plant breeding

    International Nuclear Information System (INIS)

    Naqvi, S.H.M.

    1985-01-01

    Ionizing radiation could cause genetic changes in an organism and could modify gene linkages. The induction of mutation through radiation is random and the probability of getting the desired genetic change is low but can be increased by manipulating different parameters such as dose rate, physical conditions under which the material has been irradiated, etc. Induced mutations have been used as a supplement to conventional plant breeding, particularly for creating genetic variability for specific characters such as improved plant structure, pest and disease resistance, and desired changes in maturity period; more than 200 varieties of crop plants have been developed by this technique. The Pakistan Atomic Energy Commission has used this technique fruitfully to evolve better germplasm in cotton, rice, chickpea, wheat and mungbean; some of the mutants have become popular commercial varieties. This paper describes some uses of radiation induced mutations and the results achieved in Pakistan so far

  3. Linear induction accelerators

    International Nuclear Information System (INIS)

    Briggs, R.J.

    1986-06-01

    The development of linear induction accelerators has been motivated by applications requiring high-pulsed currents of charged particles at voltages exceeding the capability of single-stage, diode-type accelerators and at currents too high for rf accelerators. In principle, one can accelerate charged particles to arbitrarily high voltages using a multi-stage induction machine, but the 50-MeV, 10-kA Advanced Test Accelerator (ATA) at LLNL is the highest voltage machine in existence at this time. The advent of magnetic pulse power systems makes sustained operation at high-repetition rates practical, and this capability for high-average power is very likely to open up many new applications of induction machines in the future. This paper surveys the US induction linac technology with primary emphasis on electron machines. A simplified description of how induction machines couple energy to the electron beam is given, to illustrate many of the general issues that bound the design space of induction linacs

  4. Effects of the umuC36 mutation on ultraviolet-radiation-induced base-change and frameshift mutations in Escherichia coli

    International Nuclear Information System (INIS)

    Kato, T.; Nakano, E.

    1981-01-01

    The effects of the umuC36 mutation on the induction of base-change and frameshift mutations were studied. An active umuC gene was necessary in either the uvr + or uvr - strains of Escherichia coli K12 for UV- and X-ray-induced mutations to His + , ColE and Spc, which are presumably base-change mutations, but it was not essential for ethyl methanesulphonate or N-methyl-N'-nitro-N-nitrosoguanidine-induced His + mutations. In contrast, only 1 out of 13 trp - frameshift mutations examined was UV reversible, and the process of mutagenesis was umuC + -dependent, whereas a potent frameshift mutagen, ICR191, effectively induced Trp + mutations in most of the strains regardless of the umu + or umuC genetic background. These results suggest that base substitutions are a major mutational type derived from the umuC + -dependent pathway of error-prone repair. (orig.)

  5. Mutation breeding in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Neto, A T; Menten, J O.M. [Centro de Energia Nuclear na Agricultura, Piracicaba (Brazil); Ando, A

    1980-03-01

    How mutation induction is used for plant breeding in Brazil is reported. For upland rice, the combined treatment with gamma-ray and mutagens (ethylene imine or ethylmethane sulfonate) has been used on the variety, Dourado Precoce, and some mutants with shortculm length and/or earliness without altering the productivity have been obtained. A project on the quantitative and qualitative protein improvement in upland rice was also started in 1979. In corn, the effect of gamma-irradiation on heterosis has been analyzed, and it was found that the single hybrids from two parental lines derived from irradiated seeds had increased ear productivity. For beans (Phaseolus yulgaris), gamma-irradiation and chemical mutagens have been used to induce the mutants with different seed color, disease resistance to golden mosaic virus and Xanthomonas phaseoli, earliness, high productivity and high protein content. Some mutants with partly improved characters have been obtained in these experiments. Two varieties of wheat tolerant to aluminum toxicity have been obtained, but the one showed high lodging due to its unfavorable plant height, and the other was highly susceptible to culm rust. Therefore, irradiation experiments have been started to improve these characters. The projects involving the use of gamma-irradiation have been tested to obtain the mutant lines insensitive to photoperiod and resistant to bud-blight in soybean, the mutant lines resistant to mosaic virus in papaya, the photoperiod-insensitive mutants in sorghum, the mosaic virus resistant and non-flowering mutants in sugar cane, and the Fusarium and nematode-resistant mutants in black pepper.

  6. Mechanisms and secondary factors involved in the induction of radiation transformation in vitro

    International Nuclear Information System (INIS)

    Little, J.B.

    1983-01-01

    The long term of this research program was to gain information concerning the mechanisms that determine the carcinogenic effects of ionizing radiation, particularly high LET radiation exposure. The experimental approach involves parallel studies of the induction of malignant transformation in BALB/3T3 cells and of specific gene mutations in human lymphoblastoid cells. Emphasis was on the biologic effects of internally incorporated Auger electron emitting radionuclides and the initiation of studies to determine the effects of low dose-rate neutron exposure. Auger electron irradiation sever as a model for high LET-type radiation effects and as an experimental tool for studying the effects of radiation at specific sites within the cell. Auger-emitting radiosotopes are commonly used in clinical nuclear medicine, rendering them a potential hazard to human populations. We examined the influence of cellular localization of Auger-emitting radionuclides and the spectrum of energy distribution in DNA on their mutagenic, cytogenetic, and transformational effects. The effects of 125 I (an energetic beta emitter) were compared. We studied the induction of cytogenetic changes by 125 I exposure of the cell membrane, as well as its potential to promote (enhance) transformation initiated by low dose external x-ray exposure. We will investigate the Relative Biological Effectiveness for mutagenesis and transformation of low doses of fast neutrons delivered continuously at variable low dose-rates. 34 refs., 1 tab

  7. The dual nature of mismatch repair as antimutator and mutator

    DEFF Research Database (Denmark)

    Bak, Sara Thornby; Sakellariou, Despoina; Pena Diaz, Javier

    2014-01-01

    MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly...

  8. Estrogen response of MCF-7 cells grown on diverse substrates and in suspension culture: promotion of morphological heterogeneity, modulation of progestin receptor induction; cell-substrate interactions on collagen gels.

    Science.gov (United States)

    Pourreau-Schneider, N; Berthois, Y; Mittre, H; Charpin, C; Jacquemier, J; Martin, P M

    1984-12-01

    In this study we observed the incidence of hormone sensitivity in the response of MCF-7 cells to estrogen stimulation when the cells were cultured in different contact environments (hydrophilic plastic, bovine corneal extracellular matrix, type I collagen and in suspension culture). The major purpose was to describe the influence of cell to cell and cell to substrate contacts on the morphological response to estrogen treatment. However, other parameters including growth and induction of progestin receptor were also explored, keeping in mind that the MCF-7 cell line, although representative of normal mammary epithelium in that it contains a similar hormone receptivity, was selected in vitro from a metastatic population in a pleural effusion. Although substrate conditions did not modify growth enhancement by estrogens, progestin receptor levels were significantly higher in three-dimensional spheroid cultures in which cell to cell contacts were optimal due to elimination of basal contact. A careful morphological survey of large surfaces lead to an objective opinion of the overall effect of the hormone treatment on the non-cloned cell line in which a marked heterogeneity in the response of individual cells was observed. In terms of morphofunctional differentiation, the edification of acini with dense microvillus coating was best in suspension culture. When sections were made perpendicular to the plane of cultures on collagen gel rafts two other phenomena were noted: decrease in intercellular junctions, resulting in reduced cell to cell cohesion, and accumulation biodegradation products in the collagen lattice. This suggested a hormone-mediated interaction between the metastatic cells and the fibrillar substrate, collagen I, one of the major constituents of tissue stroma. This estrogen response might be related to the metastatic phenotype and must be distinct from their hormone sensitivity in terms of growth and differentiation since hormone receptivity is generally

  9. Relationship between the induction frequency and LTE in inductively coupled plasmas

    International Nuclear Information System (INIS)

    Mostaghimi, J.; Boulos, M.I.

    1990-01-01

    In this paper, the effect of the induction frequency on the local thermodynamic equilibrium (LTE) conditions in an inductively coupled plasma is investigated. Using generators with frequencies ranging from 5 to 56 MHz, a previous study investigated demonstrated the importance of this effect. Their measurements of the excitation temperatures of the iron atomic lines showed a sharp decrease in this temperature as a result of the increase in frequency. Another conclusion was that, all other parameters constant, increase in frequency will help the promotion of non-LTE effects

  10. Inductive dielectric analyzer

    International Nuclear Information System (INIS)

    Agranovich, Daniel; Popov, Ivan; Ben Ishai, Paul; Feldman, Yuri; Polygalov, Eugene

    2017-01-01

    One of the approaches to bypass the problem of electrode polarization in dielectric measurements is the free electrode method. The advantage of this technique is that, the probing electric field in the material is not supplied by contact electrodes, but rather by electromagnetic induction. We have designed an inductive dielectric analyzer based on a sensor comprising two concentric toroidal coils. In this work, we present an analytic derivation of the relationship between the impedance measured by the sensor and the complex dielectric permittivity of the sample. The obtained relationship was successfully employed to measure the dielectric permittivity and conductivity of various alcohols and aqueous salt solutions. (paper)

  11. The effect of spermine on spontaneous and UV-induced mutations in Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Prendergast, J.A.; Kamra, O.P.; Nasim, A.

    1984-01-01

    The effect of different concentrations of spermine on spontaneous and UV-induced mutation in the adenine forward mutation system of Schizosaccharomyces pombe was investigated. The effect of spermine on spontaneous mutation was studied in 5 mutator strains (mut 1-4, mut 1-23, mut 2-9, mut 2-20 and mut 3-21) and on UV-induced mutation in a pigmented adenine-requiring strain and its radiation-sensitive derivative (rad 13). The effect of spermine exposure on mutation induction before and after UV irradiation was also investigated. Spermine increased spontaneous forward mutation in the mut 1-4 strain by 47% and enhanced UV-induced forward mutation 2-fold in the rad 13 and normal pigmented strains. No antimutagenic effect of spermine was seen in any of the strains tested. This is in marked contrast to the antimutagenic effect of spermine observed with bacteria. (Auth.)

  12. The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's Macroglobulinemia.

    Science.gov (United States)

    Cao, Y; Hunter, Z R; Liu, X; Xu, L; Yang, G; Chen, J; Patterson, C J; Tsakmaklis, N; Kanan, S; Rodig, S; Castillo, J J; Treon, S P

    2015-01-01

    CXCR4(WHIM) somatic mutations are common Waldenstrom's Macroglobulinemia (WM), and are associated with clinical resistance to ibrutinib. We engineered WM cells to express the most common WHIM (Warts, Hypogammaglobulinemia, Infections and Myelokathexis), CXCR(S338X) mutation in WM. Following SDF-1a stimulation, CXCR4(S338X) WM cells exhibited decreased receptor internalization, enhanced and sustained AKT kinase (AKT) and extracellular regulated kinase (ERK) signaling, decreased poly (ADP-ribose) polymerase and caspase 3 cleavage, and decreased Annexin V staining versus CXCR4 wild-type (WT) cells. CXCR4(S338X)-related signaling and survival effects were blocked by the CXCR4 inhibitor AMD3100. SDF-1a-treated CXCR4(S338X) WM cells showed sustained AKT and ERK activation and decreased apoptotic changes versus CXCR4(WT) cells following ibrutinib treatment, findings which were also reversed by AMD3100. AKT or ERK antagonists restored ibrutinib-triggered apoptotic changes in SDF-1a-treated CXCR4(S338X) WM cells demonstrating their role in SDF-1a-mediated ibrutinib resistance. Enhanced bone marrow pAKT staining was also evident in CXCR4(WHIM) versus CXCR4(WT) WM patients, and remained active despite ibrutinib therapy in CXCR4(WHIM) patients. Last, CXCR4(S338X) WM cells showed varying levels of resistance to other WM relevant therapeutics, including bendamustine, fludarabine, bortezomib and idelalisib in the presence of SDF-1a. These studies demonstrate a functional role for CXCR4(WHIM) mutations, and provide a framework for investigation of CXCR4 inhibitors in WM.

  13. Modeling Induction Motor Imbalances

    DEFF Research Database (Denmark)

    Armah, Kabenla; Jouffroy, Jerome; Duggen, Lars

    2016-01-01

    This paper gives a study into the development of a generalized model for a three-phase induction motor that offers flexibility of simulating balanced and unbalanced parameter scenarios. By analyzing the interaction of forces within the motor, we achieve our main objective of deriving the system d...

  14. Mutated clones of sweet orange cv. pera with late ripening obtained through mutation induction

    International Nuclear Information System (INIS)

    Rocha Latado, Rodrigo; Tulmann Neto, Augusto; Ando, Akihiko; Iemma, Antonio Francisco; Pompeu Junior, Jorgino; Figueiredo, Jose Orlando; Pio, Rose Mary; Machado, Marcos Antonio; Namekata, Takao; Ceravolo, Leonardo; Rossi, Antonio Carlos

    2001-01-01

    Sweet orange cv. Pera (Citrus sinensis L. Osbeck) harvested from July to November, is the most important cultivar in growing area and consumption in Brazil. To obtain mutants for many characteristics, one-year-old shoots were irradiated at 40 Gy of gamma-rays and the axillary buds were budded. After two cutting-backs, about 7,580 V3M1 plants were obtained. Total of 127 putative mutants were selected from these plants for further examination. The main purpose of this experiment was to obtain late ripening clones which have good fruit quality. These all plants were divided into 15 groups based on the characteristics and random blocks design with 5 replications, including one control plant in each block, was used. The plants were planted 4 X 7 meters and were grown in field condition without artificial irrigation. Ten fruits from each tree were used in evaluating the fruit characteristics such as contents of soluble solid (TSS), acidity, ratio of juice content and skin color, for four years. The data was analyzed by Dunnett test using SAS program. Six clones (9, 10, 16, 21, 58 and 84) were considered as late ripening mutants because they showed lower level of TSS or less ratio of juice content, comparing with the control, in more than one evaluation. The color of the skin of some mutants indicates that they have later ripening characteristics. Other agronomic characteristics are under evaluation in order to see if these mutants can be released as new cultivars

  15. Chloroplast mutations induced by 9-aminoacridine hydrochloride are independent of the plastome mutator in Oenothera.

    Science.gov (United States)

    GuhaMajumdar, M; Baldwin, S; Sears, B B

    2004-02-01

    Oenothera plants homozygous for the recessive plastome mutator allele ( pm) show chloroplast DNA (cpDNA) mutation frequencies that are about 1,000-fold higher than spontaneous levels. The pm-encoded gene product has been hypothesized to have a function in cpDNA replication, repair and/or mutation avoidance. Previous chemical mutagenesis experiments with the alkylating agent nitroso-methyl urea (NMU) showed a synergistic effect of NMU on the induction of mutations in the pm line, suggesting an interaction between the pm-encoded gene product and one of the repair systems that corrects alkylation damage. The goal of the experiments described here was to examine whether the pm activity extends to the repair of damage caused by non-alkylating mutagens. To this end, the intercalating mutagen, 9-aminoacridine hydrochloride (9AA) was tested for synergism with the plastome mutator. A statistical analysis of the data reported here indicates that the pm-encoded gene product is not involved in the repair of the 9AA-induced mutations. However, the recovery of chlorotic sectors in plants derived from the mutagenized seeds shows that 9AA can act as a mutagen of the chloroplast genome.

  16. Induced mutations in chickpea (Cicer arietinum L.) II. frequency and spectrum of chlorophyll mutations

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    1998-01-01

    A comparative study of frequency and spectrum of chlorophyll mutations induced by two physical (gamma rays, fast neutrons) and two chemical mutagens (NMU, EMS) in relation to the effects in M1 plants and induction of mutations in M2 was made in four chickpea (Cicer arietinum L.) varieties, two desi (G 130 & H 214) one Kabuli (C 104) and one green seeded (L 345). The treatments included three doses each of gamma rays (400, 500 & 600 Gy) and fast neutrons (5, 10 & 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU [0.01% (20h), & 0.02% (8h)] and EMS [0.1% (20h) & 0.2% (8h)]. The frequencies and spectrum of three different kinds of induced chlorophyll mutations in the order albina (43.5%), chlorina (27.3%) and xantha (24.2%) were recorded. Chemical mutagens were found to be efficient in inducing chlorophyll mutations in chickpea. Highest frequency of mutations was observed in green seeded var. L 345 (83% of M1 families and 19.9/1000 M2 plants). Kabuli var. C 104 was least responsive for chlorophyll mutations

  17. High current induction linacs

    International Nuclear Information System (INIS)

    Barletta, W.; Faltens, A.; Henestroza, E.; Lee, E.

    1994-07-01

    Induction linacs are among the most powerful accelerators in existence. They have accelerated electron bunches of several kiloamperes, and are being investigated as drivers for heavy ion driven inertial confinement fusion (HIF), which requires peak beam currents of kiloamperes and average beam powers of some tens of megawatts. The requirement for waste transmutation with an 800 MeV proton or deuteron beam with an average current of 50 mA and an average power of 40 MW lies midway between the electron machines and the heavy ion machines in overall difficulty. Much of the technology and understanding of beam physics carries over from the previous machines to the new requirements. The induction linac allows use of a very large beam aperture, which may turn out to be crucial to reducing beam loss and machine activation from the beam halo. The major issues addressed here are transport of high intensity beams, availability of sources, efficiency of acceleration, and the state of the needed technology for the waste treatment application. Because of the transformer-like action of an induction core and the accompanying magnetizing current, induction linacs make the most economic sense and have the highest efficiencies with large beam currents. Based on present understanding of beam transport limits, induction core magnetizing current requirements, and pulse modulators, the efficiencies could be very high. The study of beam transport at high intensities has been the major activity of the HIF community. Beam transport and sources are limiting at low energies but are not significant constraints at the higher energies. As will be shown, the proton beams will be space-charge-dominated, for which the emittance has only a minor effect on the overall beam diameter but does determine the density falloff at the beam edge

  18. High mutation rates limit evolutionary adaptation in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Kathleen Sprouffske

    2018-04-01

    Full Text Available Mutation is fundamental to evolution, because it generates the genetic variation on which selection can act. In nature, genetic changes often increase the mutation rate in systems that range from viruses and bacteria to human tumors. Such an increase promotes the accumulation of frequent deleterious or neutral alleles, but it can also increase the chances that a population acquires rare beneficial alleles. Here, we study how up to 100-fold increases in Escherichia coli's genomic mutation rate affect adaptive evolution. To do so, we evolved multiple replicate populations of asexual E. coli strains engineered to have four different mutation rates for 3000 generations in the laboratory. We measured the ability of evolved populations to grow in their original environment and in more than 90 novel chemical environments. In addition, we subjected the populations to whole genome population sequencing. Although populations with higher mutation rates accumulated greater genetic diversity, this diversity conveyed benefits only for modestly increased mutation rates, where populations adapted faster and also thrived better than their ancestors in some novel environments. In contrast, some populations at the highest mutation rates showed reduced adaptation during evolution, and failed to thrive in all of the 90 alternative environments. In addition, they experienced a dramatic decrease in mutation rate. Our work demonstrates that the mutation rate changes the global balance between deleterious and beneficial mutational effects on fitness. In contrast to most theoretical models, our experiments suggest that this tipping point already occurs at the modest mutation rates that are found in the wild.

  19. Variable mutation rates as an adaptive strategy in replicator populations.

    Directory of Open Access Journals (Sweden)

    Michael Stich

    2010-06-01

    Full Text Available For evolving populations of replicators, there is much evidence that the effect of mutations on fitness depends on the degree of adaptation to the selective pressures at play. In optimized populations, most mutations have deleterious effects, such that low mutation rates are favoured. In contrast to this, in populations thriving in changing environments a larger fraction of mutations have beneficial effects, providing the diversity necessary to adapt to new conditions. What is more, non-adapted populations occasionally benefit from an increase in the mutation rate. Therefore, there is no optimal universal value of the mutation rate and species attempt to adjust it to their momentary adaptive needs. In this work we have used stationary populations of RNA molecules evolving in silico to investigate the relationship between the degree of adaptation of an optimized population and the value of the mutation rate promoting maximal adaptation in a short time to a new selective pressure. Our results show that this value can significantly differ from the optimal value at mutation-selection equilibrium, being strongly influenced by the structure of the population when the adaptive process begins. In the short-term, highly optimized populations containing little variability respond better to environmental changes upon an increase of the mutation rate, whereas populations with a lower degree of optimization but higher variability benefit from reducing the mutation rate to adapt rapidly. These findings show a good agreement with the behaviour exhibited by actual organisms that replicate their genomes under broadly different mutation rates.

  20. Preleukemic and second-hit mutational events in an acute myeloid leukemia patient with a novel germline RUNX1 mutation.

    Science.gov (United States)

    Ng, Isaac Ks; Lee, Joanne; Ng, Christopher; Kosmo, Bustamin; Chiu, Lily; Seah, Elaine; Mok, Michelle Meng Huang; Tan, Karen; Osato, Motomi; Chng, Wee-Joo; Yan, Benedict; Tan, Lip Kun

    2018-01-01

    Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear. We describe a patient of Malay descent with an unreported 7-bp germline RUNX1 frameshift deletion, who developed second-hit mutations that could have brought about the leukaemic transformation from a pre-leukaemic state. These mutations were charted through the course of the treatment and stem cell transplant, showing a clear correlation between her clinical presentation and the mutations present. The patient was a 27-year-old Malay woman who presented with AML on the background of hereditary thrombocytopenia affecting her father and 3 brothers. Initial molecular testing revealed the same novel RUNX1 mutation in all 5 individuals. The patient received standard induction, consolidation chemotherapy, and a haploidentical stem cell transplant from her mother with normal RUNX1 profile. Comprehensive genomic analyses were performed at diagnosis, post-chemotherapy and post-transplant. A total of 8 mutations ( RUNX1 , GATA2 , DNMT3A , BCORL1 , BCOR , 2 PHF6 and CDKN2A ) were identified in the pre-induction sample, of which 5 remained ( RUNX1 , DNMT3A , BCORL1 , BCOR and 1 out of 2 PHF6 ) in the post-treatment sample and none were present post-transplant. In brief, the 3 mutations which were lost along with the leukemic cells at complete morphological remission were most likely acquired leukemic driver mutations that were responsible for the AML transformation from a pre-leukemic germline RUNX1 -mutated state. On the contrary, the 5 mutations that persisted post

  1. Combination of the mutation process with the sensitization and repair processes leading to increased frequencies of mutations in algal populations

    International Nuclear Information System (INIS)

    Necas, J.

    1977-01-01

    The possibility of combining the mutation process with the induction of the repair processes was studied to increase the mutation frequencies in algal populations after UV treatment. The repair process induced by visible light was found to be much more effective than the dark repair processes in the chlorococcal algae used. In these algae, visible light possibly does not induce only those repair processes which affect their DNA, but probably also certain recovery processes which affect their damaged structures and physiological functions. A suitable combination of the sensitization of algae cells by a DNA-base analogue before UV treatment and the induction of the light repair and recovery processes resulted in a rather high increase of viable mutations in chlorococcal algae. These findings may be useful in breeding chlorococcal algae, which have no possibility of hybridization other than somatic. (author)

  2. The use of optical markers for mutation breeding

    International Nuclear Information System (INIS)

    Makino, Takahiro

    2003-01-01

    The use of radiation for mutation breeding has produced many kinds of practical varieties in crops and ornamental plants over the last several decades. Cold-tolerant rice and disease-resistant apple and pears are well-known varieties resulting from radiation breeding in Japan, and X-ray mutations were used routinely for the expansion of petal color in the chrysanthemum. Recently, the use of ion-beams for mutation induction was investigated as an effective source for producing varieties in cereal crops and flowers in Japan and China (Harten, 1998). Although we have not produced many varieties through radiation breeding, the success rate could increase with the addition of more resources. The success of mutation breeding greatly depends on the rate of mutation, the number of screened plants, and the mutation efficiency. The mutation rate is mainly a function of the total dose of the mutagen employed, although it can be modified by physical and biological factors. A large number of reports have been produced and effective methods of mutation treatments, such as gamma rays, established. Using higher doses inevitably brings about mortality, high pollen and seed sterility, and deleterious mutations. A practical useful dosage is usually found in the range much less than the maximum dose that can be applied. To increase the efficiency of mutation breeding, improvement of screening methods is more important than trials used for raising mutation probabilities. For this reason, we began studies to develop non-destructive and non-invasive optical high-throughput screening systems to increase the efficiency of mutation breeding. (author)

  3. Pathoadaptation of a Human Pathogen Through Non-Coding Intergenic Mutations

    DEFF Research Database (Denmark)

    Khademi, Seyed Mohammad Hossein

    in CF adaptation of P. aeruginosa and their expressions are altered by the mutation. It was established that mutations upstream ampR increased tolerance of P. aeruginosa to some β-lactam antibiotics. Mutations in promoter of phuR, encoding receptor of pseudomonas heme uptake system, conferred growth...... advantage in the presence of hemoglobin demonstrating that P. aeruginosa has adapted towards utilization of iron from hemoglobin. Further investigation of phuR promoter mutation revealed pleiotropic effects on expression of many other genes. The pleiotropic effect by this mutation was contingent...

  4. Inductive Communication System Design Summary

    Science.gov (United States)

    1978-09-01

    The report documents the experience obtained during the design and development of the Inductive Communications System used in the Morgantown People Mover. The Inductive Communications System is used to provide wayside-to-vehicle and vehicle-to-waysid...

  5. Identification of distal silencing elements in the murine interferon-A11 gene promoter.

    Science.gov (United States)

    Roffet, P; Lopez, S; Navarro, S; Bandu, M T; Coulombel, C; Vignal, M; Doly, J; Vodjdani, G

    1996-08-01

    The murine interferon-A11 (Mu IFN-A11) gene is a member of the IFN-A multigenic family. In mouse L929 cells, the weak response of the gene's promoter to viral induction is due to a combination of both a point mutation in the virus responsive element (VRE) and the presence of negatively regulating sequences surrounding the VRE. In the distal part of the promoter, the negatively acting E1E2 sequence was delimited. This sequence displays an inhibitory effect in either orientation or position on the inducibility of a virus-responsive heterologous promoter. It selectively represses VRE-dependent transcription but is not able to reduce the transcriptional activity of a VRE-lacking promoter. In a transient transfection assay, an E1E2-containing DNA competitor was able to derepress the native Mu IFN-A11 promoter. Specific nuclear factors bind to this sequence; thus the binding of trans-regulators participates in the repression of the Mu IFN-A11 gene. The E1E2 sequence contains an IFN regulatory factor (IRF)-binding site. Recombinant IRF2 binds this sequence and anti-IRF2 antibodies supershift a major complex formed with nuclear extracts. The protein composing the complex is 50 kDa in size, indicating the presence of IRF2 or antigenically related proteins in the complex. The Mu IFN-A11 gene is the first example within the murine IFN-A family, in which a distal promoter element has been identified that can negatively modulate the transcriptional response to viral induction.

  6. Duodenal ulcer promoting gene 1 (dupA1 is associated with A2147G clarithromycin-resistance mutation but not interleukin-8 secretion from gastric mucosa in Iraqi patients

    Directory of Open Access Journals (Sweden)

    N.R. Hussein

    2015-07-01

    Full Text Available Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8 secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU and duodenal ulcer (DU was significantly higher than those isolated from non-ulcer disease (NUD (90% and 57.9% versus 33.3%; p 0.01. The vacA s1m1 genotype was more prevalent in patients with DU (73.7% and GU (70% than in those with NUD (13.3% (p 0.01. The prevalence of dupA1 was higher in DU patients (36.8% than those with GU (10% and NUD (8.9% (p 0.01. Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD with increased odds of developing PUD (p 0.03; OR = 2.1. We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6. While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01. Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.

  7. Duodenal ulcer promoting gene 1 (dupA1) is associated with A2147G clarithromycin-resistance mutation but not interleukin-8 secretion from gastric mucosa in Iraqi patients.

    Science.gov (United States)

    Hussein, N R; Tunjel, I; Majed, H S; Yousif, S T; Aswad, S I; Assafi, M S

    2015-07-01

    Helicobacter pylori causes peptic ulceration and gastric adenocarcinoma. The aims were to study the influence of dupA1 positivity upon interleukin-8 (IL-8) secretion from gastric mucosa and determine the prevalence of mutations responsible for clarithromycin and fluoroquinolone resistance. DNA was extracted from 74 biopsies and the virulence factors were studied. Levels of IL-8 in gastric mucosa were measured using ELISA and the mutations responsible for clarithromycin and fluoroquinolone resistance were determined using a GenoType-HelicoDR assay. The prevalence of cagA in strains isolated from gastric ulcer (GU) and duodenal ulcer (DU) was significantly higher than those isolated from non-ulcer disease (NUD) (90% and 57.9% versus 33.3%; p 0.01). The vacA s1m1 genotype was more prevalent in patients with DU (73.7%) and GU (70%) than in those with NUD (13.3%) (p 0.01). The prevalence of dupA1 was higher in DU patients (36.8%) than those with GU (10%) and NUD (8.9%) (p 0.01). Multivariate analysis showed that a cagA+/vacA s1i1m2 virulence gene combination was independently associated with the developing peptic ulcer disease (PUD) with increased odds of developing PUD (p 0.03; OR = 2.1). We found no significant difference in the levels of IL-8 secretion in gastric mucosa infected with H. pylori dupA-negative and H. pylori dupA1-positive strains (dupA-negative: mean ± median: 28 ± 26 versus 30 ± 27.1 for dupA1; p 0.6). While 12 strains were clarithromycin resistant, only three isolates were levofloxacin resistant. A significant association was found between dupA1 genotype and A2147G clarithromycin resistance mutation (p <0.01). Further study is needed to explore the relationship between virulence factors and disease process and treatment failure.

  8. Turning up the volume on mutational pressure: Is more of a good thing always better? (A case study of HIV-1 Vif and APOBEC3

    Directory of Open Access Journals (Sweden)

    Wong Joseph K

    2008-03-01

    Full Text Available Abstract APOBEC3G and APOBEC3F are human cytidine deaminases that serve as innate antiviral defense mechanisms primarily by introducing C-to-U changes in the minus strand DNA of retroviruses during replication (resulting in G-to-A mutations in the genomic sense strand sequence. The HIV-1 Vif protein counteracts this defense by promoting the proteolytic degradation of APOBEC3G and APOBEC3F in the host cell. In the absence of Vif expression, APOBEC3 is incorporated into HIV-1 virions and the viral genome undergoes extensive G-to-A mutation, or "hypermutation", typically rendering it non-viable within a single replicative cycle. Consequently, Vif is emerging as an attractive target for pharmacological intervention and therapeutic vaccination. Although a highly effective Vif inhibitor may result in mutational meltdown of the viral quasispecies, a partially effective Vif inhibitor may accelerate the evolution of drug resistance and immune escape due to the codon structure and recombinogenic nature of HIV-1. This hypothesis rests on two principal assumptions which are supported by experimental evidence: a there is a dose response between intracellular APOBEC concentration and degree of viral hypermutation, and, b HIV-1 can tolerate an elevated mutation rate, and a true error or extinction threshold is as yet undetermined. Rigorous testing of this hypothesis will have timely and critical implications for the therapeutic management of HIV/AIDS, and delve into the complexities underlying the induction of lethal mutagenesis in a viral pathogen.

  9. Induction technology optimization code

    International Nuclear Information System (INIS)

    Caporaso, G.J.; Brooks, A.L.; Kirbie, H.C.

    1992-01-01

    A code has been developed to evaluate relative costs of induction accelerator driver systems for relativistic klystrons. The code incorporates beam generation, transport and pulsed power system constraints to provide an integrated design tool. The code generates an injector/accelerator combination which satisfies the top level requirements and all system constraints once a small number of design choices have been specified (rise time of the injector voltage and aspect ratio of the ferrite induction cores, for example). The code calculates dimensions of accelerator mechanical assemblies and values of all electrical components. Cost factors for machined parts, raw materials and components are applied to yield a total system cost. These costs are then plotted as a function of the two design choices to enable selection of an optimum design based on various criteria. (Author) 11 refs., 3 figs

  10. Glass manufacturing through induction

    International Nuclear Information System (INIS)

    Boen, R.; Paya, B.; Roscini, M.; Fautrelle, Y.; Tuaz, F.; Delage, D.

    1991-01-01

    Oxides and glasses are electrical and thermal insulators, but show the characteristic of being weakly conductors of electricity when they are melt. It is then possible to heat them through HF induction. This interesting property allows the development of a melting process in cold crucible induction furnace. The process is being studied and developed by a consortium made up of CFEI, CEA Marcoule, ELECTRICITE DE FRANCE and MADYLAM laboratory. The studies include 2 parts: a) One experimental part to develop the technology and research for satisfying configurations, through a small size platform (10 to 30 kg/h). The long run continuous pouring melting tests made on different kinds of glass allow to go-on with industrial range units. b) One theoretical part to understand the magneto-thermo-hydraulic phenomenon hardly in relation with the heavy dependence of the physical characteristics (electrical and heat conductivities, viscosity) according to temperature. 6 refs., 4 figs [fr

  11. Inductive energy storage commutator

    International Nuclear Information System (INIS)

    Gavrilov, I.M.

    1987-01-01

    An inductive energy storage commutator is described. The value of commutated current is up to 800 A, the voltage amplitude in the load is up to 50 kV, the working frequency is equal to 1-50 Hz, the commutated power is up to 40 MW. The commutating device comprises of the first stage commutator having two in-series connected modules of the BTSV - 800/235 high-voltage thyristor unit, the second stage commutator containing three GMI-43A parallel connected powerful pulsed triodes, a commutating capacitor, an induction coil, two supplementary high-voltage thyristor keys (20 in-series connected thyristors T2-300 (13 class)), load, control pulse shapers, thyristor keys, power supply

  12. Pulse induction heating

    Energy Technology Data Exchange (ETDEWEB)

    Vasiliev, A S; Kachanov, B Y; Kogan, B V

    1993-12-31

    Induction heating and three types of pulse processes were studied. It was found that in pulse processes the frequency and pulse duration of heat treatments do not remain constant. High frequency pulse heat treatments can be used on sprayed coatings; such treatments will result in stronger surfaces with no cracks. For induction hardening, the rate of specific power was 1 to 1.5 kW/sq.cm, for forging it was 0.2 to 0.3 kW/sq.cm and for melting it was 0.05 to 0.1 kW/sq.cm. The application of pulse heating will result in higher rates of specific power.

  13. UV induction of coliphage 186: Prophage induction as an SOS function

    Energy Technology Data Exchange (ETDEWEB)

    Lamont, I.; Brumby, A.M.; Egan, J.B.

    1989-07-01

    Our results show that UV induction of the 186 prophage depends upon the phage function Tum, with the mutant phenotype of turbid plaques on mitomycin plates and the expression of which is controlled by the host LexA protein. Tum function, encoded near the right-hand end of the coliphage 186 chromosome, is under the control of promoter p95. This promoter is overlapped by a sequence closely related to the consensus sequence of the LexA-binding site. It is proposed that inactivation of LexA after UV irradiation (or by genetic means) leads to prophage induction by permitting expression of Tum which, by unknown means, induces prophage. This mechanism is basically different from that seen with the UV-inducible lambdoid coliphages, which are not regulated by LexA.

  14. Inductive Reasoning: A Training Approach

    Science.gov (United States)

    Klauer, Karl Josef; Phye, Gary D.

    2008-01-01

    Researchers have examined inductive reasoning to identify different cognitive processes when participants deal with inductive problems. This article presents a prescriptive theory of inductive reasoning that identifies cognitive processing using a procedural strategy for making comparisons. It is hypothesized that training in the use of the…

  15. Lexicographic Path Induction

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Sarnat, Jeffrey

    2009-01-01

    Programming languages theory is full of problems that reduce to proving the consistency of a logic, such as the normalization of typed lambda-calculi, the decidability of equality in type theory, equivalence testing of traces in security, etc. Although the principle of transfinite induction......, and weak normalization for Gödel’s T follows indirectly; both have been formalized in a prototypical extension of Twelf....

  16. Radiation oxidative stress in cancer induction and prevention

    International Nuclear Information System (INIS)

    Meher, Prabodha Kumar; Mishra, Kaushala Prasad

    2017-01-01

    Exposure of cells to ionizing radiation causes generation of intracellular reactive oxygen species (ROS) which are implicated in the mechanism of carcinogenesis. Molecular steps involved in the transformation of normal cells to cancer cells have been enigmatic but generally believed to arise from aberration in cellular redox homeostasis. In normal cell function, a delicate balance is maintained between ROS generated in the metabolic process and level of endogenous antioxidant defense. ROS are known to regulate various cellular functions, such as cell division, signal transduction, and apoptosis. Cells experience oxidative stress when excess production of ROS occurs inside a cell upon exposure to external stress or agents. This redox imbalance affects the cellular functions due to DNA strand breaks, chromosomal aberrations, gene mutations, alteration in signal transduction, and inhibition of apoptosis leading to induction of cancer and other diseases. Radiation-induced ROS are involved in initiation and promotion of carcinogenesis. Therefore, detoxification of ROS by exogenous antioxidants including dietary polyphenols offers an important strategy for cancer prevention. Recent research results have shown that resistance of cancer stem cells to therapies is linked to low level of ROS. Interestingly, in vitro and in vivo experiments have reported that radiotherapy- and chemotherapy-induced ROS in cytosol sensitize the tumor cells to death, resulting in tumor growth retardation. This review is an attempt to delineate mechanisms of ROS in carcinogenesis and prevention by dietary compounds. Natural polyphenols and dietary antioxidants hold potential to prevent cancer. Interventions in ROS-mediated signal alteration, apoptosis activation, and modulation of epigenetic processes may offer effective cancer prevention strategy. (author)

  17. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960's to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore's Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail

  18. Diagnostics for induction accelerators

    International Nuclear Information System (INIS)

    Fessenden, T.J.

    1997-01-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at Lawrence Livermore National Laboratory (LLNL) from the early 1960s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400-ns pulses. The Advanced Test Accelerator (ATA) built at Livermore close-quote s Site 300 produced 10,000-Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and Lawrence Berkeley National Laboratory (LBNL). This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high-current, short-pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail. copyright 1997 American Institute of Physics

  19. Impact of mutation breeding in rice

    International Nuclear Information System (INIS)

    Rutger, J.N.

    1992-01-01

    More cultivars have been developed in rice through the use of mutation breeding than in any other crop. Direct releases of mutants as cultivars began some 30 years ago, and now total 198 cultivars. During the last 20 years, increasing use has been made of induced mutants in cross-breeding programs, leading to 80 additional cultivars. Principal improvements through mutation breeding have been earlier maturity, short stature, and grain character modifications. Rice has been a popular subject of mutagenesis because it is the world's leading food crop, has diploid inheritance, and is highly self-pollinated. In recent years induced mutation has been exploited to develop breeding tool mutants, which are defined as mutants that in themselves may not have direct agronomic application but may be useful genetic tools for crop improvement. Examples include the eui gene, hull colour mutants, normal genetic male steriles, and environmentally sensitive genetic male steriles. The environmentally sensitive genetic male steriles, especially those in which male sterility can be turned on or off by different photoperiod lengths, show promise for simplifying hybrid rice seed production both in China and the USA. Future applications of mutation in rice include induction of unusual endosperm starch types, plant types with fewer but more productive tillers, dominant dwarfs, dominant genetic male steriles, extremely early maturing mutants, nutritional mutants, and in vitro-derived mutants for tolerance to herbicides or other growth stresses. Refs, 4 figs, 2 tabs

  20. Inductive reasoning 2.0.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan

    2018-05-01

    Inductive reasoning entails using existing knowledge to make predictions about novel cases. The first part of this review summarizes key inductive phenomena and critically evaluates theories of induction. We highlight recent theoretical advances, with a special emphasis on the structured statistical approach, the importance of sampling assumptions in Bayesian models, and connectionist modeling. A number of new research directions in this field are identified including comparisons of inductive and deductive reasoning, the identification of common core processes in induction and memory tasks and induction involving category uncertainty. The implications of induction research for areas as diverse as complex decision-making and fear generalization are discussed. This article is categorized under: Psychology > Reasoning and Decision Making Psychology > Learning. © 2017 Wiley Periodicals, Inc.

  1. A taxonomy of inductive problems.

    Science.gov (United States)

    Kemp, Charles; Jern, Alan

    2014-02-01

    Inductive inferences about objects, features, categories, and relations have been studied for many years, but there are few attempts to chart the range of inductive problems that humans are able to solve. We present a taxonomy of inductive problems that helps to clarify the relationships between familiar inductive problems such as generalization, categorization, and identification, and that introduces new inductive problems for psychological investigation. Our taxonomy is founded on the idea that semantic knowledge is organized into systems of objects, features, categories, and relations, and we attempt to characterize all of the inductive problems that can arise when these systems are partially observed. Recent studies have begun to address some of the new problems in our taxonomy, and future work should aim to develop unified theories of inductive reasoning that explain how people solve all of the problems in the taxonomy.

  2. Compilation and analysis of Escherichia coli promoter DNA sequences.

    OpenAIRE

    Hawley, D K; McClure, W R

    1983-01-01

    The DNA sequence of 168 promoter regions (-50 to +10) for Escherichia coli RNA polymerase were compiled. The complete listing was divided into two groups depending upon whether or not the promoter had been defined by genetic (promoter mutations) or biochemical (5' end determination) criteria. A consensus promoter sequence based on homologies among 112 well-defined promoters was determined that was in substantial agreement with previous compilations. In addition, we have tabulated 98 promoter ...

  3. Mutation induced with ion beam irradiation in rose

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, H. E-mail: yhiroya@nias.affrc.go.jp; Nagatomi, S.; Morishita, T.; Degi, K.; Tanaka, A.; Shikazono, N.; Hase, Y

    2003-05-01

    The effects of mutation induction by ion beam irradiation on axillary buds in rose were investigated. Axillary buds were irradiated with carbon and helium ion beams, and the solid mutants emerged after irradiation by repeated cutting back. In helium ion irradiation, mutations were observed in plants derived from 9 buds among 56 irradiated buds in 'Orange Rosamini' and in plants derived from 10 buds among 61 irradiated buds in 'Red Minimo'. In carbon ion, mutations were observed in plants derived from 12 buds among 88 irradiated buds in 'Orange Rosamini'. Mutations were induced not only in higher doses but also in lower doses, with which physiological effect by irradiation was hardly observed. Irradiation with both ion beams induced mutants in the number of petals, in flower size, in flower shape and in flower color in each cultivar.

  4. Induced mutations for disease resistance in wheat and barley

    International Nuclear Information System (INIS)

    Hanis, M.; Hanisova, A.; Knytl, V.; Cerny, J.; Benc, S.

    1977-01-01

    The induction of mutations in cultivars of wheat (Triticum aestivum), barley (Hordeum vulgare), and field beans (Phaseolus vulgaris) has been part of the breeding programme at the Plant Breeding Station at Stupice since 1960. A total of 26 cultivars or selections of winter wheat, 4 cultivars or selections of spring wheat, 2 cultivars of field beans, and 43 selections of spring barley have been treated since 1960. A total of 140 mutant lines of wheat and 37 mutant lines of barley with improved disease resistance of a race-specific type have been obtained. Several mutation programme derived cultivars have been registered in Czechoslovakia (''Diamant'', ''Ametyst'', ''Favorit'', ''Hana'', ''Rapid'', and ''Atlas'' in barley, and ''Alfa'' in field beans), but none of them is a mutation for disease resistance. A series of mutants have been used in crossing programmes. Approaches to improve the efficiency of mutation breeding for disease resistance are suggested. (author)

  5. Mutation and premating isolation

    Science.gov (United States)

    Woodruff, R. C.; Thompson, J. N. Jr

    2002-01-01

    While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

  6. Plant Mutation Reports, Vol. 2, No. 3, April 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-04-15

    Enhancing crop yields, improving food quality and value in an environmentally friendly manner, and sustaining crop biodiversity continue to be key goals for improving agricultural production. Mutation induction techniques are undergoing a renaissance in crop improvement because of advancements in modern efficiency enhancing biotechnologies - irreplaceable tools in the tool box of the breeder. In the context of climate change and variability, mutation induction is a proven way to generate diversity in existing crop varieties, to widen the extent of adaptability and enhance productivity of crop biomass. We are encouraged by the contributions from our Member States to this journal. In many countries, we see that a broad variety of plant species and target traits are addressed using mutation induction. In this issue, the technical papers highlight studies on induced mutagenesis using either physical or chemical mutagens in a range of food and industrial crops. Dr Tulmann Neto gives an extensive review of 40 years of induced mutations in plant breeding in Brazil. A number of mutant derived varieties ranging from cereals, legumes, fruits and spices were developed together with commercial breeding companies and have significant economic value in Latin America. We trust that these reports will reignite a drive in experienced users of induced mutants in plant breeding and stir an interest in younger scientists

  7. Plant Mutation Reports, Vol. 2, No. 3, April 2011

    International Nuclear Information System (INIS)

    2011-04-01

    Enhancing crop yields, improving food quality and value in an environmentally friendly manner, and sustaining crop biodiversity continue to be key goals for improving agricultural production. Mutation induction techniques are undergoing a renaissance in crop improvement because of advancements in modern efficiency enhancing biotechnologies - irreplaceable tools in the tool box of the breeder. In the context of climate change and variability, mutation induction is a proven way to generate diversity in existing crop varieties, to widen the extent of adaptability and enhance productivity of crop biomass. We are encouraged by the contributions from our Member States to this journal. In many countries, we see that a broad variety of plant species and target traits are addressed using mutation induction. In this issue, the technical papers highlight studies on induced mutagenesis using either physical or chemical mutagens in a range of food and industrial crops. Dr Tulmann Neto gives an extensive review of 40 years of induced mutations in plant breeding in Brazil. A number of mutant derived varieties ranging from cereals, legumes, fruits and spices were developed together with commercial breeding companies and have significant economic value in Latin America. We trust that these reports will reignite a drive in experienced users of induced mutants in plant breeding and stir an interest in younger scientists

  8. Linear induction motor

    International Nuclear Information System (INIS)

    Barkman, W.E.; Adams, W.Q.; Berrier, B.R.

    1978-01-01

    A linear induction motor has been operated on a test bed with a feedback pulse resolution of 5 nm (0.2 μin). Slewing tests with this slide drive have shown positioning errors less than or equal to 33 nm (1.3 μin) at feedrates between 0 and 25.4 mm/min (0-1 ipm). A 0.86-m (34-in)-stroke linear motor is being investigated, using the SPACO machine as a test bed. Initial results were encouraging, and work is continuing to optimize the servosystem compensation

  9. Antibody induction versus corticosteroid induction for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, André; Wilson, Colin H

    2014-01-01

    BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation....... OBJECTIVES: To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register...... to identify additional trials. SELECTION CRITERIA: We included all randomised clinical trials assessing immunosuppression with T-cell specific antibody induction versus corticosteroid induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should...

  10. Pulsed inductive HF laser

    Energy Technology Data Exchange (ETDEWEB)

    Razhev, A M; Kargapol' tsev, E S [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation); Churkin, D S; Demchuk, S V [Novosibirsk State University, Novosibirsk (Russian Federation)

    2016-03-31

    We report the results of experimentally investigated dependences of temporal, spectral and spatial characteristics of an inductive HF-laser generation on the pump conditions. Gas mixtures H{sub 2} – F{sub 2}(NF{sub 3} or SF6{sub 6}) and He(Ne) – H{sub 2} – F{sub 2}(NF{sub 3} or SF{sub 6}) were used as active media. The FWHM pulse duration reached 0.42 μs. This value corresponded to a pulsed power of 45 kW. For the first time, the emission spectrum of an inductive HF laser was investigated, which consisted of seven groups of bands with centres around the wavelengths of 2732, 2736, 2739, 2835, 2837, 2893 and 2913 nm. The cross section profile of the laser beam was a ring with a diameter of about 20 mm and width of about 5 mm. Parameters of laser operation in the repetitively pulsed regime were sufficiently stable. The amplitude instability of light pulses was no greater than 5% – 6%. (lasers)

  11. Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity

    DEFF Research Database (Denmark)

    Larsen, Lesli H; Echwald, Søren Morgenthaler; Sørensen, Thorkild I A

    2005-01-01

    )) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared...

  12. Utilization of radiations in mutation breeding of tuber crops

    International Nuclear Information System (INIS)

    Kukimura, H.

    1981-01-01

    Most of the tuber crops are vegetatively propagated and their spontaneous mutations have been constructively utilized to practical farming. Significance of utilization of mutations to breeding should not be overlooked, since mutation can be articially induced by various mutagenic agents. In tuber crops, ionizing radiations are mostly applied to induce mutations. Radiosensitivity varies with species, genotypes and organs. For the purpose of mutation induction, 10-20 kR of gamma-rays is given to tubers and/or shoots in sweet potato and 2-10 kR in potato. It should be noted that radiation damage is more or less transmissible to later vegetative generations. A useful characters in practical agriculture, following mutations have been obtained so far: skin colour, short stemmed, changes in dry matter content, total sugars content and tuber yield, earlier maturity and sculf resistance in sweet potato. And, skin colour, changes in starch content and stolon length, day-neutral tuberization and cyst-nematode resistance in potato. Apart from mutations, radiation can be utilized for breaking down the incompatibility in sweet potato. Promising mutant clones with probable release in Japan are Kyushu 78 of sweet potato and Koniku 16 and Konkei 55 of potato. (author)

  13. Comparative studies of dose-response curves for recessive lethal mutations induced by ethylnitrosourea in spermatogonia and in spermatozoa of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, I.; Ayaki, T.; Ohshima, K.

    1984-01-01

    Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.

  14. Improvement of bambara groundnut production using induced mutations

    Energy Technology Data Exchange (ETDEWEB)

    Amoatey, H M; Klu, G Y.P. [Biotechnology and Nuclear Agricultural Research Inst., Ghana Atomic Energy Commission, Legon (Ghana)

    1997-12-01

    Induction of variation in bambara groundnut using gamma radiation has been tried before. However, no mutants with the desired determinate flowering habit and synchronous pod maturity were obtained. This project is aimed at: conducting a nationwide exploration exercise to collect germplasm of bambara groundnut for agronomic evaluation with respect to flowering and fruiting characteristics and their effects on yield; and, applying the technique of mutation induction to create variability (if this is not found in the germplasm to be collected) from which mutants with determinate flowering and fruiting habit may be selected for use in breeding. 6 refs.

  15. Improvement of bambara groundnut production using induced mutations

    International Nuclear Information System (INIS)

    Amoatey, H.M.; Klu, G.Y.P.

    1997-01-01

    Induction of variation in bambara groundnut using gamma radiation has been tried before. However, no mutants with the desired determinate flowering habit and synchronous pod maturity were obtained. This project is aimed at: conducting a nationwide exploration exercise to collect germplasm of bambara groundnut for agronomic evaluation with respect to flowering and fruiting characteristics and their effects on yield; and, applying the technique of mutation induction to create variability (if this is not found in the germplasm to be collected) from which mutants with determinate flowering and fruiting habit may be selected for use in breeding. 6 refs

  16. RBE-LET relationships of high-LET radiations in drosophila mutations

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Takatsuji, Toshihiro; Nagano, Masaaki; Takada, Jun; Endo, Satoru; Hoshi, Masaharu

    1999-01-01

    The relative biological effectiveness (RBE) of 252 Cf neutrons and synchrotron-generated high-energy charged particles for mutation induction was evaluated as a function of linear energy transfer (LET), using the loss of heterozygosity for wing-hair mutations and the reversion of the mutant white-ivory eye-color in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change (2.96 kb-DNA excision) in the white locus on the X-chromosome. The measurements were performed in a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clone can be detected simultaneously in the same individual. Larvae were irradiated at the age of 3 days post oviposition with 252 Cf neutrons, carbon beam or neon beam. For the neutron irradiation, the RBE values for wing-hair mutations were larger than that for eye-color mutation by about 7 fold. The RBE of carbon ions for producing the wing-hair mutations increased with increase in LET. The estimated RBE values were found to be in the range 2 to 6.5 for the wing-hair. For neon beam irradiation, the RBE values for wing-hair mutations peak near 150 keV/μm and decrease with further increase in LET. On the other hand, the RBE values for the induction of the eye-color mutation are nearly unity in 252 Cf neutrons and both ions throughout the LET range irradiated. We discuss the relationships between the initial DNA damage and LET in considering the mechanism of somatic mutation induction. (author)

  17. Vector control of induction machines

    CERN Document Server

    Robyns, Benoit

    2012-01-01

    After a brief introduction to the main law of physics and fundamental concepts inherent in electromechanical conversion, ""Vector Control of Induction Machines"" introduces the standard mathematical models for induction machines - whichever rotor technology is used - as well as several squirrel-cage induction machine vector-control strategies. The use of causal ordering graphs allows systematization of the design stage, as well as standardization of the structure of control devices. ""Vector Control of Induction Machines"" suggests a unique approach aimed at reducing parameter sensitivity for

  18. Genetic Mutations in Cancer

    Science.gov (United States)

    Many different types of genetic mutations are found in cancer cells. This infographic outlines certain types of alterations that are present in cancer, such as missense, nonsense, frameshift, and chromosome rearrangements.

  19. AIP mutations and gigantism.

    Science.gov (United States)

    Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F; Beckers, Albert

    2017-06-01

    AIP mutations are rare in sporadic acromegaly but they are seen at a higher frequency among certain specific populations of pituitary adenoma patients (pituitary gigantism cases, familial isolated pituitary adenoma (FIPA) kindreds, and patients with macroadenomas who are diagnosed ≤30 years). AIP mutations are most prevalent in patients with pituitary gigantism (29% of this group were found to have mutations in AIP gene). These data support targeted genetic screening for AIP mutations/deletions in these groups of pituitary adenoma patients. Earlier diagnosis of AIP-related acromegaly-gigantism cases enables timely clinical evaluation and treatment, thereby improving outcomes in terms of excessive linear growth and acromegaly comorbidities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Borehole induction coil transmitter

    Science.gov (United States)

    Holladay, Gale; Wilt, Michael J.

    2002-01-01

    A borehole induction coil transmitter which is a part of a cross-borehole electromagnetic field system that is used for underground imaging applications. The transmitter consists of four major parts: 1) a wound ferrite or mu-metal core, 2) an array of tuning capacitors, 3) a current driver circuit board, and 4) a flux monitor. The core is wound with several hundred turns of wire and connected in series with the capacitor array, to produce a tuned coil. This tuned coil uses internal circuitry to generate sinusoidal signals that are transmitted through the earth to a receiver coil in another borehole. The transmitter can operate at frequencies from 1-200 kHz and supplies sufficient power to permit the field system to operate in boreholes separated by up to 400 meters.

  1. Inductive circuit arrangements

    International Nuclear Information System (INIS)

    Mansfield, Peter; Coxon, R.J.

    1987-01-01

    A switched coil arrangement is connected in a bridge configuration of four switches S 1 , S 2 , S 3 and S 4 which are each shunted by diodes D 1 , D 2 , D 3 and D 4 so that current can flow in either direction through a coil L depending on the setting of the switches. A capacitor C is connected across the bridge through a switch S 5 to receive the inductive energy stored in coil L on breaking the current flow path through the coil. The electrostatic energy stored in capacitor C can then be used to supply current through the coil in the reverse direction either immediately or after a time delay. Coil L may be a superconductive coil. Losses in the circuit can be made up by a trickle charge of capacitor C from a separate supply V 2 . The device may be used in nuclear magnetic resonance imaging. (author)

  2. Induction heating using induction coils in series-parallel circuits

    Science.gov (United States)

    Matsen, Marc Rollo; Geren, William Preston; Miller, Robert James; Negley, Mark Alan; Dykstra, William Chet

    2017-11-14

    A part is inductively heated by multiple, self-regulating induction coil circuits having susceptors, coupled together in parallel and in series with an AC power supply. Each of the circuits includes a tuning capacitor that tunes the circuit to resonate at the frequency of AC power supply.

  3. A novel p53 mutational hotspot in skin tumors from UV-irradiated Xpc mutant mice alters transactivation functions.

    Science.gov (United States)

    Inga, Alberto; Nahari, Dorit; Velasco-Miguel, Susana; Friedberg, Errol C; Resnick, Michael A

    2002-08-22

    A mutation in codon 122 of the mouse p53 gene resulting in a T to L amino acid substitution (T122-->L) is frequently associated with skin cancer in UV-irradiated mice that are both homozygous mutant for the nucleotide excision repair (NER) gene Xpc (Xpc(-/-)) and hemizygous mutant for the p53 gene. We investigated the functional consequences of the mouse T122-->L mutation when expressed either in mammalian cells or in the yeast Saccharomyces cerevisiae. Similar to a non-functional allele, high expression of the T122-->L allele in p53(-/-) mouse embryo fibroblasts and human Saos-2 cells failed to suppress growth. However, the T122-->L mutant p53 showed wild-type transactivation levels with Bax and MDM2 promoters when expressed in either cell type and retained transactivation of the p21 and the c-Fos promoters in one cell line. Using a recently developed rheostatable p53 induction system in yeast we assessed the T122-->L transactivation capacity at low levels of protein expression using 12 different p53 response elements (REs). Compared to wild-type p53 the T122-->L protein manifested an unusual transactivation pattern comprising reduced and enhanced activity with specific REs. The high incidence of the T122-->L mutant allele in the Xpc(-/-) background suggests that both genetic and epigenetic conditions may facilitate the emergence of particular functional p53 mutations. Furthermore, the approach that we have taken also provides for the dissection of functions that may be retained in many p53 tumor alleles.

  4. Mechanisms of neuroimmune gene induction in alcoholism.

    Science.gov (United States)

    Crews, Fulton T; Vetreno, Ryan P

    2016-05-01

    Alcoholism is a primary, chronic relapsing disease of brain reward, motivation, memory, and related circuitry. It is characterized by an individual's continued drinking despite negative consequences related to alcohol use, which is exemplified by alcohol use leading to clinically significant impairment or distress. Chronic alcohol consumption increases the expression of innate immune signaling molecules (ISMs) in the brain that alter cognitive processes and promote alcohol drinking. Unraveling the mechanisms of alcohol-induced neuroimmune gene induction is complicated by positive loops of multiple cytokines and other signaling molecules that converge on nuclear factor kappa-light-chain-enhancer of activated B cells and activator protein-1 leading to induction of additional neuroimmune signaling molecules that amplify and expand the expression of ISMs. Studies from our laboratory employing reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA, immunohistochemistry and Western blot analysis to assess protein expression, and others suggest that ethanol increases brain neuroimmune gene and protein expression through two distinct mechanisms involving (1) systemic induction of innate immune molecules that are transported from blood to the brain and (2) the direct release of high-mobility group box 1 (HMGB1) from neurons in the brain. Released HMGB1 signals through multiple receptors, particularly Toll-like receptor (TLR) 4, that potentiate cytokine receptor responses leading to a hyperexcitable state that disrupts neuronal networks and increases excitotoxic neuronal death. Innate immune gene activation in brain is persistent, consistent with the chronic relapsing disease that is alcoholism. Expression of HMGB1, TLRs, and other ISMs is increased several-fold in the human orbital frontal cortex, and expression of these molecules is highly correlated with each other as well as lifetime alcohol consumption and age of drinking onset. The persistent and

  5. Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis.

    Science.gov (United States)

    Fan, Yu; Wang, Ye; Wang, Ke

    2015-12-18

    Cyclooxygenase-2-derived prostaglandin E2 (PGE2), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE2 stimulated lung cancer cell growth and progression through PGE2 receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE2 in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2. The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE2. PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE2 receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. We demonstrated that PGE2 increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE2 on normal cell growth. The PGE2-induced PDK1 expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE2 was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE2. In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. PGE2 increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell

  6. Mutation of Rice BC12/GDD1, Which Encodes a Kinesin-Like Protein That Binds to a GA Biosynthesis Gene Promoter, Leads to Dwarfism with Impaired Cell Elongation[W][OA

    Science.gov (United States)

    Li, Juan; Jiang, Jiafu; Qian, Qian; Xu, Yunyuan; Zhang, Cui; Xiao, Jun; Du, Cheng; Luo, Wei; Zou, Guoxing; Chen, Mingluan; Huang, Yunqing; Feng, Yuqi; Cheng, Zhukuan; Yuan, Ming; Chong, Kang

    2011-01-01

    The kinesins are a family of microtubule-based motor proteins that move directionally along microtubules and are involved in many crucial cellular processes, including cell elongation in plants. Less is known about kinesins directly regulating gene transcription to affect cellular physiological processes. Here, we describe a rice (Oryza sativa) mutant, gibberellin-deficient dwarf1 (gdd1), that has a phenotype of greatly reduced length of root, stems, spikes, and seeds. This reduced length is due to decreased cell elongation and can be rescued by exogenous gibberellic acid (GA3) treatment. GDD1 was cloned by a map-based approach, was expressed constitutively, and was found to encode the kinesin-like protein BRITTLE CULM12 (BC12). Microtubule cosedimentation assays revealed that BC12/GDD1 bound to microtubules in an ATP-dependent manner. Whole-genome microarray analysis revealed the expression of ent-kaurene oxidase (KO2), which encodes an enzyme involved in GA biosynthesis, was downregulated in gdd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that GDD1 bound to the element ACCAACTTGAA in the KO2 promoter. In addition, GDD1 was shown to have transactivation activity. The level of endogenous GAs was reduced in gdd1, and the reorganization of cortical microtubules was altered. Therefore, BC12/GDD1, a kinesin-like protein with transcription regulation activity, mediates cell elongation by regulating the GA biosynthesis pathway in rice. PMID:21325138

  7. Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations | Office of Cancer Genomics

    Science.gov (United States)

    Large-scale sequencing efforts are uncovering the complexity of cancer genomes, which are composed of causal "driver" mutations that promote tumor progression along with many more pathologically neutral "passenger" events. The majority of mutations, both in known cancer drivers and uncharacterized genes, are generally of low occurrence, highlighting the need to functionally annotate the long tail of infrequent mutations present in heterogeneous cancers.

  8. Probabilistic inductive inference: a survey

    OpenAIRE

    Ambainis, Andris

    2001-01-01

    Inductive inference is a recursion-theoretic theory of learning, first developed by E. M. Gold (1967). This paper surveys developments in probabilistic inductive inference. We mainly focus on finite inference of recursive functions, since this simple paradigm has produced the most interesting (and most complex) results.

  9. A Student Teamwork Induction Protocol

    Science.gov (United States)

    Kamau, Caroline; Spong, Abigail

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  10. Sampling Assumptions in Inductive Generalization

    Science.gov (United States)

    Navarro, Daniel J.; Dry, Matthew J.; Lee, Michael D.

    2012-01-01

    Inductive generalization, where people go beyond the data provided, is a basic cognitive capability, and it underpins theoretical accounts of learning, categorization, and decision making. To complete the inductive leap needed for generalization, people must make a key "sampling" assumption about how the available data were generated.…

  11. From Inductive Reasoning to Proof

    Science.gov (United States)

    Yopp, David A.

    2009-01-01

    Mathematical proof is an express